lupron side effects Archives

Short and Long Term Consequences of Lupron for Precocious Puberty

Published on May 8, 2024

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As a child, at around age 5, I started experiencing severe pain in my legs and back. I had migraines from hell that made me feel as if my head were going to explode. I had hair in places that no five-year-old should and I needed a bra for kindergarten. I looked down on all my peers because I was a good 12 inches taller than most of them. I always had to be the mom when playing house in kindergarten. My parents struggled to find help for me because no doctor could explain why I hurt and felt the way I did. Finally, after being hospitalized for over a week my parents had answers. I was diagnosed with a hormone imbalance. The doctors in the area where I lived had no answers about how to treat me, so I was sent to a specialist in Augusta Georgia. He then called my diagnosis precocious puberty, a hormonal imbalance. After more needles and tests, he decided to start me on Lupron.

I took Lupron as a child from 1989 to 1994 for my hormone imbalance. I received a shot once a month in my thigh and sometimes in my butt cheek. I can remember the burn of the Lupron going into my body like it was yesterday. The injection always took me a week to recover from. I experienced soreness in the injection spot and redness every time I received Lupron. I could not run and play as a child. My legs either hurt or my mind would make me feel as though I had no purpose. From the outside, the Lupron shots were a success. The shots slowed my abnormal hair growth in private places and stopped my breast from growing, but on the inside, where it counts, what was the Lupron doing to me?

After being on the Lupron for half a year, I had lumps in my thighs where I received the injections (which I still have today). One time it crippled my legs, leaving me on crutches for two months when I was 7 years old. Yet still, I guess my doctor felt it would be more beneficial for me to continue my treatment with the Lupron because I received injections for 3 to 4 more years.

While on Lupron, I struggled daily to focus. I had blurred vision. I battled depression and I hurt daily. I couldn’t be active in sports due to my low bone mass and what kid feels like playing ball when her body feels like it’s been beaten with the bat already? By age 11, I finished up my treatment. I saw my doctor a handful of times after and then I was written off as cured, and I did feel good and enjoyed life for a few years.

At age 15, I began to battle depression. I struggled to remember things. I was diagnosed with asthma. My sight was getting worse and I had an eating disorder where I never wanted food due because my stomach felt like someone was squeezing it with all their might. I fainted several times because I was dizzy. I struggled to stand and I would walk holding onto things. My legs, arms, fingers, and toes would tingle and go numb. My doctor at the time seemed to always just prescribe me Lortabs for the pain and never dug any further to figure out why I felt the way I did. At age 17, I overdosed on Lortabs not trying to hurt myself but only trying to find relief from the pain. I didn’t realize that my body couldn’t handle all the medicine I was putting into it. My mom found me in my room and rushed me to the hospital where my stomach was pumped and I had to drink this disguising chalky drink. My pain seemed to decrease shortly after I turned 20. I looked and felt like the average healthy person. I had my first baby at 21 and my second at age 22. I had healthy pregnancies and healthy babies. I had my third baby at age 32 and again I was a healthy mama and had a healthy baby.

For the past two years, however, I have been experiencing a pain that is all too familiar. I feel as though my body and mind are failing me. I cannot pinpoint why all of this is happening to me. I am now 34 years old and experiencing horrific body aches and pains. I’m searching for answers as I struggle to hold my baby and even get out of bed due to the pain I feel. I hurt in all my joints, my back, my neck and I have leg pains that put me on my knees and unable to walk. My feet and ankles swell, my arms, fingers, and toes tingle with pain. I sometimes drop things because I can’t squeeze my fingers together to hold them. I am experiencing night sweats, hot flashes, nausea, and abnormal weight loss. I have dropped 90 pounds in 15 months. My stomach hurts every day and I never feel hungry. I have so many other symptoms, I feel as though I’m falling apart. I am working with my doctor now to try and find answers. I want to find quality in my life again. I want to feel good when I wake up and not have to lay in bed for at least an hour (waiting for pain meds to kick in) before I can move. Most importantly, I want to be able to pick my baby up out of her crib and hold her and not cry because it hurts my body so bad.

