lupron precocious puberty

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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This article was published originally on April 18, 2017.

Photo by Pepi Stojanovski on Unsplash.

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.

Share your Story

If you have a Lupron story, please consider sharing it on Hormones Matter.

We Need Your Help

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

Yes, I would like to support Hormones Matter. 

This article was originally published on March 15,  2017.

Photo by Jasmin Egger on Unsplash.

Lupron for Precocious Puberty and Beyond: Two Decades of Regulatory Silence

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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 second part in a 6-week series exploring  numerous issues associated with the use of Lupron in the pediatric and teen populations. The series began last week with the voices of the mothers of harmed children and the now-adult suffering children.

FDA Inaction on Lupron Safety Issues: What They Knew When

Like so many Lupron issues, the lack of acknowledgment of adverse effects in the children has been baffling. Lupron was approved for precocious puberty in 1993, and concerns were raised early on. My questions in 1994 about Lupron’s safety in the pediatric population began simply, but by 2005 my worries and opposition were spelled out in public comment to the FDA’s Pediatric Advisory Committee. At that time, a panel meeting had been convened to discuss proposals for using Lupron as an experimental diagnostic tool in healthy control children as well as in precocious puberty. The panel experts proclaimed:

the rarity of significant side effects from this drug especially in children” (page 73), and also erroneously stated Lupron is “not a hazardous drug requiring chemotherapy precautions” (page 75). This Pediatric Advisory Committee “d[id]n’t want to focus on the very few adverse events related to the use of Lupron” (p. 158-9) – “the risks are indeed minimal” (p. 162).

This disregarded over a decade of reports detailing the safety issues associated with this drug and class of drugs (GnRHas), issues that ranged from the basic handling to chronic and sometimes severe side effects.

Hazardous Drug Status

In 2005, I submitted a public comment in opposition to the panel’s proposal (Lupron Protocol #13472A), and cited Lupron’s designation as “a hazardous drug'” according to NIH, Occupational Safety and Health Administration (“OSHA” – see “Appendix VI:2-1, Some Common Drugs Considered Hazardous”), and the Material Safety Data Sheets (MSDS )”. The Chair of this Pediatric Ethics Subcommittee panel, after reading my comment to the panel members, admitted “I’m not sure what MSDS is” (page 141). (MSDSs are documents required in accordance to codified regulations (29 CFR 1910.1200 – i.e., see section “.1200(g)8”) to be at all facilities containing hazardous drugs, and are manufacturer summaries of the drug/chemical’s properties and hazards: Lupron’s MSDS contains ‘Special Protection Information’ advising the use of rubber gloves and goggles or protective gloves and chemical safety goggles for healthcare workers to employ when handing Lupron.)

In 1999, OSHA‘s ‘Technical Manual’ listed Lupron as a “hazardous drug” and an “antineoplastic“, and detailed specific precautions healthcare workers should use to protect themselves from occupational exposure.  Beginning in 2000, NIOSH (National Institute for Occupational Safety and Health) “began working with multiple partners and stakeholders to address the issue of occupational exposure to hazardous drugs”. This led to an “Alert” published by NIOSH in 2004, Publication # 2004-165 (entitled “Preventing Occupational Exposure to Antineoplastics and Other Hazardous Drugs in Health Care Settings”), identifying “a sample list of major hazardous drugs”, and “leuprolide [Lupron], an antineoplastic” remained on the list.  And Lupron (leuprolide), as well as other GnRH analogs, remain currently on the list.

Why is this important? Not one of the experts seemed to understand the most basic hazards associated with this chemical,but were nonetheless tasked with evaluating its safety. How can these pediatricians and pediatric endocrinologists be unaware of such vital information pertaining to the hazardous status of a drug they are prescribing and injecting into children? And if the experts are not aware of hazards, then how can the parent and child make an informed decision about whether to accept treatment? Without this information, and the subsequent informed consent, this treatment becomes an experiment by definition;an experiment many parents may not be willing to involve their children in.

