Lupron: What’s the harm?

Worried Mom and her son, Worried Brother, co-wrote this post.  Worried Mom is an attorney who currently works in the non-profit area, and Worried Brother is employed in the pharmaceutical industry, with a background in chemistry.  This piece is sourced in the scientific literature; click superscripted footnotes to follow links.

For recent mainstream coverage about the potential harms of pubertal suppression, see here and here.

by Worried Mom & Worried Brother

Before we can have a sensible discussion about Lupron and its hormone-suppressing effects, it is important to understand what normal hormonal balance means in a healthy teenager or adult.

Normal body functioning requires a certain latent amount of testosterone and estradiol (estradiol is the major estrogen in humans).  Men and women both have some of these hormones naturally present in their bodies, produced by testes in men and ovaries in women.  Testosterone is involved in the development of muscle bulk and strength, the maintenance of proper bone density, the creation of red blood cells, the sleep cycle, mood regulation, sex drive, hair growth, and cholesterol metabolism.1,2,3  Low testosterone levels can lead to deficiencies in any of these areas.  For example, lack of testosterone can cause fatigue, insomnia, and interference with mood and sleep, together with a host of other impacts on, for instance, a person’s sex drive.

Like testosterone, estradiol is involved in the maintenance of proper bone density, mood regulation, skin health, and reproductive health.4,5,6  Lack of estradiol can lead to adverse impacts in those areas.  Because estradiol is a crucial component in maintaining bone density, individuals who lack sufficient amounts of estradiol will fail to undergo proper bone development, because the growth plates on the ends of the bones will never close.7  This profoundly alters the physical structure of the body.

Lower levels of estrogen are also associated with significantly lower mood.  The primary regulators of mood in the brain, according to our current understanding of neurochemistry, are the systems relating to the neurotransmitter serotonin.  Estrogen receptors are prevalent along the mid-brain’s serotonin systems, and they are believed to play an important role in serotonin-mediated behaviors such as mood, eating, sleeping, temperature control, libido and cognition.  Mice that are bred missing this particular sub-type of estrogen receptor show enhanced anxiety and decreased levels of serotonin and dopamine.8

As noted, both men and women naturally produce testosterone and estradiol in their bodies.  The levels of these hormones fluctuate greatly depending on the person’s stage of life.  At the start of puberty, a child’s body will begin to produce either testosterone or estradiol in much greater quantities than it had previously.  This increased production leads to the development of secondary sexual characteristics.  As men and women age, their levels of testosterone and estradiol also decrease, leading to well-known age-related effects, such as thinning bones and hair in both men and women.

A current focus in the treatment of transgender children and teenagers is to arrest, or delay, the impact of testosterone and/or estradiol in adolescence.  Arresting the impact of these hormones will prevent the development of secondary sexual characteristics.  Moreover, many clinicians recommend–if a child or teen is unsure as to whether he or she wishes to become a transgender adult–that the administration of so-called “blockers” will “delay” puberty and “buy time” for the teen to make a more informed or mature decision.  Theoretically, a teen could always desist from taking blockers and then normal puberty would ensue, although there is very little data in this area.  It is also currently unknown whether, if a teen takes a puberty blocker during what would otherwise have been his or her normal puberty and then stops, whether puberty will proceed entirely as normal or whether there will be some other effects from having delayed it for a period of years.  The “puberty blocker” discussed in this article is leuprolide acetate, better known by its trade name Lupron.