I am in the beginning stages of trying to figure out why I feel this way. I have had blood work drown which was good and I have a CT scan this week. It never even crossed my mind that all of this could be the side effects of taking Lupron as a child until I started reading other people’s stories. Please help?? What test do I need to take to help find answers? What meds are helping restore bone mass? What are other past Lupron patients experiencing and what is working to help them find quality in life again? Thanks in advance for your help!

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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 story was published originally on June 18, 2018.

Lupron Induced Osteoporosis?

by Samantha Bowick

Published on May 1, 2024

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Women who suffer with endometriosis do not have many options for treatment. As a result, many women try Lupron because they are desperate to be pain and symptom free. I was one of these women. In 2011 and 2013, I tried Lupron for a total of three doses and wish I knew then what I know now.

In 2010, I was diagnosed with endometriosis laparoscopically. After that, I tried everything from many different types of birth controls and pain medications to depression medications that can also be used to treat pain. Nothing worked. My doctor at the time suggested Lupron to me and I was desperate. I felt like I had already put my life on hold long enough because of this disease and just wanted to be out of pain. However, now I feel like I am suffering the consequences and it didn’t even get rid of my pain.

In 2015, I was diagnosed with osteoporosis. Prior to this, I had never had a bone scan done, not even before being administered Lupron. In 2009, I was diagnosed with Vitamin D deficiency and have been taking a supplement ever since. Three months before being diagnosed with osteoporosis, I stress fractured my knee and was told at my age, it should not have happened. In 2014, I had a hysterectomy because of endometriosis; I couldn’t take the pain anymore and had disease on both ovaries.

Before this, I had never had bone problems or been told that I could. I blame Lupron and strongly believe using it as a treatment for endometriosis led to me having osteoporosis. At 27 years old, I am still trying to work with doctors to determine if there are any treatments I can do because people my age having osteoporosis is rare. Many medications women use for osteoporosis could negatively impact my bones even more because of my age. If I don’t use any treatment, I could suffer from even more fractures or bone breaks the older I get. Right now, my average T-score for my left hip is -3.6 and was -3.3 when I was first diagnosed. I have no idea when my bones became so brittle. In my case, I wish I would have never tried Lupron as now I know this is one of the many side effects of this terrible treatment for endometriosis and something I will have to deal with for the rest of my life.

There are not studies done on medications for osteoporosis in my age group because there are not enough people with the disease to study. The medications my current doctor wants me to try would be a daily injection I would give myself in the abdomen for two years. They are known to possibly cause osteosarcoma, a bone cancer. Based on my history, I don’t like my odds. At this time, I don’t know how I will try to treat osteoporosis. I am planning on looking into natural ways of treating the disease and see how that goes.

As a result from my knee injury two years ago, I had to have an arthroscopic surgery. My doctor repaired my torn meniscus and removed scar tissue. It is taking me longer to heal than I anticipated and I wonder if it is because I have osteoporosis.

If doctors use Lupron for patients, they should be required to give these patients bone scans before their first dose and do follow ups yearly. It is a known fact that Lupron should not be administered in more than 12 doses over a patient’s LIFETIME. I wonder why this is?

I hope my story helps someone make a decision that is best for their body and raise awareness about Lupron. I am not a doctor, nor do I claim to be, but I am a patient that continues to live with the outcomes of having 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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If you have experience with Lupron or other GnRH altering drugs, please share your story.

Image credit: Laboratoires Servier, CC BY-SA 3.0, via Wikimedia Commons.

This article was published originally on December 13, 2017.

