#Clinical outcome

[religion-is-a-mental-illness]

By: PITT

Published: Sep 30, 2023

Our son recently started graduate school. He began hormone therapy during his final year of undergraduate education. Because he began to identify as a lesbian, transgender woman at 20 and showed no sign of gender dysphoria before that, we never had a chance to reflect – or advise him – on his choices. Going through the published medical research on the effects of estrogen made me aware that psychologically, excess estradiol in the serum causes depression among males, and physiologically, there are potentially much more severe side effects, including some impacting the brain and the immunological system. More of that in a minute.

Fast forwarding to the present day, before our son left for graduate school at a University with one of the country's most renowned medical schools. I decided to write to their student health center and share the studies I had found and, more relevantly, the psychological history of our child. What follows is the text of the letter and, after deleting potentially identifying information, the response from a high-ranking official within the health center. They are, for the lack of a better phrase, quite revealing.

First, my letter (I have not disclosed the name of the university and have changed the name of our child here, with apologies to the real Jonathans of the world; furthermore, apologies for the triggering usage of pronouns – I did not want to be dismissed as the “usual, hateful, bigoted transphobe”; rather, I wanted to be considered as the deadly serious parent who would do anything in their power to prevent their child from coming to harm):

-

Dear Apex University Health Center,

Our child, Jonathan, who is joining the graduate program at Apex University this Fall, identified themself as transgender during their sophomore year in college (2021) and started estrogen therapy in early 2023. Since every one of these interventions is off-label, I have been looking up the peer-reviewed literature on the effect of estrogen and whether there are any risks that our child needs to be aware of as they continue on this path. My findings, which I summarize below (and link to the sources), have been alarming. Several endocrinologists – some who publish extensively – have told me they were unaware of the new literature. I have also been in touch with the Endocrine Society, and their response heightened my alarm.

While we respect our child's identification with their gender identity, we felt that they exhibited several psychological symptoms right before identifying as a lesbian, transgender woman (Jonathan was assigned male at birth and did not show any inclinations to identify as female before April 2021), and these co-occurring symptoms were not considered at all before he started on the prescribed medicines. Most tellingly, just before identifying as transgender, Jonathan's romantic advances were rebuffed by the woman of their affection. Subsequently, Jonathan also lost every friend they had, thereby remaining completely alone in their dorm room for the greater part of their last two years of undergraduate education. However, these psychological symptoms were never explored. Jonathan was recommended to start on estradiol and spironolactone immediately, which they did – and their physical and mental health symptoms have deteriorated since. Jonathan is also quite depressed, spending all their time without emerging from their room.

That is not surprising since, when it comes to the recent research on estrogen in natal males, excess estrogen in the serum in natal males has been associated with depression – studies among adult men and adolescent boys show that. Clinical studies (i.e., studies that recruit actual subjects and follow them clinically rather than rely on anonymous, online, non-probability surveys) that promote gender medicine fail to show any improvement in psychosocial outcomes among natal males. For example, the New England Journal of Medicine study from early 2023 concluded that hormone therapy is psychologically beneficial for transgender youth. However, in the main text, the study finds no improvement in depression, anxiety symptoms, or life satisfaction among natal male youth (the relevant paragraph is at the bottom of page 244 of the journal issue).

Thus, psychologically, there is ample evidence that excess estrogen is associated with depression among natal males. Physiologically, recent research shows that estrogen might have far more deleterious effects. A study showed that 12 months of estrogen treatment among transgender women leads to a decrease in serum BDNF levels. That is significant because a separate study shows that this decrease in serum BDNF level is associated with increased risks of developing MDD (or major depressive disorder).  Lower levels of brain BDNF levels have also been associated with neurodegenerative disorders and found in the brains of patients with Alzheimer's, Parkinson’s, MS, and Huntington’s disease.

A high-quality rodent study shows that estrogen therapy among adult male rats leads to changes in their brains that resemble the changes in the brains of trans women. (There have been several other studies (2 links) among trans women that have shown these changes, but the rodent study indicated the mechanism by which these changes occurred in the brain.) Specifically, estrogen seemingly reduced the water content in the astrocytes and thereby disturbed the delicate homeostasis in the brain by increasing the relative concentration of glutamate (the brain's most abundant excitatory neurotransmitter), leading to glutamate excitotoxicity. As the Cleveland Clinic informs us, an increase in glutamate in the brain is associated with higher risks of neurological disorders like Alzheimer's disease, ALS, and many other diseases like multiple sclerosis. The research also showed that estrogen decreased brain cortical thickness and volume (which other studies have linked to patients with schizophrenia and bipolar disorder and lower levels of general intelligence). Furthermore, it was found to reduce cortical white matter integrity (which is related to cognitive instability). There is also empirical evidence of the lowering of cognitive abilities among transgender women that was presented at the EPATH conference in April 2023 (in Killarney, Ireland) - the researchers noted this decline among long-term patients at Amsterdam's famed gender clinic.