What is Lupron?  Lupron is a gonadotropin-releasing hormone analog.  The primary pharmacological effect of Lupron administration is a decrease in the concentrations of testosterone and estradiol throughout the body.9,10  How does it achieve this decrease?  It does so by tinkering with a hormonal feedback loop between the hypothalamus and the pituitary gland, and interferes in the release of gonadotropins (“Gn”), which is a catchall term for 2 separate hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH).  Gn acts as the primary means by which the body controls the release of testosterone and estradiol.  Gn interacts with the tissues that are involved with the release of these two hormones.  It stimulates specialized tissues in the ovaries and the testes to produce testosterone and estradiol.  LH stimulates the Leydig cells in the testes and the theca cells in the ovaries to produce testosterone11.  FSH stimulates the spermatogenic cells in the testes and the granulosa cells in the ovarian follicles (the granulosa develop to produce a layered structure around the egg), as well as stimulating the production of estrogen by the ovaries12,13,14. There are Gn receptors embedded in the cell membranes of these tissues and binding with Gn results in those tissues producing the hormones.  The hormones are released into the bloodstream, and travel to specialized receptors that are located systemically, in most major tissue groups.  The systemic distribution of these receptors is responsible for Lupron’s effect on the entire body.

The hypothalamus releases GnRH (Gn-releasing hormone) which binds with GnRH receptors on the pituitary gland15.  The hypothalamus responds to the concentrations in the blood of testosterone and estrogen, as well as the presence of Gn16,17.  Since Lupron is chemically similar to GnRH, it is essentially repeatedly stimulating the GnRH receptors on the pituitary gland.  This artificially high activation of these receptors desensitizes the pituitary gland to the presence of GnRH18.  There is an initial flare-up of Gn release in response to the presence of the Lupron, but it eventually results in down-regulation or deactivation of these receptors19.  In physical terms, this means that the pituitary, in an effort to restore normal functioning, will cull the number of GnRH receptors.  This results in a significantly lowered response to a given concentration of GnRH in the blood. Why is this?

This is the key point, because the strength of an organ or tissue’s response to any drug is directly proportional to how many receptors are activated by the presence of the drug.  So, using this idea, lower the number of receptors, lower the response, and if there is an absolutely lower number of receptors present, there is an absolutely lower potential response20.  Once the drug is removed from the body, the pituitary is left in a desensitized state, rendering it unable to respond to ‘normal’ activation by GnRH.  This results in decreased production of Gn, which in turn means decreased production of both testosterone and estradiol in the tissues with which Gn would normally interact.

Lupron use in otherwise normal teenagers to delay puberty is both relatively new and off-label.  Lupron does have a history in treating a condition called ‘precocious puberty,’ which is what happens when a child’s body enters puberty too quickly for his or her age.  However, this is a clinical condition typified by concentrations of sex hormones deemed wildly abnormal in the course of normal development.  As such, the usage of this drug may be more appropriate in  these particular individuals, because the marginal benefit of leaving this condition untreated is higher than it would otherwise be. Any competent medical professional would not generalize from outcomes observed in a population of individuals affected by abnormal hormone levels, to individuals with normal hormone levels.

Industry standards21 judge the usage of Lupron in treating gender dysphoria as providing at best no proven benefit and hold that there is an insufficient quantity of published evidence to prove its safety for this purpose.  UnitedHealthcare, the nation’s largest insurer, makes its stance clear on Lupron for usage in treating gender dysphoria on their Drug Policy page:22

‘Hayes compiled a Medical Technology Directory on hormone therapy for the treatment of gender dysphoria dated May 19, 2014.  Hayes assigned a rating of D2, no proven benefit and/or not safe, for pubertal suppression therapy in adolescents. This rating was based upon insufficient published evidence to assess safety and/or impact on health outcomes or patient management.’

A D2 rating is the lowest rating possible on that particular institution’s scale of safety and efficacy.  The Hayes Technology Review is considered to be the industry standard in linking treatments with patient outcomes.

In Lupron’s case, the vast majority of clinical data is found in samples of middle-aged or older men with late-stage prostate cancer.  This means the aggregate of the medical community’s understanding of Lupron’s safety profile relates to its use in this context, in terms of both the condition it is meant to treat and the individuals for whom it is approved.  When using Lupron as a “blocker,” medical professionals are, in both senses, treading untested waters, for the dual reason that it is not approved or recommended to “treat” this particular condition, and clinical studies relating to its long-term or even short-term safety in treatment of gender dysphoria are vanishingly rare.  To further illustrate this second point, the population to whom Lupron is most commonly prescribed on-label, middle-aged and elderly men, has a much shorter life expectancy from the date of administration than do teenagers.  In other words, based on the current state of research, one would not expect to see data collected from groups who are 40, 50 or 60 years “out” from administration.

