On Conducting Research Studies on the Physical Effects of Puberty Blockers and HRT

[ThatZanyFatball]

So, not a scientist here. But like many of you I'm disgusted and appalled at the prospect of conducting science experiments on vulnerable children in ways that can permanently damage them both physically and emotionally.

Most of the arguments in favor of gender medicine focuses on the (supposed) positive mental outcome for children. But the physical impact of artificially stopping a mammal's puberty phase and then immediately forcing their body into an unnatural path of development can be tested on animals.

I know most people's gut reaction is that animal testing is cruel, but look if that's how you feel about it then isn't testing on children a million times crueller? And I'm not talking about chimps or pandas here I'm talking about mice or rats. And newsflash, like it or not most of the beauty products and medications we use at some point are tested on animals.

An argument frequently make by TRAs is that puberty blockers are completely reversable. But here in the US puberty blockers have only been FDA approved for precocious puberty. Drugs that receive FDA approval have to go through a rigorous testing process in order to receive it, meaning that at least here in the US the drug was only ever tested for children with precocious puberty. What's the difference?

Well, when puberty blockers are given to kids with PP it is a) treating a physical abnormality of normal human development, b) given only long enough to allow the body to adjust itself to a normal phase of human development, c) stopped so the body can resume the path of development natural to its sex (DNA). Presumably, that is how the drug was tested.

But for kids with GD who are given PBs, a) the drug is not being used in conjunction with the physical abnormality it was tested to treat, b) they may be on PBs for much longer period than those who have PP assuming they're taking their "time to decide," c) since the vast majority of kids who go on PBs transition onto HRTs, their bodies do not resume a natural development path but instead are artificially forced into a path that goes against what their DNA is trying to instruct the body to do. PBs have never, ever been tested for this scenerio (AFAIK) so any argument claiming that they are proven to be safe are false bc they have not been proven against these conditions.

Testing the physical effects of longer-term PB and HRT use in otherwise physically healthy organisms can and should be done on small animals rather than children. And arguably, this is the more important thing to test than the mental outcomes. If a parent and child who has GD are told that "sure, you may or may not be less depressed we really don't know for sure, but what we do know for sure bc of rigorous scientific testing that of you go down this pathway the likelihood of having xyz long-term physical issues dramatically increases, that at the very least will help all parties make a much more informed decision without subjecting today's children to dangerous experiments.

Why is animal testing for the physical impacts of short and long term gender medicine use not being proposed? And again, if you think animal testing is cruel but testing on children is humane, like seriously I don't know what to say.

@ThatZanyFatball there was 1 study on animals with puberty blockers and it showed brain damage amongst others well known issues. This study should have been expanded and prevented the use of them in children. Also even when used for a short time for precious puberty they cause life long harms (look up the lupron class action law suit).
Nobody wants to investigate the long-term harms from the use of puberty blockers in those who were already given them or go back to animal testing due to the fact that they'd have to admit that they gave harmful drugs to children in the name of an ideology with no evidence in a completely uncontrolled experiment that has sterilised thousands of children. Its all about protecting the adults behind the experimentation on vulnerable children

Good to know, and I hear you about the reluctance. But testing is apparently going to happen regardless - however in a very unethical way. People and organizations who are against the testing as it is slated to move forward shouldn't just be arguing that it's inhumane, they should be offering a much more logical, humane, medically sound, and ethical alternative.

TRAs are happy with the study bc at the end of the day kids will be getting medicated and they'll just skew any results that come out of it. But they don't have much ammunition against testing on mice and rats.

Here is that test on sheep

https://pmc.ncbi.nlm.nih.gov/articles/PMC5333793/

A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep
D Hough, M Bellingham, IR Haraldsen, M McLaughlin, JE Robinson, AK Solbakk , NP Evans

March 2017

Highlights

-Peripubertal GnRHa impaired long-term spatial memory.
-This impairment was not reversed after discontinuing GnRHa-treatment.
-Spatial orientation and learning performance remained unaffected following GnRHa withdrawal.
-Speed of progression through these spatial tasks was altered after discontinuing GnRHa.
-GnRH irreversibly alters these cognitive functions during critical window of development.

