Sex, Gender, Genome and Hormones: Part II

February 13, 2022

VI. the origins of homosexuality

Among the sexually dimorphic regions of the brain – that is, the parts that develop differently for males and females under hormone exposure within the womb and after birth – is a tiny part of the hypothalamus called the third interstitial nucleus of the anterior hypothalamus, abbreviated as INAH-3. The hypothalamus is a part of the limbic system that lies beneath the temporal lobe of the cerebral cortex. It regulates much of the hormone secretion within the human body and thereby controls body temperature, hunger, thirst, fatigue, sleep, circadian rhythms, and attachment behaviors. INAH-3 is significantly larger in males than in females, and the difference affects the connectivity and chemical sensitivity of particular sets of neurons. These differences account, for example, for the fact that males of most species prefer the odor and appearance of females over males and are thus more sexually aroused by females.

Heterosexual preferences are, of course, naturally selected in evolution because they favor sexual reproduction and the survival of the species. Debra Soh points out that evolution and the difference in male vs. female “investments” in sexual reproduction also account for the average differences in sexual behavior between gender-typical males and females. The time and energy investment a woman must invest in sex with the possibility of pregnancy (evolutionary history precedes birth control pills and devices) is 9 months, compared to the several minutes males invest in intercourse. Thus, women have evolved to be more selective in sexual partners than men, and to be attracted to males who appear to have good genes and the ability to provide financial and emotional support during the raising of children. Charles Darwin first explained in The Descent of Man, and Selection in Relation to Sex (1871) that natural selection is complemented in evolution by sexual selection, e.g., by females exerting mating preferences for different traits among males of the species. Men are more evolutionarily focused on using their small intercourse investment to “try out” many women, and are attracted mostly to women who also appear, from physical characteristics, likely to be fertile. These evolutionary features play a greater role than societal biases in determining the attraction of the sexes.

What, then, accounts biologically for homosexuality? Relevant research was carried out by British-American neuroscientist Simon LeVay, who examined the brains of heterosexual and homosexual men, as well as several heterosexual women, who had recently died, some of AIDS (aiding homosexual determination), in the early 1990s. On average, LeVay foundthat the INAH3 in the brains of heterosexual men were more than twice as large as that found in the homosexuals. In fact, the INAH3 size of the homosexual group was the same size as the women.” Although LeVay’s study included a total of only 41 brain samples, heincluded six heterosexual men who had also died of AIDS in the sample. These straight individuals showed no difference in the size of the INAH-3 compared with the other straight men who had died of causes unrelated to AIDS.” It thus appeared from his results that contracting AIDS had no discernible effect on INAH-3 size, and the size differences he observed among men were characteristic of their sexual preference differences.

Functional MRI brain studies reveal that the same brain regions, which regulate sexual behavior, are activated in straight men when they view heterosexual pornography and in gay men when they view gay porn. Bisexual men show similar brain activation when exposed to pornographic images of both sexes.

There is research that suggests both genetic and epigenetic possible origins of these brain differences between heterosexual and homosexual individuals. For example, a large 2014 study of gay brothers found evidence for “gay” alleles both on the X chromosome and on non-sex chromosomes. Why would alleles that favor homosexuality survive millions of years of evolutionary natural selection pressure? Jenny Graves speculates that there are alleles on chromosomes shared between men and women that enhance either “male-loving” or “female-loving.” When a male-loving allele occurs in men it favors homosexuality, but the same allele in women may predispose the affected individuals to mate earlier and have more children, thus offering an evolutionary advantage. A similar evolutionary advantage may occur in men who have the female-loving allele, while in women that allele favors lesbianism. Indeed, an Italian study found that maternally inherited (thus, likely X-chromosome) alleles enhanced both female fecundity and male homosexuality. They found that in their sample female relatives of gay men have 1.3 times as many children as the female relatives of straight men.

The same Italian study alsoconfirms previous reports, in particular that homosexuals have more maternal than paternal male homosexual relatives, that homosexual males are more often later-born than first-born and that they have more older brothers than older sisters.” The earlier study that had reported the latter observation was carried out by Ray Blanchard and it led Blanchard to hypothesize that some of the brain differences in gay men arose from female immune responses during pregnancy with boys. “When a woman becomes pregnant with a male fetus, her body interprets it as a foreign substance due to antigens produced by the Y-chromosome. This sets off an immune response in her body, with antibodies rendering the masculinizing process inoperative, a response that strengthens with each subsequent male child.” His research team then found that “mothers who had gay sons – particularly those with gay sons with older brothers – had higher levels of antibodies against NLGN4Y (a protein involved in brain development in males) than did mothers who had heterosexual sons or no male offspring. This led to differences in the way the baby’s brain is masculinized in the womb.”

