Lupron

Lupron, Brain Function, and the Keto Diet

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Reproductive senescence, the time in a woman’s life marked by the slowing and eventual cessation of reproductive function, frequently coincides with an increased risk of a host of neurodegenerative disorders from memory impairment to dementia and Alzheimer’s disease. Researchers have long postulated that the loss of ovarian hormones was responsible; estradiol, in particular, but likely others as well.

This begs the question, what happens to the brain when we abruptly and artificially derail ovarian hormone synthesis in young women using drugs such as Lupron (leuprolide) and the other GnRH agonists and antagonists or by removing the ovaries altogether as in surgical oophorectomy? Is it the same damage we see in aging, only expedited and perhaps magnified, or does it run a different course? Along those same lines, though perhaps a topic for another day, what happens when we chronically supplant endogenous ovarian hormone production with synthetic hormones such as those used in hormonal birth control or menopausal hormone replacement therapies? I suspect, and there is evidence to back up my suspicions, that in all cases brain function is altered, and not for the better.

Estrogens and the Brain

The mechanisms by which estradiol and other steroid hormones influence brain function are myriad and complicated. Beyond just reproduction, steroid hormones influence all aspects of neurological function, with estrogen, androgen, glucocorticoid (cortisol), and mineralocorticoid (electrolyte balance, blood pressure) receptors located throughout the brain. Steroid hormones produced in the body, because of their fat solubility, easily cross the blood-brain barrier where they bind to their receptors and regulate all sorts of processes. Perhaps even more remarkable, the brain has all of the machinery to synthesize its own steroid hormones and so when body concentrations fall, at least for a time, the brain can compensate. Eventually, however, brain synthesis declines and that is where we begin to have problems. Fortunately, natural reproductive senescence occurs later in life and the risk of neurodegenerative diseases is just that, a risk, not a foretold conclusion. This suggests that other variables are at play, ones that we may be able to modulate to improve health, offset and/or reduce the severity of the natural neurodegenerative processes. Again, however, we must ask, what happens when we induce reproductive senescence in young women? By all accounts, the effects are often devastating, leaving many to wonder if they will ever recover.

Estradiol and Mitochondrial Energy

Among the myriad of functions mitochondria control, perhaps the most important is energy production. That is, mitochondria take the nutrients supplied by diet and convert them into adenosine triphosphate (ATP), the energy currency that cells use to perform all of the functions that keep us alive. The loss or diminishment of ATP is deleterious to health and can ultimately be deadly, by invoking a series of complicated processes

Estradiol is a critical component of that process and directly impacts mitochondrial energy production. That’s right, estradiol is part of the mitochondrial bioenergetic machinery such that when estradiol wanes, so too does energy production or ATP. As one might suspect, waning ATP is deleterious to brain health. In previous posts, I detailed the research showing how the loss of estradiol deforms mitochondrial morphology essentially disabling mitochondrial membrane potential while turning the mitochondria into misshapen donuts and blobs ripe for a slow, messy necrotic death; a process that evokes all sorts of deleterious reactions.

The Lupron Brain and Ketosis

Just recently, I stumbled upon research showing yet another mechanism of damage. In the absence of estradiol, brain glucose transport diminishes significantly. This effectively starves the brain for energy inducing severe bioenergetic deficiencies with all of the concordant neuronal damage one might expect. The reduction in glucose affects the mitochondria severely. Recall that glucose is one of the major fuel substrates of the brain, particularly where the Western diet predominates. The decline of glucose transport, therefore, is significant, and alone, without any other changes to the mitochondria, elicits a cascade of deleterious reactions. Oxidative phosphorylation and associated enzymes are downregulated, ATP production wanes, and ultimately may initiate the deformation of the very shape of the mitochondria, as observed in the research cited above. The ensuing reduction of ATP starves the brain of critical energy but also induces a state of hypoxia with the mitochondria incapable of utilizing molecular oxygen. With that hypoxia, inflammatory pathways are initiated further cementing mitochondrial death spirals and associated neuronal damage.

Interestingly, this reduction in aerobic activity coincides with the emergence of a ketogenic phenotype. That is, with the loss of one fuel substrate, ketones become the dominant source of fuel and the associated enzyme machinery is upregulated. Unfortunately, the Western diet is highly dependent upon carbohydrates and so a woman experiencing this loss of estradiol is not likely to consume sufficient fats and proteins to effectively weather this shift. Nevertheless, it does provide an opportunity for recovery. What if women who have lost the ability to produce sufficient estradiol either because of surgically (oophorectomy) or chemically (Lupron and other GnRH analogs) induced menopause adopt a ketogenic diet? Could we maximize the preferred energy source of the post-menopausal brain and reduce the neurological symptoms? I do not know the answer to that question, but given the severity of the suffering with surgical and chemical menopause, it seems worth the try.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

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This article was originally published on November 15, 2018.

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Lupron, Estradiol, and the Mitochondria: A Pathway to Adverse Reactions

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Leuprolide, more commonly known as Lupron, is the GnRH agonist prescribed for endometriosis, uterine fibroids, cysts, undiagnosed pelvic pain, precocious puberty, during infertility treatments, to treat some cancers, and a host of other off-label uses. It induces a chemical castration in both women and men. In women, Lupron stops menstruation and ovulation and crashes endogenous estradiol synthesis rapidly and completely, inducing menopause and menopause-associated symptoms like hot flashes, sweats and osteoporosis, to name but a few. In men, where it is used as a treatment for prostate cancer, it prevents the synthesis of testosterone, pharmacologically castrating its users and evoking a similar constellation of symptoms.

Lupron for Endometriosis: Questionable Research

Lupron’s widespread use for pain-related, female reproductive disorders, such as endometriosis or fibroids is not well supported, with little research indicating its efficacy in reducing pain and no research delineating its effects on disease progression. Conversely, evidence of safety issues have long been recognized, especially within the patient communities where reports of chronic and life-altering side effects are common. We have many case reports on our site alone. Although, class-action and marketing lawsuits have arisen, Lupron continues to be mis-prescribed regularly to diagnose or treat pelvic pain disorders like endometriosis, generating over $700 million in revenue in 2010 and 2011 for the manufacturers and an array of serious and chronic health issue for its recipients.

The reported side effects of Lupron are staggering both in the breadth of physiological systems affected and the depth of symptom severity experienced (a partial list). Indeed, everything from the brain and nervous system to the musculature, skeletal, gastrointestinal and cardiac systems are affected by Lupron, sometimes irreversibly. This is in addition to  thyroid, gallbladder and pancreatic side effects. How can one drug evoke so many seemingly disparate side effects? Is it possible that the magic of chemical castration is not as safe as we were led to believe; and that hormones regulate a myriad of functions beyond reproduction? It is.

Beyond Reproduction and Reproductive Disease

A major fallacy in medical science, and indeed medical research, is the total compartmentalization of physiological systems and by association an insoluble marriage of hormones to their respective reproductive organs, functions, and gender. Lupron, and drugs like it, were developed based upon this fallacy; that somehow suppressing estradiol and the other endogenous estrogens would affect solely the reproductive system. If only human physiology were that simple.

Hormones, even those inappropriately designated sex hormones, like estradiol and testosterone, regulate all manner of physiological adaptations in every tissue and organ in the body and they do so in conjunction with other hormones and by decidedly non-linear trajectories. That is, the dose-response functions are curvilinear where both too little and too much of a particular hormone can evoke serious negative consequences in body systems totally unrelated to reproduction. Chemical and surgical castration would fall into the ‘too little’ category.

Hormone Receptors are Ubiquitous

Hormones mediate these reactions via hormone receptors. Estrogen and androgen receptors are located throughout the brain and the nervous system, on the heart, in GI system, in fat cells, in immune cells, in muscle, the pancreas, the gallbladder, the liver,  everywhere. When hormones bind to these receptors, whether they are membrane bound, nuclear, or other types, the hormone-receptor complex activates or deactivates what are called signal transduction pathways, essentially message lines. Those messaging lines tell the cell to do something. Too much or too little of any one type of hormone sends mixed messages, skewing cell behavior just slightly at first and when there are only small changes in hormone concentration, but with more chronic or more severe hormone changes, the signals become increasingly more deranged and the compensatory reactions, meant only for short term, become more exaggerated and self-perpetuating. This is where problems emerge. Even if estradiol or more appropriately, estrogens (there are many estrogens) feed endometriosis, tanking estradiol concentrations is dangerous and sets into motion complex reactions that we are only now beginning to understand.

Hormones Influence Everything

Since the hormones and receptors are broadly located throughout the body, it doesn’t take a genius to figure out that if we kill off one or more hormones completely, as Lupron does with estradiol, there are going to be negative effects globally, and they are likely to be pretty serious. So, even a surface level evaluation of the safety of drug like Lupron, would suggest a strong possibility of negative outcomes in regions of the body not associated with reproductive function. And with just a little bit of endocrinology under one’s belt, it should be clear that negative outcomes would compound over time, as additional reactions meant to compensate for short term changes in hormone concentrations, become increasingly entrenched and self-perpetuating, and in many cases, increasingly damaging to the health of the cells – but it isn’t. Despite the range of serious side effects, Lupron is a commonly and cavalierly prescribed drug and newer versions of Lupron like drugs are expected to take the market by storm.

Estradiol Is Critical to Human Health

While the pharmacological mechanism of action for Lupron and drugs like it is clear, they override pituitary control of the tropic hormones that signal the ovaries or testes to synthesize new hormones, how these drugs induce the array of side effects, many of them long term and even permanent, has not been explored as seriously as it should be. Certainly, one can hypothesize the effects of estradiol elimination on different systems based upon receptor distribution within each tissue and the signaling pathways therewith, but the effects are diverse and sometimes contradictory or highly tissue specific. One has to wonder if there might be a final common pathway by which the elimination of estradiol could disrupt multiple physiological systems in a predictably discriminate manner. Indeed, there might be.

Estradiol Regulates Mitochondrial Function: Mitochondria Regulate Everything Else

If you’ve read any of our articles over the last year, you’re aware that we have become increasingly interested in mitochondria, particularly how drugs and nutrients or nutrient deficiencies, impact mitochondrial functioning. Mitochondria take nutrients from food we eat and convert them to the biochemical energy required to power cellular life – ATP. Without appropriate cellular energy all sorts of things go wrong. Energy is fundamental to life and so functioning ATP pathways are critical for cellular and organismal health (and so is proper nutrition!). A number of disease states emerge when the mitochondria are damaged or inefficient at producing ATP, from chronic fatigue, muscle wasting and autonomic system dysregulation to name but a few. Estradiol, and likely other hormones, (most of the research focuses on estradiol), influences mitochondrial functioning and the production of ATP via a number of mechanisms.

Estradiol Is Needed for the Production of ATP

Though not a component of what is called the citric acid or TCA cycle or the electron transport chain (also called the mitochondrial respiratory chain), estradiol appears to be intimately involved in up – and down-regulating the enzymes and other proteins within those energy production cycles. Estradiol directly and indirectly modifies the types fuel used to produce ATP (glucose, fatty acids or proteins) and impacts the efficiency and flexibility with which ATP is produced. Essentially, estradiol impacts the substrate inputs and keeps the cogs in electron transport chain cycles moving. When estradiol is eliminated, fuel sources shift (by tissue) and those cogs, called complexes, begin to slow, become less efficient and send off more damage signals (reactive oxygen species – ROS) than can be effectively cleaned up. Since functioning mitochondria and sufficient ATP are required for cellular health in all cells, where energy demands are greatest, symptoms emerge: the brain and nervous system, the  heart, the GI system, muscles, and bone formation/turnover.

In the brain, we see serious cognitive deficits and derangement of mood and perception with damaged mitochondria relative to estradiol elimination. We also see autonomic instability that impacts mood (flipping between depression and anxiety) but also heart rhythm and balance.

In the heart, the estradiol directly impacts mitochondrial fuel preferences and availability by regulating cardiac glucose and fatty acid metabolism. Without estradiol, the machinery within the mitochondria are not as flexible in their ability to switch between glucose, fat or proteins for precursor fuels to make ATP. The lack of flexibility, particularly during other physiological stressors, leads to impaired cardiac functioning and increased inflammation in affected tissues.

Bone formation is particularly hard hit as estradiol is required bone growth, maturation and turnover. Estradiol deficiency leads to increased osteoclast formation and enhanced bone resorption – destruction of bone or osteoporosis. Proper bone formation is also highly dependent upon vitamin D concentrations. Vitamin D deficiency leads to bone loss. Vitamin D activates estradiol synthesis, while estradiol activates vitamin D receptors. Lupron tanks estradiol and by association vitamin D, a double hit to bone health. At the level of the mitochondria, the third hit, reduced ATP, further damages bone health.

Estradiol is an Antioxidant

Antioxidants scavenge ROS. Antioxidants are needed to keep ROS concentrations at bay as too much ROS, though a natural byproduct of ATP production, will damage the mitochondria and initiate a damaging, self-perpetuating cycle. The body has a number of anti-oxidants to temper ROS. Many nutrients are included in this category: Vitamins C and E, CoEnzyme Q10 and glutathione are among the most well known. It turns out that estradiol and progesterone are potent anti-oxidants as well. So chemically or surgically eliminating estradiol reduces the body’s ability to detoxify and eliminate damaging ROS, evoking further mitochondrial damage.

Estradiol Modulates Mitochondrial Hormone Synthesis

That’s right, the mitochondrial estrogen receptors impact what is called steroidogenesis – steroid hormone synthesis – for multiple hormones, not just those pesky ‘female’ hormones. Like a thermostat that turns on or off when the temperature changes, mitochondrial estrogen (and other hormone) receptors sense hormone changes and up or downregulate the synthesis of pregnenolone (and the use of cholesterol to make pregnenolone). Pregnenolone is the precursor for all steroid hormones. So when Lupron or ovariectomy tank estradiol, not only is the synthesis of estrogens affected, but so too is the synthesis of other steroid hormones.

Estradiol Tempers Mitochondrial Ca2+ Homeostasis

Ca2+ balance is a complicated topic, a bit beyond the scope of this paper but is an important function modified by mitochondrial estrogen receptors. Ca2+ influx into cells is excitatory and turns on the cellular machinery. As one might expect, too much or too little Ca2+ activity could be damaging. Too much Ca2+ is cytotoxic or neurotoxic (if in the brain), killing the cells. The mitochondria are largely responsible for controlling the influx of Ca2+, sequestering Ca2+ when there is too much in order to save the cells. So when mitochondria become damaged or inefficient by any mechanism, Ca2+ homeostasis becomes an issue and cell death, tissue and organ damage become very real outcomes. Estradiol influences the mitochondria’s ability to sequester and temper Ca2+, so that the cells don’t become too turned on or over-active and die. (This is an interesting mechanism because estradiol itself is an excitatory hormone, increasing the activity of the cell when bound to the cell membrane or nuclear receptors but when bound to receptors on the mitochondria, estradiol tempers that excitation.)