Lupron, Thyroid Disease, and the Broken Scales of Justice

by Lynne Millican, RN, BSN, Paralegal

Published on December 5, 2023

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Even though women being prescribed Lupron (leuprolide) have, understandably, no clue about its adverse thyroid effects, it is no secret that Lupron adversely affects the thyroid gland. (The same could be said for adverse effects from Lupron on many other organs and bodily systems, but the focus here will be on the thyroid.) For decades, a wide variety of adverse thyroid effects during or following this drug have been reported to the FDA: according to RxISK.org’s compilation of Lupron FDA Adverse Event Reports (‘AERS’, for the years 2004 – 2014), Thyroid cancer, Hypothyroidism, Thyroid disorder, Thyroidectomy, Hyperthyroidism, Thyroid neoplasm, Thyroid function test abnormal, Autoimmune thyroiditis, Thyroid cyst, Blood thyroid stimulating hormone increased, Blood thyroid stimulating hormone abnormal, Blood thyroid stimulating hormone decreased, Anti-thyroid antibody positive, Thyroid cancer metastatic, Biopsy thyroid gland abnormal, Follicular thyroid cancer, Thyroiditis, and Thyroiditis subacute have all been reported (search “thyroid” in “Side effects reported” here; also Open Vigil, which contains FDA AERS for the years 2003 – 2013, can be searched.)

Different Warnings for Different Countries

For decades foreign labels for Lupron have identified “thyroid enlargement” as an adverse event ( i.e. 1998 Australian label for “Lucrin [Lupron]”, MIMS Annual 1998, Australian Edition, page 9-804; also 2010 Danish label – Danish Medicines Agency, Product Resume for “Procren [Lupron] Depot”). As early as 1986 the US product label for the initial formulation of Lupron (5 mg/mL vial, administered as 1 mg daily subcutaneous injections) identified “thyroid enlargement” as an adverse event (1986 Package Insert No. 3626, “Lupron/leuprolide acetate 5 mg/mL. Manufactured for TAP Pharmaceuticals by Abbott Laboratories, Rev[ised] Nov. 1986”; 1992 Physicians’ Desk Reference [PDR] , “Lupron/leuprolide acetate 5 mg/mL”, p. 2310). The US product label for the intramuscular injection of monthly Lupron Depot 3.75 mg (and other depot dosages) likewise identified warnings for thyroid enlargement (i.e., 1995 PDR, “Lupron Depot 3.75 mg.”, p. 2506; 1996 PDR – “Lupron Depot 3.75 mg”, p. 2558.) Between 2004 and 2012, there were 22 reported cases of thyroid cancer, and Lupron was considered “highly suspect” by a number of physician opinions, and according to RxISK.org’s FDA AERS database, there’s been 6 more cases (search “thyroid cancer” in “Side effects reported” here).

But, despite this history, all thyroid adverse events have been removed from the current labels of US Depot formulations of Lupron, and no thyroid warnings have been identified since the mid-2000’s – i.e., the current Lupron 3.75 mgs product label as well as the current labels for other depot dosages no longer contain any mention of thyroid adverse effects. The daily 1 mg formulation of leuprolide continues to identify warnings of thyroid enlargement and thyroid nodule, and foreign labels for Lupron continue to identify adverse thyroid effects, but the labels for US Lupron Depot formulations (which are prescribed the most for women with endo and fibroids) are devoid of any warning.

In the Courts

It is worthwhile here to revisit the atrocities committed during the only Lupron lawsuit to make it to trial (Karin Klein v. TAP/Abbott, Case 2:08-cv-00681-RLH-RJJ, 2011) – many prior lawsuits having been quietly settled with secrecy agreements. Karin Klein, at age 17, was prescribed Lupron Depot 3.75 mgs in 2005 when Lupron’s label no longer contained the prior-listed warnings about adverse thyroid events. Karin developed, among others, chronic autoimmune Hashimoto’s thyroiditis. Belatedly learning of Lupron Depot 3.75 mgs’ prior US label warnings of adverse thyroid effects, as well as the prior and current similar warnings in foreign labels, Klein sued for failure to warn.