Animal studies reinforce the importance for sexual preferences of testosterone exposure in the womb. “Across a variety of animal models (including rats, mice and ferrets, since it’s not ethical for us to use human fetuses as test subjects), changing the amount of testosterone that an animal [embryo] is exposed to changes whether they are sexually interested in same-sex or opposite-sex mates.” Soh also mentions supporting evidence from the study of girls with congenital adrenal hyperplasia (CAH): “these girls are exposed to higher than usual levels of testosterone in the womb. Roughly 3 percent of girls with CAH will grow up to identify as male, and of those who don’t, a large proportion will identify as lesbian. The opposite is also true; children whose mothers took anti-androgenic medication (which lowers their testosterone levels) during pregnancy tend to prefer female-typical toys.”

Marianne Legato in her work Untangling the Gordian Knot of Human Sexuality concludes by pointing out: “The search for the specific biological factors that determine a sense of being male or female, the anatomy of the reproductive system, and whether sexual inclination is homosexual or heterosexual is accelerating, but the data are still far from complete.” They do, however, suggest that there are biological effects on gender and sexual preferences; they are not, as maintained by some on both ends of the political spectrum, merely social constructs or reversible personal choices.

VII. stages of gender transitioning

Treatment of Childhood Gender Dysphoria:

Many cases of gender dysphoria begin in early childhood when the child can already sense that they should have been born with the opposite sex to match their brain. The treatment of childhood gender dysphoria has become yet another battlefield, complicated by the fact that a child’s brain is not yet fully developed, and their sense of gender may well change during the hormonal surges at puberty. Nonetheless, the child’s feelings can be intense and should be addressed.

According to the guidelines produced by the World Professional Association for Transgender Health, the recommended treatment for gender dysphoria in children Is the following: “Parents can seek help from a range of health professionals, who may then refer the child to mental health clinicians. A full psychiatric assessment follows, with the aim of engaging the child in ongoing psychotherapy to monitor both their emotional well-being and whether their dysphoria remains persistent. No other medical treatment will occur until the child nears puberty.” However, depending on the circumstances, “social transitioning” – changing names, dressing and playing with friends as the opposite sex – may be encouraged to relieve psychological distress.

Medical interventions become serious typically for ages 10-13 if acute gender dysphoria continues, and it is here that the battles are engaged. “Stage 1 treatment involves the administration of puberty “blockers” which suppress the hormones responsible for puberty… A pediatric endocrinologist establishes the child’s pubertal stage, excludes disorders of sex development, and discusses with the child and parents the effects and risks of puberty suppression.” According to studies that have tracked children with gender dysphoria for long times, a majority become comfortable with their birth sex after puberty, but are often sexually attracted to individuals of the same sex – that is, their early gender dysphoria manifests as gayness after puberty, rather than as ongoing desire to transition. But blocking puberty may simply remove this option for children. Furthermore, the use of puberty blockers to delay the onset of puberty has little studied impacts on the long-term physical and psychological well-being of the child. The counterpoint is that parents of children with gender dysphoria are often told that their child may commit suicide if not allowed to begin transitioning before puberty.

Meanwhile, social conservatives engage in this battle by denying gender science altogether. Ricki Lewis describes the following situation: “If legislation being developed [in 2020] by State Rep. Ginny Ehrhart, (R-Powder Springs, Georgia) goes forward, a physician who provides surgery or hormones to assist a transgender individual age 18 or under in transitioning will be committing a felony… If the language in the press release is an indication of the coming legislation, then the rhetoric implies that gender dysphoria and even transgender identity do not exist. Ehrhart’s press release, echoed widely in the media, quotes Dr. Quentin VanMeter, an Atlanta-area pediatric endocrinologist: ‘Children should be protected from medical experimentation based on wishful social theory. These children are suffering from a psychological condition without biologic basis.’”

If the child and parents can survive this gauntlet of opposing views and continue with puberty blockers, they can proceed to Stage 2 treatment: “Stage 2 treatment for gender dysphoria occurs at approximately 16 years of age. That involves the administration of cross-sex hormones, which cause the child to develop the pubertal characteristics of the sex with which they identify. Some of these characteristics, such as voice deepening, are irreversible, while others, such as breast development, require surgery to reverse. A list of the side effects of cross-sex hormone treatment can be found hereSurgery is not considered in patients aged less than 18 years and is only offered after transition to adult medical services.”

The steps taken at a gender identity clinic for patients of any age with gender dysphoria are summarized in Fig. VII.1. Note that, in addition to cross-sex hormone treatment and non-surgical modifications (e.g., chest binding of females transitioning to male), there is a variety of surgical options, depending on how far along the transitioning path an individual wants to proceed. The final stage is often what is known as “bottom surgery” or “genital affirmation surgery,” transforming the genitals.