Research in the last few years shows that estrogen therapy among trans women has been associated with higher risks of various autoimmune diseases, from multiple sclerosis (recall, too, the association of MS with an increase in glutamate) to rheumatoid arthritis and many others in between. It has been associated with increases in the risks of prostate cancer and breast cancer. It increases risks of cardiovascular diseases (2 links), often by as much as tenfold compared to their cisgender counterparts.

Empirically, we see a much higher incidence of many of these physical and neurological diseases in the transgender population. It is perhaps not a coincidence, therefore, that population cohort studies (2 links) show that trans women, on average, die decades earlier than either cisgender men or women.

When I approached the Endocrine Society with what I had found and pointed out that many of these findings came out after the publication of their guidelines in 2017, I received an email from their Director of Clinical Practice Guidelines that they are currently fast-tracking a revision of those guidelines. She also mentioned that their evidence evaluation criteria have changed since the guidelines were published and that they now use the GRADE criteria for evaluating evidence. This is encouraging, but I have no idea how long it will take for the new guidelines to appear.

I point all of this out because Jonathan has the chance to start afresh and be reevaluated at Apex University's healthcare system. We increasingly see them stumbling with their memory, something that we could not even think of a year earlier – Jonathan used to have a photographic memory ever since they were a child. Having heard so much about Apex's medical school, we have high hopes that Jonathan's evaluation at Apex University's medical system will be more thorough than it has been so far. Let me be clear: We have no doubt about their gender dysphoria or their intense discomfort in their traditional gender role – we worry about that all the time. It is just that we have observed that medicalization has not brought them any balm so far – in fact, just the opposite. While the absence of any upsides (and the possible significant downsides) in the literature – psychological or otherwise – heightens our alarm.

After all, it is not only a lone voice like ours, but even mainstream media like the Economist (their April 5 issue with the cover story “The evidence to support medicalized gender transitions in adolescents is worryingly weak” comes to mind) and storied institutions like the British Medical Association and the systematic reviews of the literature from national medical associations of very transgender-friendly countries like Sweden, Finland, Norway, the UK, and (most recently) Denmark that are raising the alarm on the lack of high-quality evidence of any benefits from hormone therapy. (And these reviews I mention above cover only the evidence of the psychological effects of the hormones – they do not even consider the long-term physiological consequences.)

If all the evidence from the past few years is to be believed, there is now quite a body of evidence of genuine harm from administering estrogen to the natal male body (I have not researched the effects of excess testosterone on the natal female body, and so I cannot comment on that.)

As one of the world's leading lights in healthcare to nudge society toward better outcomes through research, Apex University will be well placed to lead the march for evidence-based care in gender-affirming care.

Thank you very much for reviewing the evidence that I have found and considering our child's health as they start their journey at Apex University. Please let me know if you have any questions. I look forward to hearing back from you.

With warmest regards,

XXX

-

A few days later, I got their response. I have highlighted the relevant portions of their email and annotated them within brackets [all formatting mine]. As I said, it’s quite revealing.

-

Dear XXX:

Thank you very much for sharing your concerns about your child with us.

…Apex U's Student Health Center (Apex SHC) is not directly affiliated with Apex Medical School and we do not provide care under the umbrella of the hospital. [Is the respondent making sure that the medical school is not implicated if something goes wrong with our son?] However, we do collaborate closely with our colleagues at the hospital and medical school, including in the management of our student receiving gender affirming care.