The judge at trial refused to allow the jury to learn of Lupron Depot’s pre-2005 US labels warning of adverse thyroid effects; the judge refused to allow the jury to learn of Lupron’s past and current foreign labels identifying adverse thyroid events; and the judge refused to allow the jury to learn of published medical literature identifying Lupron’s adverse thyroid effects (See Judge’s rulings, “Document 265, filed 07/25/11, page 13 of 40”, which can be found on p. 101 in this document). The judge would only allow the jury to learn of the 2005 US label. Moreover, Abbott’s mendacious defense medical “expert” stated under oath that “it was absolutely biologically impossible for Lupron to affect the thyroid gland. No textbook, no article has ever supported that contention. It’s simply biologically impossible.” (See “Page 20 of 131” here). A simple PubMed search shows this “expert statement” to be absolutely false – and this is without-a-doubt perjury (here, here, here and here). The first published report that “demonstrate[d] the association of thyroid disorder with leuprolide” occurred in 2000 – five years prior to Klein’s Lupron Depot prescription. Rhetorically speaking, exactly how does a paid “medical expert” get away with outright perjury concerning Lupron Depot’s – or any other drug’s – known risks?

This court’s curious restriction of limiting disclosure to only the 2005 Lupron Depot label (devoid of any thyroid warning) created the illusion for the jury that there were NO thyroid adverse effects from Lupron Depot for Klein to have been warned about — and so by a legal sleight of hand, Klein’s claim of “failure to warn” was made to disappear. The jury, unknowingly dis-informed and ‘educated’ in misinformation only, believed that it was ‘biologically impossible for Lupron to affect the thyroid gland’, and the jury found against Klein and found in favor of the drug company.

An appeal – bewilderingly – resulted in the Circuit Court making false statements and misstating facts. As argued on appeal by Klein’s attorneys:

“[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, only for them to be shut down before the jury and precluded from offering competing expert opinions. The pattern shown by the record [of the Klein trial] is deeply disturbing. Virtually every discovery and evidentiary ruling, and other orders of significance, went for one party [TAP/Abbott and never for Klein]. … Such a one-sided proceeding was not the fair trial our system demands.” The multitude of rulings against Klein’s request for admission of evidence can be found delineated the afore-mentioned in “Document 265, filed 7-25-11”.

But the Circuit Court, in a 2-day deliberation, concluded: “… The district court did not abuse its discretion in excluding the challenged Lupron labels because they all contained information regarding the side effects of different formulations of Lupron, rendering them insufficiently relevant, unduly prejudicial, and likely to confuse the jury.” Here the Circuit Court misstates facts and conveys the opinion that “the pre-2005 US Lupron Depot 3.75 mg label for endometriosis” is a “different formulation” from “the 2005 US Lupron Depot 3.75 mg label for endometriosis”. This is utter hogwash from a high court – “Lupron Depot 3.75 mgs” is identical to “Lupron Depot 3.75 mgs” regardless of the year of the label. And it should not be terribly difficult for anyone (including the Court) to comprehend that the drug comprising the initial 1 mg. daily-injected subcutaneous Lupron was subsequently put into a “depot” (“long-acting”) ‘delivery form’, allowing one intramuscular injection to slowly deliver the same drug — Lupron – over the course of one (or three) month(s). The courts had access to the 2010 Danish label (Klein v. TAP/Abbott, Document 175, filed 06/12/11) in which it is stated “Leuprorelin [leuprolide] acetate is released at a constant rate over a period of 4 weeks (3.75 mg) or 12 weeks (11.25 mg) … which is equivalent with what is seen with a daily injection of 1 mg leuprorelin acetate.” (To date, I have not located that same statement in a US Lupron label.) This appellate court concludes that “Klein has not even remotely established that the district court exhibited such a high degree of favoritism or antagonism as to make fair judgment impossible.”