Adverse Effects: Concerns Were Raised Early

In 2005, other women also voiced opposition and concerns to the FDA’s Pediatric Advisory Committee’s proposed Lupron protocol in children (see here and here; pro-Lupron industry comments can be found here). And six years prior, in 1999, a study alerted the medical community to the risks of GnRHa (Lupron is the most frequently prescribed GnRHa) for use in PP. In this 1999 study, researchers stated:

“Concerns have recently been expressed and are now widely disseminated via electronic media that the GnRH analogs may have long lasting adverse effects on reproductive function as well as on physical and mental well-being. At present, there are few long term studies that address these issues objectively” (emphasis mine).

This study also noted the occurrence of seizures, as well as identifying that after discontinuation of the GnRHa, emotional lability, depressive behavior, and mood swings developed.  The latter statement “concerns have recently been expressed and are now widely disseminated via electronic media” listed as a reference the web address of the (now-defunct) ‘National Lupron Victims Network’. Clearly in the 1990s, the issue of adverse effects upon children prescribed Lupron/GnRHas, and the awareness of the lack of research was recognized and identified, but few seemed to pay attention.

The Kaiser Report revealed an FDA official stated:

“it was ‘regrettable’ that the [FDA] panel approved the drug [for PP in 1993] after minimal study.”

Why has it taken 24 years for the FDA to conduct a “specific review of nervous system and psychiatric events [and “reviewing deadly seizures”] in association with the use of GnRH agonists, including Lupron, in pediatric patients“? After more than 24 years of FDA approval, and more than 30 years of prescriptions to children, isn’t it time an objective and independent study be conducted?

Ethical Issues When Used for Benign Conditions

In 1989, in relation to Lupron’s use in women for endometriosis, an FDA Medical Review Officer of GnRH drugs for gynecology closed her comments at a public hearing with her “experience in observing the course of GnRH analog research over the past year.”   Dr. Ragavan said:

“Most of the studies that have been presented for [GnRH] analog research are presently being conducted in young women for benign indications…The number of studies trying to use these drugs has by no means slowed down recently. Industrial sponsors have been quick to fund these studies on the drugs seeing a potential market…[The Committee] may wish to consider the ethical issues of continued intellectual searches for the use of analogs and the possible risks associated with such studies in this study population. We have always used with extreme caution in our abilities [sic] to render men hypogonadal albeit for different reasons. And have reserved this treatment for life threatening conditions in the male, such as prostate cancer. Should we use the same caution in women, especially when we treat benign chronic non-life threatening conditions such as endometriosis? In fact, I propose for you an even more caution [sic] in this population who must live with the consequences of treatment for a very long time.” (Ragavan, Vanaja, M.D., F.D.A. Review of the new drug application for Nafarelin acetate. Fertility and Maternal Health Committee. Hearing 4/28/89. Transcript, p.47.)

In 1999, the FDA conducted an investigation into the adverse events reported for Lupron and concluded:

“the nature of reported adverse events for males and females is quite similar – indicating that the events are much more likely to be due to the drug than age, gender, or underlying disorder.” (emphasis mine). The FDA decided to take no action at that time (see “1999 FDA Review of Lupron“).

Pediatric Deaths Following Use of Lupron

In a ‘Freedom of Information Act’ (FOIA) request to the FDA for adverse event reports for Lupron Depot-PED, an “Event Tally Report” was received in May 2016, and 6 reported events of “cardiac failure” for Lupron Depot-PED were cited. However, in a subsequent  356-page “Detailed Report” of all adverse events reported for Lupron Depot-PED, no case of pediatric cardiac failure is to be found (yet reports of adult male cardiac failure for “Lupron Depot-PED” are found).

It does not appear that the FDA’s adverse event reporting system for Lupron Depot-PED is accurate or properly organized. In further illustration, the “Event Tally Report” for “Lupron Depot-PED” cites a total of “49 deaths” (as opposed to the tally of “962 deaths” for “Lupron Depot”, and the tally of “151 deaths” for daily “Lupron”), yet the “Detailed Report” for Lupron Depot-PED adverse events displays “1 death” (report dated “3-28-12”). Unfortunately, I have seen a number of other pediatric deaths which contradict this FDA adverse event database report of one pediatric death. For example, in a search of deaths for “1 to 13 years olds” here, 3 deaths appear; in a one-year study of selected case reports, 2 female pediatric deaths are reported here (reports dated “5-10-12” and “8-23-12”); another death occurred during a PP clinical trial here; and in a similar FOIA years ago, a detailed report of a pediatric death was filed on “6-17-02” (see here).

