Science regarding transexualism

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#36
Medical transition & biological sex
There are many ways to arbitrarily divide humans into 2 sexes but what actually make sense is to look at the body itself.
https://vintologi.com/threads/about-the-gender-binary.846/

Reproductive sex
Humans can produce sperm nand eggs to reproduce. As far as i know there is no case of a human being able to produce both or transition from producing one type of gamete into producing the other.

This is relevant when it comes to partner selection since both sperm and egg are required for successful fertilization.
Unfortunately HRT will over time prevent your body from producing sperm without you getting the ability to produce eggs in return, this does change your reproductive sex from male to infertile unless you find away around in such as by banking sperm.

One of the advantages with cis + trans female relationships is the ability for them to have biological children together, two cis lesbians currently do not have that option.

Breastfeeding
HRT will give you fully functional female breasts

https://www.reddit.com/r/transmaxxing/comments/j4gf1h/breastfeeding/

Appearance
HRT alone can give you a body that looks like that of a female except for genitals (you would still need surgery for that) if it's started early enough and you have genetics for it, in other cases a female appearance is obtained after surgery.
With a female appearance you will function in society socially mostly like a female, early social transition result in early female socialization which will make it easier to fit in with cis females.

The brain
Trans females have brains somewhere between the male and female (average) prior to HRT and after male puberty.
Trans females in general (prior to HRT) https://www.ncbi.nlm.nih.gov/pubmed/25720349
Trans female attracted to females (prior to HRT) https://sci-hub.se/http://dx.doi.org/10.1093/cercor/bhr032

The study (picture and link above) is a bit strange since they have an abstract that doesn't fit with their actual results. The sample size is also smaller than ideal making the results a bit unreliable.

HRT will of course have a powerful feminizing effect on the brain changing it towards female proportions https://www.researchgate.net/public...e_and_estrogen_on_adult_human_brain_structure unfortunatily that study used "Cyproterone Acarate" at 10 times the appropiate dosage which may have skewed the results.

Sexuality
HRT will affect your penis so it will no longer be the same as a male penis

https://www.reddit.com/r/transmaxxing/comments/e438lk/how_a_girldick_differ_from_a_male_penis/

I will try to find some good studies regarding this but based on what trans females have written about this it does seem like a change in sexual function (multiple full body orgasms, less visually focused, etc) is to be expected from HRT. Some people have also resorted a change of sexuality resulting in them becoming more interested in sex with men.

https://www.youtube.com/watch?v=sLiLBLD1Ynk

Cis females like trans females often enjoy things like revealing clothing, this is not to attract male attention, it's for themselves.

https://digitalscholarship.unlv.edu/cgi/viewcontent.cgi?article=3350&context=thesesdissertations

https://vintologi.com/threads/surveys-by-me.899/#post-5108

https://www.mirror.co.uk/3am/celebr...ashian-discusses-autosexuality-being-23225442

This can unfortunately get out of control in individuals who are not yet on HRT due to the resulting powerful sex-drive. You will still likely enjoy having a beautiful female body on HRT but it will be more like comfort and less of a sexual thing.
 

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#37
Yes some people are incel prior to transitioning
But i have not seen any stats showing that incels (for any definition of the "incel") are more likely to transition. Sexually unsuccessful males being less likely to transition make sense since they have more to lose, if you have a wife and want (more) children you will be very likely to delay transition even if you suffer from severe body dysphoria.

I have for fun encouraged some cis incels to transition but almost universally they are very much against that, most people in incel spaces are transphobes it seems.

Makes we wounder if people with problematic views will be more likely to drop them if they start on estrogen, people associate estrogen with being a nice/submissive individual but i am not sure if that's really true. I have been pushing for a Randomized Controlled Trial on this so we can find out.
 

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#38
Are men treated better than women? A trans man's point of view.
The following story was written by an FtM individual thinking transitioning to male was a good idea:

I've always thought that sexism, be is misogyny or misandry, can best be understood through experience. I am transsexual which means that I have experienced both being perceived as a woman and a man by society. So here's my experience and the reason I'm an MRA.

Background
I'm ftm transsexual. I spent the first 18 years of my life as a girl/woman and these last 2 as a man.

The good aspect of being a woman
Most people treated me very well. Those who didn't mistreated me because I'm autistic, not because I was a girl. I was never made to feel bad whenever I asked for help, people were happy to help me. Guys were happy to help with emotional issues particularly. Whenever I was having a bad day, they were happy to talk with me and keep me company. Overall, my mental health and well-being was taken more seriously. Additionally, it was easier to make friends. From what I can tell, others just felt more comfortable around me and felt safer sharing their problems with me.

The bad aspects of being a woman
I honestly can't think of anything. I've never experienced misogyny. I wasn't exactly attractive so I never got any sexual/romantic attention from guys be that positive or negative. The only thing I can think of was that a few girls at school were mean to me but again that's because of my mental disability, not because I was a girl. That and they were just shitty friends in general. I think this too would have been worse if I was attractive as I would have been seen as competition.

My bad experiences as a man
Socially, nothing really improved. I hear some people say that men are taken more seriously with certain things, especially when it comes to the workplace, but at my work men and women are treated the same. I feel more confident now, but that's because my gender dysphoria has lessoned considerably.

I don't feel comfortable asking for help anymore, especially when it comes to mental health. Whenever I do people are less enthusiastic about helping me. I've also seen a decrease in the quality of help I receive. I also find that it's harder to talk to people. It's like they just aren't as comfortable around me and don't trust me as much. It's hard to make friends compared to a few years ago. People overall treat me neutrally and sometimes slightly negatively. I've noticed strangers are more wary around me. Nothing like pulling their kids away or clutching their purses harder, but they tend to stay at a farther distance and don't make eye contact with me as often (not that I mind, but it is something I've noticed).