Figure VII.1. The assessment and management stages at gender identity clinics for patients with gender dysphoria. Oophorectomy refers to the surgical removal of an ovary or ovaries.

Most of these stages in post-puberty treatment are costly and have the danger of significant side-effects. Individuals undertaking them have to be strongly confident that the transition will improve their lives. Ricki Lewis quotes the following statistic: “of 6,793 people who attended gender identity clinics in Amsterdam spanning 1972-2015, only 0.6% of trans women and 0.3% of trans men who’d undergone affirmation surgery regretted the decision.” Those that regret the change may choose to detransition. While reversal of cross-sex hormone regimens and even transitioning surgery are possible, they involve large costs and serious side-effects, with some effects of the cross-sex hormones being permanent (e.g., lower voice and body hair among women who detransition). Debra Soh explains: “The process of detransitioning usually begins with the realization that a person wasn’t any happier post-transition. In many cases, they were actually less functional than before because their underlying problems were never addressed – whether it was a discomfort with being gay, disliking women’s roles in society, or…comorbid psychopathology or a history of sexual abuse.”

Two Classes of Transgender Women:

Not all individuals who choose to transition have similar motivations or similar brain differences from those typical of their birth sex. Especially among men who transition to women, there appears to be a bimodal age distribution at which they undergo gender affirmation surgery (see Fig. VII.2). Those that experience early gender dysphoria and transition before the age of 35 or so seem to conform to the descriptions of ordinary (as opposed to rapid-onset) gender dysphoria described in section V. The individuals in this group typically show signs of being quite effeminate at a young age and are attracted to masculine, heterosexual men post-puberty. Their desire to transition, according to Soh, is “primarily motivated by the type of sexual and romantic partners they sought to attract.” For these reasons this ensemble is usually referred to as the gay subtype or, more scientifically according to Blanchard, the androphylic subtype.

Figure VII.2. Age distribution among 40 male-to-female patients who presented to a surgical clinic in Germany for gender-affirming surgery (GAS). The orange bars represent the age at which they first experienced gender dysphoria, while the green bars represent the age when they underwent GAS. The vertical dotted line to the left represents the median age when the patients reported first experiencing gender dysphoria. The vertical line to the right represents the low point between the 2 peaks for the bimodal distribution in age at the time of GAS. The data support the hypothesis that individuals who had an early onset of gender dysphoria and GAS before the age of 35 years are significantly more likely to be androphylic than the late-onset individuals, who had GAS after 35 years.

The second group, which experience late-onset gender dysphoria, have been labeled by Blanchard as autogynephilic – they love the idea of themselves as women. They are attracted to women and often they transition later in life after being married with children. Soh describes the typical characteristics of this group: “These individuals usually first experimented with cross-dressing at a young age. Upon reaching puberty, they were sexually attracted to women, but also experienced sexual arousal to [wearing] women’s clothing and the idea of becoming a woman. Their gender dysphoria is considered ‘late-onset’…stemming from a desire to become the women they were attracted to… Autogynephilic individuals often self-report difficulties getting dressed in women’s clothing without having an erection or ejaculating.” It should be noted that not all men who engage in cross-dressing choose to transition to women.

MRI scans of brains of autogynephilic transgender women, compared to control groups, showed brain differences, but not in brain regions that are sexually dimorphic (i.e., distinguishable between men and women generally). “This suggests that the neural differences seen between nontransgender men and people who experience autogynephilia are due to something other than feeling female.”

Despite the appearance from the small sample in Fig. VII.2, autogynephilic individuals presently dominate referrals to gender clinics among men desiring to transition. The autogynephilic fraction increased from 60% in 1987 to 75% in 2010. It should be noted, however, that the entire concept of autogynephilia, despite its inclusion in the Mental Disorders Manual DSM-5, is often dismissed by feminist social scientists, who object to Blanchard’s scientific methods and attribute his interpretations to “male-centric presumptions about women and LGBTQ+ people.” In addition, “Many transwomen find Blanchard’s theories insulting, and his insistence that these are evidence-based scientific truths, has only further enraged both the professional and activist communities.” This, then, is one more battleground in the discussions of gender identity, perhaps to be further clarified by future research on genetic and brain differences between the two classes of trans women.

VIII. transgender rights and issues

Trans activists have been demanding respect for their rights across several areas of public policy. The issues have been intensified by the fact that presently about 10% of millennials self-identify as “non-binary,” or “genderfluid.” One of the most visible controversies came to wide public attention with the 2016 North Carolina “bathroom bill.” The bill — subsequently overturned by a federal court – barred self-declared transgender people from using their preferred (i.e., consistent with their declared gender identity) restrooms if they had not undertaken a legal and surgical change (in other words, if their anatomy did not match their gender identity). The bill was undoubtedly motivated by social conservative ideas that gender identity and physical sex (i.e., genitalia) are indistinguishable. But the advertised selling point for this and similar bills introduced in other states – a selling point that unexpectedly led social conservatives and feminists to become unusual political bedfellows in opposition to the trans activists – was that allowance for people who merely identify as trans to use female bathrooms would open them up to sexual predators using the ruse of trans identity to take advantage of the women in those rooms.