Denied her right to a fair trial a second time, Klein petitioned the US Supreme Court. One would (and should) assume the Supreme Court would inherently recognize the serious ramifications and public health impact of a case (any case) where perjury of the known dangers of a drug was committed by a defense expert (effectively hiding this information from the jury and ensuring a defense ‘win’), and where a Circuit Court completely misstated facts (upon which it had relied to deny Klein’s appeal). But, in fact, the denial of a plaintiff’s right to a fair trial, the denial of a jury’s right to truthful and accurate expert medical testimony, and the denial of society’s right to expect that court rulings will be based on authentic factual information were all issues the US Supreme Court deemed unworthy of review.

Broken Justice: Precedent for Medication Adverse Events Cases

These circumstances resulted in a devastating miscarriage of justice – not just for Karin Klein, but for all Lupron victims – and to society at large as well. What kind of precedence could this Klein verdict have upon future litigation – with this or any other drug? In fact, lawyers throughout the US, with potential plaintiffs seeking redress post-Lupron, were closely following the Klein case, and had Klein prevailed the floodgates of litigation were poised to spring open. But by securing a defense ‘win’ via, in my opinion, a multitude of highly questionable actions, those floodgates were slammed shut. (In May 2015 an RN disabled post-Lupron filed a lawsuit, and this case is presently making its way through the court system.) At least a few ethical and powerful legal experts should be examining the events in the Klein case – it could (and should) become renowned as a classic case of injustice personified. (Links to additional court documents and further details on the Klein case can be found at bottom of page, left column).

What does it mean when a young woman’s health and life are irreparably damaged and there is no recourse? How does a disabled victim fight against a system that has clearly indicated it is obfuscating and is the antithesis of justice? How does a society ensure that truth prevails, and harmful effects of drugs are exposed rather than shielded?

Recently, in attempts to achieve transparency in clinical trial data, many drug companies have put their clinical trial data online. The endometriosis clinical trial data for Lupron 3.75 mgs remains under a court seal – ensuring this data will never see the light of day.

There are many, many questions, and many, many victims, but as of yet – there are no substantive answers.

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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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If you have a Lupron story to share, send us a note: Write For Us.

This article was published originally on January 20, 2016.

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

by Chandler Marrs, PhD

Published on August 3, 2023

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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.

Lupron: The Cycle of Negligence

by E. S.

Published on July 25, 2023

6925 views

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 4^th 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.

Post Lupron Mitochondrial Collapse: A Case Story

by Derrick Lonsdale MD, FACN, CNS

Published on April 3, 2023

5581 views

Dr. Marrs and I became aware of the symptoms and some of the laboratory results in a 38 year old woman. We wish to describe the case because it represents what should be an entirely new approach to medicine in general.

Before Lupron

The patient had been an active 38-year-old woman caring for her home and two children, ages 7 and 9 that were her focus, prior to Lupron. She had walked her dog daily, worked out at the gym twice a week and she had renovated her home in the summer of 2017. She had had her gallbladder removed in 2016, said to be because of a polyp. She had received allergy shots once a month for a couple of years. She took birth-control pills. Her history revealed that she had had a severe reaction to penicillin as a child, resulting in a rash and joint swelling causing inability to walk for a short time. She also had a history of frequent sinus infections and antibiotic treatment. In 2017, she began experiencing heavy menstrual bleeding and hysterectomy was recommended. She refused this and a second doctor recommended Lupron in an attempt to change her hormonal balance before hysterectomy.

After Lupron

She had received an injection of Lupron into her left hip and side effects, beginning within a few days, included:

Fatigue
Skin redness
Severe weakness in the legs, and tingling in the left side of the head and right leg.
A few days later she developed severe headaches and vomiting.

An initial estradiol patch caused no improvement, so another one at double the dose was prescribed with some improvement (presumably in menses). By November 2017 the patches were discontinued. She began to experience

Joint pain
Pain throughout her body
Nervousness
Shaking
Panic attacks
Changes in personality.
In December she experienced cyclic vomiting and weight loss.