Estradiol Regulates Immune Function

Estradiol bound to the estrogen receptors on immune and other cells activate and deactivate a number of signal transduction pathways that turn on/off inflammation and other immune responses. The mitochondria also regulate immune function via ROS signalling. Depletion of estradiol, particularly at the mitochondrial level, guarantees disrupted immune function and hyper inflammation by way of mitochondrial structural damage, derangement in function, and the loss of estradiol mediated anti-oxidant abilities. So by multiple mechanisms Lupron, drugs like it, and ovariectomy, damage mitochondria and initiate cascades of ill health.

Lupron, Maybe Not Such a Good Idea

Estradiol bound to mitochondrial receptors, controls a whole host of functions in the mitochondria, which then control cellular health throughout the brain and body. Without estradiol, the mitochondria become misshapen and dysfunctional and eventually die a messy death (necrosis), but not before inducing mutations in next generation mitochondria (mitochondrial life cycles include the regular birth of new mitochondria and the necessary death of old and damaged mitochondria). As the damage and mutations build and the ratio of healthy to damaged mitochondria shifts, cell death, tissue/organ damage and disease develop. Lupron, other drugs that tank estradiol, and ovariectomy, initiate mitochondrial damage. The mitochondrial damage represents a possible final common pathway by which Lupron induces the myriad of side-effects and adverse reactions associated with this drug.

A question that remains, is whether this damage can be offset by supporting mitochondrial machinery by other mechanisms. This is particularly important since millions of women have been exposed to Lupron and/or have had their ovaries removed. Other hormones and a myriad of nutrient factors are necessary for the enzymes within the mitochondrial machinery to work properly. Could we offset the damage evoked by too little (or too much) hormone by maximizing the efficiency of the other reactions. I think it is possible, at least theoretically and at least partially. That will be addressed in a subsequent post. For now, however, I think we ought to reconsider the use Lupron, other GnRH agonists, antagonists and the surgical removal of women’s ovaries. The damage evoked by eliminating estradiol is likely far greater than any potential benefit in an ill-understood disease process like endometriosis.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was first published on January 16, 2015. 

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Lupron: The Cycle of Negligence

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My pelvic pain first started at age 13 with menses, but I was blacking out at 28-day intervals from the age of nine. I was told it was normal by both my grandmother and mother because they experienced the same thing. The abdominopelvic symptoms got severe after the birth of my daughter when I was 33 years old. I didn’t get a diagnosis for another 14 years at the age of 47 years. It has been nothing but a steady stream of dismissive and abusive doctors with absolutely nobody offering an explanation. The only solutions that I was offered were a hysterectomy and Lupron. Neither helped and in fact, made everything worse.

Physician Abuse

When I was 44, I had a hysterectomy, and adenomyosis was found but I was told everything was removed. Four months after my subtotal hysterectomy in December 2014, I was still having the same pelvic pain symptoms. My gynecologist didn’t know what else to do other than to use Lupron for 3-6 months to see if it would diminish my pelvic pain. If the pain persisted, she said the ovaries would have to come out. She told me she was using it as a diagnostic tool and if I didn’t try it she “would drop me as a patient.” More accurately, she screamed at me, started frantically waving her hands above her head and hit me with her pen. There were times I wish I had a witness to some of the behavior I was subjected to over the years; this was definitely one of them. I took the prescription home but didn’t fill it. I was not only shocked by her behavior but also, a little leery about being souped-up on yet another medication with horrible side effects.

Worsening Symptoms While on Lupron

I held off until Sept 2015 when I decided I couldn’t stand the pain anymore.  My first injection was in October and I seemed to handle it quite well. I had relief from my pelvic pain within two days and a bit of mild dizziness that went away after about a week. The reduction in pain allowed me to go out for walks 2-3 times per day, which is something I hadn’t experienced for quite a long time—it was great to be walking again. Then I started noticing some strange symptoms every two weeks after the injection.

The first time it happened the symptoms were so mild I brushed them off as a minor cold bug: body aches and pains, sniffles, lungs slightly congested, watery eyes, my hearing was off and my eardrums felt plugged up. I thought maybe my daughter brought a cold bug home from school but these same symptoms happened exactly two weeks after the Lupron injection and every time the symptoms kept getting stronger. When I was due for my 4th injection I knew something wasn’t right. My regular gynecologist wasn’t in and I’m glad she wasn’t. The one I did speak to about my symptoms told me to not take it anymore. He looked up my symptoms in a large pharmaceutical reference book; Lupron was listed as having “flu-like symptoms” in its trial phase but had no further information. I was told to go home and just let the effects “wear off.”

From December 2015 to February 2016, I had 11 visits to the ER for worsening flu-like symptoms that included: strong body aches and pains that felt like I had been hit by a train, congested lungs, and coughing up greenish-yellow fluid. The same gross mucous was coming out of my eyes and ears. My lungs were so congested I was gasping for air and I was terrified! They tested for bacteria, throat and nasal swabs, and full blood work—everything came back negative and it wasn’t pneumonia. I didn’t even have a fever. The last ER doctor I saw actually called the drugmaker to see what to do. He told me they have something similar to a WHMIS or Workplace Hazardous Materials Information System on all their products in case of adverse events. Well, guess what? They didn’t! The representative told him they knew about the severe flu-like symptoms in their trials with Lupron but they did not follow those patients to record their outcomes. In other words, there was no due diligence before releasing their product to the public. They don’t even know if those patients are still alive.

I was given an IV to prevent dehydration and placed on oxygen until my vitals improved; even then I was sent home without any concrete advice on how to deal with the side effects other than “it should wear off” and “if it gets worse don’t hesitate to come back”—like now isn’t worse. I asked the ER doctor if he is filing an adverse event report to Health Canada or the FDA and he said “that is for the patients to do but in your case, I wouldn’t worry about it. We don’t know if that is what is causing your symptoms. It could just be a viral thing.” I was about ready to flip my lid!  He told me earlier if it was viral I would have a fever because that is what your body does to fight off infection and viral infection symptoms build up, peak and then you start feeling better. These symptoms occurred two weeks after each and every injection.  I felt like I was talking to a brick wall. Do you know it took another four months for that damn Lupron to wear off?  The entire time I was terrified. I was gasping for air while this green mucus is pouring out of my ears, eyes, and lungs. I would panic, cry, and then have to calm myself down because crying would congest my lungs making it harder to breathe. I have never been so scared in all my life.

Lupron Side Effects and Gynecological Ignorance

I did go back to the gynecologist that prescribed the Lupron and she had the nerve to tell me it was not her problem and to go see my GP. My GP told me since she didn’t prescribe it that it was the gyn’s problem. I went back to the gynecologist to tell her what my GP said and she threw another hissy fit because, apparently, I wasn’t on Lupron long enough to satisfy her 6-month requirement. My husband didn’t believe what I was telling him so I had him call the office to rebook an appointment so that we both could talk to her. At this next appointment, she placated my husband and refused to look me in the eye while she was speaking. I reminded her of everything she said previously;  that it is her problem because she is the prescribing doctor; that my pelvic pain symptoms did improve while on the Lupron; that my adverse effects were directly related to the drug as my worsening symptoms occurred exactly two weeks after each and every injection; that I was tested at the ER and it was not viral or bacterial; that the ER doctor called the drugmaker and they had severe flu-like symptoms listed during their drug trials but never not followed up. I informed her I filed complaints with both Health Canada and the FDA.

She got up to check on my ER visit reports. While she was gone even my husband noticed she wasn’t talking directly to me, only to him and that I did meet her requirements—Lupron for at least 3 months, if the pain is relieved then it means the ovaries need to come out. My husband was ready to have it out with her when she came back.  She kept trying to placate us, saying things like “I don’t know what to do”. I kept pushing for an answer—what was causing my pelvic pain if Lupron was the diagnostic tool—what was she using it to diagnose?  She never mentioned “endometriosis”. I asked her if it could be cancer–no answer. I finally said, “If you don’t know what to do then send me to someone who has more experience dealing with complex gynecological issues. I want a referral to the Women’s Health Sciences Centre in Halifax.”

I hate to think of what would have happened if my husband wasn’t there to keep me centered; even he was getting frustrated by this gynecologist. She finally agreed to send a referral to Halifax.  As we were leaving, she told my husband she was retiring in a couple of months so do not bother contacting her for any further concerns. I found out just a few days ago she is still working as a gyn—so she basically lied to my husband. What a piece of work!

I don’t understand how doctors can behave like this. There has to be some kind of benefit, either monetary kickbacks or endorsements, to blindly stand behind a drug like this and totally ignore what the patient is telling you to your face.

Recovering From Lupron

It took four months for the Lupron effects to “wear off” and for my lungs, ears, and eyes to return to normal. It was a terrifying experience that I don’t wish on anyone. I realize I was one of the lucky ones to walk away from this experience whereas others haven’t. To this day, I keep asking myself why I was put through this Hell in the first place. Why are doctors so ignorant in prescribing this drug as a diagnostic tool if they know about the adverse effects? We trust that drug companies are performing due diligence with regards to adverse reactions in trials and long-term follow up and they are NOT!  How is it that the drug maker can get away with this? Why are there not more strict checks and balances before releasing a drug and when problems are being reported afterward? It is absolutely insane that this drug, with all its reported adverse effects and deaths, is still on the market. Why are the FDA and Canada Health dragging their heels and not banning this drug?

Two years after the hysterectomy and Lupron, I was still in excruciating pain. I had a cervical cyst removed and pathology indicated that I had endometriosis. My ovaries were removed in 2017 and both were completely “disintegrated”. Once again I had to fight to get my diagnosis. The surgeon had the nerve to try to hide the biopsy report so I wouldn’t have proof.  Luckily, the medical records clerk did some searching and found it, but she also told me she could have lost her job because of what this doctor did.

My NP, although supportive in the beginning, has now resorted to telling me “this is your new normal, you’re just going to have to get used to it.”  I am at my wit’s end trying to get help dealing with what is left of my health. I am not able to work or enjoy any quality of life anymore. I’ve been given the run-a-round by 5 GPs, 1 NP, 11 OBGYNs, and 35+ ER doctors. I don’t have any faith left in our health care system. My only alternative is to seek legal advice, but I really don’t know how to move forward in a system that is so dismissive and corrupt in how it treats women’s health issues. I’m beyond whatever “disgusted” is.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

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This story was published originally on June 8, 2020. 

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Healing From Lupron and Endometriosis With Thiamine

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I was diagnosed with stage 4 endometriosis in 1996. In 2017, I was ready for a hysterectomy. I had two children and was finished with childbirth. I was having a lot of pain on my left side where my ovary was located. My Veterans Administration GYN refused to do a hysterectomy without first giving me Lupron shots assuming that my pain was due to the endometriosis. I was trying to hold down a very demanding government job and missing a lot of work from the pain. I had two laparoscopic surgeries in 1996 and 2001, respectively. Both were to excise the endometriosis. At the time, I was required to take Lupron in order to have a hysterectomy, I was 46 years old. I was denied a hysterectomy after my son was born in 2000 because I was considered too young at 30 years old to have a hysterectomy.

Endometriosis in the Colon and Lupron

After the injections of Lupron, a colonoscopy confirmed a diverticula pocket in that spot that was painful and others on my large intestine. The laparoscopy and excision in 1996 confirmed that my endometriosis extended to my large intestine. The colonoscopy found that I have so many pockets of diverticulosis, a resection surgery was not possible. Basically, if I were to become septic due to an endometriosis/diverticulosis flare, they would need to remove all of my large intestine. My options were very limited. My GYN wouldn’t perform a hysterectomy and laparoscopy under the assumption that the pain I was having was due to endometriosis. He convinced me to start the shots to see if they would help the pain because he assumed the pain was due to endo. I didn’t research the Lupron injections much prior to receiving them. I fully trusted my GYN. He mentioned hot flashes and suppression of symptoms with estradiol.

Immediately I noticed a difference. I don’t take prescription drugs of any kind unless I am really sick. I had nothing for any preexisting conditions. I could not tolerate the injections and function at work. I had severe hot flashes every few seconds 24/7 for three months even with add back estradiol. Worse, the estradiol made my migraines flare and so I was a hot mess. After stopping estradiol, my migraines continued to flare and still do without supplementation. I was also having diverticulosis flares every month sometimes twice a month. I had terrible gas and severe IBS symptoms. My work leave, FMLA and advanced sick leave were dwindling from all the visits to the various doctors. Within three months of my last Lupron injection, I was forced to retire or be fired for not being able to work. I never fully recovered from the Lupron.

Finally, a Hysterectomy

My GYN finally agreed to the hysterectomy in 2018 where they found my left ovary and left fallopian tube in one mass of adhesion scarring with my large intestine. The GYN removed the left polycystic ovary, left and right fallopian tubes along with my uterus, which had fibroids, and cervix leaving me with just my right ovary. Prior to the hysterectomy, I began noticing some numbness and cramping or burning in my feet at work that was much worse at night. I had the same kind of cramping and burning in my lower back too. I would later learn that these are symptoms of thiamine deficiency. Trying to keep it together at work with all of this was a nightmare.

Around this time, I also began having severe nausea and pain in my stomach. The GI doctors did an upper GI scope to confirm duodenal ulcers. The digestive issues, especially the diverticulosis should disqualify anyone from having Lupron as Lupron causes major digestive upset according to the FDA fact sheet. My digestive tract was inflamed from mouth to anus post Lupron. I had an inflamed esophagus and ulcers, diverticulosis flares, IBS with constipation and diarrhea and hemorrhoids that I couldn’t heal with meds. The low FODMAP diet helped though.

No More Pharmaceuticals

In 2019, I finally stopped taking all pharmaceuticals. No pharmaceutical made me feel better. Every medication I took for GI issues and neuropathy made me worse. I only took one for one or two weeks at a time to log all my side effects from each so I could have them added to my growing list of allergic reactions. I did have some sensitivity issues with prescription drugs prior to Lupron, just not as bad. I have the MC1R redhead gene. Redheads are more sensitive to pharmaceuticals and have more adverse reactions. I struggle with topical solutions as well. I couldn’t use estradiol patches because I’m allergic to the adhesive. Thankfully, my primary care physician also has endometriosis and suggested herbal supplements and remedies. All of this ,surprisingly, is from the veteran’s hospital. I was ordered by her to stop working. This was a final attempt to heal my ulcers, as they would eventually kill me if I could not find relief.

How I Healed Myself With Thiamine and Diet

I decided to try high dose thiamine after researching it via Drs. Lonsdale and Marrs and Elliot Overton. I started with 100mg daily for 6 months. Then 500mg for 3 months and currently 1000mg (500mg 2x daily). The thiamine works as well as the acupuncture with EMS. I also take Alpha Lipoic Acid and Dandelion root daily. The increases in thiamine are proving to be a significant factor in recovery. If I miss one day of supplements I’m sick for several days so I’m convinced that it is working.

To help myself heal, I no longer work a 9 to 5 job. I follow a low FODMAP diet with modification for diverticulosis and supplement with elderberry or dandelion for inflammation and immunity, turmeric, prebiotic + probiotics, magnesium for bone loss, palpations, anxiety, alpha lipoic acid for neuropathy, high dose thiamine for neuropathy, fatigue anxiety and brain fog, b vitamins and D3+K2 for b1 uptake regulation and delta 8 CBD for fibromyalgia pain and fatigue. I have regular chiropractor adjustments of my neck and lower back. Acupuncture and light therapy on my feet helped with the burning and cramping.