Previous FOIAs requests for adverse event reports for Lupron Depot-PED, Lupron Depot, and Leuprolide (daily Lupron) resulted in one combined report for all three formulations. But in the 2016 FOIA response, three separate reports were provided and and all were all mixed up. Does it need to be stated that there needs to be accurate recording within the appropriate database?

The FDA needs to immediately attend to their adverse event reporting system (AERS, a.k.a. FAERS), so that case reports are accurately sorted and properly stored. The above mentioned “6-17-02” report of pediatric death not found within the “Lupron Depot-PED Detailed Reports” can be found in the “Lupron Depot Detailed Reports”. Would a researcher of Lupron’s pediatric adverse effects be prone to search a database that excludes pediatric use? And even though it is well known that 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]), it nonetheless is critical that adverse event reports (especially deaths) received by the FDA be precisely cataloged.

Multi-system Injury

And the FDA also needs to expand its pediatric review to include examination of the effects of Lupron/GnRHas on children and teens (and women) upon multiple systems, including (but not limited to) reproductive, immune system, musculoskeletal, gastrointestinal, and cardiovascular systems;  and the FDA should mandate that substantive, independent, retrospective study of these children begin.

In the rat studies submitted to the FDA for the drug’s initial approval for prostate cancer, all rats at all doses developed pituitary adenomas (tumors) – and it was stated:

“there is no obvious reason to suggest that the same process could not occur in humans.” (New Drug Application 19-010, Summary Basis of Approval. Leuprolide for palliative treatment of prostate cancer.)

Years following these animal studies, it would be reported:

“[w]e cannot exclude that [GnRHa] may cause not only adenomas in rat pituitary glands as reported previously, but also a (nodular) hyperplasia of the pituitary gland in man.”

And it is noteworthy to cite a report on 2 cases of fibroids treated with leuprolide/Lupron:

striking vascular changes and histologic features of vasculitis and atherosclerosis” were observed, and it was identified that “[t]hese changes may cause ischemic damage if they occur in other organs… he florid and rapid development of vascular inflammation, fibrinoid deposits, and thrombosis after leuprolide acetate therapy suggest an immune-mediated process. Acute vascular changes are rarely seen in non-leuprolide-treated leiomyomas… hese observations are significant and worrisome if such changes affect other organs.”

Cardiovascular System Morbidity

In the 1990s, I attempted to question the suspect cardiovascular data involved with Lupron’s initial 1985 FDA approval (i.e., see “Was Lupron’s Initial FDA Approval Based Upon Safety & Efficacy?”, pages 4-6 here). More than a decade and many large-scale studies later, in 2010, the FDA conducted a safety review of the use of Lupron (and other GnRHas) for prostate cancer treatment in adult males, and an increased risk for diabetes, heart attack, sudden cardiac death and stroke was identified, and warnings issued. This safety review also stated there are

no known comparable studies that have evaluated the risks of diabetes and heart disease in women and children taking GnRHa’s.”

The first case of a woman experiencing angina and heart attack while on Lupron was reported in the medical literature in 1994.  There have now been numerous other case reports published (see ‘Cardiovascular Effects‘). Lupron Depot’s 3.75 mg label for women states:

“Cases of serious venous and arterial thromboembolism have been reported, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and transient ischemic attack.  Although a temporal relationship was reported in some cases …[i]t is unknown if there is a causal association between the use of GnRH analogs and these events.”

Regarding a case report of a young woman with endometriosis experiencing a stroke 4 days after receiving Lupron,

“[t]his circumstance suggests the possibility that treatment with GnRHa may cause ischemic stroke in young women.” 