Putting together what we know about how the body normally reacts and develops during puberty with what we know about how Lupron works, we can conclude the following: administration of Lupron to young people for the purposes of blocking puberty is a disruption of a delicate hormonal balance that has the potential to cause adverse health effects.  The risk is further compounded by the off-label usage of the drug for this purpose, as well as the lack of long-term data related to safety.


28 thoughts on “Lupron: What’s the harm?

  1. Thanks for writing this! When I had to take Lupron as an adult (2x for 3 months each time), I was told very clearly that Lupron should not be taken for more than 6 months in a person’s lifetime. How long are these children on Lupron? Children are put on Lupron to “buy time” to make a decision. So let’s say a child is put on the drug when they turn 12. Are they really ready to make the decision to go on cross-sex hormones at 12 1/2?
    Why is it that we won’t let a 12-year-old drink, smoke, drive a car, or sign any legal document? It’s because they are not mature enough to make adult decisions, and drinking and smoking are bad for them. But we should let them make decisions about taking an off-label drug and then cross-sex hormones to destroy their fertility.
    What happens to those kids who have adverse reactions to Lupron and have to go off of it? These children have been told by the adults they trust that they are indeed in the wrong body. It’s pretty messed up when we tell children that their only option for happiness is major body modifications.

    Liked by 8 people

  2. This should prompt the headline ‘The child lab rats being fed harmful drugs by parents and Medics'(paid for by you). Given how quick tabloids are to demonise school, hospitals, police, in how they interact with children it is sinister and chilling that this is not reported.

    Liked by 3 people

  3. There is a petition to congress to investigate into the side effects of Lupron with over 10,500 messages from people who have suffered from this drug. I’m sure TheMom can relate to what these patients have gone through. Just take a look.

    And parents are willing to administer this to their children?
    Also, kids who go on Lupron “puberty blockers” are almost 100% likely to continue onto cross sex hormones which insures sterility and they will never have the opportunity to return to the normal function of their biological sex, if they realize that they have made a mistake. They will have to live in a kind of in between life with all of the health consequences that come with the use of artificial hormones.

    Parents and doctors should not be allowed legally to make such decisions for the life of a human being who has just started out in this world. Let them decide when they are adults – preferably over 25 when the brain has developed enough.

    Liked by 6 people

    • Thanks for sharing! I wonder when the kids given this drug for gender dysphoria will start suing. Maybe then doctors won’t be so enthusiastic about prescribing it to growing children.

      Liked by 1 person

  4. Thank you for writing this! The thing is that kids/teens are forming their identities on the internet. It is not real but the horrible consequences of being treated are all-too real.

    Liked by 4 people

    • You could bring up the subject of GMO food and crops as well. “Oh, no, can’t have any of those, err on the side of caution, better safe than sorry….”

      Liked by 2 people

      • Wow, so vaccines, which are pretty safe are bad, GMOs are bad (even though literally everything you eat is a GMO), but a drug with a D2 rating is natural and safe. Makes sense. This is why I hate hipsters and the organic movement.

        I say literally everything you eat is a GMO because wheat sure doesn’t look like it did 10,000 years ago before agriculture.


    • Histrelin belongs to the same class of GnRH analogues as Leuprolide does. The side effects and safety profile of Histrelin are comparable to Leuprolide since they work in the same pharmacological manner, so many of the adverse effects found in patients where Leuprolide is used can also be seen in patients that are administered Histrelin.

      Liked by 2 people

      • Can you tell me anything about Triptorelin?

        I have been doing some research and coming up empty.

        I read somewhere that it is not much better than Lupron but there was no citation provided.


      • @Cindy Triptorelin is in the same class of GnRH agonists as Lupron. It’s used in cases of advanced prostate cancer and has similar effects as Lupron, in addition to sharing the same side effect profile.