Where I Am Now

Currently, I have no endometriosis pain, only some lingering PMDD. I have no ovarian cysts and the migraines are not as frequent. Now only a couple a month versus weekly. I still have some burning and cramping in my legs and feet, but it is tolerable. Before thiamine, I was bedridden. The back and neck pain I had previously has improved with thiamine along with physical therapy/yoga and regular chiropractic care. I no longer experience diverticulosis flares with the new diet and supplements for inflammation like dandelion root, turmeric, and elderberry. I switch out the dandelion and elderberry because they work about the same. Depends on what is on sale.

I am able to stand for longer periods of time. My anxiety is significantly reduced, my palpations are gone, I can remember things, and my ADHD flare ups are minimal. In 2022, I only had two mild diverticulosis flares. Prior to the diet changes and supplements, I was having them once a month. I went from being bedridden completely to cooking (I still need to sit some), cleaning with short breaks, gardening with a sit on garden cart, and walking about a half mile every few days. I still have numbness in both feet. I am hopeful that lowering my A1C will resolve this. It may be permanent. Only time will tell. I’m going to the VA this week for a checkup and requesting more PT to see if it will help. They did an EMP on both legs with normal results. That was pretty painful but I felt nothing in my 3 little toes on both feet. Overall, I am doing much better with the higher dose thiamine and have much more energy.

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The Catastrophic Effects of Polypharmacy and Medical Incompetence

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Polypharmacy and Iatrogenic Injury: More Common Than Recognized

My life should never have taken the catastrophic negative turns that it did. I am well educated, was a minivan driving soccer mom and a devoted wife. I enjoyed a successful career as a pediatric audiologist working in a variety of fast-paced medical settings. I was well liked, a loyal friend to many and an active member of my community. My very vibrant and blessed life was obliterated by a perverse cascade of errors from a broken medical system. This affected my loved one’s lives as profoundly as mine. Had medical providers looked for, and addressed root causes, I’d still be driving that minivan.

It has taken me a long time and immense research to piece together and understand what happened to me. I would like to share my story for whatever understanding can do to ease the pain, and for whatever help it could give to prevent others from experiencing what our family did. First and foremost, however, I want my husband and children to understand the truth of what happened to me.

I did not suddenly develop perverse mental illness out of thin air. I was a victim of repeated misdiagnoses, unrecognized adverse drug reactions/drug toxicity and profound polypharmacy.

This is described in the literature as “medication induced iatrogenic chronic health syndrome, or iatrogenic injury.” It is more common than one would think and it unnecessarily destroys lives.

The First Hit: Toxic Mold Effects Misdiagnosed as Depression

The circumstances which led to my catastrophic outcome are cumulative. It was no one thing, but several hits to my system.

In the late 1990’s, my husband and I were a happy, newly married couple enjoying a carefree dual income lifestyle. We had successful and fulfilling careers, great friends, and loved life; the world was our oyster. Despite all this, however, we both found ourselves incredibly tired all the time and experienced frequent brain fog. My husband also began having recurrent sinus infections. I developed unrelenting headaches, fibromyalgia, dry eyes, vision issues, G.I. disturbance, frequent urination, skin rashes, excessive thirst, irregular menstruation, and disorientation – I was getting lost going to familiar places.

When seeking medical attention for this cluster of symptoms, we were both told we were suffering from mild depression and were prescribed an anti-depressant (SSRI). Neither one of us actually felt “depressed,” though. Yet, we trusted our doctors knew best and so took the anti-depressant medication as prescribed.

It’s absurd that we were given a psychiatric diagnosis given the physiologic symptoms we were experiencing. More unbelievable is that we did not even question the doctor. I would later learn that the constellation of symptoms we had is consistent with toxic mold illness, a subcategory of biotoxin illness known as Chronic Inflammatory Reactive Syndrome (CIRS). I was, in fact, subsequently diagnosed with CIRS.

We unknowingly lived in a home with hidden toxic mold, where up to two feet of water collected in the crawlspace underneath the home seasonally every winter. The root cause of our symptoms which doctors diagnosed as “depression” was completely missed. We did not need antidepressant medication. We needed out of our water damaged home and treatment for mold illness/CIRS. Instead, we got put on an unnecessary neurotoxic medication with serious adverse health risks including the effects “medication spellbinding.”

The Second Hit: IVF Treatments Lupron and Synarel

When we decided to start our family, I experienced infertility. My husband and I utilized in vitro fertilization (IVF) to conceive our two children. During this process many different pharmaceuticals are prescribed for women. The doctors assured us the medications were all “safe”.

I was given Lupron and Synarel as part of my IVF treatment protocols. Both are antineoplastic agents, meaning they are cancer chemotherapy drugs, used off label for fertility treatment. Like all antineoplastics, they are harmful to both cancerous and non-cancerous cells — particularly to pregnant women and developing fetuses. It’s incredibly scary that it is actually used for conception, isn’t it? They are neurotoxic and can induce systemic damage-CNS, connective tissue, mitochondrial, immune, etc.; damage that unfolds over time.

Equally disturbing is that I was advised to stay on an antidepressant throughout pregnancy for a depressive disorder, it turns out, I never had. When I requested to be tapered off of the SSRI before attempting to achieve pregnancy, I was told that the risk of harm to the baby of a mother with untreated depression was greater than any potential adverse effects of in utero exposure to an anti-depressant medication. Really? This made absolutely no sense to me in my circumstance; the only qualifier for my diagnosis of mild depression was unrelenting fatigue. Yet, the doctor instilled such terror in me that I would be irrevocably harming my child if I did not not stay on an antidepressant during pregnancy, I reluctantly followed his advice. Prenatal exposure to an SSRI can be damaging to a developing brain and nervous system. Both my children were born with severe nervous system dysregulation and have developmental and immunological issues.

Toxic mold exposure and SSRIs can both cause various hormonal issues. My infertility was due to anovulatory cycles likely induced by the antidepressants that were inappropriately prescribed for the toxic mold. I had also been on hormonal birth control for many years prior to our attempts at conception. Suffice it to say, I was not healthy. Despite my compromised health, the fertility doctors added more toxic chemicals to my body to initiate conception.

The Third Hit: Fluoroquinolones

My children were both born via Cesarean section-my daughter due to vasa previa, my son due to failed VBAC, failure to descend. In each instance, IV Cipro (drug class fluoroquinolone) was given prophylactically.

Fluoroquinolones are associated with prolonged (up to months or years), serious, disabling and potentially irreversible drug reactions affecting several, sometimes multiple, systems, organ classes and senses”. Fluoroquinolone toxicity can lead to a subsequent systemic health cascade.

Within a couple days after receiving IV Cipro, I experienced acute onset of significant arm weakness and severe wrist pain, requiring the use of wrist guards for several months. I had difficulty physically caring for my children after their birth because of this. I also experienced photosensitivity, hyperacusis, drenching night sweats, constipation/G.I., hair loss, hyperactivity, brain fog, short term memory issues and fatigue. Additionally, I had irritability, emotional blunting, and personality changes after my son’s C-section. All of these symptoms were much more severe after my son’s delivery and they did not ever resolve completely.

After my son’s birth, I was prescribed multiple consecutive courses of oral Levaquin plus steroids for persistent pneumonia I developed during the second trimester of my pregnancy with him. The concomitant use of steroids with fluoroquinolones exponentially magnifies the damage to the body.

Levaquin and Cipro belong to the class of medication known as fluoroquinolones. They are essentially chemotherapy drugs, that negatively impact the immune system, CNS/ANS/PNS, alter DNA, cause mitochondrial and connective tissue damage as well as severe neuropsychiatric/cognitive issues.

“Fluoroquinolone adverse-reactions are categorically different from allergic reactions, rather, fluoroquinolone toxicity is a syndrome of multi-symptom, chronic illness that does not go away when administration of the drug has stopped. Fluoroquinolone adverse-reactions are similar in symptoms and scope to autoimmune diseases, fibromyalgia, ME/CFS, POTS, psychiatric illnesses, neurodegenerative diseases (like ALS and Parkinson’s), and other chronic, multi-symptom, illnesses that involve multiple bodily symptoms. Like many of those diseases, fluoroquinolones adversely affect gut healthmitochondrial healthliver healthneurotransmitter balancemineral homeostasishormones, and more. Fluoroquinolone toxicity is a multi-symptom, chronic, syndrome, that, for many, is incurable.”

Following the fluoroquinolone exposures, my health declined significantly and systemically over the next several years. Extreme fatigue, fibromyalgia, persistent headache, head pressure, G.I. issues, recurrent infections, cognitive issues, muscle wasting and visual disturbances. I also began to develop multiple chemical sensitivities, food sensitivities and electro-hypersensitivity. I have been told by physicians and researchers this is all consistent with fluoroquinolone toxicity which can lead to a progressive health cascade. However, this went unrecognized and, instead I was given large doses of antidepressants which only exacerbated my declining status.

The Fourth Hit: Multiple Viral and Fungal Infections and More Medications

Next, I was diagnosed via lab testing with neurological Lyme disease, bartonella, erichliosis, parasitosis, babesia, CIRS, systemic fungal infections, Epstein Barr and other chronic viral infections (2010). As my health had been decreasing for many years, I was relieved to finally have what doctors thought was the “root,” and I was eager to address it. I was a compliant patient and followed their complex protocols. An utterly insane amount of pharmaceuticals were given over the next six years (listed at the bottom of this post) for treatment, including more rounds of fluoroquinolones (Levaquin, Avelox) and their “second cousins” -Mepron, Malarone, Flagyl. The years of aggressive treatment proved disastrous.

Very well-intentioned doctors missed the pre-existing fluoroquinolone and SSRI toxicity. No regard was taken for the growing burden on organs, most notably the liver and brain. My G.I. system was decimated by dozens of antibiotics. Aggressive “Lyme” treatment involving years of polypharmacy only served to poison me more, further impairing my CNS and immune system. My health status continued to decline.

The Fifth Hit: Sedatives and Anticonvulsants to Quiet the Immune System

After years of Lyme treatment and with medication toxicity already through the roof, the next approach was to add Ativan, a benzodiazepine, and Gabapentin, an anticonvulsant. This was to calm mast cell activation and aide intractable insomnia that had developed. Both were used for off label purposes. Fluoroquinolone exposure can trigger mast cell activation. Toxic mold exposure can also trigger mast cell activation.

I suffered an immediate adverse drug reaction to Gabapentin in February 2015. Within the first day of beginning this medication my handwriting changed. I could not walk straight and began dropping things. I had an obvious and immediate decrease in executive function and short-term memory, along with hyperactivity, twiddling my fingers and other symptoms that I would later learn fall under the umbrella condition called akathisia. According to the Akathisia Alliance for Research and Advocacy:

“[Akathisia] …is an extremely distressing neuropsychiatric syndrome with symptoms including severe agitation, inability to remain still and an overwhelming sense of terror implicated in many suicides and acts of violence. It is a medication side effect.”

I reported all this to my doctor who instructed me to stay on the medication and that my body would “adjust with time”. These were not harmless “side effects” that would fade. This was a serious adverse drug reaction which went unrecognized as such and led to more polypharmacy.

Progressing Neurotoxicity: Let’s Up the Doses of the Contributing Medications

Over the next several months, my cognition and proprioception continued to rapidly decline. Additionally, I experienced the onset of deeply troubling new symptoms – an extreme fear to be alone, intense inner restlessness, confusion, blurry vision, severe headache, hand tremor, worsening insomnia, terror, and derealization/ depersonalization. Repeated changes were made to my Lyme treatment protocol with the assumption that these new symptoms and decline were related to that chronic health condition. The gabapentin and ativan doses were also increased. Changes were made to the SSRI. The adverse drug reaction and increasing toxicity was missed completely and, in fact, additional pharmacy worsened it.

Something was very, very wrong; I just kept declining. In no way did this feel like it was simply an exacerbation of Lyme. By the fall of 2015, things had deteriorated to the point to where I had to stop driving for safety reasons as my vision and motor skills had become too impaired. We had to hire household help and childcare because I had become essentially non-functional. I was acutely aware that my decline was negatively impacting my children and I wanted to make sure there was a capable adult in the home at all times with them. I tried hiding in the bedroom away from their view because my presentation and behavior had become very disturbing…and, I knew it. I would later come to understand that all the new symptoms beginning with the adverse reaction to gabapentin were consistent with medication induced akathisia.

Confirmation: It Was the Medications All Along

In December 2015, after ten months of searching for answers to my abrupt and progressive decline, I finally got confirmation from my doctor and own research that indeed I was experiencing numerous, severe negative medication effects and not solely an exacerbation of Lyme disease.

“In summary, the benzodiazepines can produce a wide variety of abnormal mental responses and hazardous behavioral abnormalities, including rebound anxiety and insomnia, psychosis, paranoia, violence, antisocial acts, depression, and suicide.” Dr Peter Breggin

I also learned that a supervised slow taper off of these psychotropic medications was required for my safety. I was referred by my doctor to a psychiatrist for a guided taper.

I was not “addicted” to the medications, rather my brain had become dependent on them and cessation had to be gradual and monitored.

The psychiatrist advised me to crossover from Ativan to Valium because it has a longer half-life to reduce inter-dose withdrawal effects. Then, once stable on an equivalent dose of Valium, taper slowly off of that. She also wanted to add in other medications to counter the negative side effects of the withdrawal process.

Crossing over to Valium was extremely problematic for me. I experienced an immediate adverse reaction to it with increased agitation and pacing on the very first dose. (It turns out I cannot metabolize Valium properly). Upon reporting this to my physician, she told me just to “go slower” with the process and things would “even out” over time. Despite following her instructions to slow down the crossover, nothing “evened out”. I experienced ever-increasing negative and disturbing symptoms. I now I understand that I suffered multiple drug-to-drug interactions and adverse drug reactions, drug toxicity that went unrecognized for what it was. I had developed medication induced akathisia.

Even So, Let’s Add More Medications

To counter these growing negative effects, the doctors continually changed dosages of existing drugs and added many new ones, all trial and error, with no discernible rationale. This only worsened things, causing even more frightening and violent new symptoms – rapid pacing, twisting dystonia, severe depersonalization, disinhibition, myoclonic jerking, derealization, panic, agitation, aggression, severe insomnia, paranoia, vocal tics including profanity, mono-phobia, agoraphobia, rage, stuttering, disequilibrium, severe confusion, heart palpitations, visual disturbances, air hunger, motor slowing, oppositional behavior and more. My environmental sensitivities also escalated.

The tapering protocol involved adding Valium to cross taper Ativan according to the Ashton Method recommended by my physician. I had a severe adverse drug reaction to Valium which the doctor failed to recognize, escalation of negative symptoms increased. At one point low-dose Seroquel, an antipsychotic, was prescribed to me in an off label use for the extreme insomnia that developed on this cocktail of drugs. Off label use of low dose antipsychotics for insomnia is NOT recommended.