Conclusion

"Spatial orientation and learning performance (i.e. traverse times) were not different from untreated rams, when assessed at 83 and 95 weeks of age, following the discontinuation of peripubertal GnRHa-treatment at 44 weeks of age. However, the effects of peripubertal GnRHa-treatment to increase emotional reactivity, persisted into the second year of life after GnRHa-treatment had been discontinued, because the manner in which rams moved through the maze (i.e. maze progress pattern) over multiple same-day maze attempts differed from the Controls. Interestingly, these aspects of how the rams progressed through a maze appeared to be dependent on the level of gonadal steroid exposure (i.e. quicker maze progression during breeding season vs. slower maze progression during non-breeding season).

The reduction in long-term spatial memory induced by peripubertal GnRHa-treatment persisted in rams into adulthood even after GnRHa-treatment was discontinued. Development of this cognitive function is, therefore, likely to occur during a critical window of development, which may reflect a time-limited period of hippocampal plasticity. Perturbations in GnRH signaling during this peripubertal period may also have long lasting effects on other brain areas and/or aspects of cognitive function."

I have been reading Sally Baxendale's paper and this might be interesting for you OP.

https://onlinelibrary.wiley.com/doi/10.1111/apa.17150

Animal studies

The wider search strategy identified experimental studies on the physiological impacts of GnRH blockade in 17 species of animals (including hyenas, sheep, goats, rats, naked mole rats, giant pouched rats, mice, hamsters, macaques, rhesus monkeys, marmoset monkeys, carp, gilt, chicken, pigs, cows and dogs). Eleven of these studies reported the impact of pharmacological puberty suppression on indices of behavioural function in the animal. These studies are summarised in Table 1. The majority of these studies (n = 8) have been conducted in the same flock of sheep using twin controls. Two studies in monkeys and one mouse study were also identified. Measures of brain structure were reported in five studies and included structural MRI, resting state functional MRI and histopathology

These are the animal studies

Hough D, Robinson JE, Bellingham M, et al. Peripubertal GnRH and testosterone co-treatment leads to increased familiarity preferences in male sheep. Psychoneuroendocrinology. 2019

Nuruddin S, Krogenaes A, Brynildsrud OB, et al. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep. Psychoneuroendocrinology. 2013

Wojniusz S, Vögele C, Ropstad E, et al. Prepubertal gonadotropin-releasing hormone analog leads to exaggerated behavioral and emotional sex differences in sheep. Horm Behav. 2011

Evans NP, Robinson JE, Erhard HW, Ropstad E, Fleming LM, Haraldsen IRH. Development of psychophysiological motoric reactivity is influenced by peripubertal pharmacological inhibition of gonadotropin releasing hormone action – results of an ovine model. Psychoneuroendocrinology. 2012

Nuruddin S, Bruchhage M, Ropstad E, et al. Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep- a magnetic resonance imaging study. Psychoneuroendocrinology. 2013

Wojniusz S, Ropstad E, Evans N, et al. Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids. Psychoneuroendocrinology. 2013

Hough D, Bellingham M, Haraldsen IRHH, et al. Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep. Psychoneuroendocrinology. 2017

Hough D, Bellingham M, Haraldsen IR, et al. A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep. Psychoneuroendocrinology. 2017

There are links in the paper linked.

I came across a study, Changes in Suicidality among Transgender Adolescents Following Hormone Therapy: An Extended Study - The Journal of Pediatrics. Has anyone here seen the full article? Does anyone know anything about that journal?