And most peculiarly, a recent article examining ‘Nurses’ Health Study II’ data concluded an association of coronary heart disease and endometriosis, while simultaneously failing to collect data on whether the woman with endometriosis had been treated with Lupron or any GnRHa [see “March 2016 … Harvard” here]).

More recently, the “Lupron Side Effect Survey” found evidence of dysregulated blood pressure and heart rate, with at least 10 women reporting a heart attack, 36 women developed mitral valve prolapse, 10 women developed blood clots in the leg and 8 women had pulmonary emboli.

Lupron Depot-PED’s label, while providing a list of adverse events from other Lupron formulations, does not contain the above quoted language concerning adverse cardiovascular effects found in Lupron Depot 3.75 mg label for women, nor does the Lupron Depot-PED label contain any reference to the warnings of increased risk of sudden cardiac death, heart attack, and stroke issued to adult males. Of note, the PED label states “Reactions [seen in the precocious puberty clinical trials] which are not considered drug-related are excluded.” What those reactions were, and why they were deemed not drug-related remains unanswered at this time.

The PED label does mention vasodilation as an adverse event (2% of subjects) and states that less than 2% of subjects experienced bradycardia, hypertension, peripheral vascular disorder and syncope. I have heard from several teenagers and adults who used Lupron for precocious puberty (as well as from many women who used it for gyn/IVF purposes) and report irregular heart rhythms and tachycardia (rapid heartbeat).

Cognitive Ability and Neurological Disruption Post Lupron/GnRHa

A study of GnRHa’s in 2001 showed “IQ levels decreased significantly” (a mean 7 point drop, but “doubts exist about the clinical relevance”), and in 2016 another GnRHa study reported an IQ drop of around 8 points was noted (which was found in the study to be “not significant”). These studies were conducted outside the US, but within the US Lupron dominates the market. Where are the pediatric (or adult) Lupron IQ studies, and why do these pediatric studies dismiss the significant decreases in IQ?  Wouldn’t any IQ drop of 8 points be significant?  This is information that would be critical to the decision-making of any parent/child. And the “doubts” about clinical relevance and ‘non-significance’ of GnRHa-induced intelligence decline should be pursued by the media – and medicine.

One mother who contacted me reported after the first Lupron injection her child experienced:

“Complete inability to focus on anything – grades plummeted … couldn’t remember where either tooth paste or brush were located, or sock drawer.  Could not repeat simple instructions or follow them. Our sunshine child was sad and without typical ‘I can do anything’ attitude.”

As the FDA is currently conducting its review of nervous system and psychiatric events, they should include intelligence quotient queries in its review; and it should take note that in 1997 an expert statement to the courts detailed a dentist’s drastic decline in IQ post-Lupron  (dropping to 97 on an IQ test). Other drops in IQ have been posted online by adult Lupron victims (i.e. “July 27, 2016” here).

In a 2002 follow-up study of more than 3,000 women using Lupron, 35.5% reported depression (and 76.7% reported joint pain). A 41 year old woman, after two injections, was diagnosed with dementia. Lupron has been reported in the medical literature to have induced extrapyramidal symptoms, is known as a common cause of increased intracranial pressure  (experienced by one subject in a PP Lupron clinical trial) and it is postulated that Lupron may act directly to modulate brain function.

Since 1994, it was reported that Lupron “shuts down blood flow to the frontal lobes of the brain” (Gannett News Service, 11/17/94). In women, vasospasm of intracerebral blood vessels resulting in transient cerebral ischemia has been posited as an explanation for GnRHa-induced headaches, numbness, paresthesia and paresis seen in a study titled ‘Adverse neurological symptoms after GnRHa therapy in women undergoing IVF cycles’.

Another study, “Neuropsychologic Dysfunction in Women Following Leuprolide Acetate Induction of Hypoestrogenism”, found 72% of (18) subjects showed difficulty with memory while on Lupron, and some subjects had “significant cognitive deficits during therapy particularly in the areas of memory, fine motor coordination, and two-point discrimination. Two of the 18 subjects showed very substantial neuropsychological sequelae including memory gaps and disturbances in a variety of neuropsychological test performances.”