Final thoughts
It was a jarring experience. I went from being treated like how a person should be treated (trusted, listened to, etc.) to being treated, well, like a man. In my experience I have been treated far worse as a man. I by no means regret transitioning in any way, but I really wish someone would have prepared me for this.

Keep in mind, these experiences are my own. For others it can be much different. Additionally, I've only been a man for two years now so maybe that "male privilege" I keep hearing about will kick in sometime soon (that's a joke of course). That or I'll experience more and worse misandry, especially as I get further along in my transition and become even more masculine.
 

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#39
Typical detrans story
I have looked at too many detrans stories and i do see a rather disturbing pattern.

She is born female.

She suffered from severe dysphoria.

She started transitioning to alleviate the dysphoria, it worked.

Then she regrets it and feels like this was the wrong way to deal with the dysphoria.

Of course this is just my impression but here is some actual studies on it
https://vintologi.com/posts/4444

That tells us that social factors are most prominent in causing people to have regrets.

A lot of social problems men have are swept under the rug since it goes against feminist dogma (feminists claim that females have it worse & we should have equality). People transitioning from female to male often find out being male isn't what they thought it would be and then it can be too late to really go back.

Male privilege does exist but it's reserved for elite males(people like Donald Trump). Being a typical male really isn't that great, being a male at the bottom of society is really bad.

This is less of a problem among MtF individuals since issues females have are talked about more openly and thus people that transition from male to female know what to expect.

I would like to make clear while i do think females are being treated overall better in western societies it's still not that great, i do not think we should have equality as a goal.

What we are not seeing
I am not really seeing stories like "i transitioned to get a transbian girlfriend, i regret it" or "i detransitioned due to reverse body dysphoria".
I have also not heard many FtM individuals say they transitioned because they felt like males were treated better by society. Most probably know transitioning will come with difficulties and do it anyway due to dysphoria, some still regret it obviously.
 

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#40
Refuting: "cis females cannot be AGP since they are more androphilic"
The worst issue is assuming cis females being more androphilic than trans females would imply that cis females are never autogynephilic, that is obviously false and illustrates the mental gymnastic the cult-followers of R. B. engage in.

What it would mean is that trans females as a group do not have exactly the same sexuality as cis females which really wouldn't be surprising, this however has not yet been properly shown as far as i know.

It would not refute the notion "trans females have female brains" since you could still explain the difference in sexuality by trans females having brains similar to that of lesbian cis females more often than straight cis females.

But the notion of trans females as a group having female brains prior to HRT has already been refuted https://www.ncbi.nlm.nih.gov/pubmed/25720349

HRT will however have a significant feminizing effect on the brain researchgate.net/publication/46671034_Changing_your_sex_changes_your_brain_Influences_of_testosterone_and_estrogen_on_adult_human_brain_structure

The study above did however involve the usage of Cyproterone Acarate at at least 10 times the ideal dosage.
 

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#41
Dating as androphilic FtM
You will not be a total incel but your dating options will still not be great, not even close.

u/HomersDonutMan wrote:

Trans people overestimate the willingness of cis people to date/be intimate with trans people.
I will say that this is almost exclusively talking about FtMs because I have no idea how everything works with trans women and that's not my territory. However, I see a lot of FTMs say that there are many cis people that will date and be intimate with trans people when that's simply not true. There are a shit ton of fetishists that don't see us as male and just want to get off or feed into their own sexual/romantic fantasies and that's different than a healthy relationship.

At least from the homosexual point of view, most gay cis men aren't into trans men even post op from what I've seen. The ones that do are bottoms that mysteriously will top trans men (even after being told by the trans guy that they are not a bottom) or creepy dudes that have basically been blocked by most of the local community.

Maybe it's just me, but I've found trans people who have been around longer and been transitioning longer attest to this too.
Edit: Most of the people insulting me have said previously they would never date another trans person which further proves my point, but ok.
 

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#42
Intersex study: gender identity is 40% environmental
The intersex children with Cloacal exstrophy identified as female 40% of the time when they were raised as female. They developed a male gender identity 100% of the time where they were raised as male

1651096625432.png


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421518/

All but two whose parents disclosed their birth status chose a male name within a day of parental announcement; one of these two was only 2 years old (and was reassigned male by the parents),
 

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#43
Article: 5 of 5 people born with micropenis identified as female when raised as such
This is an interesting forced transition experiment and it did not go bad for the reason many people would assume. The issue was that they were subjected to very questionable genital surgeries causing 4 of 5 to be dissatisfied with their neo-vagina.

https://www.webmd.com/baby/news/20020125/baby-boys-with-micropenis-happier-as-males

This does still refute the notion of gender identity being innate.

Due to the genitalia not looking like a normal male baby, infants born with micropenis are sometimes raised as females. This involves reconstructive surgery to form a vagina and hormone treatments.

Although all of the 13 men and 5 women born with micropenis who participated in the study identified closely with their gender, only 20% of the babies raised as females were satisfied with their genitalia, compared to 50% of the males.

"Patients reared male considered themselves to be masculine, and those raised female considered themselves to be feminine," said study author Amy Wisniewski, PhD, of the Johns Hopkins Children's Center, in a news release. "Our recommendation that babies be raised male is based not on problems with gender identity but on the difficulties associated with the surgical construction of a vagina and subsequent hormone treatment."

The actual study
Someone was nice enough to link me this and it turns out that the individuals with micropenis had partial androgen insensitivity (intersex condition)

web.archive.org/web/20060909211109id_/http://facstaff.l3.drake.edu/abwisniewski/papers/13.pdf

While 4 of 5 had doubt regarding their gender they were all satisfied with their female role:

1649170349897.png


The ones raised as male largely viewed themselves as masculine while the ones raised as female largely viewed themselves as feminine:

1649160806530.png


Alternative: raising them as girls while not subjecting them to surgery
This is an obvious alternative that hasn't been tried. Instead of trying to force people into some sex-binary we need to look at what medical interventions people actually benefit from.