After Seroquel was added, I developed vocal tics, suicidal ideation, extreme terror, delirium, the pacing and other movements increased dramatically. Despite reporting this immediate negative side effect of feeling intense agitation and rage, the doctor denied that a low dose of Seroquel could cause this and told me it must be underlying or emerging psychiatric illness. They continued to add and abruptly remove many other medications.

I lost my sense of human connection and self. I felt completely lobotomized. The collateral damage on my children and husband was and is INHUMANE.

Despite my reporting the immediate negative side effects with the addition of Seroquel, doctors denied that a low dose could cause them and told me it must instead be symptoms of an underlying or emerging psychiatric illness. Really? How do you suddenly develop severe psychiatric illness out of nowhere?

Prior to being put on Ativan and Gabapentin and the subsequent polypharmacy, I had NEVER before experienced suicidal ideation or the other extreme negative behavioral and cognitive changes. I was repeatedly told that my very classic symptoms of akathisia were not akathisia and not related to medications. The Barnes Scale, a standardized tool to assess drug induced akathisia, was never administered.

The very behaviors that were unfolding right before the physicians’ eyes and that I was reporting are known and dangerous medication side effects, included on manufacturers’ warnings. So why then did so many doctors fail to recognize this?

Spinning Out: Let’s Go Cold Turkey. What Could Possibly Go Wrong?

My physical/cognitive/mental health continued to spin out of control with the medication merry-go-round. In August 2016, I was admitted to a psychiatric unit from the ER due to severe confusion, pacing akathisia, and dystonia. The uninformed doctor there forced an abrupt discontinuation of the polypharmacy cocktail I had wound up being put on (in the name of “safe” tapering). Cold turkey off of four psychotropic medications overnight. This severely shocked my CNS. Over the next few weeks, I experienced what I felt were seizures, difficulty forming words, severe vertigo, worsening cognitive function, visual disturbances, racing heart, auditory hallucinations etc. Fearing for my life, as I spiraled into mania, psychosis and suicidality from this abrupt cessation, I sought reinstatement of some of the medications six weeks later. I was accused of “drug seeking” for this decision. It’s not that I wanted to be on any of these poisons ever again; I was simply trying not to die.

The partial reinstatement did stabilize me a bit.

Then, only one month later, I was again rapidly tapered off the polypharmacy cocktail at an outpatient facility. Originally, I understood, the program was completed over 15 days. I have since learned from my medical records that my rapid detox was longer and more intense than the prescribed protocol. According to my records, I received 23 days of treatment with the administration of daily six hour infusions of IV NAD+ with B complex and amino acids (December 2016). My dose was significantly greater than the maximum standard dose of 250 mg, provided at too fast a drip rate and over a treatment course that was many times longer than is typical. I also learned that it was done without proper methylation support.

From what I have learned, this treatment is purported to protect the brain and ease medication withdrawal syndrome. However, this was not at all what happened for me. I had a severe negative response to it, utterly catastrophic, inducing permanent profound physical disability. During the IV administration, I experienced extreme brain burning, increased heart rate/blood pressure, auditory hallucinations, seizures, extreme agitation, terror, tremors, fever, hypomania, worsened akathisia with pacing, violent dystonia, hand clawing, delirium, jerking and twitching, homicidal and suicidal ideation. Most horrifically, the severe adverse reaction caused an impulsive akathisia induced suicide attempt.

With pre-existing mitochondrial issues, a suspected underlying connective tissue disorder and years of cumulative toxicity (medication and environmental), it has been suggested by physicians and researchers that NAD+ would increase the cytotoxic effects through reactive oxygenation species. This seems to have accelerated my mitochondrial dysfunction leading to catastrophic connective tissue damage and a progressive musculoskeletal collapse.

There is a genetic/epigenetic researcher, Bob Miller, whose work focuses on Lyme patients and others with complex chronic diseases. He discusses NAD+ in an interview where he mentions that while for some it can be a miraculous molecule, improving many things metabolically, for others it can have serious adverse effects. He believes this could be caused by something he coins the “NADPH-steal”, where NADPH starts acting like a free radical due to other compromised enzymes stealing away the NADPH (excess of sulfites, glutamate, histamine, things like that). With the compromised methylation and Kreb’s cycle that I have, treating all those things prior would be necessary to not to overload the system and cause serious damage. No provider recognized this serious contraindication with their recommendation of NAD+.  In fact, they blindly touted the opposite claiming it to be neuroprotective for all. An interview with Bob Miller’s latest research and perspective can be seen here and here. Another researcher, who specializes in drug neurotoxicity, confirmed the negative effects of NAD+.

The Results of Polypharmacy and Failed Treatments

I have experienced profound progressive connective tissue destruction since the IV NAD+. At the age of only 54, I am now non-ambulatory, bed-bound requiring full physical care in an assisted living facility. This has left me unable to bathe or dress myself. I have difficulty feeding and swallowing. I have very limited use of my hands; my manual dexterity is poor. I have profound autonomic nervous system dysfunction and cannot tolerate even supported sitting. It feels as though my entire spine has collapsed, bone on bone-discs and other supportive connective tissue severely compromised. My tendons and ligaments feel too lax systemically throughout my body, head to toe-my feet now literally curl and bend in ways that they should not. My upper palate has fallen and my lower jaw swings so much so that it often feels like I’m being choked. Speech articulation is difficult because of the laxity in my oral cavity. Systemic collagen and cartilage loss. My internal organs don’t feel supported and I’m experiencing prolapse.  I am right side lying 24/7, propped up at an angle and need assistance repositioning my body. Toileting is difficult. My vascular and lymphatic system have been severely affected. I have full body tissue swelling, like an exploded baby diaper.

It feels as if the structural integrity of my connective tissues, the glue that holds *everything* together, is gone…like chewing gum on hot pavement or stretched out pantyhose. I quite literally feel as if I’m melting from the inside out. Additionally, I have constant severe acid burning sensation throughout my body and deep bone pain, head pressure, central vision and auditory processing issues.

And Yet They Insist It Was All In My Head

It has been a grueling 35 months since that IV NAD and rapid taper of toxic medications. During this time period, my mental and cognitive state has steadily and dramatically improved. I no longer have any psychiatric symptoms and my personality has fully returned. I am once again gentle, kind, funny thoughtful and empathetic. Doctors kept insisting that the extreme cognitive and behavioral changes I experienced, beginning with that original adverse reaction to Gabapentin, was an emerging, intrinsic psychiatric illness. It most definitely was not. Rather, it was severe psychogenic effects of drug toxicity that they failed to recognize as such.

They wanted me to continue on various psychotropic medications and strongly recommended I seek treatment in a long-term inpatient psychiatric facility for the severe mental illness they thought I had. If they had been correct in their assessment, I would not have experienced the dramatic return to a healthy mental and cognitive state that I have despite declining their medication/treatment.

I NEVER had emerging severe psychiatric illness that the doctors said I had. Rather, the perverse neuropsychiatric manifestations were actually CAUSED by repeated misdiagnosis and careless polypharmacy. The medications caused these problems.

Misinformed doctors told my family I became perversely mentally ill versus I suffered extreme adverse drug reactions and toxicity. Because of their ignorance, my family believes I abruptly lost my mind at the age of fifty. When I rejected the false diagnoses of emergent psychiatric illness and refused further treatment (i.e., re-starting psychotropic medication), I was labeled non-compliant. This caused my family to believe I didn’t care enough about them to seek “treatment”. In fact, it is because I love them so deeply that I refused treatment. I knew my decision would appear non-compliant, but had I gone back on the poisons that induced this catastrophe in the first palace, I would not have regained my mental and cognitive health. I may have lost my life.

Without an authentic understanding of what happened to me, how are my children supposed to process this trauma? I absolutely did not just lose my mind one day. I was successively and cumulatively poisoned.

In today’s modern world, physicians are grossly misinformed regarding the very real dangers of pharmaceuticals, especially the grave dangers of polypharmacy and adverse drug reactions. Our medical system does not look for root cause. The healthcare system is dangerously broken. Patients are dismissed and gas-lighted when reporting negative side effects and misdiagnosed with psychiatric illnesses instead of recognizing medication toxicity.

I was systematically poisoned into oblivion by modern medicine and labeled with perverse psychiatric illness that did not exist prior. My children deserve to know the truth of what happened. This absolutely never should have happened to me, to my husband, nor to my children.

Over the last 6-12 months, I have had multiple objective tests completed that verified my cognitive, psychological and physical status. As a result, four separate doctors concluded that my past decline was due medical error and polypharmacy. While this is validating, it does not change the fact that my family is now gone and I am left permanently physically disabled due to a fatally flawed medical system and its love affair with prescription drugs.

What They Prescribed

These are most of the medications I was prescribed for the complex umbrella of Lyme disease, co-infections, CIRS, etc. with no regard for toxicity to the liver, brain or organs. Many of these were extended courses, long-term, and given concurrently. Looking back, I cannot believe that I survived. This is what medical polypharmacy looks like. It is not one or two drugs, it is dozens.

  • Macrobid (nitrofurantoin)
  • Ceftin (cefuroxime)
  • Cephalexin
  • Moxatag (amoxicillin)
  • Cefdinir
  • Minocylcline
  • Doryx (doxycycline)
  • Cedax (ceftibuten)
  • Tindamax (tindazole)
  • Minocycline
  • Clindamycin
  • Biaxin (clarithromycin)
  • Rifampin (rifampicin)
  • Augmentin (amoxicillin and clavulanate potassium)
  • Deplin/Duleek-DP (l-methylfolate)
  • Fluconazole
  • Ketoconazole
  • Itraconazole
  • Voriconazole
  • Rocephin (ceftriaxone ) – IV via Hickman catheter
  • Azithromycin – IV via Hickman catheter
  • Mepron(atovaquone)
  • Alinia (nitazoxanide)
  • Malarone (atovaquone/proguanil)
  • Biltricide (praziquantel)
  • Nystatin
  • Bicillian (penicillin G benzathine) – IM injection
  • Albendazole
  • Mebendazole
  • Stromectol (ivermectin)
  • Bactrim/Septra (sulfamethoxazole/trimethoprim)
  • Vancomycin – IV peripheral
  • Cortef (hydrocortisone)
  • Testosterone/progesterone (BHRT)
  • NAD/B complex – IV
  • Meyers cocktails – IV
  • Glutathione – IV
  • Phosphatidylcholine – IV
  • Cholestyramine (CSM)
  • Ketotifen
  • Hydroxyzine
  • Vitamin B12 – Subcutaneous Injection
  • Low-dose naltrexone (LDN)
  • Cipro (ciprofloxacin) – IV
  • Levaquin (levofloxacin) – Repeated and extended courses
  • Avelox (moxifloxacin) – Repeated and extended courses
  • Valtrex (valaciclovir)
  • Medrol (methylprednisolone) – Given concurrently with fluoroquinolones
  • Symbicort (budesonide/formoterol)
  • Synarel (nafarelin acetate)
  • Lupron (leuprorelin)
  • Vioxx (rofecoxib)
  • VSL-3 (bifidobacterium, lactobacillus, and streptococcus probiotics)
  • Singulair (montelukast)
  • ProAir (albuterol)
  • Xopenex (levalbuterol)
  • DuoNeb (ipratropium/albuterol)
  • Alvesco (ciclesonide)
  • Prednisone
  • Promethazine/codeine
  • Chloestyramine
  • Probalan (probenecid)
  • Ursodiol – Given because of rocephin
  • Ferrous gluconate (iron)
  • Nexium (esomeprazole magnesium)
  • Xyzal (levocetirizine)
  • Allegra (fexofenadine)

…And HUNDREDS of oral herbal medicines and supplements

The cascade into unnecessary and catastrophic psychotropic polypharmacy:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Zoloft (sertraline)
  • Remeron (mirtazapine)
  • Buspar (buspirone)
  • Benzodiazepines
  • Ativan (lorazepam)
  • Valium (diazepam)
  • Clonazepam
  • Antipsychotics
  • Seroquel (quetiapine)
  • Risperidone
  • Zyprexa (olanzapine)
  • Antihistamines
  • Benadryl (diphenhydramine)
  • Hydroxyzine
  • Anticonvulsants
  • Gabapentin
  • Lyrica (pregabalin)
  • Baclofen

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

This article was published originally on: November 13, 2019. 

 

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They Say Lupron Is Safe

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In addition to the adverse event of dizziness reported during and post Lupron use, just reading and trying to understand Lupron’s literature can also be dizzying. So much of the research and information about this drug is utterly baffling; some circumstances have been manipulated by slick design, with information hidden or suppressed, other Lupron information can be readily disproved by known facts, and all this is admixed with conflicts of interest. In the process, decades of victims have accumulated and are without any real medical or legal advocacy. All the while, the powers that be have essentially appeared inert.

The contradictions found within Lupron documentation are indeed baffling and Lupron’s history is littered with instances of nefarious machinations. In prior installments of this series, the conflicting information about Lupron’s metabolism has been explored (part 4), as well as addressing the fact that Lupron is categorized as a hazardous, Pregnancy Category X drug (meaning it should be avoided by any woman who is or who may become pregnant), yet Lupron is prescribed to women in IVF, egg donation and surrogacy (part 3).  Since there are numerous other examples of puzzling – just plain wacky (inexplicable and unacceptable) – ‘circumstances’ surrounding Lupron, this final installment will look at a number of these head-scratchers, as well as reviewing some of the more notorious slick maneuvers associated with Lupron. (The other installments in this series were Part 1, Part 2, and Part 5.)

Why has Lupron’s manufacturer made statements that can be proven inaccurate?

Oral Lupron:  No — Yes — Maybe so?

Lupron’s labels and the literature ubiquitously proclaim that Lupron “is not active when given orally” – yet early investigation shows information to the contrary. None other than Andrew Schally, who is responsible for the isolation of the GnRH molecule (allowing the subsequent manufacturing of its analogs), and who won the 1977 Nobel Prize in Medicine for doing so, co-authored a 1975 article on the oral administration of Lupron. Thirteen healthy men were given Lupron (known only chemically, at the time, as “D-Leu-6 des-Gly-NH2-10”) by mouth, and within 45 minutes “the analogue had produced a statistically significant increase in mean plasma LH concentration”, and “the times of maximum LH activity noted … by mouth were not much different from those observed after parenteral injection”.

While the majority of men in this study did not have raised FSH concentrations, the remaining subjects had a significantly different mean change in plasma FSH concentrations “24 hours after the oral dose”. The article notes that “[a]lthough [Lupron] seemed to have little effect on FSH release, the interpretation depends upon how the results are expressed.” Discussion of Lupron’s parenteral effects decades later noted “the lack of long-term suppression of FSH observed in some patients” (American Hospital Formulary Service, Drug Information, 1994; p. 644). So it would appear that both oral and parenteral routes of Lupron have induced similar LH and FSH responses.

Andrew Schally stated 42 years ago that “oral administration [of Lupron] can now be added to the previously established effective methods [of intravenous, subcutaneous, and intramuscular administration].” Yet Lupron’s labels continue to state that it is “not active when given orally”.