Neurological researchers working with male mice found “a sudden decrease of testosterone … may cause Parkinson’s like symptoms“.  Any examination of the Lupron-impacted brain should take into consideration the following recent comment (posted “January 31, 2017” here) by clinical psychologist Michael Villanueva:

“…a week ago I never heard of Lupron. Now I have a young female client with a host of conflicting symptoms.  I map brain and routinely do QEEGs.  I have never seen a cortex in so much disarray. …my client only had two injections 30 days apart. I have never seen a 19 channel recording of the human EEG this dysregulated before.”

Two Decades of FDA Silence

These findings beg for further attention and exploration, as does the need for a comprehensive assessment of Lupron’s impact upon all bodily systems.

One year after Lupron’s FDA approval for precocious puberty (1994), a prostate cancer investigator wrote:

“GnRH and its analogs have led to exciting new avenues of therapy in virtually every subspecialty of internal medicine as well as in gynecology, pediatrics, and urology … virtually every subspecialty of medicine will be touched by the GnRH analogues …”.

Indeed they have been – virtually every sub-specialty of medicine receives referrals and office and hospital visits from injured victims searching for answers, help and remedy for their multi-faceted, wide-ranging, acute and chronic, iatrogenic symptoms and diseases. Isn’t it time this fact is acknowledged – and for plans to be formulated and put in place to address these victims’ needs?

Share your Story

If you have a Lupron story, please consider sharing it on Hormones Matter.

We Need Your Help

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

Yes, I would like to support Hormones Matter. 

This article was published originally on March 9, 2017. 

Photo by Michael Carruth on Unsplash.

Lupron for Precocious Puberty: Parents and Patients Speak Out

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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. In a 28 year battle to expose the dangers of Lupron (see herehere, and here), I’ve encountered few occasions which have held hope that a spotlight would be trained on Lupron’s risks. When my website, Lupron Victims Hub, was contacted last spring by this Reveal/Kaiser investigative reporter, who developed an interest in the pediatric Lupron victim, I had hope that these young children, the now-adult ‘children’, and the parents of these children could finally get some recognition and validation of their adverse experiences through lay news coverage. Until this reporter’s interest and her Kaiser Report, no media had ever been interested in addressing the pediatric population. (The investigation’s initial focus was into Lupron’s effects in IVF and the offspring [see reply to “January 19, 2016 comment by Connie” here], but thankfully there was a shift to precocious puberty.)

Lupron in the Media

Media coverage of Lupron’s adverse effects in fertility treatment/IVF (for which Lupron has never gained FDA approval) occurred in a 2-part series in 1996 (August  4 & 5; Boston Globe, p 1: “What Price Pregnancy – The Painful Quest for Fertility” by Dolores Kong); and media coverage of Lupron’s adverse effects in endometriosis took place in 1999 (9 years after Lupron’s FDA approval for endometriosis) in a 3-part Boston Herald series (see here, here and here).  But it took 24 years from the time of Lupron’s FDA approval for precocious puberty (in 1993) for Lupron’s adverse effects on the children to make news.  This has been a disgrace, and more than frustrating.  So thank you Christina Jewett, Reveal and Kaiser Health News Report.

A considerable amount of my research on Lupron, its history, and adverse effects (as found in links on my website, including  “Risks” page, under “Precocious Puberty”) was provided to the reporter and included in the Kaiser report (though surprisingly mention of my website was not);  however, there is so much ground to cover that neither the Kaiser Report, nor the next article published on Lupron’s pediatric risks, nor the next article published (nor this HormonesMatter series or my website), nor any pending article could ever possibly address all aspects of the many troubling issues surrounding  treatment of the youth (or adults!) with Lupron (or any ‘GnRH analog’, the class of drugs to which Lupron belongs).