We shouldn't subject children to surgeries that are not medically necessary.

It's very difficult to construct a decent neo-vagina even in the case of adults who started HRT after puberty (it's very hard to find any good results) and of course the situation is much worse for children, this simply shouldn't be done. There is also some ethnical issues with regard to the lack of consent.
 

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#44
Intersex study: 7 of 9 who was raised as female identified as such
All patients raised as male had a normal male gender identity, displayed masculine gender role behaviour in childhood, and had a heterosexual sexual orientation. Seven of the 10 male patients had experienced heterosexual intercourse. Two out of nine women did not identify with the female gender. The majority had masculine gender role interests in childhood. The female patients were significantly less likely to have experienced sexual activity with a partner than the male patients.

https://www.sciencedirect.com/science/article/abs/pii/S1083318807001660
 

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#45
5 of 16 children with Cloacal Exstrophy identified as female when raised as such
For 3 it was unclear what gender identity they had (1 refused to discuss) and 8 identified as male.

https://www.nejm.org/doi/full/10.1056/nejmoa022236

They were all fairly masculine in terms of their behaviour

1649351125765.png


It is worth noting that the study did not regard Cloacal Exstrophy as an intersex condition. You can expect a similar result if you transition random males early.
 

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#46
Gender Identity Outcome in Female-Raised 46,XY Persons with Penile Agenesis, Cloacal Exstrophy of the Bladder, or Penile Ablation

https://sci-hub.hkvisa.net/10.1007/s10508-005-4342-9

Raised as female (penile Agenesis):
Penile_Agenesis.png


Raised as male (Penile Agenesis):

Penile_Agenesis_M.png


Raised as female (Cloacal or Bladder Extrophy):
Cloacal_Bladder_Extrophy.png


Raised as male (Cloacal or Bladder Extrophy):

Cloacal_Bladder_Extrophy_M.png


Raised as female (after traumatic loss of penis):

Lost_penis.png
 

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#47
Unwillingness to reproduce
Something i did notice anecdotally was that most trans people did not desire to have biological children. I did recommend to people that they bank sperm prior to transitioning in the transmaxxing manifesto but most just ignored that advice.

Currently only around 5% preserve fertility (4 AMAB, 1 AFAB).
In our sample of 105 transgender adolescents, a total of 13 (seven transgender men and six transgender women) between the age of 14.2 and 20.6 years were seen in formal consultation for FP before initiating hormones. Of these adolescents, four completed sperm cryopreservation and one completed oocyte cryopreservation.
https://www.jahonline.org/article/S1054-139X(17)30065-4/fulltext

During this period, 28 birth-assigned males were started on estrogen and 77 birth-assigned
females were started on testosterone for medical transition.
https://sci-hub.hkvisa.net/10.1016/j.jadohealth.2017.01.022

So 1/7 MtF and 1/77 FtM pursued fertility preservation prior to transitioning.

The rate was much higher in the following study:

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2764075

Among 49 individuals who were AFAB, none attempted FP, with 16 stating no reason; among the other 33, the main reason was a plan to reassess fertility options when older (Figure). Conversely, 33 of 53 individuals who were AMAB (62%) pursued FP (Table), of whom 22 successfully froze sperm after providing a masturbatory sample (mean [SD] age, 15.6 [1.4] years). The remaining 11 underwent testicular biopsy (which is well suited to those in early puberty), and this group was significantly younger (mean [SD] age, 13.9 [1.5] years; P = .003). Five of these 11 individuals were found to have mature sperm, while the other 6 had germ cells only, all of which were cryopreserved.

To understand why some patients chose not to pursue fertility preservation, we examined reasons recorded in the medical record. Of the 49 young people assigned female at birth (AFAB) who declined FP, 16 gave no reason. The remaining 33 gave a variety of responses, the proportions of which are displayed. Of the 19 young people assigned male at birth (AMAB) who declined FP, 9 gave no reason.
fertility-preservation.png
 

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#48
Is low dose E to blame for disappointing results in some studies?
In this analysis MtF HRT was found to reduce distress but results are not as great as i expected so we need to figure out what went wrong here. Feel free to look at this publication and see if you find any issues with it.

1655549843845.png


https://figshare.com/articles/journ...ental_health_outcomes_for_either_sex/19018868

One issue with prescribed MtF HRT is that typically it will be aggressive testosterone suppression combined with low estradiol dosage resulting in the body not getting the sex hormones it needs.

I suggest doing an RCT comparing estradiol monotherapy with low dose E + anti-androgen to see if the mental health outcomes is be better when no anti-androgen is used.

There is some weak evidence in favor of low starting dosage when it comes to estradiol (might be better for breast growth, etc) but if you are going to go that route you might be better off not suppressing testosterone accepting T level above the normal female range.

https://vintologi.com/threads/male-to-female.5/page-2#post-1808

Another potential reason is that estrogen will make you more emotional which is a problem if your are subjected to a lot of negative stuff in life.

Issues with the study
Unfortunatily this is just an observational trials, it does attempt to control for confounding factors but even if the study author does their best doing so it will still be inferior to a decent randomized controlled trial.

The study does for example adjuist for "relationship status" and "harrassment at school" but these are things that may be affected by HRT itself (such as allowing trans females to pass so they don't get harassed) then if you 'adjust' for that you are removing a benefit from HRT. Similarly if FtM transition causes people to become incel adjusting for relationship status will remove that affect making it appear better than it really is.