…

Gender affirming care is a unique process in medicine in that we are not aiming to treat and eliminate a disease process. [Ah, an admission that there is no real goal of treatment through this care. Finally! But read on…it gets better.] Instead, we are using the tools of medicine to help individuals achieve very personal and sometimes nebulous [nebulous? WTF? After all these years of "settled science," all we have is “nebulous?”] physical and emotional goals. Success is not based on a clinical metric but usually involves a better quality of life balanced with potential risks including morbidity and mortality. [So, finally, an explicit admission – success is not based on any clinical metric. That makes complete sense to us inconvenient parents. After all, how can there be? There never have been any metrics, ever. At. All. All we have are some "nebulous" ideas of "better quality of life" – as decided by the patient right now, with no consideration of what might happen in the future as a result of the free dispensation of off-label medication. And oh, by the way, that "better quality of life" includes morbidity factors and dying much faster.] We at the Apex SHC make every effort to ensure that our patients are well-informed [in other words, make sure that they have signed the informed consent forms!] about each decision that they make and have time to consider these impacts without pressure [The irony of the sentence – “have time to consider these impacts without pressure.” Wow! really?]

Should your child decide to engage with us in care, our commitment to them is to prioritize their safety [oh, the irony, once more!], the elements of their well-being that we can support [the rest – whether caring for them for the rest of their lives or paying for their illnesses and hospitalizations, with a big fuck you to your dwindling retirement funds – is up to you, you bigoted parents!], and to help them make a bright future for themselves.

Very best,

AAA

-

As I read and re-read the email, all I could think was – Wow! What an amazing letter! AAA has no qualms admitting that there are no clinical goals of treatment when it comes to gender-affirming care. This is really quite convenient if you think about it—if there are no aims, any outcome is fine! No wonder these physicians get all flustered when we inconvenient parents ask them about clinical goals and outcomes.

All that these caring physicians want to achieve are some nebulous (which the dictionary defines as unclear, vague, or indefinite) goals. Oh, and please remember – once again – that those are personal goals, so please don’t ask about evidence of well-being. (An inconvenient question, though – why should such personal goals be funded by others, whether it is the government or private insurance?)

And what if, as a result of those nebulous goals, the patients go through psychological, emotional, and physical distress for the rest of their lives, as detailed in the medical literature? Really, shame on you, you bigoted parents! Always such a nag! Always the party pooper. Why do you have to ask such inconvenient questions? Haven’t these caring physicians already made it clear that these are personal goals and that it really doesn’t matter that young children who are distressed might have no idea how to make a rational choice about the future? Who cares if they become hyper-fixated about something, as young children are wont to?

But then again, really, there is no pressure. No pressure at all. These kids are otherwise well-adjusted grown adults who know exactly who they are. Probably from the time they were toddlers. (What? You want evidence? This is getting really tiring. Give it a break, will you?) These are kids who are not immersed online, who do not gulp down narratives about “gender euphoria.” They are stable, rational human beings with a very clear idea of what the future holds.

All these well-meaning saints – these gender-affirming physicians – want is to give these kids a bright future: a future so bright that it will probably include that intense bright light these pitiable young men will see when they die decades earlier than their non-medicalized peers. Who are you parents to stand in their way?

==

This is quite a remarkable admission. If there are no metrics and the objectives are "nebulous," then that's the very definition of not-scientific, not-medical. How can this be "necessary," and even "life-saving" if it's also "nebulous"? God is both real and undetectable?

How can it be "settled science"?

You're letting people self-diagnose and self-prescribe in order to chase something nebulous? What the hell?

[confusedhostage]

Which dilemma (and its outcomes) made you the most emotional?

[sexynetra]

I haven’t slept in 2 days and this comment is my thirteenth reason I think

[penrose-quinn]

Okay I can't finish GL till my long break on December because work is demanding and I'm actually in a horrible place rn.

[polycrallc]

So, you’ve heard about clinical trials, but you’re not quite sure what they’re all about? At PolyCRA, we are passionate about the research clinical practice in Texas. We’ll help you get in the know.

[dermatology-cro]

[zerovapes]

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[fprepairs]

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[probablyasocialecologist]

The study itself is titled, “Long-Term Regret and Satisfaction With Decision Following Gender-Affirming Mastectomy,” and sought to study the rate of regret and satisfaction after 2 years or more following gender affirming top surgery. The study’s results were stunning - in 139 surgery patients, the median regret score was 0/100 and the median satisfaction score was 5/5 with similar means as well. In other words… regret was virtually nonexistent in the study among post-op transgender people. In fact, the regret was so low that many statistical techniques would not even work due to the uniformity of the numbers: In this cross-sectional survey study of participants who underwent gender-affirming mastectomy 2.0 to 23.6 years ago, respondents had a high level of satisfaction with their decision and low rates of decisional regret. The median Satisfaction With Decision score was 5 on a 5-point scale, and the median decisional regret score was 0 on a 100-point scale. This extremely low level of regret and dissatisfaction and lack of variance in scores impeded the ability to determine meaningful associations among these results, clinical outcomes, and demographic information. The numbers are in line with many other studies on satisfaction among transgender people. Detransition rates, for instance, have been pegged at somewhere between 1-3%, with transgender youth seeing very low detransition rates. Surgery regret is in line with at least 27 other studies that show a pooled regret rate of around 1% - compare this to regret rates from things like knee surgery, which can be as high as 30%. Gender affirming care appears to be extremely well tolerated with very low instances of regret when compared to other medically necessary care.