For some time I have been trying to further research the effects of using Lupron in the pediatric and teen population, and have a collection of information not yet posted on my website. The heart-wrenching emails I’ve received from distraught mothers or now-adult treated children compelled me to start writing a “Call to Action” to the pediatric endocrinology community – an ‘Open Letter’ seeking to acknowledge and address these children’s and now-adults’ problems. This draft paper has hundreds of hyperlinks, and was being fortified with data from recently received FDA Lupron Depot-PED adverse event reports. But due to my own personal exposure to Lupron (for endometriosis and IVF), I keep getting sick with sudden and repeated gastroparesis episodes, and this ‘Call to Action’ remains unfinished. (Lupron has destroyed the neurological impulses in my gut, resulting in 61 hospitalizations between 2003 and 2014. Lupron has also caused abnormal electrical rhythms in my heart.) These gastric episodes are debilitating and continue unabated and frequent, kicking life and all plans to the curb, and forcing everything into a ‘stall mode’ (more like chaos).

In the meantime, I feel that the ‘Kaiser Report’ was a ‘Call to Action’, and I believe it should be viewed and treated as such. As a result, I now have a considerable amount of information that doesn’t need a ‘finish’, and which can be cobbled together here – with the hopes of amplifying the need to substantively address the problems these children and now-grown kids have. And so, over the course of the next 6 weeks, numerous issues addressing the use of Lupron in the pediatric and teen population will be explored.

What Lupron for Precocious Puberty Really Looks Like

My website’s mailbox has received cries of help since 2008 (many frantic in nature) from a number of mothers of children treated with Lupron for precocious puberty or growth issues, as well as hearing from the now-adult treated children, who continue to experience serious physical and emotional adverse events.  Since only a few of these women were able to be included in the ‘Kaiser Report’, this series will begin with a few additional testimonies from some very worried mothers and injured former child patients. Their voices speak volumes:

A mother writes:

“I injected my daughter daily with this poison for 9 years…I was told that there were no known long term side effects. My daughter is now 20 years old and has suffered from pain and soreness in her neck, back, hips, arms, wrists, hands, fingers, legs, ankles, and feet. She suffers from fear, anxiety, depression, and has self-harmed. There are days that she cannot get out of bed and times when her fear, depression and anxiety are so out of control that she sleeps all day and stays up all night. It doesn’t seem as if any doctors understand or care what she has gone through … She has been denied SSI/Disability, has no job. She cannot sit or stand for very long. The worst part of this is that I injected this in her and I have no way to help her…I do not know where else to turn.”

A teenager formerly treated with Lupron as a child writes:

“I am currently 15 years old. When I was 5/6 I was diagnosed with precocious puberty and quickly started on Lupron injections monthly. Originally, I was a happy child, before all this began. I rec’d it monthly for approx. 5 years.  During this time I had a very weak immune system and began to become miserable. I was 8 years old saying I wanted to commit suicide. That’s not normal.  But no one thought it had anything to do with the medications…I now have mild Borderline Personality Disorder and major depressive disorder. I also now have EXTREMELY high heart rate (110 beats per minute)…Is there any cleansing or anything similar to that that would work to help? I feel as though my life has been destroyed by a choice my parents made for me.”

A mother beside herself with worry writes:

“Please help my daughter!!  She was given Lupron at age 6 until she was 9 for CPP…We finally stopped the injections because we couldn’t watch her go through the pain anymore.  She is now 16 and suffering.  We were only told of 4 possible side effects :  1. Redness at injection site, 2. headache, 3. nausea and/or vomiting, 4. possible pain in the joint where the injection was given…We are now dealing with: IBS, weight gain/loss, headaches, bone and joint pain, memory loss, insomnia, depression.  The list goes on and on and the symptoms keep getting worse!! No lawyer will help, no Dr’s will step up to the plate!  I will do what I have to do to help my daughter!!  Somebody please help us!!”

A young woman formerly treated with Lupron as a child writes:

“I was diagnosed with precocious puberty at the age of 6…I was given monthly injections over the course of about 5 years…I was diagnosed with depression at about 8 years of age, and it has gotten worse over the years.  I have been hospitalized 5 times due to my mental health. I also have joint pain very bad in just about all my joints and I am only 23. I also get crippling migraines very often…I feel Lupron was the cause of a lot of my pain both physically and emotionally.”