One issue with "suicide attempt requiring hospitalization" data is that the word "hospitalization" is often used as euphomism for forced psychiatric treatments (not real healthcare) and this will depend on arbitrary judgement by psychiatrists.

People who pursue HRT will typically have more contact with therapists increasing the risk for psychiatric abuse.

If more dysphoric AMAB people are more likely to get HRT prescribed that will make the group on HRT look worse for that reason (this wasn't controlled for AFAIK). This is of course not something we should merely assume without actually doing the study, we should not give medical treatments the benefit of the doubt.
 

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#49
Formal study on tavistock data
The study confirm that suicidal trans people are more likely to get access to medical treatments.

https://link.springer.com/article/10.1007/s10508-022-02287-7

To calculate the annual suicide rate, the total number of years spent by patients under the clinic’s care is estimated at about 30,000. This yields an annual suicide rate of 13 per 100,000 (95% confidence interval: 4–34). Compared to the United Kingdom population of similar age and sexual composition, the suicide rate for patients at the GIDS was 5.5 times higher.
This is for people seeking care in general and hasn't been adjusted for any confounding factors (such as mental illness diagnosis prior to seeking care).

Respondents who report suicide attempts are not necessarily indicating an intent to die. One survey of the American population found that almost half the respondents who reported attempting suicide subsequently stated that their action was a cry for help and not intended to be fatal (Nock & Kessler, 2006). In two small samples of non-heterosexual youth, half the respondents who initially reported attempting suicide subsequently clarified that they went no further than imagining or planning it; for the remainder who did actually attempt suicide, their actions were usually not life-threatening.
So reports of suicide attempts should be interpreted largely as cries for help rather than people actually wanting to die.

The suicide rate of the GIDS patients is not necessarily indicative of the rate among all adolescents who identify as transgender. On the one hand, individuals with more serious problems (and their families) would be particularly motivated to seek referral and more likely to obtain it, and so the clinical subset would be more prone to suicide. One study suggests that a child who frequently attempted suicide was more readily referred to the GIDS (Carlile et al., 2021). On the other hand, young people facing hostility from their families would be less able to seek referral, and this hostility could make them especially vulnerable to suicide.
Generally when it comes to seeking care like that it will of course be weighted towards people who are the most unwell.

The study linked did talk about the numerous issues trans children are facing

https://www.tandfonline.com/doi/abs/10.1080/26895269.2020.1870188?journalCode=wijt21
 

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#50
Transmaxxing survey 52.5% identified as incel at some point prior to transitioning
The fact that the figure for in the same community was only 18.75% for people who didn't transition in the same space is a good indication that failed males are more prone to transitioning such as due to having less to lose.

1674034697744.png


https://www.reddit.com/r/transmaxxi...you_at_some_point_identify_as_incel_prior_to/

https://archive.ph/NJZPs

https://ghostarchive.org/archive/wsSEI?wr=true

https://ghostarchive.org/archive/8Gqiw?wr=true

It doesn't really make sense to transition to female if you already live a great life as a male. It makes much more sense to transition if your current life is bad and it seems like transition would improve your life. These people may believe "i failed in life because i was born in the wrong body" and you are probably better off believing that in terms of your own mental well-being. Masculine men do indeed do better in life

eviemagazine.com/post/study-shows-very-masculine-men-are-more-likely-to-be-happy-and-married

It is worth noting that the transmaxxing community is focused on transition for personal gain instead of focusing on gender identity.
 

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#51
Psychosocial Functioning in Transgender Youth after 2 Years of Hormones
  • Diane Chen, Ph.D.,
  • Johnny Berona, Ph.D.,
  • Yee-Ming Chan, M.D., Ph.D.,
  • Diane Ehrensaft, Ph.D.,
  • Robert Garofalo, M.D., M.P.H.,
  • Marco A. Hidalgo, Ph.D.,
  • Stephen M. Rosenthal, M.D.,
  • Amy C. Tishelman, Ph.D.,
  • and Johanna Olson-Kennedy, M.D.
Background
Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol).

Methods
We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory–II, the Revised Children’s Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome.

Results
A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants.

Conclusions
In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.)

Transgender and nonbinary youth comprise 2 to 9% of high-school–aged persons in the United States.1-3 Many transgender and nonbinary youth have gender dysphoria, the persistent distress arising from incongruence between gender identity and external phenotype. Increasingly, transgender and nonbinary youth receive medical care to alleviate gender dysphoria, including gonadotropin-releasing hormone (GnRH) agonists to suppress gender-incongruent puberty and gender-affirming hormones (GAH; testosterone or estradiol) to foster gender-congruent secondary sex characteristics. An important goal of such treatment is to attenuate gender dysphoria by increasing appearance congruence — that is, the degree to which youth experience alignment between their gender and their physical appearance.

The available prospective research indicates that gender-affirming medical care is associated with improvements in psychosocial functioning.4-9 Previously published studies with modest sample sizes5,6,9 have examined outcomes for relatively short follow-up periods (approximately 1 year on average),5,6,9 focused exclusively on outcomes of GnRH agonists,7,8 or examined outcomes for mixed samples of youth initiating GnRH agonists or GAH,4,6,9 despite evidence that such cohorts have distinct psychosocial profiles.10 Evidence has been lacking from longitudinal studies that explore potential mechanisms by which gender-affirming medical care affects gender dysphoria and subsequent well-being.

We characterized the longitudinal course of psychosocial functioning over a period of 2 years after GAH initiation in a prospective cohort of more than 300 transgender and nonbinary young people in the United States. We hypothesized that appearance congruence, positive affect, and life satisfaction would increase and that depression and anxiety symptoms would decrease. We also hypothesized that improvements would be secondary to treatment for gender dysphoria, such that increasing appearance congruence would be associated with concurrent improvements in psychosocial outcomes. We also explored the potential moderating effects of demographic and clinical characteristics, including age, designated sex at birth, racial and ethnic identity, and the initiation of GAH in early as compared with later stages of puberty.