[...]

The intense conservative backlash, to the point of disputing reputable scientific journals, likely stems from the fact that reduced regret rates weaken a central narrative these figures have championed in legal and legislative spaces. Over the past three years, anti-trans entities have showcased political detransitioners, reminiscent of the ex-gay campaigns from the 1990s and 2000s, to argue that regrets over gender transition and detransition are widespread. Some have even asserted detransition rates of up to 80%, a claim that has been broadly debunked. Yet, research consistently struggles to find substantial evidence supporting this narrative. The rarity of detransition and regret is underscored by Florida's inability to enlist a single resident to bear witness against a lawsuit challenging the state's ban on gender-affirming care.

[headspace-hotel]

I forget why, but I was on the Wikipedia page for polycystic ovarian syndrome, and I started researching hirsutism in women, and I learned the following things in this order:

there's a diagnostic criteria used to evaluate how hairy a woman is

This is important because being too hairy is a diagnostic criteria of most disorders that cause hyperandrogenism

Disorders that cause hyperandrogenism can be diagnosed by...measuring how hairy you are (this is the main and most important diagnostic criterion for PCOS)

Disorders that cause hyperandrogenism are important because they are correlated with obesity, infertility, and...being too hairy?

I think to myself, wait, what is a normal range for testosterone in women? I find this article...which set reference ranges for "normal" testosterone levels in women...EXCLUDING WOMEN WITH PCOS?

Quote: "Polycystic ovary syndrome (PCOS) is another notable condition in genetic (XX) females, which is characterized by excessive ovarian production of androgens. This condition is included for comparison with DSD, as the affected females with PCOS are genetic and phenotypic females. The elevated levels of testosterone in these females can lead to hyperandrogenism, a clinical disorder characterized variably by hirsutism, acne, male-pattern balding, metabolic disturbances, impaired ovulation and infertility. PCOS is a common condition, affecting 7%-10% of premenopausal women."

So: the study claims to demonstrate a clear distinction between the normal range of hormone levels in "Healthy" men and "healthy" women...with "healthy" being defined in the study as...having hormones within the "normal" range.......................

So I researched what the clinically established "normal" range for testosterone in women is

THERE ISN'T ONE????

Quote from the above article: "Several different approaches have been used to define endocrine disorders. The statistical approach establishes the lower and the upper limits of hormone concentrations solely on the basis of the statistical distribution of hormone levels in a healthy reference population. As an illustration, hypo- and hypercalcemia have been defined on the basis of the statistical distribution of serum calcium concentrations. Using this approach, androgen deficiency could be defined as the occurrence of serum testosterone levels that are below the 97.5th percentile of testosterone levels in healthy population of young men. A second approach is to use a threshold hormone concentration below or above which there is high risk of developing adverse health outcomes. This approach has been used to define osteoporosis and hypercholesterolemia. However, we do not know with certainty the thresholds of testosterone levels which are associated with adverse health outcomes."

What the fuck?

What the fuck?

It's batshit crazy to make a diagnostic criteria for medical disorders by placing arbitrary cutoffs within 2-5% of either end of a statistical distribution. What the actual fuck?

"The results came back, you have Statistical Outlier Disease." "What treatments are available?" "Well, first, we recommend dietary change. You should probably stop eating so many spiders."

Another article which attempted to do this

Quote: "Subjects with signs of hirsutism or with a personal history of diabetes or hypertension, or a family history of polycystic ovarian syndrome (PCOS) were excluded."

"We're going to figure out the typical range of testosterone levels that occur in women! First, we're going to exclude all the women that are too hairy from the study. I am very good at science."

Anyway I got off topic but there are apparently race-specific diagnostic tools for "hirsutism." That's kinda weird on its own but when I looked more into this in relation to race I found this article that straight-up uses the term "mongoloid"

[envil22100]

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