Judging by the "snippets" allowed for public consumption, the study had no control group, and in some unspecified way selected 432 teenagers treated at a US midwestern gender facility. They call it a retrospective study, by which they seem to mean they selected teenagers who'd had hormone treatment of varying durations at least two years earlier and then checked current records to see how things had gone for them. At the same facility. (Swimmingly, according to the study. Which, in the short time frame and selecting for people who were still at the same facility, is not unexpected.)

How did that get past peer review? Or isn't that a peer-reviewed journal? Or are the "snippets" skipping all the important parts? Anyone here have any further info on this study, supposedly on the effects of hormone therapy??

Sorry. Forgot the link: https://www.jpeds.com/article/S0022-3476(25)00424-X/abstract

Im not a scientist either but, due to endometriosis, I do have experience of zoladex, one of the drugs used as a puberty blocker.

It was only allowed to be prescribed for 6 months maximum at that time and for that condition due to the risk of osteoporosis. At the time I was about 33 and trying for a family.

I can honestly say I would not wish it on my worst enemy. The physical, emotional and mental effects were horrific.

In the end it gave me a very short reprive from my symptoms but given that 12 months or so later I was told by my fertility specialist that I was in peri-menopause (admittedly this could have been due to various other endo related things but I will never know for sure) and that aged 45 I had a spontaneous hip fracture the thought of experimenting on children breaks my heart especially as i truly do not believe they are "reversible".

That’s awful. I’ve heard similar about either this or another GNrh drug.

I am so sorry to hear this. Can I ask if your medical team have traced your current symptoms back to the drug?

I have a friend who had a horrific fracture just over a decade after a procedure which I have read used one of this group of drugs. That fracture was about a decade ago though. Since then she has had teeth fall out, she breaks bones very easily, she has pancreatitis and other organs are damaged too.

However her medical team are so busy helping her day to day that none of them are interested in understanding why. They have told her they don’t know why and made her feel like it is just her genes/lifestyle/bad luck.

She had a medical issue where I believe one of these drugs were involved, and I suspect it was used a lot longer than 6 months at a time. As that procedure was done privately, there is no record of it on her NHS files. I mentioned to her that her symptoms all sound like the horrific stories we hear from women who had been prescribed Lupron for precocious puberty. But she feels it is not help to her to know this.

So I am struck that there might be many women suffering the adverse side effects of this group of drugs through different usage, but that no one with the NHS is making the connection at the moment.

@Helleofabore Unfortunately it's all circumstantial, perimenopause in mid 30's early but not unheard of and had so many gynae problems and surgeries that didn't even think of a connection at that time - 20 years ago now - and with the hip fracture (10 years ago) the hospital kept on asking if I was or had been anorexic (I was more petite then) and dismissed all my assertions that I had never had any ED's. When I mentioned the Zoladex it was dismissed as I had only been on it for the prescribed 6 months.

And hey if they looked into it there could have been a connection and lawsuit in the offing.

I do hope your friend gets the help and better health she deserves.

If however any of our lovely medical mumsneter's fancy doing a research paper into the effects of puberty blockers on adults and beyond I would be happy to open my medical records to them.

I am very sorry to hear that too pawsed. This is the same experience that my friend has had. I wish you all the best with your health.

Another one here who had GnRH antagonists for endometriosis and it was easily the worst time of my life. I felt absolutely wretched and nobody warned me about how bad the side effects would be. One of the things that first alerted me to the evil of trans ideology was hearing people who had never taken blockers confidently claiming that Lupron is a 'harmless pause button'.

I am genuinely coming to believe they invented this drug and then needed to invent a market for it.

I would also be happy to open my medical records to anyone who wanted to do a research paper.

Apologies for pedantry but HRT is incorrect. Hormone replacement therapy is supplementing the body’s natural hormone levels to get them to a level which is medically necessary.
It is the effect of taking cross sex hormones.

I worry that as peri and menopause are more widely discussed the term HRT has positive medically indicated connotations which is not the case for cross sex hormone therapy.