Methods
Study Design and Participant Recruitment
Participants were recruited from gender clinics at the Ann and Robert H. Lurie Children’s Hospital of Chicago, UCSF Benioff Children’s Hospitals, Boston Children’s Hospital, and Children’s Hospital Los Angeles from July 2016 through June 2019 for the Trans Youth Care–United States (TYCUS) Study,11 a prospective, observational study evaluating the physical and psychosocial outcomes of medical treatment for gender dysphoria in two distinct cohorts of transgender and nonbinary youth — those initiating GnRH agonists and those initiating GAH as part of their clinical care. All participating clinics employ a multidisciplinary team that includes medical and mental health providers and that collaboratively determines whether gender dysphoria is present and whether gender-affirming medical care is appropriate. For minors, parental consent is required to initiate medical treatment. Publications by individual study teams provide details on site-specific approaches to care.12-15

Study visits occurred at baseline and at 6, 12, 18, and 24 months after treatment initiation. Details on study procedures have been published previously,11 and the protocol is available with the full text of this article at NEJM.org. The present analyses focus on the GAH cohort; outcomes for the cohort initiating GnRH agonists are being analyzed separately, given differences in baseline functioning between the two cohorts10 and distinct outcomes of GnRH agonists8 as compared with GAH treatment.4 Participants provided written informed consent or assent; parents provided permission for minors to participate. Procedures were approved by the institutional review board at each study site.

The first and second authors analyzed the data and wrote the initial draft of the manuscript. All the authors critically reviewed the manuscript. The authors vouch for the accuracy and completeness of the data and for the fidelity of the study to the protocol. There were no agreements regarding confidentiality of the data among the sponsor (Eunice Kennedy Shriver National Institute of Child Health and Human Development), the authors, and the participating institutions. The sponsor had no role in the design of the study; the collection, analysis, or interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication.

Measures
Participants reported age, racial and ethnic identity, gender identity, and designated sex at birth (details are provided in the Supplementary Appendix, available at NEJM.org). A small subgroup had been treated with GnRH agonists in early puberty (Tanner stage 2 or 3) (20 participants) or had a relatively late age at onset of endogenous puberty, such that they began receiving GAH in Tanner stage 3 (at 13 to 15 years of age) even without previous treatment with GnRH agonists (4 participants). These 24 participants comprise a subcohort in that they did not undergo extensive gender-incongruent puberty. Participants with a history of GnRH agonist treatment that was initiated in Tanner stage 4 (5 participants) were not included in this subcohort, because their experience of substantial gender-incongruent puberty is more similar to that of youth initiating GAH in Tanner stage 4 or 5.

With respect to longitudinal outcomes, participants completed the Transgender Congruence Scale,16 the Beck Depression Inventory–II,17 the Revised Children’s Manifest Anxiety Scale (Second Edition),18 and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery19 at each study visit. Scoring information and sample items from each scale are provided in the Supplementary Appendix. Higher scores on these measures reflect greater appearance congruence, depression, anxiety, positive affect, and life satisfaction, respectively.

Statistical Analysis
Trajectories of psychosocial functioning were examined with the use of repeated-measures multivariate analysis of variance and mixed-effects models. Multivariate analysis of variance provided a preliminary omnibus test for significant within-person change over time. Owing to listwise deletion, 150 participants were excluded from the multivariate analysis of variance (the analysis involved 141 participants). Mixed-effects modeling was therefore selected owing to greater flexibility in accommodating missing data and nonnormal distributions and examining parallel processes. Specifically, we used latent growth curve modeling, which uses a structural equation modeling framework to examine changes in mean scores over time.20 Repeated measures are treated as indicators of latent factors: an intercept factor (estimates of initial levels) and a slope factor (rate of change). Intercept and slope factors can be regressed on covariates in adjusted models to explore moderation effects. In addition, growth curves for two different outcomes can be combined to examine how intercepts and slopes of those constructs correlate with each other. Data were Winsorized at the 95th percentile to reduce the influence of outliers.

Analyses involving latent growth curve modeling proceeded in three steps. First, we modeled trajectories of appearance congruence and psychosocial outcomes (i.e., effects of time only). Second, we adjusted models to estimate the effects of covariates on baseline scores and rates of change over time. Third, because changes in appearance congruence and psychosocial outcomes occur as parallel, simultaneous processes during GAH treatment, we examined how initial levels and rates of change in appearance congruence correlated with those of each psychosocial outcome. Standardized β levels were used as indicators of effect sizes for longitudinal models using conventional ranges (small, 0.20; medium, 0.50; and large, 0.80). Our conceptual model is shown in Figure S1 in the Supplementary Appendix. All statistical analyses were conducted with the use of SPSS software, version 27, and Mplus software, version 8.8.