Lupron Induces Menopause – NOT

In Lupron brochures for its use in endometriosis, the manufacturer states: “GnRH … acts on the pituitary to stimulate two other hormones, LH and FSH. … When LUPRON DEPOT is administered monthly, production of these hormones is reduced to the very low levels found after menopause” (emphasis mine). Yet, any medical textbook describes menopause as “FSH and LH (mainly FSH) are produced thereafter in large and continuous quantities” (emphasis mine) (‘Textbook of Medical Physiology’, A.C. Guyton.  1981.  6th Edition.  W.B Saunders Co. Philadelphia; p. 1016).

And most astoundingly, the hormonal profile of a menopausal woman – increased FSH/LH, decreased estrogen (“hypergonadotropic hypogonadism”) does not match the hormonal profile of a woman on Lupron – decreased FSH/LH, decreased {sometimes} estrogen (“hypogonadotropic hypogonadism”).  (See ‘Chart 1″ on page 2 here.)  Yet women are repeatedly told Lupron will put them into a temporary “menopause”.

Endometriosis Clinical Trials’ Data versus Claim in Lupron’s Label

Lupron’s female labels state the drug’s hypoestrogenic effect “is reversible on discontinuation of therapy”. However, an independent analysis of the endometriosis clinical trials’ raw data conducted during a product liability litigation revealed “62.5% of study subjects had failed to return to baseline ovarian function one year after stopping Lupron.” (Issue discussed in further detail below.)

Lupron-induced Impotence 

Initial 1980s clinical trials for FDA approval of Lupron for use in palliative treatment of prostate cancer found that 2 out of 98 subjects experienced the adverse event of impotence. More than a decade later, it was reported that Lupron “strongly suppresses erectile function and sexual activity” and “sexual desire, sexual interest and sexual intercourse were totally annulled.”  Large scale studies have revealed “80%” of subjects using GnRHas reported being impotent, and a “267% increase in impotence was observed after one year of treatment”

A decrease in sex drive (reported by both sexes) and impotence are such well-known, expected, adverse effects of Lupron that the drug has for some time been used (court ordered at times) as ‘treatment’ for sex offenders (see here, here, and here).

It should be found curious that what has become accepted as a near-universal adverse event to Lupron (impotence) was claimed, in the initial clinical trials, to affect a mere “2 out of 98” subjects.

Infamous Fraudulent Marketing Schemes and Unlawful Off-label Promotion of Lupron

There is quite a history of Lupron being unlawfully promoted for off-label indications, including the company receiving “Notices of Adverse Findings” from the FDA about the company’s Lupron symposiums (deemed ‘indoctrinations‘ by the FDA).

In 2001, Lupron’s manufacturer paid $875 million, the then-highest criminal and civil fine in U.S. history, for its fraudulent marketing scheme to promote sales of Lupron, involving violations of the False Claims Act, 31 U.S.C. §§ 3729.  The landmark case highlighted the company’s monetary incentive schemes to physicians to boost Lupron sales. Internal confidential company memos detailed how urologists could earn $105,011.40 annually by prescribing Lupron to just 65 patients.  The U.S. government’s investigation revealed that the company provided many sales incentives, such as products, cash prizes, and trips, including a vacation referred to as the “Excalibur” – and the “Excalibur party was awarded annually to the top 30% of the [] sales force. …  At times in the 1990s, the annual budget for the Excalibur party exceeded $4,000,000” (see page 9 here).

More recent ideation can be gleaned from anonymous postings in a pharmaceutical ‘sales rep chat room’;  i.e., a few noteworthy 2010 posts state: “ABBOTT PAYS MILLIONS UNDER THE TABLE SO DOCS USE LUPRON” (emphasis in original) (posted 3/27/10 @ 7:45 PM);  and “the docs know who has buttered their bread, and we [Abbott] got very deep pockets” (posted 3/27/10 @ 9:41 AM)

Why was the preservative in daily Lupron given only to humans, and not given to the “study rats”?

The daily formulation of Lupron is prescribed to both the pediatric and adult population, and was the very first FDA approval Lupron received, in 1985.  This initial, approved formulation contains the preservative “benzyl alcohol”.  But curiously, the animal toxicology studies required for Lupron’s initial FDA approval were not done using Lupron and benzyl alcohol, but were done using Lupron and “normal saline” (NDA 19-010).  Shouldn’t these animal toxicology studies reflect the exact injection intended for humans?

The National Institute for Occupational Safety and Health (NIOSH) lists pages of toxicity data for benzyl alcohol, while the Material Safety Data Sheet (MSDS) for benzyl alcohol identifies that there is “no information available” for numerous areas (such as teratogenicity, neurotoxicity, reproductive effects – See ‘Section 11’ here). Why were rats spared the exposure to benzyl alcohol in their Lupron injections, when humans were and are exposed to the benzyl alcohol day after day in their daily Lupron injections?

Funny Business with Bones

In this discussion, it is important to note that human bones contain 2 different types of bone – cortical (or compact) bone and trabecular (or cancellous or spongy) bone (see here and here).

While there are studies which claim no adverse effect of Lupron/GnRHas on the bones of treated children (i.e., here), other published reports on treated children note leuprolide/GnRHas “may have an adverse effect upon bone health“. As early as 1991, “a small but significant decrease in bone mass” was noted in a small Italian study using another GnRH analog (triptorelin) in children with precocious puberty. Another small Italian study in 1995 using leuprolide to treat precocious puberty found a “reduction of trabecular bone mass”. In a small Taiwanese follow-up study of girls treated with either leuprolide or triptorelin, “45% of patients had lumbar bone mineral density less than 1 SD below that of normal young Taipei adults”, evidencing “45% of patients had decreased bone accretion during therapy“. And recently a small study in Turkey using leuprolide in children concluded “GnRHas may have an adverse effect on bone health” perhaps via an impact upon vitamin D levels.

As early as 1991, in gynecological uses of GnRHas, evidence indicated that there was little or no change in cortical bone density, however “[t]he great majority of studies of trabecular bone show a significant reduction in bone mass in both spine and distal radius during 6 months of agonist therapy … between 5-10% of baseline”. Another early study in treatment of endometriosis found “bone loss induced by GnRH analogs may be associated with adverse effects on cancellous [trabecular] microstructure which are unlikely to be reversed following cessation of therapy.”  (An increased rate of bone loss in men receiving Lupron and other GnRHas has also been reported, i.e. here.)

It is important to note that most of the bone mineral testing done using Lupron or other GnRHas in adults have been done using DEXA (Dual-energy X-ray absorptiometry) or DPA (Dual-photon absorptiometry) scans; and there have been GnRHa studies using DEXA in precocious puberty bone mineral density assessments. Another study, using triptorelin in precocious puberty subjects, evaluated bone mineral density by assessment with DEXA and concluded that while bone mineral density was significantly lower at discontinuation of GnRHa, later DEXA scans showed values “not significantly different from controls.”  (But what would QCT [quantitated computerized tomography] scans have revealed?)

Bone density scans such as DEXA/DXA and DPA assess both cortical and trabecular bone – and studies using DEXA and DPA scans have revealed adverse effects from GnRHas  (i.e. bone mineral density “decreased significantly [6 months: -6.0%, 12 months: -8.0%]”).  However, QCT scans assess only trabecular bone and are most effective at detecting “the significant trabecular bone loss of the vertebrae and hip [associated] with GnRH agonists”.  (See also here.)

GnRHas appear to have “a significant negative impact on trabecular bone mass.  … Initial studies [in women] with dual-photon absorptiometry [DPA] were unable to detect any appreciable bone loss with GnRH agonists.  … Quantitated computerized tomography [QCT] always shows significant trabecular bone loss of the vertebrae and hip with GnRH agonists. Depot preparations appear to produce more marked loss than daily intranasal sprays.”  (emphasis mine).

Early investigations of leuprolide and buserelin’s effect upon cortical and trabecular bone mineral content in women with endometriosis identified that “[b]ecause QCT of the spine measures only the trabecular bone … any significant change affecting mainly the trabecular bone is more readily detected earlier by the QCT”, and “[b]ecause DPA measures both trabecular and cortical bone, a significant reduction in true trabecular bone mass actually may be diluted … thus giving a lack of significant change.”

In further illustration of this point, note that Lupron’s label for endometriosis from 1991 through 1996 stated “after 6 months the vertebral trabecular bone density as measured by QCT was decreased by an average of 13.5%”, however in 1996 Lupron’s endometriosis label was changed to read the “vertebral bone density as measured by DEXA was decreased by an average of 3.9%” (1991 – 1995 Physicians Desk Reference, Lupron Depot 3.75 mg).  By using data only from DEXA scans, the significant bone density loss previously detected by QCT was eliminated.  Current Lupron Depot 3.75 mg label states “vertebral bone density as measured by dual energy x-ray absorptiometry (DEXA) decreased by an average of 3.2%”.   By continuing to use data only from DEXA scans, the “significant” bone density loss detectable by QCT is ensured to remain undetected.

In a 2000 study of bone markers and bone mineral density during growth hormone treatment in children with growth hormone deficiency, it was noted that future research should be carried out “by the direct measurement of bone density using quantitative computer tomography [QCT]. Mineralization is only one facet of bone strength, however; other important components (e.g. bone structure and geometry) should be addressed in future paediatric studies.”  (See also here.)  A PubMed literature search of ‘QCT bone pediatric GnRHa’ produced zero results for humans, but one result was found for a report on rats  (in which bone mineral density was “significantly decreased in GnRHa-treated rats” and concluded “a delay in the onset of sexual maturation may cause prolonged, possibly irreversible defect in bone mineralization”).

In a 1995 study, bone biopsies and microscopic analyses (histomorphometric analysis) were done on women treated with GnRHas and the “results suggest that bone loss induced by GnRH analogs may be associated with adverse effects on cancellous [trabecular] microstructure which are unlikely to be reversed following cessation of therapy.”  Microscopic scan photographs of a 28 year old woman treated with GnRHa for 6 months show “severe disruption of the cancellous microstructure in the post-treatment biopsy” – see photo on page 6 here.

It would appear that without a body of data specific for QCT results, appropriate conclusions cannot be reached about the effects of GnRHas upon the type of bone (trabecular) that is most impacted by GnRHas. All the above points to the need to assess Lupron/GnRHas effect upon trabecular bone through QCT scans – and it would seem that to do otherwise would hinder data collection.

Yet many Lupron studies and follow-up studies have been designed using non-QCT bone density scans, and often it is wrist (and not hip or vertebral) scans that are performed. A perverse analogy comes to mind, relating to the heinous act of sick individuals who hide dangerous items (i.e., needles, razor blades) into the center of Halloween candy – and the community safeguards that have been enacted to X-Ray the candy in order to assess and ensure safety (i.e., here and here): What if these community resources were not offering to X-Ray the candy but instead were offering to merely photograph the candy in attempts to ‘assess and ensure safety’?

Tricks in the Courtroom Yield Treats for Lupron’s Manufacturer

The only lawsuit to make it to trial (in 2011), the case of Karin Klein v. TAP, Abbott, stemmed from Karin’s prescription of Lupron Depot 3.75 mg in 2005 as a 17 year old for endometriosis – and resulted in the development of (among others) a thyroid disorder. Pre-2005 Lupron Depot 3.75 mg labels, and post-2005 Lupron Depot 3.75 mg labels (domestic and foreign), warned of thyroid adverse events, but the company removed this warning for the 2005 label – the year of Karin’s prescription.

At trial, Karin was prevented from presenting to the jury any pre-2005 or post-2005 Lupron Depot 3.75 mg labels acknowledging thyroid adverse events, and the trial judge only allowed the jury to consider the 2005 label which lacked the warning. Lupron manufacturer’s principal medical expert, Dr. Richard Blackwell, under oath falsely stated “the thyroid gland … There are no receptors for GnRH. So there is no basic key on the thyroid gland for Lupron. Therefore, it is absolutely biologically impossible for Lupron to affect the thyroid gland. No textbook, no article has ever supported that contention. It’s simply biologically impossible” (emphasis mine) – see page 20 here.

Of note, Dr. Richard Blackwell has a history of receiving monies to study Lupron in women – see ‘Birmingham Center’ in this ‘Multicenter Lupron Study Group’. Also note that the latter study’s lead investigator, Dr. Andrew Friedman, was found guilty of fabricating and falsifying approximately 80% of data in 4 Lupron studies.

When the Klein jury heard Lupron’s expert medical witness proclaim it was “biologically impossible” for Lupron to affect the thyroid gland, they could not possibly know this physician was committing perjury. (Perjury is a felony, and if convicted involves fines and/or imprisonment up to 5 years – see here and here). If only the jury had known that evidence of this misinformation was just a keyboard away – a simple PubMed search (up to, and including, 2005) reveals the following published medical journal articles that evidence it is absolutely biologically possible for Lupron to affect the thyroid gland’:

“The first report to demonstrate the association of thyroid disorder with leuprolide [Lupron] injections” (2000), “Possible induction of Grave’s disease & painless thyroiditis by GnRHa’s” (2003), “The role of leuprolide acetate therapy in triggering auto-immune thyroiditis” (2005).

Serving as an “expert”, this is information that must certainly have been known, yet as a ‘hired gun’ for the drug company, the existence of this information was emphatically denied – leading the jury to believe it was impossible for Lupron to cause Karin’s thyroid disorder, and resulted in the jury finding in favor of the drug company. And thus the queue of Lupron litigation that was forming in anticipation of a Klein victory suddenly evaporated in the face of unmitigated, unethical, unlawful, unseemly, unchallenged ‘expert’ machinations.

To quote a ‘friend of the court’ brief filed on behalf of Klein by the organization “Consumer Attorneys of California”:

“[Klein was] entirely shackled in the evidence she was allowed to present. It is particularly galling to have qualified (and expensive) expert witnesses on hand to testify [on behalf of Klein], only for them to be shut down before the jury and precluded from offering competing expert opinions. The pattern shown by the record is deeply disturbing. Virtually every discovery and evidentiary ruling, and other orders of significance, went for one party [Lupron’s manufacturer]. Klein was not entitled to a perfect trial, but at least an evenhanded one. Such a one-sided proceeding was not the fair trial our system demands” (emphasis mine) – see page 6 here.

Klein ultimately petitioned the U.S. Supreme Court which refused to hear the case – great news for Lupron’s manufacturer, terrible news for young, disabled Klein, and chilling repercussions for society at large and Lupron victims in particular. Apparently, perjury under oath by paid medical experts, grossly misleading a jury, and the denial of a right to fair trial are issues deemed not significant by the U.S. Supreme Court.  For further information on the Klein matter, see here, here and here.

Obscuring the Drug’s Hazardous Status

Lupron is categorized by the FDA as a “Pregnancy Category X drug” (page 20, “leuprolide” – meaning any woman who is or who may become pregnant should avoid exposure), yet it became a staple of ovulation induction medication regimens in infertility, egg donation, and surrogacy. Lupron’s labels do state there is “a potential hazard to a fetus” (and oddly the most wording is found within the male Lupron Depot label). Lupron is classified by the National Institute for Occupational Safety and Health (NIOSH) as a “hazardous drug” (page 20, “leuprolide”), however nowhere in any of Lupron’s labels is there identification that Lupron is classified as a “hazardous drug” (i.e., pediatric, female, male);  nor does the label advise that as a result of this classification by NIOSH, special requirements apply for the handling, preparation, and administration of “hazardous drugs” (see here and here).