  5. The author seems to think treating Central Precocious Puberty with Lupron is practically a cosmetic decision. That’s bullshit. My daughter had CPP and was treated with Lupron. Most people don’t undertand that CPP is actually asynchronous puberty–the child’s bone age is higher than her chronological age. This means her growth plates will fuse prematurely, causing short stature. While one could say short stature isn’t a big deal, would you want YOUR daughter to go through life at 4 feet tall? Really?

    That said, using Lupron to keep physically normal children from having puberty is sick and wrong. Any doctor prescribing it should be sued for medical malpractice.


    • I totally agree with you that Lupron is a great thing for children who have precocious puberty. Lupron given to children whose puberty is proceeding normally is a misuse of this drug that can have life-long, drastic negative effects.

      I’m 5’2″, and have adult relatives as short as 4’8″, and totally understand why you would want to help your child maximize her adult height. At 5’2″, there are many things that aren’t designed for tiny adults – like car seats windows & mirrors, and seats on most public transit. (I’m one of the few adults with no complaints about the size of airplane seats).


  6. I’m sorry if that was your take-away because it certainly wasn’t meant that way (unless you are referring to the California Healthline article linked at the beginning of the piece, rather than to this article). The distinction we tried to draw was between treating a condition, precocious puberty, that represents a departure from normal hormonal balance, and treating a non-condition (normal hormonal balance). The point was that it’s inappropriate to generalize from one to the other. I don’t believe that this piece implied that precocious puberty is a “cosmetic” problem and in fact we suggested that the risks of treating precocious puberty, even with a drug like Lupron, might in that case be outweighed by possible benefits.

    With that said, I am very sorry that you have an ill daughter. I have an ill son of my own and I know that it is a very difficult and upsetting situation.

    Liked by 1 person

  7. The site Hormones Matter is running a six-part series on Lupron. Here are links to the first three posts:

    1. Lupron for Precocious Puberty: Parents and Patients Speak Out (also linked at the start of the post above)

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

    Among much other interesting information, this post links to a study published in 1999 that ‘noted [among the side effects] the occurrence of *seizures*, as well as identifying that after discontinuation of the GnRHa, emotional lability, depressive behavior, and mood swings developed.’ [My emphasis. Article may be accessed here, free of charge]

    The post also links to this very recent comment on another website:

    ‘I am a clinical psychologist and 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 disregulated before.’

    3. Lupron and Reproductive Injury.

    This post includes a brief discussion of the use of Lupron as a ‘puberty blocker’:

    ‘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.”’

    This third post also discusses the claim that the effects of Lupron are “reversible”, concluding:

    ‘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.’

    The Hormones Matter website that has posted these excellent pieces (and has three more in the pipeline) has lost its research funding and is seeking to crowdfund support.


  8. Yes there are situations in which Lupron might have more benefits than dangers, but that is not the case for still-growing children who are going through perfectly normal puberty, and to delay puberty in normally-developing children is to put those children at risk of those dangers with no demonstrable physical benefit.

    At this point, our society is so uptight about sex that age-of-consent laws that were written and sold to the public as a way to protect children from predatory adults result in life-long sex-offender status for young men who, as teens, dated teen girls slightly too young (e.g., an 18 or 19 year old boy with a 14 or 15 year old girl). By law – and now by opinion of a lot of the public – the girl “cannot give consent” to sex.

    But kids of an age “too young to consent” to even a single sex act are of an age to consent to a much more drastic situation involving hormone blockers, cross-sex hormones and even surgery?


  9. I took Lupron for a couple years due to endometriosis. Soon after I got off it, I developed Rheumatoid arthritis, fibromyalgia, migraines, and other random issues like Raynauds. Left me unable to work outside the home anymore. If Lupron is what is being used to suppress hormones in teens…for any reason, I’d be highly concerned about the effects these kids will suffer from in terms of autoimmune illness later.

    Liked by 1 person

    • I took it 2x for 3 months each, so a total of 6 months. I too have Raynauds, and I’m hypothyroid and have a goiter. There is a chance that I have Lupus, or another autoimmune disorder (no diagnosis yet). I don’t know if any of these things are connected to Lupron use. I would love to see some extensive studies done on children who were given Lupron for precocious puberty, and on women who took it for extended periods of time for reproductive issues.

