lupron endometriosis

Lupron: The Cycle of Negligence

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

Physician Abuse

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

Worsening Symptoms While on Lupron

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

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

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

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

Lupron Side Effects and Gynecological Ignorance

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

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

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

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

Recovering From Lupron

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

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

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

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

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This story was published originally on June 8, 2020. 

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Healing From Lupron and Endometriosis With Thiamine

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

Endometriosis in the Colon and Lupron

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

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

Finally, a Hysterectomy

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

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

No More Pharmaceuticals

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

How I Healed Myself With Thiamine and Diet

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

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

Where I Am Now

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

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

We Need Your Help

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

Yes, I would like to support Hormones Matter. 

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They Say Lupron Is Safe

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

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

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

Oral Lupron:  No — Yes — Maybe so?

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

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

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

Lupron Induces Menopause – NOT

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

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

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

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

Lupron-induced Impotence 

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

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

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

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

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

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

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

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

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

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

Funny Business with Bones

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

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

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

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

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

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

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

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

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

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

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

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

Tricks in the Courtroom Yield Treats for Lupron’s Manufacturer

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

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

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

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

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

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

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

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

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

Obscuring the Drug’s Hazardous Status

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

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

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

Measures Undertaken to Silence Critics

The Cardiac Stent Internal Memo

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

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

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

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

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

Suppression of Lupron’s Risks in Physician Continuing Medical Education

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

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

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

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

Bone Density Loss

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

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

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

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

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

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

Coronary Heart Disease

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

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

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

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

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

Conclusions

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

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

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

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

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

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

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The Lupron Money Trail

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

Ignoring and Dismissing Side Effects: Follow the Money

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

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

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

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

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

How Lucrative is Lupron Use in Precocious Puberty?

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

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

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

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

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

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

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

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

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

Pain and Agony of Adverse Effects Is Not a Lucrative Message

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

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

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

Marketing Indoctrination and Coercion

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

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

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

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

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

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

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

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

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

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

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

History of Fraudulent Data

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

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

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

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

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

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

Considered Not Related to Study Drug by the Investigator

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

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

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

Questionable Data Found in Adult Male and Adult Female Studies

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

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

Illegal Marketing Schemes in Gynecology and Urology

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

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

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

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

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

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

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

Paying the Patient Support Groups

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

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

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

Transgender Use of Lupron Noted as Lucrative for Some Providers

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

Benefits of Orphan Drug Status

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

Lupron is Lucrative

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

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

Postscript: Correction

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

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

Original Text

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

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

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

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

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Lupron and Reproductive Injury

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

Lupron and Reproductive Injury

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

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

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

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

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

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

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

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

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

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

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

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

Precocious Puberty, Lupron, and PCOS

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

Lupron and Torsion

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

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

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

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

Off-Label Use for Gender Dysphoria

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

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

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

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

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

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

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

Reproductive and Developmental Toxicant

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

Lupron, Endometriosis, and Hypoestrogenism

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

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

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

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

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

What Does the Future Hold?

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

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

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

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This article was originally published on March 15,  2017.

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Why Lupron is a Poor Diagnostic Tool for Endometriosis

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In my work with The Endometriosis Network Canada, I have heard many women say that their doctors told them that if their pain does not go away on Lupron, then the pain must not be from endometriosis. Lupron never has and never will be an effective tool for diagnosing whether pain is due to endometriosis. Not only does Lupron have the potential for significant side effects, which alone should abrogate its use as a diagnostic tool, but it also is not at all effective at diagnosing endometriosis and distinguishing it from other conditions.

Lupron is a synthetic version of a naturally occurring hormone called gonadotropin-releasing hormone, and its action is actually stronger than the naturally occurring GnRH. It is a long-acting medication that initially stimulates hormones in the pituitary gland that control the menstrual cycle, and then suppresses these functions. It is typically given as a 1 month or 3 month injection.

Lupron Side Effects

Lupron therapy is associated with a significant potential for side effects. One of the biggest problems with Lupron is its effect on bone density (it can decrease bone density), and this effect is not always completely reversible after Lupron is discontinued. Lupron can also cause joint pain, which in some cases is permanent. Other potential side effects include hot flashes, vaginal dryness, headaches, mood swings, decreased interest in sex, depression (in some cases severe), cognitive problems, fatigue, acne, headaches, and upset stomach. Personal stories of women’s experiences of the downside of Lupron can be found here, here, here, here, and here.