The estrogen patches were prescribed again. She saw an endocrinologist and some laboratory tests were abnormal, including what was described as a borderline high blood glucose.

These symptoms continued and in February 2018, three drugs were prescribed (Celexa, Neurontin, Ambien). They were discontinued two weeks later because there was no relief of symptoms.

In March, she experienced severe fatigue and had episodes of difficulty in walking which were intermittent and described as “almost like being paralyzed”.

In April, she saw a geneticist and some lab tests were performed that I will comment on shortly. A diagnosis of fibromyalgia and possible chronic fatigue syndrome were each entertained. The endocrinologist said that test results indicated that she was not producing estrogen or progesterone.

Based upon conversations with us, she began supplements of thiamine, fish oil, alpha lipoic acid, B complex, folinic acid, ferrous sulfate and methyl B12. Estradiol patches were resumed. We suggested the use of intravenous water-soluble vitamins, since Dr. Marrs and I agreed that giving the nutrients by mouth probably could not reach the necessary concentration of vitamin therapy needed. This was not followed through on by her current physician.

Discussion of Symptoms and Side Effects

The patient’s medical history indicated that she had experienced many different symptoms throughout her life. These included a severe reaction from penicillin and multiple sinus infections. The side effects from Lupron were fatigue, leg weakness, headaches, general body pain, panic attacks and cyclic vomiting. In other words, she had been a classic “problem patient” to her physicians. Since the symptoms could not be defined by usual and customary laboratory evidence the general conclusion was repeatedly that this was evidence of psychosomatic disease. Curiously, this common diagnosis in modern medical circles appears to be that the patient is thought of as inventing her symptoms neurotically without ever considering an underlying mechanism. Even worse, polysymptomatic disease of this nature is usually experienced by the brightest and the best. This is because high intelligence is developed within a brain which is more energy consuming than that of a less intelligent person. Such individuals are much more prone to unforeseen stress events, making them more susceptible to side effects from medication and inoculations. A car engine uses more energy to climb a hill. Stresses that we meet in life are like “hills to be climbed” and involve a commensurate supply of energy.

Laboratory Results: Low Amino Acids, Vitamin Deficiency and Defective Energy Metabolism

Many tests were performed on this patient. Two amino acid tests were performed, one measuring the amino acids found in blood plasma, the other measuring those excreted in urine. A word of explanation is necessary. Amino acids are the building blocks of proteins in the body and finding a given amino acid in very low or unusually high concentration can be used to define important aspects of body chemistry. Of 34 amino acids recorded in the plasma of this patient, aspartic acid, serine, ethanolamine, and tyrosine were severely decreased, while glutamine, histidine, alanine, ethanolamine and tyrosine were severely decreased in urine. All the others were in their expected normal concentration.

Amino acids are used in the body to create proteins, and this is an energy consuming mechanism. One of the deficient amino acids was aspartic acid whose metabolism is important in a mechanism known as transamination. The enzyme that carries out this function requires vitamin B6.

Two of them, ethanolamine and serine, play an important part in transmethylation, a mechanism that is dependent on folate and B12.

The fourth one was tyrosine and it is involved in the synthesis of thyroid hormone.

These low levels suggested that their respective vitamin dependent mechanisms were at fault. Since all the vitamins involved are water-soluble, it invited their administration by intravenous infusion. However, because they were energy dependent reactions, it is likely to construe the possibility that the underlying common fault was energy synthesis.

Was there any evidence from these laboratory results for defective energy metabolism? Yes.

Isocitric and citric acids were reported to be low in the urine and they are vital metabolites in the citric acid cycle, the “engine” of the cell. Also, there was a deficiency of pyruvic acid and this is the fuel that enables the citric acid cycle to function. This constituted strong evidence for energy deficiency with its major effect on the brain and nervous system.