Results
Analytic Sample
There were a total of 6114 observations from 315 participants, who were assessed up to five times over a period of 2 years (data were available for 81% of all possible observations). Most participants (238 [75.6%]) completed either four study visits (76 participants) or five visits (162 participants). Tables S1 and S2 show the number of completed visits by time point and data coverage for key variables. The analytic sample for longitudinal models included 291 participants with follow-up data on primary outcome variables (Fig. S2). The analytic sample did not differ substantially from the overall sample with respect to age, designated sex at birth, racial and ethnic identity, initiation of GAH in early puberty, or baseline scores on psychosocial measures (Table S3).
Sample Characteristics
Table 1. Demographic and Clinical Characteristics of the Participants.Table 2. Adverse Events.
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We enrolled 315 eligible participants 12 to 20 years of age (mean [±SD], 16±1.9 years) (Table 1). Most were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum; 60.3%), designated female at birth (64.8%), and non-Latinx or non-Latine White (58.7%). Transmasculine, non-Latinx or non-Latine White, and multiracial participants were overrepresented and nonbinary and Black participants were underrepresented as compared with the study sample in the Williams Institute Executive Report21 (Table S4); however, the study sample was representative of transgender and nonbinary youth presenting to pediatric subspecialty gender programs22 and generalizable to this population. Two participants died by suicide during the study (one after 6 months of follow-up and the other after 12 months of follow-up), and 6 participants withdrew from the study. For these eight participants, data that had been collected before death or study withdrawal were included in the analyses. Data on adverse events are provided in Table 2.
1674166033019.png


Appearance Congruence and Psychosocial Outcomes over Time
Table S5 depicts mean scores for appearance congruence, depression, anxiety, positive affect, and life satisfaction at baseline and 24 months. Results for multivariate analysis of variance indicated that there were significant within-participant changes over time for all psychosocial outcomes in hypothesized directions (Wilk’s lambda, 0.32; F statistic with 20 and 122 degrees of freedom; 12.86; P<0.001). Specifically, scores for appearance congruence, positive affect, and life satisfaction increased significantly, and scores for depression and anxiety decreased significantly.

Table 3. Variable Estimates for Individual Latent Growth Curve Models of 2-Year Outcomes.
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Means and variances of the variables for latent growth curve modeling, with estimated baseline levels and change over time for both time-only and adjusted models, are provided in Table 3. Scores for appearance congruence increased (annual increase on a 5-point scale, 0.48 points; 95% confidence interval [CI], 0.42 to 0.54; standardized β=1.47), as did T scores for positive affect (annual increase on a 100-point scale, 0.80 points; 95% CI, 0.08 to 1.54; β=0.19) and life satisfaction (annual increase on a 100-point scale, 2.32 points; 95% CI, 1.64 to 3.00; β=0.52). We observed decreased scores for depression (annual change on a 63-point scale, −1.27 points; 95% CI, −1.98 to −0.57; standardized β=−0.29) and decreased T scores for anxiety (annual change on a 100-point scale, −1.46 points; 95% CI, −2.13 to −0.79; β=−0.35) over a period of 2 years of GAH treatment.

Unadjusted models can be interpreted on their original scale. For instance, depression scores range from 0 to 63 (ranges of severity, minimal, 0 to 13; mild, 14 to 19; moderate, 20 to 28; and severe, 29 to 63). The model had an intercept (baseline mean) of 15.46 and estimated slope (change per year) of −1.27. Thus, on average, depression started in the mild range and decreased to the subclinical level by 24 months. Table S6 shows the percentages of youth scoring in the clinical range for depression and anxiety at each time point. Of 27 participants with depression scores in the severe range at baseline, 18 (67%) reported a depression score in the minimal or moderate ranges at 24 months. Similarly, 21 of 33 participants (64%) with depression scores in the moderate range at baseline reported a depression score in the minimal or moderate ranges at 24 months (chi-square statistic with 9 degrees of freedom, 49.85; P<0.001). With respect to anxiety, 47 of 122 participants (38.5%) with baseline scores in the clinical range (T scores, >60) were in the nonclinical range at 24 months (chi-square statistic with 1 degree of freedom, 22.05; P<0.001).

Associations between Appearance Congruence and Psychosocial Outcomes
Figure 1. Appearance Congruence and Depression, Anxiety, Positive Affect, and Life Satisfaction.
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Figure 1 depicts parallel processes between appearance congruence and each psychosocial outcome as analyzed by means of latent growth curve modeling. As described above, we used linear latent growth curve modeling to estimate baseline scores (intercepts) and linear rates of change (slopes) of each outcome (see Table 3 for details of each model). In parallel-process models, we examined how the components for latent growth curve modeling for appearance congruence related to those for scores for depression (Figure 1A) and T scores for anxiety (Figure 1B), positive affect (Figure 1C), and life satisfaction (Figure 1D). Higher appearance congruence at baseline was associated with lower baseline scores for depression (r=−0.60) and T scores for anxiety (r=−0.40), and increases in appearance congruence were associated with decreases in scores for depression (r=−0.68) and T scores for anxiety (r=−0.52) over time. In addition, higher appearance congruence at baseline was associated with higher baseline T scores for positive affect (r=0.46) and life satisfaction (r=0.72), and increases in appearance congruence were associated with increases in T scores for positive affect (r=0.74) and life satisfaction (r=0.84) over time.

Moderating Effects of Demographic and Clinical Covariates
Table 3 shows the effects of covariates on scores for appearance congruence and depression and T scores for anxiety, positive affect, and life satisfaction. Age was not associated with any outcomes at baseline or over time.

Designated Sex at Birth
Depression and anxiety scores decreased among youth designated female at birth but not among those designated male at birth. Similarly, T scores for life satisfaction increased among youth designated female at birth but not among those designated male at birth (Fig. S3). Designated sex at birth was not associated with any other outcomes at baseline or over time.

Effects of Racial and Ethnic Identity
At baseline, youth of color had higher scores for appearance congruence, lower scores for depression, and higher scores for positive affect than non-Latinx or non-Latine White youth. With respect to change over time, non-Latinx or non-Latine White youth had greater decreases in depression scores than youth of color (Fig. S4). Racial and ethnic identity were not associated with any other outcomes at baseline or over time.