Given all of these side effects, you might be wondering: why would anyone subject themselves to the potential for at best, a month of these side effects, and at worst, a lifetime of some of them, for the purpose of diagnosis? Even from the side effect perspective, using Lupron to try to diagnose endometriosis seems like a bad idea. But now we come to the more technical part of the discussion, which will address whether Lupron could even work as a diagnostic tool for endometriosis.

How to Evaluate a Diagnostic Tool

To evaluate the effectiveness of a diagnostic tool, the two measures that are used are called sensitivity and specificity. Sensitivity addresses the question of how often the diagnostic tool will pick up the disease, in people who have that disease. Specificity addresses the question of how often the test will be positive in people who actually do not have the disease (but may have conditions other than the one you are testing for). A good diagnostic test will pick up the presence of the condition in most people who have it, while not testing positive in people who may have similar symptoms but have a different disease. In other words, a good diagnostic test will have fairly high sensitivity and specificity.

All devices or tests that are approved by regulatory agencies as diagnostics have to undergo testing to demonstrate sufficient sensitivity and specificity. Lupron has not undergone such testing, because it was not developed as a diagnostic, and is not meant to be used as one. However, given the clinical trials that were done looking at the effectiveness of Lupron as a drug therapy, it is clear that the sensitivity and specificity of it as a diagnostic would not support its use in that way.

Lupron as a Diagnostic?

The clinical trial data published by the manufacturer in its prescribing information can be illuminating when considering its sensitivity and specificity for diagnosing endometriosis. The clinical trials used several measures to assess response to the drug, such as pelvic pain, dyspareunia (pain with intercourse), dysmenorrhea (pain with periods), and pelvic tenderness. The results showed that Lupron was by far the most effective at treating dysmenorrhea, compared to the other symptoms. Almost 90 percent of study participants had dysmenorrhea before taking Lupron, and after 6 months of treatment, fewer than 10 percent still had dysmenorrhea. (Not surprisingly, within 6 months after completing treatment, about 80 percent had dysmenorrhea again.) Looking at endometriosis symptoms other than pelvic pain, about 75 percent of study participants had pelvic pain at the start of the study, and 45 percent still had pelvic pain at the end. Lupron was similarly less effective at treating other symptoms of endometriosis.

From these results, we can get an idea of what the sensitivity of Lupron as a diagnostic would be. Imagine giving Lupron to a group of women with endometriosis, whose symptoms will vary from primarily dysmenorrhea, to all different types of pelvic pain at different times (or in some cases, all times) of the menstrual cycle. Those who have primarily dysmenorrhea will feel that their pain has been treated, whereas, because it is less effective on all other types of pain and symptoms, some women may feel that their pain did not decrease at all (remember, 45 percent of women still had pelvic pain after 6 months of Lupron). This is why it is completely incorrect for any doctor to say that if a woman’s pain did not decrease on Lupron, the pain cannot be from endometriosis. Therefore, the sensitivity of Lupron as a diagnostic for endometriosis is predicted to be poor, because in a significant number of women who actually do have endometriosis, it will not treat their pain substantially.

The specificity of Lupron as a diagnostic would be even worse. Clearly Lupron is effective at treating dysmenorrhea, because by its very mechanism of action it puts a woman into chemically-induced menopause, and you cannot have dysmenorrhea when you are not having periods. However, there are many causes of dysmenorrhea other than endometriosis. So even if Lupron does work to treat a woman’s pain (by preventing periods), this does not ensure that the cause of the pain was endometriosis.

A Call for More Research

There is no doubt that women would benefit greatly from a non-invasive diagnostic test for endometriosis, given that surgery is currently the only way to definitively diagnose it. However, Lupron is not sensitive or specific enough to be useful diagnostically. New diagnostic tests have been developed for many other diseases using recent advances in technology such as imaging methods, blood biomarkers, next generation sequencing, and others. A sensitive and specific diagnostic test for endometriosis is desperately needed. However, with so little funding going to basic and applied research into endometriosis, it is unlikely that this need will be met until this funding situation improves. As Siddhartha Mukherjee said about cancer in his book The Emperor of All Maladies:

“A disease needed to be transformed politically before it could be transformed scientifically.”

This is the situation that cancer research was in, during the 1940s, and sadly this is where we are at now, with endometriosis, a disease that affects one in ten women and has for centuries, in 2016.

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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 published originally on March 14, 2016. 

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Why is Endometriosis in Fetuses Important?

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Inaccurate theories about how and why endometriosis develops are widely accepted by medical practitioners, despite much evidence against them. Acceptance of these theories leads to the perpetuation of medical therapies that do not work. It is important to understand the origins of endometriosis in order to move forward and develop effective treatments for this devastating disease.