Mitochondrial Energy Synthesis

Our bodies consist of 70 to 100 trillion cells that are being broken down and reconstructed throughout life. Relatively simple molecules are acted on by enzymes in a series of chemical reactions known by biochemists as “pathways”. Each enzyme requires a vitamin and/or essential mineral that assists the action of the enzyme and are known as cofactors to the enzyme. Several pathways reflect the synthesis of energy that is stored in the cell as ATP (adenosine triphosphate). ATP is a little like a battery that is being continuously charged and discharged and most of this occurs in the mitochondria. All the other pathways consume energy, either in enabling function or rebuilding cells. They might be compared loosely to the transmission in an automobile. In other words, the healthy body functions because energy synthesis meets energy demand. The abnormally low amino acids each could be used to suggest a defect in the energy consuming pathways and possibly a reflection of missing cofactors, making the “transmission” defective.

Vitamin Cofactors, Energy Deficiency, and Symptomology

The symptoms expressed by this unfortunate patient pointed strongly to cofactor deficiencies derived from diet that could easily be tested by their administration and clinical effect. The net effect is produced by a gap between energy synthesis and its utilization to meet the stresses of life in general. The administration of cofactors does not necessarily answer the underlying question because of the possibility of unknown genetically determined factors. However, it is safe, non-toxic, may have an epigenetic effect and is relatively cheap. It therefore should be the first approach. The greater the urgency or the severity of symptoms, the stronger the indication for intravenous administration of all the water-soluble vitamins. I have successfully treated many polysymptomatic patients this way, suggesting that mitochondrial function is as much an acquired disease as well as being genetically determined.

A Note About Oxidants and Antioxidants

Think of the body as a machine that consumes fuel by uniting it with oxygen to produce energy. This combination is called oxidation. Like a fire or any form of burning, it can be slow or fast and cellular oxidation seeks an intermediate level. If the oxidation is too slow, energy production is imperiled. If it is too fast or too vigorous, oxygen atoms are “thrown out” of the oxidation process like sparks are thrown out of a vigorously burning fire. These are referred to as “free oxygen radicals”. Like sparks from a fire, they can do damage. Some vitamins act to assist or accelerate oxidation, an example being B complex. They are known as oxidants. Others quench the free oxygen radicals (sparks) and are known as antioxidants. Vitamins C and E are examples.

Without going into the highly technical details, thiamine acts as an oxidant and an antioxidant, thus increasing its importance in metabolism. From this it is easy to see the essential importance of these substances that are obtained from naturally occurring foods and why their deficiency causes disease. Of course, we have known this for a long time, but current medical belief is fixed in the concept that “vitamin deficiency disease has been conquered and the resultant diseases are only of historical interest”. For example, this patient had “borderline high glucose”, something that would occur in the thiamine deficiency disease beriberi. She also had frequent “infections”, now known to be related to free oxygen radical production, indicating that her regulation of metabolism was extremely inefficient. The amino acids that were extremely low in the plasma and urine could be used to interpret the possibility of missing cofactors, reflecting a chaotic state of metabolism. I must end this by saying that the use of vitamins and minerals in this manner is not (repeat not) simple vitamin replacement. We believe that the vitamin/mineral combination used in high-doses is resuscitating the activity of the corresponding enzyme and it is therefore acting as a drug. Identifying the underlying biochemical lesion is the essential nature of future diagnosis.

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This article was published originally on July 25, 2018.

The Lupron Money Trail

by Lynne Millican, RN, BSN, Paralegal

Published on January 27, 2023

18505 views

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 pressure. Inclusion 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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This article was published originally on April 18, 2017.

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Lupron and Reproductive Injury

by Lynne Millican, RN, BSN, Paralegal

Published on January 25, 2023

14480 views

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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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 originally published on March 15, 2017.

Photo by Jasmin Egger on Unsplash.

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Postscript: Correction

Original Text

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Lupron, Endometriosis, and Hypoestrogenism

What Does the Future Hold?

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