Initiation of GAH in Early Puberty
Figure 2. Psychosocial Outcomes during 2 Years of GAH.
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Youth who had initiated GAH in early puberty had higher scores for appearance congruence, positive affect, and life satisfaction at baseline and lower scores for depression and anxiety at baseline than those who had initiated GAH in later puberty. Tables S7, S8, and S9 provide more information regarding differences between youth initiating GAH in early puberty and those initiating GAH in late puberty. With respect to change over time, youth initiating GAH in later puberty had greater improvements in appearance congruence than those initiating GAH in early puberty (Figure 2).

Discussion
Understanding the effect of GAH on the psychosocial outcomes of transgender and nonbinary youth would appear crucial, given the documented mental health disparities observed in this population,10,15,23,24 particularly in the context of increasing politicization of gender-affirming medical care.25 In our U.S.-based cohort of transgender and nonbinary youth treated with GAH, we found decreases in depression and anxiety symptoms and increases in positive affect and life satisfaction as assessed through validated instruments. Our findings are consistent with those of other longitudinal studies involving transgender and nonbinary youth receiving GAH, which showed reductions in depression6,9 and anxiety6 and increases in overall well-being5 with small-to-moderate effects over a follow-up period of up to 1 year. We replicated these findings in a larger sample of racially and ethnically diverse transgender and nonbinary youth recruited from four geographically distinct regions in the United States and found sustained improvements over a period of 2 years.

Increasing appearance congruence is a primary goal of GAH, and we observed appearance congruence improve over 2 years of treatment. This was a moderate effect, and the strongest effect observed across our outcomes, consistent with the effect seen in research involving other samples, which has noted large effects of GAH on body image and small-to-moderate effects on mental health.6 Appearance congruence was also associated with each psychosocial outcome assessed at baseline and during the follow-up period, such that increases in appearance congruence were associated with decreases in depression and anxiety symptoms and increases in positive affect and life satisfaction. These findings suggest that appearance congruence is a candidate mechanism by which GAH influences psychosocial functioning.

The importance of appearance congruence for psychosocial well-being is further highlighted by the effect of avoiding gender-incongruent pubertal changes. Youth who had not undergone substantial gender-incongruent puberty had higher scores for appearance congruence, positive affect, and life satisfaction and lower scores for depression and anxiety at baseline than youth who had undergone substantial endogenous puberty. These observations align with other published reports that earlier access to gender-affirming medical care is associated with more positive psychosocial functioning.10,26 Alternatively, youth who first recognize their gender incongruence in adolescence may represent a distinct subgroup of transgender and nonbinary youth who have more psychosocial complexities than youth recognizing gender incongruence in childhood.27

The effects of GAH on some psychosocial outcomes varied on the basis of designated sex at birth. Depression and anxiety symptoms decreased significantly, and life satisfaction increased significantly, among youth designated female at birth but not among those designated male at birth. Given that some key estrogen-mediated phenotypic changes can take between 2 and 5 years to reach their maximum effect (e.g., breast growth),28 we speculate that a longer follow-up period may be necessary to see an effect on depression, anxiety, and life satisfaction. Furthermore, changes that are associated with an endogenous testosterone-mediated puberty (e.g., deeper voice) may be more pronounced and observable than those associated with an endogenous estrogen-mediated puberty. Thus, we hypothesize that observed differences in depression, anxiety, and life satisfaction among youth designated female at birth as compared with those designated male at birth may be related to differential experiences of gender minority stress, which could arise from differences in societal acceptance of transfeminine (i.e., persons designated male at birth who identity along the feminine spectrum) as compared with transmasculine persons. Indeed, gender minority stress is consistently associated with more negative mental health outcomes,29 and research suggests that transfeminine youth may experience more minority stress than transmasculine youth.30

Our study has certain limitations. Because participants were recruited from four urban pediatric gender centers, the findings may not be generalizable to youth without access to comprehensive interdisciplinary services or to transgender and nonbinary youth who are self-medicating with GAH. In addition, despite improvement across psychosocial outcomes on average, there was substantial variability around the mean trajectory of change. Some participants continued to report high levels of depression and anxiety and low positive affect and life satisfaction, despite the use of GAH. We plan to examine other factors that are known to contribute to psychosocial functioning among transgender and nonbinary youth and may not be affected by GAH, such as parental support,31,32 in this cohort. Finally, our study lacked a comparison group, which limits our ability to establish causality. However, the large effects in parallel-process models examining associations between improvements in appearance congruence and improvements in psychosocial outcomes provide support for the concept that GAH may affect psychosocial outcomes through increasing gender congruence.

Despite these limitations, our findings showed improvements in psychosocial functioning across 2 years of GAH treatment, which supports the use of GAH as effective treatment for transgender and nonbinary youth. We are now following this cohort to see whether gains in functioning are sustained over a longer follow-up period, and — given substantial variability in outcomes even after controlling for a number of factors — we hope to discover additional predictors of change to identify youth for whom GAH alone is not adequate to address mental health challenges. We intend to initiate further work with this cohort to focus on understanding reasons for discontinuing GAH among the small subgroup of youth who stopped medical treatment. Overall, our results provide evidence that GAH improved appearance congruence and psychosocial functioning in transgender and nonbinary youth.

Supported by a grant (R01 HD082554) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the participants, their families, their referring clinicians, and the many research staff for their contributions in conducting this study, and Norman Spack, one of the original principal investigators, for his contributions to the study.