Endometriosis and Sampson’s Theory

Endometriosis is defined as the presence of endometrium-like tissue outside of the uterine cavity. Many medical practitioners and lay press oversimplify this to state that endometriosis occurs when the lining of the uterus is found outside the uterine cavity. However, there are many publications enumerating the differences between endometriosis lesions and the endometrium found inside the uterus. Evidence for this goes back at least to 1981, and possibly earlier, and research into these differences is still ongoing. However, the common perception that endometriosis is merely endometrium outside of the uterus persists.

One prominently cited theory as to how endometriosis develops is known as Sampson’s theory. This theory suggests that retrograde menstruation, menstrual blood flowing backwards (away from the uterus) through the Fallopian tubes towards the pelvic cavity, deposits fragments of endometrium into the pelvis, which can then implant and grow into lesions.

There are numerous problems with this theory. First of all, there is no evidence that endometrial cells in the peritoneal fluid can attach to the lining of the pelvis (the peritoneum), and in addition, endometrial cells are not commonly present in peritoneal fluid. Furthermore, as stated earlier, there are many differences between the endometrium inside the uterus, and endometriosis lesions. In addition, 90 percent of women have retrograde menstruation, but only approximately 10 percent have endometriosis. Sampson’s theory cannot explain the presence of this disease in fetuses, in men, and in girls who have symptoms with the onset of puberty or even prior to puberty. And it cannot explain the presence of endometriosis in areas outside of the pelvis, such as the lungs and skin.

Alternate Theories – A Fetal Component

Alternate theories that fit better with the available evidence have been proposed, including metaplasia (changing of one cell type into another cell type), developmental defects (also known as Mullerianosis), genetic factors and environmental factors. However, no single theory has been proven to be correct, and most likely a combination of various influences contribute to the development of the disease. According to the current evidence, there is most likely some embryological component. The theory of Mullerianosis explains the development of endometriosis as endometrial tissue that was misplaced during fetal development, that later develops into endometriosis lesions. Evidence in support of this comes from the fact that endometriosis has been found in female fetuses with the same incidence as in women, about 10 percent.

The Persistence of Sampson’s Theory – A Safety Net for Inadequate Treatment

Why has Sampson’s theory continued to be so persistent despite all the evidence to the contrary? First, no alternative theory has been sufficiently proven enough to displace it, although certainly enough evidence against it exists that it ought to be displaced. Second, most doctors who treat endometriosis do not specialize in the disease, and the science behind its development is probably not something they have much interest in.

It is damaging to endometriosis patients to have Sampson’s theory continue to be accepted despite evidence to the contrary. It gives gynecologists a reason not to strive for complete removal of the disease from all organs, because there’s no point in trying to remove all of it, if it will just be re-implanted with the next period. Sampson’s theory provides justification for the high recurrence rates observed from surgeons who do not specialize in treating endometriosis.

However, surgeons who specialize in it, who carefully excise all disease, have shown that it is possible to have low recurrence rates following complete excision. This requires not only the knowledge of all the possible visual appearances of endometriosis, but the surgical ability to excise disease from areas most gynecologists cannot, such as bladder, ureters, intestines, or diaphragm.

Sampson’s Theory and Medications that Prevent Menstruation

Acceptance of Sampson’s theory gives pharmaceutical companies an excellent tool to convince doctors to prescribe medications that prevent menstruation. If Sampson’s theory is correct, then any hormonal treatment that stops women’s periods will treat endometriosis. Several drugs that are currently on the market can stop periods—Lupron and similar drugs, by inducing a menopausal state, and birth control pills, used continuously. However, as would be expected, since Sampson’s theory is not correct, these medications have never cured endometriosis. Some patients may experience temporary relief of symptoms, especially when the symptoms are primarily connected to having periods, but hormonal medical therapies do not treat the underlying disease.

The Origins of Disease Matter

Though debating disease origins may seem like an arcane point, not relevant to most endometriosis patients on a daily basis, it is highly relevant because it is so linked to the inadequate and ineffective treatment most patients receive. In order to truly move forward and make progress in how this disease is treated, wider recognition of Sampson’s theory as fatally flawed must occur. If endometriosis is present in the fetus, then it is an entirely different disease than one of retrograde menstruation. Understanding this is critical for better treatments options.

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lunar caustic, CC BY-SA 2.0, via Wikimedia Commons.

This article was published originally on October 2013. 

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Lupron Induced Osteoporosis?

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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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