Around 2008, curious changes took place within Lupron labels (multiple indications) whereby it appears that cleverly, as if hiding evidence in plain sight, the “References” section of the labels now contained 4 citations – yet there are no corresponding footnotes within the label’s text for any one of these 4 citations. These 4 new “References” are as follows: (#1) NIOSH Alert, Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings; 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, NIOSH Publication No. 2004-165;  (#2) 1999 OSHA Technical Manual on Hazardous Drugs; (#3) 2006 ASHP guidelines on hazardous drugs; and (#4) 2005 Oncology Nursing guidelines on hazardous drugs (see pages 6, 14, 25, 36, and 47). Again, most curiously, not one of these 4 citations/”References” — or the information the citation source contains — were referred to, mentioned, identified, or discussed, at all, within the Lupron labels.

And presently, revised labels no longer contain the 4 citations mentioned above (see pediatric, female, male); and the labels continue to omit any identification of Lupron as a “hazardous drug”.

Measures Undertaken to Silence Critics

The Cardiac Stent Internal Memo

When Lupron’s manufacturer was under investigation for potential fraud related to its cardiac stents, numerous critical articles were written by a Baltimore Sun news columnist – and the drug company apparently targeted this columnist. As reported in a 2010 Senate Committee on Finance (examining a “clear example of potential fraud, waste and abuse”), “one Abbott official suggested that local connections or the “Philly mob” should intervene to silence Baltimore Sun columnist Jay Hancock for his coverage of the scandal, saying “someone needs to take this writer outside and kick his ass!”

Not a ‘seal of approval’ – the Hidden Lupron Endometriosis Clinical Trials’ Data

To the best of my knowledge, no one other than Dr. Redwine has independently analyzed the thousands of pages of raw data from the 1980s clinical trials for Lupron’s initial use in adult females (Lupron Depot 3.75 mg, for endometriosis). The conclusion from this independent analysis was that fraudulent data and misleading outcomes were found within these trials’ raw data. In one example, the raw data showed that “62.5%” of subjects had failed to return to baseline ovarian function one year after stop of study – yet Lupron’s label states Lupron’s hypoestrogenic effect “is reversible on discontinuation of drug therapy.” (For further information, see Part 3 of this series; the FDA’s response to Dr. Redwine’s request for an investigation into this serious matter; and here.)

It certainty appears that Lupron’s manufacturer intends to keep this raw data hidden from public view. Years ago the company sought and obtained a court-ordered seal on the raw data from these endometriosis clinical trials (see page 6 here), ensuring that this data will remain concealed from the public and any inquiring eyes.

Several years ago, when my assistance was sought by a Lupron victim whose attorney had retired in the middle of her case, the opportunity was used to file a motion to request the Court remove this seal (see “Reply Motion … and a Request that Court Seal on Defendants’ Clinical Trial Data Be Lifted”, Document # 135, Case 1:11-cv-04860, filed 2-20-14,  Paulsen v. Abbott, Takeda, TAP, US District Court, Northern District of Illinois, Eastern Division). No response from the Court was ever forthcoming from this request to unseal the raw data. The Paulsen case remains pending (see also here). A request to Lupron’s manufacturer to lift their seal also was unsuccessful (personal correspondence, 2015).

Suppression of Lupron’s Risks in Physician Continuing Medical Education

Renowned endometriosis surgeon Dr. Redwine became an outspoken critic of the use of Lupron in gynecology, and his opinion was reinforced by more than 700 women in his surgical practice who relayed harm from prior Lupron exposure. Dr. Redwine had most honorably refused the Lupron sales representative’s offer of $100,000 if he would prescribe Lupron to his patients. In 1994, Dr. Redwine wrote a ‘letter to editor’ in a fertility journal stating

“Inclusion of patients with a poor response to GnRHa therapy has not always occurred in outcome analysis in the published medical literature” (Letters:  Pros and Cons of “Add-Back” Therapy. 1994. Fertility and Sterility, 61:2:404).

According to Dr. Redwine’s expert medical testimony in the Klein case (in which he describes Lupron as being “unsafe and harmful in addition to being ineffective”), the following incident from the 1990s is described: Dr. Redwine was scheduled to be a speaker at a continuing medical education forum but was prevented from doing so by Lupron’s manufacturer because of his opposition to the use of Lupron. The drug manufacturer “interfered in the continuing medical education of physicians in order to enhance the sales of Lupron Depot” (see other excerpts of Dr. Redwine’s testimony here).

Peculiar Omission of Lupron/GnRHa Data in Studies of Health Disorders in Women With Endometriosis

Bone Density Loss

In 1989, a leading Lupron/GnRHa investigator in precocious puberty and gynecology concluded in a study that reduced bone mass (“significantly decreased cortical and trabecular bone mass”) was associated with the disease endometriosis. However, another study which found contrasting findings reported that “women with endometriosis do not have reduced bone density … One explanation for the difference between the results of this study and those of Comite et al. is that they included women who previously had been treated with GnRH agonists and these agonists are associated with bone loss.” (For further elaboration on these studies, see here.)

In my opinion, claims that the disease of endometriosis is associated with bone density loss, while appearing to deliberately omit the endometriosis patients’ common history of prior use of Lupron (which is known to causes bone density loss), is a treacherous concept and a slick maneuver — seeming to shield and manipulate iatrogenic, adverse drug effects into an ‘endometriosis-disease-related’ (and non-tort) phenomenon. This is something that deserves attention.

Autoimmune and Endocrine Disorders, Fibromyalgia, Chronic Fatigue Syndrome and Atopic Diseases

A 2002 publication (“High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis”) also failed to make any mention of Lupron or other GnRHas as treatment for endometriosis. This survey analysis, co-authored by the President of the Endometriosis Association (which has received hundreds of thousands of dollars from Lupron and other GnRHa manufacturers) also failed to identify the reported adverse events to Lupron (the most commonly prescribed medical therapy for endometriosis) – which have included autoimmune and endocrine disorders, fibromyalgia-like syndrome, chronic fatigue syndrome, and atopic diseases.

Yet, the survey upon which this analysis drew its conclusion does contain reference to Lupron/GnRHa use in the survey participants. In fact, of the 4000 surveys tabulated, 59% of survey respondents reported a history of Lupron/GnRHa use (‘Key Results from North American Membership Survey’, Endometriosis Association, 1998.  Presented at VI World Congress on Endometriosis). Given that the majority of the endometriosis respondents reported a history of Lupron/GnRHa use, how could this fact and highly significant confounding factor be ignored?

In my opinion, claims that the disease of endometriosis is associated with autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases, while appearing to deliberately omit the endometriosis patients’ common history of prior use of Lupron (which is known to cause autoimmune and endocrine disorders, fibromyalgia-like symptoms, chronic fatigue syndrome and atopic diseases), is a treacherous concept and a slick maneuver — seeming to shield and manipulate iatrogenic, adverse drug effects into an ‘endometriosis-disease-related’ (and non-tort) phenomenon.  This is something that deserves attention.

Coronary Heart Disease

Upon initial FDA approval for men in 1985, Lupron was alleged to have ‘insignificant cardiac adverse events’. (For further details on cardiac adverse events provided to and withheld from FDA by the manufacturer prior to approval, see page 4 here.) Subsequently, Lupron became the most prescribed GnRH analog. Decades later, a large study would show that the use of Lupron (and other GnRH analogs) for androgen deprivation therapy in management of prostate cancer was associated with a “10 – 50% increase” in the risks of coronary heart disease, myocardial infarction and sudden cardiac death (as well as fractures, strokes, and diabetes).

As a result of this and similar studies, the FDA issued a warning in 2010 concerning an increased risk of developing cardiovascular problems in men prescribed Lupron/GnRHas. The FDA acknowledged that there are no studies evaluating the cardiovascular risks of Lupron/GnRHas in children or women.  (To the best of my knowledge, there remains today no studies looking at Lupron/GnRHas cardiovascular risks in pediatric or female use; however there is presently an FDA “specific review” of nervous system and psychiatric events in children, and the NIH is in the midst of a study of long-term outcomes in transgender youth’s use of Lupron/GnRHas, evaluating “physiological and psychosocial impact, as well as safety”.)

In 2016, a cardiology journal published a study based on survey responses from the large-scale ‘Nurses’ Health Study II’ database, and this study associated endometriosis with an increased risk of coronary heart disease. Can you guess which drug was not queried in this ‘Nurses’ Health Study II’ survey? This survey sought information on the woman’s use of alcohol, cigarettes, post-menopausal hormones, oral contraceptives, multivitamins, analgesics (including acetaminophen, aspirin, ibuprofen, indometacin, naproxen, nabumetone, ketoprofen, celecoxib, rofecoxib, and valdecoxib), but omitted any questions about the woman’s exposure to the most frequently prescribed treatment for endometriosis – Lupron/GnRHas.

My response to this inexcusable omission of Lupron/GnRHa exposure data was published in the journal – see “Article’s conclusions seriously flawed without data on Lupron/GnRHa use”.  The authors of the study responded with inaccurate information on Lupron (see May 11, 2016 response), prompting me to submit a reply addressing this incorrect information. The journal failed to publish this corrective information, therefore I’ve published my reply on my own website.

In my opinion, claims that the disease of endometriosis is associated with coronary heart disease, while appearing to deliberately omit the endometriosis patients’ common history of  prior use of Lupron (which is known to cause numerous cardiovascular adverse effects in women – see ‘Cardiovascular Effects’, Left column here; and here), is a treacherous concept and a slick maneuver — seeming to shield and manipulate iatrogenic, adverse drug effects into an ‘endometriosis-disease-related’ (and non-tort) phenomenon. This trend is very troubling, and is something that deserves significant attention and investigation.

Conclusions

The above information, as well as information found within this series, the Kaiser Report, and other media sources (see here) should be more than sufficient indication that numerous investigations into the effects of Lupron (and all GnRHas) are warranted.

That there are large numbers of Lupron victims cannot be disputed – one need only have computer access to verify this sad fact. (For links to a large sampling of Lupron reviews, stories, posts and comments in various medication and legal websites, see here.) The petitions to Congress requesting an investigation into Lupron appear to have fallen on deaf ears; one petition started in 2009 states more than 21,000 messages have been sent to date. (Links to multiple petitions, in the U.S. and France, containing more Lupron horror stories, can be found here.)  There are more than ample numbers of Lupron victims complaining, the problem has been identified – what is needed is action.

Investigative reporters, the FDA, Congress, public health authorities, and the medical and legal community need to do their job and focus multiple spotlights on all the aspects of this drug, its effects, its associated harms, and the lack of medicolegal advocacy for its victims.

In my opinion, this drug should have been withdrawn from the market a long time ago – just how many more victims will it take?

Someone needs to be held responsible for all the suffering, and the ruined health, and careers, and lives of so many Lupron victims and their families. The devastation that Lupron has wrought ought to be criminal. People need to go to jail.

Or perhaps, they should just get a Lupron injection themselves.

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This article was published originally on May 31, 2017. 

Image by Peter Timmerhues from Pixabay.

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The Lupron Money Trail

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Recent attention in a dual Reveal and Kaiser Health News Report (‘Kaiser Report’) to the risks of Lupron’s use in children with central precocious puberty (PP) or growth issues, and to Lupron’s risks in general, presents an opportunity to continue the disclosures on the risks of Lupron. This is the fifth part in a 6-part series exploring numerous areas addressing the use of Lupron in the pediatric and teen population. The series began with the voices of the mothers of harmed children and the now-adult suffering children. This was followed by articles on the regulatory issues that surround Lupron’s approval and continued use, the possible reproductive injuries associated with this and other drugs within its class, and issues surrounding Lupron’s metabolism and clearance from the body. Here we will take a look at some of what is known about the Lupron money trail.

Ignoring and Dismissing Side Effects: Follow the Money

WebMD, a highly ranked and promoted consumer ‘go-to’ site for health information, ‘informs’ the public about precocious puberty:  “[t]here’s no evidence that these [GnRHa] drugs cause any long-term problems”. Common neurological and musculoskeletal complaints from Lupron, such as joint and muscle pain, and mood changes are listed as “infrequent” and decreased density of bone as a “rare” side effect. WebMDs “Fertility Drugs” page fails to identify Lupron as a ‘Pregnancy Category X’ drug (as designated by FDA), but states “as many as 50% [with successful ovulation] are able to get pregnant. Most side effects are mild.” Another high-ranking consumer information website, Medscape, tells of a number of clinics “all very experienced in treating gender dysphoric youth … This [GnRHa] treatment is fully reversible.” (See ‘Lupron and reproductive injury’.)

While unrelated to Lupron, the following news story from 2009 was nonetheless thought-provoking: Medscape and WebMD were accused in a whistleblower lawsuit (involving 17 states) of being “part of an illegal conspiracy to promote the off-label use of two [drugs]” – and the details of the charges were “a mystery” due to major redactions by the judge.

Lupron is no stranger to whistleblower lawsuits (here , here, and here) or to charges of promoting off-label uses. The drug’s manufacturer has received ‘Notices of Adverse Findings’ due to its promotion (“indoctrination“) of Lupron for unapproved gynecological indications, and warnings for misleading claims in its prostate indication. The company’s schemes of fraudulent drug pricing and bribing doctors are well known and documented.

CafePharma, an anonymous industry insider message board for pharmaceutical sales reps, had a few postings in 2010 that summed the scenario up succinctly.

“[T]he docs know who has buttered their bread, and we [drug company/sales force] got very deep pockets” (see post of March 20, 2010 @ 12:25 pm here).  And “YOU DUMMY ABBOTT PAYS MILLIONS UNDER THE TABLE SO DOCS USE LUPRON (emphasis in original)” (see post of March 27, 2010 @ 7:45 pm here).

How Lucrative is Lupron Use in Precocious Puberty?

The Kaiser Report identified that in a 2 year period of time Lupron’s manufacturer, AbbVie, had paid $157,066 to the lead investigator of Lupron’s precocious puberty clinical trials, Dr. Peter Lee (a pediatric endocrinologist). According to ProPublica’s “Dollars for Docs”, for the years 2015, 2014, and 2013, Lee received from AbbVie a total of $102,325 for “Promotional Speaking/Other” for Lupron.  (Payments by AbbVie to Lee for Lupron related “Consulting”, “Travel and Lodging” and “Food and Beverage” were not tallied, but figures are available at ‘Dollars for Docs’/ProPublica for each of those 3 years.)

The Kaiser Report also identified that both AbbVie and investigator Lee did not answer specific questions about the omission of serious adverse events (a bone disorder and a pathological fracture) in a key pediatric clinical trial of Lupron. How is this acceptable? If the drug company and lead clinical trial investigator will not answer questions about adverse events in the trial – who will?

In the drug company’s campaign to promote Lupron for precocious puberty (entitled “Too Soon”), they claimed (in 2003) “[t]here are almost 5,200 children who have central precocious puberty and grow up too soon” (see Question/Answer # 10). Lee was a member of the editorial board of “Too Soon”, and Lee is a consultant  for AbbVie, and “has received payment for the development of educational materials by AbbVie”.