      Liked by 1 person

  10. I’m so sorry this happened to you. It certainly seems to correlate with the experiences of so many women who took Lupron for endometriosis.

    My husband took it for advanced prostate cancer and still feels side effects as well – of course in his case we were lucky it seems to arrested the cancer, but it’s not ungrateful to recognize the down-sides, too. Lupron is so far from being a benign or harmless drug, it’s not even funny!


  11. This article doesn’t deal with Lupron, but rather with testosterone, which as we know is given to natal females during transition to cause their bodies to become more masculine: The article deals with the results of a large and rigorous study of abnormally low-testosterone older males who received testosterone supplements.

    A couple of striking things about the study results: even when given to males, whose bodies are conditioned to synthesize “T,” it appears uncontroverted that increased amounts of endogenous testosterone lead to increased cardiac risk (due to increased plaque in the coronary arteries). This was termed an “ominous portent” of cardiovascular disease by one writer.

    And get this: “Testosterone has been available as a drug for so long that it was never subjected to clinical trials of safety and efficacy as most new drugs are today. Nor has it been tested in large government-sponsored trials lasting many years, like the one of hormone replacement therapy for older women that found hormones did not prevent heart disease in postmenopausal women and actually posed serious risks.”

    Off-label use in a population for whom it has never intended? Check.
    An under-studied drug in the first place? Check.
    Strong indications of serious and potentially fatal side effects? Check.

    But what could possibly go wrong?


  12. My daughter was given a medication like this one (suprelin) for years. They stopped the medication and her health is decreasing rapidly. No normal hormone blood tests. Gained over 75 pounds in about a year. Hardly grows. Struggles in school (cognitive issues). It is horrible. And there are not even any lawyers to help. It is not right that they do not warn you of these things on their website.


    • Dear Wendy, I am terribly sorry to hear what has happened to your daughter. May I ask, for what condition was the Suprelin prescribed? Why was she advised to stop its use now? I don’t know where you’re located, but is it possible that a pediatric endocrinologist (or a different one!) might help?


  13. We know from experience that almost 100% of kids given Lupron and other puberty blockers, to give them time to “decide” whether they are transgender, go on to a life time of cross sex hormones and often numerous surgeries. We also know that a large percentage of children presenting with gender dysphoria have the condition resolve on its own, most of them when they reach puberty. So, blocking the onset of puberty effectively blocks normal maturation and the resolution of this body dysphoria. It actually prevents the situation from resolving naturally, and assures a lifetime of medical treatments.

    Liked by 2 people

    • Unfortunately I cannot lay my hand on it right now, but a recent article by clinicians in the field indicates that apparently there is not a SINGLE case, known to the profession at any rate, of a child going on Lupron to suspend puberty and then NOT proceeding to cross-sex hormones. In other words, the “safe and reversible” mantra repeated around puberty suppression with Lupron apparently has no data or experience behind it. While we have a picture of a child simply being in “suspended animation” or “on hold” for a period of months or years with respect to physical maturation, and able to safely resume normal development should that be indicated in his/her case – it turns out that this picture may have no factual basis.

      Is it actually true that if a child were to, for instance, go on Lupron at age 12, delay puberty for four years until age 16, then cease taking Lupron but also not take cross-sex hormones or have surgery destroying the body’s ability to manufacture hormones, that child’s body and mind would mature in exactly the same way as if that child had never taken Lupron at all? What would that entail? Would a child experience four years of puberty in, say, six months? There appears to be some evidence that girls who took Lupron to forestall “precocious puberty” do, in fact, mature at a more or less normal rate once they go off it (at the time that normal puberty would begin) but this could be a very different process for someone who has not experienced puberty at the correct time. The short answer is, nobody knows what happens to kids put on Lupron to “buy time” in the transgender context. They may have good theories, but at least at this point, it’s all a giant experiment.


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