Transgender Medical: Brain Gender Identity
Published by TG Forum and
TGEA Pinnacle

For the past 40 years the idea that gender identity, the core psychological idea of seeing ourselves as only male or female, has been the driving force in identifying us as dysphoric or distressed individuals, when we do not pick the identity which corresponds to our genitalia. While most of us can pick one of the two sexes as our closer identity, we as transgendered know that we do not fit neatly into this sexual dichotomy, but are not necessarily dysphoric. When R. J. Stoller in 1964 coined the term "gender identity" he realized that there were perinatal and prenatal factors besides genitalia and the psychosocial reinforcement of rearing that determined with whom we identified. Now 40 years later we are coming closer to understanding these factors.

For the past 30 years the idea that hormones like testosterone masculinized the brain and somehow "hard-wired" the brain held sway. This hormonal bathing resulted in more masculine behavior of the individual depending on the amounts expressed during fetal development. This hypothesis was confirmed by hundreds of experiments in mammals, but not in humans. When papers were published of human behavior in intersex patients, the criteria of observation were not carefully controlled and the results fit the observation of the physical presentation. If you looked masculine, you behaved in a masculine way irrespective of your chromosomes. Now 40 years later two important papers have cast doubt on this theory in far greater numbers than the  "John/Joan" case of Money and Diamond.

These papers written in 2004 by Myer-Bahlburg (MB) and Melissa Hines (MH) have asked the important question of chromosomally female patients with classical prenatal onset of Congenital Adrenal Hyperplasia (CAH), where the genitalia have been variably masculinized in utero by maximal androgen bathing.  "Who do you most identify with male or female?" Today most of these XX females are diagnosed with CAH at birth and the masculinized genitalia are converted to female, but a few are missed or assigned to male gender status if their genitalia are completely masculinized. In 15 CAH XX females (MB) with masculinized genitalia at birth, they all identified as female with no gender dysphoria or confusion despite the fact that there were varying degrees of masculine behavior or strong female identity.  A similar paper by Reiner showed that in XY males (18) with penile inadequacy necessitating conversion to female status at birth, 60% identified as males in later life and 35% identified as female despite maximal androgen bathing in utero.  His conclusion was that gender identity was unpredictable. But the first paper comes closest to the mammalian experiments where the fetus was given testosterone during development and developed masculine behaviors. This was then extrapolated to humans. MH suggests that gender identity is remarkably flexible and that exposure to high levels of androgens in CAH does not prevent successful adoption of a female identity. She successfully draws the distinction between behavior and identity.  Now we have found the genes that determine the enzymatic defect in CAH and new evidence is emerging that the genes which affect sexual brain development may be responsible for gender identity differences. Embryologically the brain develops before the primary sex organs, ovaries or testes and stimulates the production of sex hormones by producing hormones from the pituitary at the base of the brain.  Could it be that genes which direct the brain's sexual development are responsible for our identity? Such evidence is emerging as we learn more about the brain, but again we are back to mammalian experimentation. The rest of this article details the research and speculation where this may lead just as the hormonal experiments did 20 years ago.

Now in many mammals it has been demonstrated that the X and Y sex chromosomes induce sex differences in many organs. Sex differences can be measured in the embryonic cells of the mouse brain before the gonads develop or produce hormones. In certain mice the neural tube or spinal cord closes earlier in males than females and can be made to fail in females before the gonads differentiate. Now we cannot discount the effect of testosterone on brain differentiation, but these experiments suggest that hormones are only partially responsible for brain sexual differentiation. It appears in mice that 50 candidate or possible genes are responsible for brain sexual development inducing neural differences of male and female before the gonads develop or produce sex hormones. (Dewing and Vilain)
Sex hormone receptors are abundant in the brain and hypothalamus, an area strongly associated with the reproductive axis and sexual behaviors. Many other areas of the brain associated with verbal abilities, aggression and learning have been noted to have increased uptake of estradiol and testosterone, which is converted to estradiol in the brain. Other studies show that drugs taken during pregnancy like the female hormone DES, the anticonvulsant Dilantin and phenobarbital, a sedative, are known to alter sex hormones in brain activity and are associated with an increase in Transsexualism.

Now that we have measured the sex hormone levels in the amniotic fluids of pregnant women, we find no significant differences in pregnant female serum levels or amniotic fluid levels at the crucial stage of early brain development with either male or female fetuses. The brain continues to differentiate between weeks 16 to 28 of gestation while the testosterone level in males peaks later from week 34 on. So researchers then say it doesn't take much androgen to masculinize the brain or that the timing of the hormones is increased in the third trimester of pregnancy to support their position.
 
The most recent evidence for a genetic role in human gender identity comes from a recent presentation by Dr. Milton Diamond. He noted from the literature and his own Internet survey that 48% of 27 pairs of identical male twins and 14% of 14 pairs of non-identical twins were found to be both transsexual in their gender identity. Also he noted that 20% of 10 pairs of female identical twins were both transsexual and none of the 3 pairs of non-identical female twins identified as both transsexual. These findings support the idea of a significant genetic contribution to the development of gender identity with more influence in MTFs than FTMs.
 
This is where the direction of "gender identity" is heading. What is becoming clear from scientific evidence is that variant gender identity is strongly associated with the neural development of the brain in utero under the direction of our sex chromosomes and genes initially, which may be modified to some extent by the amount of sex hormones present throughout life. What is clearer in humans is that this cannot be changed by rearing, psychosocialization or psychiatry. I can hear the psychiatrists screaming already.

Best of Luck in Your New Future,

Cerise Richards, M.D.