Author Affiliations
From the Gender and Sex Development Program, Potocsnak Family Division of Adolescent and Young Adult Medicine (D.C., R.G.), and the Pritzker Department of Psychiatry and Behavioral Health (D.C.), Ann and Robert H. Lurie Children’s Hospital of Chicago, the Departments of Pediatrics (D.C., R.G.) and Psychiatry and Behavioral Sciences (D.C., J.B.), Northwestern University Feinberg School of Medicine, and the Institute for Sexual and Gender Minority Health and Wellbeing, Northwestern University (J.B.) — all in Chicago; the Division of Endocrinology, Department of Pediatrics, Boston Children’s Hospital (Y.-M.C.), and the Department of Pediatrics, Harvard Medical School (Y.-M.C.), Boston, and the Department of Psychology and Neuroscience, Boston College, Newton (A.C.T.) — all in Massachusetts; the Department of Pediatrics, Division of Pediatric Endocrinology (D.E., S.M.R.), and the Child and Adolescent Gender Center, Benioff Children’s Hospital (D.E., S.M.R.), University of California, San Francisco, San Francisco, and the Gender Health Program, UCLA Health (M.A.H.), and the Division of General Internal Medicine and Health Services Research, Medicine–Pediatrics Section, Department of Medicine, David Geffen School of Medicine (M.A.H.), University of California, Los Angeles, the Center for Transyouth Health and Development, Division of Adolescent and Young Adult Medicine, Children’s Hospital Los Angeles (J.O.-K.), and the Department of Pediatrics, Keck School of Medicine, University of Southern California (J.O.-K.), Los Angeles — all in California.

Dr. Chen can be contacted at dichen@luriechildrens.org or at the Ann and Robert H. Lurie Children’s Hospital of Chicago, Potocsnak Family Division of Adolescent and Young Adult Medicine, 225 E. Chicago Ave., Box 161B, Chicago, IL 60611.

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adolf512

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#52
The article above is largely useless. The sample-size was small and they mixed FtM, MtF and nonbinary. We also didn't see much of an improvement as people transitioned which should raise big red flags, something isn't right here.

Something we need to look into is if anti-androgens cause MtF transitioners emotional distress but no study has bothered comparing monotherapy with lower dose e together with testosterone blocker.

Still some people did use the bad article to advocate for allowing young females to transition to male:

Article
This week in the Journal, a much-awaited primary report from Chen et al.1 on 2 years of gender-affirming hormones (GAH) in transgender adolescents appears. The approach to adolescent transgender care with early treatment with puberty blockers, and GAH in youth from 16 years of age, originated in the Netherlands (“the Dutch model”) and became the dominant medical care model for transgender adolescents.2 Especially over the past decade, marked increases in referrals but limited evidence as to long-term outcomes have led to controversies and debate regarding this approach. Indeed, some European countries are adapting their guidelines and restricting access to care for transgender youth, and some states in the United States have introduced laws to ban such care.3 Therefore, rigorous longitudinal outcome studies that provide evidence about whether this approach is effective and safe are needed.

The results of the current study — involving a large, multisite sample of 315 participants — provide such evidence. During 24 months of GAH treatment, participant-reported appearance congruence (alignment between gender identity and physical appearance), positive affect, and life satisfaction increased and depression and anxiety decreased. In addition, initial levels and rates of change in appearance congruence correlated with the psychosocial outcomes. These results corroborate the positive effects in several earlier studies of smaller samples of adolescents and add to the evidence base that GAH can have a positive effect on mental health.4
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Yet the study leaves some concerns unanswered. Although overall psychological functioning in the study participants improved, there was substantial variation among participants; a considerable number still had depression, anxiety, or both at 24 months, and two died by suicide. The correlation between appearance congruence and various psychological-outcome variables suggests an important mediating role of GAH and consequent bodily changes. However, other possible determinants of outcomes were not reported, particularly the extent of mental health care provided throughout GAH treatment. To date, international guidelines for transgender adolescent care recommend a psychosocial assessment and involvement of mental health professionals in a multidisciplinary care model.5 Whether participating centers in the current study followed that approach is unfortunately unclear. Future studies that compare outcomes with different care models are needed, preferably using similar measures.

In addition, some are concerned that young persons may not be capable of making decisions regarding medical treatments that have irreversible effects that they might regret later in life. In the 2-year study by Chen et al., 9 of 314 adolescents (2.9%) stopped GAH, but it is unclear whether they detransitioned or regretted their treatment or whether they stopped because they were satisfied with treatment-related changes. Despite concerns about detransitioning, few studies have provided data on the incidence of detransitioning, and available results are inconsistent. Although one U.S. study showed that 74% of adolescents who started GAH treatment were still receiving it 4 years later, 98% of 720 Dutch adolescents who began such therapy were receiving it after a median of 2.7 years (range, 0.0 to 20.0).6,7 Similar studies in other centers, regions, and countries are necessary to learn whether the incidence of detransitioning differs between settings and what factors are associated with these differences. It will be especially important to evaluate outcomes in adolescents starting GAH before 16 years of age, the age limit in the initial Dutch protocol.2

Furthermore, although Chen et al. investigated relevant psychological and gender outcome measures (e.g., depression, appearance congruence, and life satisfaction), additional factors such as autism spectrum disorder and the quality of peer relations and family support are also of interest. Social support has been hypothesized as explaining why Dutch transgender adolescents have better psychological function than those in other countries.8 Understanding additional factors that influence outcomes should help to determine which components of care and support other than GAH might improve the lives of transgender adolescents.

Finally, benefits of early medical intervention, including puberty suppression, need to be weighed against possible adverse effects — for example, with regard to bone and brain development and fertility. At present, studies involving young adults from the Dutch adolescent transgender cohort show that accrual of bone mineral decelerates during puberty suppression but increases during GAH treatment and also that adolescents’ educational achievements are as expected given their pretreatment status, which is reassuring.9,10 However, those results from a single Dutch center should be replicated and validated in other contexts, as in a sample followed in the current study.

Despite uncertainties that call for further study, current information shows that mental health improves with GAH, whereas withholding treatment may lead to increased gender dysphoria and adversely affect psychological functioning. The study by Chen et al. adds to the evidence of the effectiveness of the current care model that includes hormonal treatment for transgender adolescents.
 
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