A young man formerly treated with Lupron as a teenager writes:

“From the age of 13 to 17 I was on Lupron to hold back puberty so that my body would be able to grow.  After coming off the Lupron not even a year went by when I was diagnosed with severe osteoporosis. For 6 years I have been trying to battle this disease and to no avail. Because of my osteoporosis along with other things I am now paralyzed. If you could contact me I would truly appreciate it. I’m also trying to see if some of my other health conditions are caused by this.”

And another mother writes:

“I reviewed your web site and was horrified and shocked to read what has been going on for decades concerning Lupron.  I am concerned that many of my daughter’s health issues may be tied to extensive Lupron injections she rec’d…She has been plagued with health issues since starting the Lupron.  We were never given any warnings about possible side effects. We were told the only side effect was a soreness at the injection sites. She is now 16 and suffers from a multitude of illnesses…We have only been able to piece everything together because of your web site. I believe either doctors knew and withheld information or never pieced it all together. Please share any information or advice you have for us, there is precious little information about what long term use of Lupron does.”

Another mother writes:

“My daughter was prescribed Lupron for CPP at age 8.  She started having joint pain and other strange symptoms pretty soon after. I didn’t make the connection to Lupron. You see, I’m a pharmacist and I read all the provided information on the drug and none of these are listed. I also tried to research on my own and found nothing but what the manufacturer puts out. The endocrinologist assured me that he’s been prescribing it for years and has seen no side effects. Whenever we reported side effects to him, he was certain that they didn’t relate to Lupron. I eventually decided after her 6th shot (she gets them q 3 mo) to stop the Lupron and that’s when I found your website. How very distressing to read all these sad accounts…Is there anything that can be done to help negate, reverse or minimize these negative effects?”

Another mother writes:

“My daughter was diagnosed with PP at 6…She took 7-8 injections…we saw our happy-go-lucky child turn irritable and depressed…once she hit her teen years, everything exploded. She experienced depression so severe she’s been diagnosed with PTSD, Severe Anxiety Disorder and Severe Depression Disorder. She’s spent time in a mental hospital, and the last three years have been sheer hell. Her anxiety is so extreme, she couldn’t attend the last 3 years of high school … and it’s looking like she may turn into a complete agoraphobic. HELP! Is there anything anyone can do to help her? …This child has already tried to commit suicide more than once. I’m afraid we’ll lose her if we can’t address this problem and find a way to solve it or at least ameliorate the damage!”

And another mother writes:

“Lupron was prescribed to my 6 year old daughter…my husband and I were very leery, yet, we were comforted by the physician, stating this was going to help.  Since then, our daughter who just turned 8 years old is in pain ALL the time. I am overwhelmed because I knew NOTHING of all of this. I knew nothing about the adverse effects of this drug, I knew nothing period. She has been having issues that of course I have brought to her prescribing physicians attention, however, I was told everything was fine.  So I started researching myself…and now I am terrified. WHAT CAN I DO?  WHAT HAVE I DONE?”

Other emails echo similar physical and emotional adverse events. The emails I have received pertaining to precocious puberty or growth issues have not been overwhelming in number (precocious puberty is a “rare disease”), but the contents of these emails are indeed overwhelming. And the common threads are “we were told there were no long-term effects“, “my daughter’s doctors say there’s no connection to Lupron“, and “Help!“.

These stories are heartbreaking. It is very troubling that they reach out to the internet because there does not seem to be anyone else. Who can help these children, these now-grown women, these families? Someone please tell me where they can go? I would very much like to be able to provide a positive answer and instructions of where they can go and whom they can talk to, and preferably provide the name of a clinic and doctor/team dedicated for Lupron injury assistance, but the latter does not exist.

It has been indescribably difficult to respond to these hurting and frightened victims’ questions knowing there are no real answers, no definitive direction, no designated doctor or clinic, no holistic ‘cleanser’, no known antidote to provide. This is the risk information these unfortunate souls should have received from their physicians before injection, not in a post-injury search of the web.

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Photo by Markus Spiske on Unsplash.

This article was first published on March 1, 2017 and is part of a six part series.