It goes without saying that during a promotion of something (especially if one is being monetarily compensated for doing so), such promotion usually results in a loyalty to, and liking for, ‘the thing’.  And especially so if ‘the thing’ is a “cash cow” (stated in a ‘CafePharma’ post of August 8, 2011 @ 3:47 pm).

In 28 months (August 2013 through December 2015), AbbVie made 69,173 payments related to Lupron for a sum of $16.9 million to 24,910 doctors, and Lee came in second place in ‘top doctors receiving payments related to Lupron’.

How objective can Lee and the other 24,909 who are paid by the drug company to promote Lupron be? What would happen if any one of the 24,910 paid Lupron spokesmouths were to say “Hey, wait just a minute … there’s some pretty sick kids (or men and women) out there after using this drug – we need to take a serious look at this”?

Simple logic should tell you that a pharmaceutical company does not spend $16.9 million over a 28-month period to almost 25,000 doctors to hear a negative (bad) message about its product. In fact, I have seen signed consultant and scientific advisor agreements by a rheumatologist with this drug company, and there was a pledge taken to defend the company’s products at all times in all ways (documents presently unavailable, but reference to them was made in my 2003 congressional testimony, p. 12).

It seems peculiar that the #2 recipient of payments for the promotion of Lupron (the use of which spans multiple adult male and female indications that number in the millions) would involve a specialty that serves not quite 5,200 children.

Lupron’s use in the pediatric population is not limited to precocious puberty, and extends to youths and teens with gender dysphoria. Estimates from a federal database in 2016 place the numbers of adults who identify as transgender at 1.4 million (with states ranging from 0.30% to 0.75% of population), but there are no national surveys of youths; small-scale high school surveys have shown about 1.5% of surveyed students identified as transgender.

Pain and Agony of Adverse Effects Is Not a Lucrative Message

In an “ethical dilemma of choosing [between] wrongly suppressing puberty in kids who will grow out of their gender variance or refusing treatment [Dr.] Peter Lee … who had [by 2007] treated three young transgender teens with Lupron, knows on which side he’d rather err” – and that is to administer Lupron/GnRHas. Dr. Lee described one transgender adolescent 20 years ago “in so much pain and agony” that she later committed suicide. (A different perspective has been offered from a psychiatrist who has called this “Lupron treatment [for transgenders] a modern form of child abuse“.)

Where is the discussion on the pain and agony of pediatric (and adult) Lupron victims, and the psychological and psychosocial effects upon the child after development of medication adverse events?  (See Part 1 of this series for excerpts of heart-wrenching pain and agony voiced by parents and victims.) The sudden onset of migraines, weight gain, joint and bone pain, muscular pain, weakness, mobility limitations, mobility impairments, mood changes, irritable bowel, lethargy, difficulties with concentration and memory, anxiety, depression, suicidal ideation, etc., following treatment would indeed have a profound impact upon the child, their relationship to peers, and academic participation.

Given the flood of complaints about Lupron injury that is posted at various online sites, the $64,000 question remains ‘why has the pain and agony experienced by Lupron victims (of all ages and all genders) been so marginalized and often dismissed’? What causes the reported anger and defensiveness doctors have displayed when queried about the medication adverse effects? (See petitions and medication review site links – the web collectively provides millions of posted complaints, with daily additions.)

Marketing Indoctrination and Coercion

In March 1990 the FDA sent Lupron’s manufacturer a ‘Notice of Adverse Findings’, concerning its “deliberate campaign to promote this product for a wide range of unapproved uses.” A follow-up memo further detailed the FDA’s “concerns” about an upcoming drug company sponsored program at “Walt Disney World Swan”: the FDA said “it appears to be a program to indoctrinate physicians in unapproved uses of Lupron, and to specifically encourage administration of Lupron for these unapproved uses.” These unapproved uses involved gynecology and fertility. (In October 1990, Lupron received FDA approval for the indication of pain management in endometriosis; no FDA approval for fertility treatment has ever been obtained – and note that Lupron’s initial patent was for ovulation induction.)

As an IVF patient in 1990, my fertility clinic’s brochure stated “Lupron is only prescribed to persons with certain diagnoses”, but in 1991 this changed to “Lupron is widely prescribed”. What would cause the sudden universal use of Lupron at this (and just about every other) IVF clinic?  A 1992 study, which asked in its title whether there was any medical advantage for using GnRHa’s for all patients undergoing IVF, concluded:

“The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages … there have been very few prospective randomized  studies comparing the use of GnRH-a with conventional stimulation regimens”.

My IVF clinic’s doctors had become indoctrinated to use Lupron in ovulation induction in the same manner as IVF clinics throughout the country. A 1989 US Subcommittee mailed a detailed survey to 224 US fertility clinics to obtain a wide variety of IVF data, and in the process many clinics self-reported their new ‘Lupron protocol’.  These survey responses, and transcripts of an accompanying hearing, were  published in a document titled “Serial No. 101-5” (101st Congress; March 9, 1989).  Here are a few pertinent excerpts illustrating the abrupt change to using Lupron by the survey respondents:

“Changing to Lupron stimulation for all patients” (p. 333. ART Program, Birmingham AL), “us[ing] Lupron for all patients” (p.408. Fertility and Reproductive Health Institute of Northern California, San Jose, CA.), “seventy percent of all patients are administered leuprolide” (p. 417. Century City Hospital, Los Angeles, CA.); “in 1988 we initiated the use of GnRH agonist for all patients” (p. 490. Hoag Fertility Services, Newport Beach, CA.).

Of the hundreds of fertility clinics responding to the Subcommittee survey, only one clinic raised a word of caution:

“Promoting the Use of GnRHa (Lupron) … it remains entirely unclear that all patients need this costly and often painful [and “experimental”] approach” (p.852.  University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ.).

Men, told they otherwise would face treatment for prostate cancer by either castration or DES (and potentially experience gynecomastia and adverse cardiovascular effects) were ‘encouraged’ to use this drug. A survey of urologists revealed that 53% did not believe in the efficacy of GnRHa treatment but still prescribed it.

My 2003 congressional testimony  identifies (p. 7) “the badgering, and coercion, and manipulation, and threats used to convince women into taking Lupron for a variety of indications – many refer to their doctor as trying to “shove it down [their] throat”.

Women were threatened with a hysterectomy (endometriosis), the specter of bleeding to death (fibroids), or refusal to undergo IVF. My 1993 testimony  to the MA. Health Care Committee (an attempt to enact legislation which would mandate fertility clinics provide, among others, accurate information on the risks of Lupron) states:  “… nearly every IVF clinic has mandated that women take Lupron – or they will not be allowed to cycle.”

Parents of children with precocious puberty are ‘encouraged’ to use this drug to prevent the child from ‘enduring psychological distress from their precocious development’ and to ensure achievement of ‘appropriate’ height.  In the transgender population, a similar psychological premise is offered for the normal – but ‘unwanted’ – sexual development, and the specter of anxiety, depression and suicide is raised for the untreated dysphoric youth/teen.

History of Fraudulent Data

In a review of the endometriosis clinical trials’ raw data, Dr. David Redwine discovered that the raw data did not support the claims by the company. In one example, Redwine’s analysis revealed that

“62.5% of women had not regained baseline estrogen levels one year after stopping Lupron … This is definitive evidence of long-term damage to ovarian function.”

Yet, contrary to this raw data, Lupron’s endometriosis label states the effects of Lupron “are reversible upon discontinuation”.  (See p. 26 in amicus curiae for US Supreme Court.) If 62.5% of subjects one year after Lupron discontinuation evidenced long-term damage to ovarian function, then what data did the company provide to the FDA for its 1990 Lupron approval which ‘demonstrated’ its effects “are reversible upon discontinuation”?

In 2010, Dr. Redwine provided a 300-page report to the FDA concerning these instances of apparent data fabrication. The essence of his report, titled “Leuprolide – the ‘D’ is Silent”, can be seen in a somewhat redacted power point presentation here.  Years after receiving the report, the FDA decided “no regulatory action is needed”  – all the while ignoring and failing to address the issue of fraudulent data and altered outcomes delineated in this report.  ‘Lupron Victims Hub’ sent an Open Letter to FDA in 2014 with specific questions – those questions remain unanswered.

During the lawsuit ‘Klein v. TAP, Abbott’, Redwine served as an expert medical witness, and in his expert statement he describes Lupron’s “medical fraud” as being “the most egregious example of Big Pharma controlling the practice of medicine”. Dr. Redwine concludes that Lupron is “unsafe and harmful in addition to being ineffective”.

For further information on retraction of Lupron studies and other instances of problems with the data in Lupron studies, see here,  here , here , here, and here.

Considered Not Related to Study Drug by the Investigator

In the Phase 3 and Phase 4 clinical trials by Dr. Lee for 1 month Lupron Depot-PED, one subject died from respiratory infection and heart arrest. In typical Lupron clinical trials’ language, this adverse event was “considered not related to study drug by the investigator”.  Of the 7 subjects for which serious adverse events were reported, 5 of those 7 subject’s adverse events were “considered not related to study drug by the investigator”.

In another precocious puberty study, the only serious adverse event reported was increased intracranial pressure, and this also was “considered not related to treatment by the investigator”.  While this subject did have a ventricular-peritoneal shunt, it should be noted that Lupron is known to be a cause of increased intracranial pressure. And so it would be interesting to learn how long – prior to Lupron – this subject had a shunt in place without any increased intracranial pressureInclusion criteria for entrance into this study require “general good health with no uncontrolled, clinically significant disease”, and exclusion criteria preventing entrance into this study were “any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk”.  (And note  an unrelated post by a 24 year old woman who developed pseudotumor cerebri “as a result of the poison Lupron”, and who requires a shunt: see July 25, 2011 entry @ 10:38 am here.)

I suppose there could be a number of different reasons for an investigator to consider an adverse event as “unrelated” to a drug, but unless specific questions about the adverse events from these pediatric trials are actually answered — knowing the history of this drug — I can only assume the worst.

Questionable Data Found in Adult Male and Adult Female Studies

MEN: In the mid-1990s, after scouring FDA documents related to Lupron’s initial approval for prostate cancer, it appeared there was curious and questionable data related to Lupron’s cardiovascular effects. At the time, I questioned the validity of the claim Lupron had a safer cardiovascular profile than alternative treatment – a mantra that became a selling point for the drug. (See ‘Was Lupron’s Initial FDA Approval Based Upon Safety & Efficacy’, p. 4-10 here). In 2010 the FDA would issue warnings for Lupron/GnRHa use in men concerning the potential increased risk for cardiovascular problems, heart attack, sudden cardiac death, and stroke (and diabetes).

WOMEN: In my 1995 testimony to the MA. Health Care Committee, I identified “manipulated figures” (p. 8 here) in a female Lupron study – fourteen months before the Federal Register posted a Notice of Scientific Misconduct about the same Lupron investigator/author who had been found guilty of falsifying and fabricating 80% of data in 4 other Lupron studies (2 of which had been published and required retraction).

Illegal Marketing Schemes in Gynecology and Urology

Years ago I was aware of a gynecologist approached by the drug company’s sales force that indicated he could clear $98,000 to his income by prescribing Lupron” (see page 8), and would also find an internal confidential company memo unearthed during Oversight Hearings which detailed for urologists the annual $105,011.40 doctors could earn when they prescribed Lupron.

Bloomberg News summed up the impact drug money had in urology (‘Prostate Patients Suffer as Money Overwhelms Best Therapy’, November 6, 2012.  Bloomberg News;  article snippet  here):

“[In the past] Urologists could make $5,000 per patient dispensing Lupron in their offices, thanks to secret discounts and kickbacks from drug makers.  … In 1997 the 25 top-prescribing Lupron urologists each averaged $1.6 million in Medicare payments. … Two of every five patients who received hormone therapy didn’t need it, the [New England Journal of Medicine] study found. In 2005, after Medicare cut Lupron and Zoladex payment rates by over half, inappropriate use plummeted 44 percent. … Hundreds of thousands of men were chemically castrated for no reason; that’s the biggest scandal of all. … The money was too irresistible.”

There were reports of bribes from Lupron’s sales force in both urology and gynecology, and ultimately

the company pleaded guilty to participating in a criminal conspiracy by providing doctors with free Lupron samples for which doctors then billed Medicare [with] the company inflat[ing] the list price of Lupron to ensure that doctors who prescribed it would make a sizable profit when the government reimbursed them.”

The company paid the then-highest fine in US history – $875 million.

In addition to my multiple  attempts to encourage the US investigation to expand its investigation from financial fraud and into the health risks posed by Lupron, it appears others were also making similar requests: “A call to the U.S, Attorneys Office inquiring whether financial fraud in the marketing of Lupron might indicate that FDA studies may also have been fabricated brought no answer. They are simply not interested.”

Paying the Patient Support Groups

In the past, “[i]n addition to offering inducements to hospitals and doctors, [Lupron’s manufacturer] was encouraging its salespeople to approach patients in support groups” (see here, here, and here ). It is known that the manufacturer of this drug and other GnRHas contributed hundreds of thousands of dollars to an endometriosis support association , and Lupron’s manufacturer also contributed thousands and thousands of dollars to a fertility support group (at a time when Lupron was only FDA approved for men). It is only logical to question whether any pediatric support group(s) experience(d) ‘infiltration’ of Lupron money.

One pediatric group dedicated to growth disorders, the Magic Foundation, is known to have received money from growth hormone manufacturers. According to publicly available documents from Guidestar, this foundation has reported 2014 contributions of $949,348 (contributors’ identity not provided). Appearing prominently (and to me, appearing promotionally), the Foundation’s website discusses and displays Lupron Depot-PED information, as well as providing the web address for AbbVie’s Lupron Depot-PED product information. (Until recently, no other GnRHa was identified, discussed, or linked on the Foundation’s website, and presently one other 12-month injectable, non-Lupron, GnRHa drug is mentioned.)

The information posted on the Foundation’s website of risks from Lupron Depot-PED is quite sparse: there is mention of temporary mood changes, injection site redness and pain, and rarely a sterile abscess, concluding “[r]esearch to date indicates that when treatment is stopped, puberty should resume and advance normally.” “Only as a convenience” does an AbbVie “Puberty Too Soon” website provide a web link to the Magic Foundation. It should be noted that AbbVie’s lead Lupron precocious puberty investigator Dr. Peter Lee, is on the Medical Advisory Board of the Magic Foundation.

Transgender Use of Lupron Noted as Lucrative for Some Providers

A 2013 ‘GenderTrender’ article noted for years “a cluster of extremely well-funded physician providers” have been prescribing to children off-label drugs for transgender use. This article states Lupron is “so toxic” adult transgenders are advised against its use. The article includes a statement by Lee: “Suppression … can be effectively and safely accomplished using GnRHa – an intervention that is both temporary and reversible.”

Benefits of Orphan Drug Status

Lupron for use in precocious puberty (a rare ‘orphan’ disease‘ which by definition affects less than 200,000 in the US) has the designation of “Orphan Drug” status, allowing the drug company tax credits (under 26 USC 45C) for related clinical testing expenses (see here and here). It should be determined if expenses from non-precocious puberty pediatric uses (which would be ineligible for orphan status/tax credits) have been filed, i.e., transgender and acne (which affects approximately 1.4 million and 50 million people, respectively). How many off-label, unpublished studies have been conducted in the pediatric and teen population?

Lupron is Lucrative

Based upon the information provided here (and this is not an all-inclusive list), in my opinion it seems little wonder that Lupron became the most prescribed GnRHa, became prescribed for men, women, and children (and animals, fish, chickens, etc.). And it’s no surprise why Lupron has been prescribed for A – Z off-label indications, nor why its victims have met with extreme difficulty in having their adverse events acknowledged and addressed.

Lupron has not only been lucrative for a number of its opinion leaders, spokesdoctors, and prescribers – it has also resulted in a cottage industry born from Lupron-induced iatrogenic injury, requiring acute and chronic office visits and hospitalizations for virtually every practice in medicine (neurology, rheumatology, cardiology, endocrinology, oncology, gastroenterology, psychiatry, pulmonary, dermatology, etc.).  This drug isn’t just a “cash cow” – it’s a “cash pig”.

Postscript: Correction

April 25, 2017 – The above is an edited version of an article that was originally published on April 18, 2017.  In this edited version, information pertaining to adverse events in one particular pediatric clinical trial has been removed from the original article because this information has been learned to be inaccurate. In the original article, I cited adverse event numbers as found listed within this pediatric study’s results. However, in looking at this study’s list of adverse events, I read (and cited) the reported numbers that followed any particular adverse event – when, in fact, the correct reported numbers were those that preceded any particular adverse event. This list’s reverse order of coding resulted in my (erroneous) conclusion that the numbers of adverse events reported for this trial were in error. (And the list, when read in reverse, provides reported adverse event numbers that exactly match those reported in this trial, indicating no error had occurred.) I have emailed the author of this pediatric study an apologetic note, describing the confusion that resulted from this list’s atypical coding methods, and have acknowledged that the reported adverse event numbers for this trial are indeed “valid”. I apologize to anyone else who may have been inconvenienced by this error.

The original (and now known to be erroneous) text removed from this edited version is included here for your information:

Original Text

CHILDREN: And now, after looking closely at one pediatric clinical trial, there appears to be clear evidence that larger numbers of adverse events were experienced by these children which were not recorded or identified in the final results of this study.

In this pediatric trial, my review counted six adverse events which did not contain the correct number of reported adverse events in the final study results. For purposes here, one adverse event – vomiting – will be used as an example to describe this inexplicable disappearing act of adverse events.

The medical journal publication of this clinical trial, and the ‘study results’ of this trial (housed at ‘ClinicalTrials.gov’) both claim there were “0” reports of “vomiting” in Group 1 (3-month Lupron Depot 11.25 mg) and “4” reports of vomiting in Group 2 (3-month Lupron Depot 30 mg). However, in looking at the history of this trial at ClinicalTrials.gov, which identifies the changes and additions made to this trial, it can readily be seen that the changes made on December 9, 2013 (the additions of reported adverse event numbers) display that for the adverse event of vomiting, Group 1 had “10” reports of vomiting, and Group 2 had “9” reports of vomiting. That is a significant difference in numbers of reported vomiting than is found in the journal publication and in ClinicalTrials.gov study results. And when these documented (but not counted) adverse event reports of vomiting are properly tallied, the claimed incidence of vomiting changes from the published 5.6% to an actual incidence of 26.4%.

In emails to the lead author in attempts to learn the explanation(s) for these missing, untallied adverse events, I was informed that the data as published in the medical journal “is valid” and he is “not the responsible person for this data.” Numerous attempts to learn exactly who is responsible for the data in this clinical trial have proved fruitless to date. How can the lead author not be responsible for the validity of the data from his own study?

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Lupron and Reproductive Injury

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Recent attention in a dual Reveal and Kaiser Health News Report (‘Kaiser Report’) to the risks of Lupron’s use in children with central precocious puberty or growth issues, and to Lupron’s risks in general, presents an opportunity to continue the disclosures on the risks of Lupron. This is the third part in a 6-week series exploring numerous areas addressing the use of Lupron in the pediatric and teen population (part 1, part 2).

Lupron and Reproductive Injury

The original patent for Lupron (leuprolide), granted in 1977, was for ovulation induction. Because of Lupron’s hazardous drug status and its categorization by the FDA as a Pregnancy Category X drug (any woman who is or who may become pregnant should avoid because of risk to fetus), it could not gain FDA approval for the indication of ovulation induction. Therefore, Lupron’s manufacturer sought, and gained, FDA approval for use in palliative treatment of prostate cancer. This then allowed the drug to be prescribed off-label for ovulation induction and many other unapproved indications. Over the next several decades, Lupron’s use has expanded into multiple areas of pediatric and women’s health.  There are three FDA approved indications (‘precocious puberty’ in children, ‘pain management in endometriosis’ and ‘the hematologic management of anemia associated with fibroids when iron therapy alone is ineffective’), and many off-label uses of Lupron (see Incomplete A-Z List of Off-Label Uses here).

In 1983, ten years before Lupron received FDA approval for precocious puberty (PP), GnRHas were being tested extensively in a variety of indications, including “as a new treatment for idiopathic precocious puberty”, and for male and female contraception. Eleven years later a pilot study using Lupron plus low-dose estrogen as a preventative for breast cancer was deemed “an adventure into the unknown”, and the FDA determined that this treatment “should not move into larger clinical trials” (The Pink Sheet 1994; 56(27):13.  ‘GnRH/low-dose Steroids Not Appropriate for Study in Breast Cancer High Risks’). The FDA Committee Chairman said at the time:

“It would be better to recommend a study of the drugs in a high-risk population as a chemopreventative for a long time, find out what its long-term effects were, and then consider it for a larger population.”

In 1993, the year of Lupron’s FDA approval for PP, a study was published of 10 girls who had been followed up to 5 years, and while concluding Lupron was safe and effective, it noted:

“[l]onger-term studies, including reproductive history, will be needed before the potential effects of treatment on fertility can be assessed.”

The following year, in 1994, the FDA recommended nonclinical safety studies of GnRH analogs be conducted. And while it is not clear whether these nonclinical safety studies were conducted, one FDA Medical Office stated at the time:

“the possibility exists that some germ cells may have been permanently affected by drug treatment. It is therefore important to investigate the effects on fetal morphology (teratogenicity) and on postnatal development of the offspring.”

In a long-term clinical study in 1999 examining GnRHa treated girls with PP (Lupron being the most frequently prescribed GnRHa), it was identified that:

“Ovarian volumes tend to increase progressively over the first 3 posttreatment years and were often larger than normal by 3 year post-therapy [and these findings] suggest that recovery of the suppressed gonad of girls treated for longer periods of time may be a more gradual process, and that a complete picture of the effects of therapy may only emerge after several years have passed.”

Similarly, the original rat studies provided to the FDA for its initial 1985 approval in prostate cancer identified that

“[t]he severity of the lesions were greater in testes of rats sacrificed 7 days after cessation of [Lupron] indicating that the effects continued after drug withdrawal (emphasis mine)”.  (“Review and Evaluation of Pharmacology and Toxicology Data‟, NDA [New Drug Application] 19-010, March 1, 1984.)

Lupron Depot-PED’s label states “[f]ollowing subcutaneous administration of LUPRON DEPOT to male and female rats before mating there was atrophy of the reproductive organs and suppression of reproductive performance.”  The label also states “[f]ollowing a study with leuprolide acetate, immature male rats demonstrated tubular degeneration in the testes even after a recovery period.”  (Even though these rats failed to recover histologically, the label claims they were as fertile as the controls.”)

Precocious Puberty, Lupron, and PCOS

In a 2010, Italian study of girls with early puberty treated with GnRHas, the prevalence of polycystic ovary syndrome (PCOS) and hyperandrogenemia  “was significantly higher” than those untreated, and “this study represented the first evidence of an independent effect of GNRHa treatment in increasing the risk for PCOS during adolescence in girls with early puberty.”  At least one earlier study noted “very large ovaries” when GnRHa treatment was stopped, and subjects “had an increased prevalence of ovaries with a polycystic appearance.”  PCOS has been associated with increased risk of metabolic syndrome, diabetes, and dyslipidemia – conditions which may increase risk of cardiovascular disease. PCOS is also associated with infertility, which can result in the need for assisted reproductive technologies which often involve the use of Lupron.

Lupron and Torsion

In a Brazilian case report of a girl with McCune Albright syndrome (which, though rare, accounts for about 10% of PP cases), a salpingo-oophorectomy (surgical removal of fallopian tube and ovary) was required after the 3rd leuprolide dose due to complete torsion of right adnexa and a necrotic, cystic right ovary.  This case report also notes that:

“treatment [for McCune Allbright syndrome] with a GnRH analog can result[] in ovarian stimulation, cyst formation, increase of [ovarian] volume and adnexal torsion” requiring surgical removal of gonads.   (See photo of this girl’s enlarged, cystic, necrotic ovary in case report’s “Figure 2”.)

In a review of FDA’s adverse event reports (“AERS”), data valid through June 2016, for “Lupron Depot-PED”, “Lupron (leuprolide; daily injection), and “Lupron Depot”, there were no reports found for “salpingo-oophorectomy”.   The above published case of a pediatric salpingo-oophorectomy should have been reported, both to the drug company and subsequently to the FDA.  The case of ovarian torsion and of ovarian necrosis that appears in a ‘Lupron Depot-PED’ search at RxISK.org  (for 1 to 13 years old) likely represents the Brazilian case, but it is baffling why this case report cannot be found within the FDA’s AERS database. In addition, the latter RxISK search engine yields a report of ovarian enlargement in a search of 1 to 13 years old, which is also not found within the FDA’s AERS database.

In a search of AERS for adult women who experienced oophorectomy post-Lupron, 42 reports were found, and all but three reports were expedited, 15-day reports (which are provided in cases of serious adverse drug reactions). In a search of the “Lupron Depot-PED” AERS, 3 cases of ovarian cyst were reported. It is well known only 1% – 10% of all serious adverse events are ever reported to the FDA – meaning 90-99% of adverse events to Lupron are not reported [see page 7 here].)

Off-Label Use for Gender Dysphoria

In the off-label use of Lupron for ‘pausing puberty’ in the transgender population, it should be understood that Lupron is rarely identified as “Lupron”, but is called a “puberty-blocker”, “hormone blocker”, or “a puberty-suppressing drug”.  No doubt this language shift is an attempt to prevent an association with the ‘dreaded Lupron’.  It should also be noted that a reproductive biologist has stated ‘puberty suppressing treatment’ “impairs the children’s reproductive capacity” and:

“[s]ome trans boys (i.e. girls) receive puberty-suppressing treatment and never produce mature ovarian follicles … the problem is accentuated with trans girls (i.e. boys) because their spermatozoa are still developing.”

Additional alarming acknowledgments within the transgender population’s off-label use of Lupron are that:

“[p]otential long-term effects can include other abnormalities of hormones, vascular complications and even potential cancer.”

According to UnitedHealthcare policy, “pubertal suppression therapy is considered unsafe in managing children and adolescents with gender identity dysphoria and is, therefore, not covered.”  Other insurers do cover treatment of gender dysphoria with Lupron. One Canadian consent form for Lupron treatment of natal females with gender dysphoria identifies a number of risks, and twice repeats the warning that “there may be long-term side effects we do not yet know about”.

In 2015, the NIH awarded $5.7 million for a 5-year multi-center study which

“will be the first in the U.S. to evaluate the long-term outcomes of medical treatment for transgender youth“, seeking data on the “physiological and psychosocial impact, as well as safety, of hormone blockers.”

Reproductive and Developmental Toxicant

Lupron is known as a “recognized reproductive and developmental toxicant“.  The manufacturer’s ‘Material Safety Data Sheet’ (MSDS) identifies that Lupron-PED “may impair fertility” and “may damage fertility”.  The product label states the effects are “reversible on discontinuation of drug therapy” and “normal pituitary-gonadal function is usually restored within six months after treatment with LUPRON DEPOT-PED is discontinued” (emphasis mine). The label also identifies that rats “demonstrated tubular degeneration in the testes even after a recovery period.”  Past product labels state “no clinical studies have been completed in children to assess the full reversibility of fertility suppression”, but in 2013 follow-up data from previous pediatric clinical trials identify that post-study surveys of 20 trial participants found 80% had normal menstrual cycles – which indicates 20% had abnormal menstrual cycles.

Lupron, Endometriosis, and Hypoestrogenism

It is pertinent to address here the findings of an independent analysis by Dr. David Redwine of the raw data from Lupron’s endometriosis clinical trials: this analysis evidenced, among others,

“62.5% of [Lupron Depot 3.75 mg.-treated endometriosis] patients had not regained baseline estrogen levels by one year after stop of study … [indicating] definitive evidence of long-term damage to ovarian function” (see ‘Alarming Facts About Lupron’s Risks’ on pg. 26 here).

In a stark and most troubling contrast, Lupron Depot’s product label states the Lupron-induced hypoestrogenism “is reversible upon discontinuation of therapy”. Lupron’s manufacturer sought and obtained a court seal (see page 6 here) upon its endometriosis clinical trial data (and my attempts to unseal this data were unsuccessful). Without access to this raw data, further independent validation is not possible. To this day, these studies remain in the published literature without any retraction or comment. And cumulatively, as of this writing, these published clinical trials have been cited – as fact – within 23 PubMed Central articles (as recently as 2016), and they have also been cited in three Cochrane Systematic Reviews.  The four published studies containing the questionable endometriosis clinical trials’ data are studies “M84-042“, “M86-031“, “M86-039“, and “M92-878“.

The alarming contradiction in data and outcomes (raw endometriosis data showing “62.5% experienced long-term damage to ovarian function” vs. Lupron’s label and published studies’ claim of “reversible upon discontinuation”), as well as the perplexing paralysis on the part of the FDA and medical journals to act on behalf of public health, begs for a high beam investigative spotlight by the media, and medicine. See FDA response  which completely ignores the issue of discovered fraudulent data in Lupron’s endometriosis clinical trials, and see 2014 letter to FDA by Lupron Victims Hub which remains unanswered.

Somebody needs to answer these questions. If the FDA is not able or willing to be in charge, then who is the responsible authority? Inaction in this matter is totally unacceptable on multiple levels.

What Does the Future Hold?

Lupron has been administered to children for 30+ years, yet no definitive conclusions about its effects upon  reproductive health can be made due to lack of data?

The NIH transgender study, which should include assessment of “hormone blockers” upon the reproductive system, won’t be completed until 2020. But even if study results were available today, would it be claimed the data from the transgender population is not transferable to the precocious puberty population?

If various medical boards can classify Lupron’s use in children with autism as “dangerous, abusive and exploitative”, then Lupron’s use in children (period) is dangerous, abusive, and exploitative.

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This article was originally published on March 15,  2017.

Photo by Jasmin Egger on Unsplash.

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