Debra Soh, herself a self-avowed feminist, argues that the concern about sexual predators is not overblown, by citing statistics from the United Kingdom, where legal acceptance has been afforded to self-identified gender in some cases.  For example, “Recent statistics show that almost 90 percent of complaints about sexual assault, voyeurism, and harassment in United Kingdom swimming pools happen in unisex changing rooms…the main threat to women in gender-neutral spaces does not come from transgender people, but from men invading these spaces.” Furthermore: “In the United Kingdom, police forces now record a male-born rapist as female if the individual wishes to identify as a woman… one convicted rapist and child molester in the United Kingdom, who was placed in a woman’s prison…subsequently sexually assaulted four female inmates.”

Figure VIII.1. Convicted pedophile Stephen Wood (left) claimed to be transitioning to Karen White (right), and was therefore sent to a woman’s prison in the U.K., where he has now been convicted of rape of other female inmates.

The perpetrator that Soh references in the latter point is shown in Fig. VIII.1. Convicted pedophile Stephen Wood (left in the figure) claimed to be transitioning to Karen White (right), but had not undergone legal or surgical transitioning, or even had a diagnosis of gender dysphoria. Because of his claim he was sent to a female prison in New Hall, United Kingdom, citing article 8 of the European convention on human rights, which allows those who do not have an official Gender Recognition Certificate, but who self-identify as a different gender to their biological sex, to be located “in the part of the estate consistent with the gender they identify with.” In the female prison White has been convicted of rape of other female inmates and sentenced to life in (non-female) prison. The prosecutors in the case were so intent to use proper self-identified pronouns for White that the trial transcript contains the following remarkable account: “The complainant, while waiting, felt something hard press against the small of her back … She could see the defendant’s penis erect and sticking out of the top of her pants, covered by her tights,” the prosecutor said. This is only one of seven such attacks in female U.K. prisons that were carried out by self-identified male-to-female transitioners between 2010 and 2018.

While there is thus legitimate concern of abuse if self-identified (as opposed to surgically transformed) transgender women use female bathrooms, it seems also disrespectful to require them to use male bathrooms, where both they and other bathroom users would likely feel quite uncomfortable. The sensible solution – albeit one that many trans activists still object to — to this dilemma is to mandate that buildings include public single-person bathrooms that are visibly identified as “all gender.” As indicated in Fig. VIII.2, most U.S. states and some cities have already adopted, or were at least considering in 2021, such mandates.

Figure VIII.2. States and localities in green have already adopted mandates that all single-person public bathrooms be designated for use by all genders. Blue states have similar mandates under consideration as of 2021. Grey states have no such mandate.

Another area of ongoing controversy regarding transgender rights came to wide public awareness when CeCe Telfer, a transgender woman and an NCAA Division II track and field champion in 2019 (see Fig. VIII.3), was ruled ineligible to compete in the women’s 400-meter hurdles in the 2021 US Olympic Trials because of her testosterone levels. In another case, Minnesota power lifter JayCee Cooper has sued USA Powerlifting for discrimination after it barred her from competing in women’s events. The legal director of Gender Justice claims that “USA Powerlifting’s ban on trans athletes is based on harmful stereotypes and it’s also based on a deeply flawed understanding of what it means to be transgender.” Actually, these decisions are based not on harmful stereotypes, but on biology and clearly measured differences in strength, size and speed between transgender women, even after transitioning and suppressing testosterone levels, and other women.

Figure VIII.3. CeCe Telfer of Franklin Pierce wins the women’s 400-meter hurdles during the Division II Men’s and Women’s Outdoor Track & Field Championships held at Javelina Stadium on May 25, 2019 in Kingsville, Texas.

These very real biological differences were emphasized, for example, in a recent letter from sixteen collegiate female swimmers at the University of Pennsylvania, requesting that transgender teammate Lia Thomas should not be allowed to compete against other women. Among NCAA swimmers as a male, Thomas had been ranked #462, while after transitioning she was ranked #1 among NCAA women. Her teammates’ letter read in part: “We fully support Lia Thomas in her decision to affirm her gender identity and to transition from a man to a woman. Lia has every right to live her life authentically. However, we also recognize that when it comes to sports competition, that the biology of sex is a separate issue from someone’s gender identity. Biologically, Lia holds an unfair advantage over competition in the women’s category…”

Until very recently, most guidelines for transgender women participating in women’s athletic events were based on a policy adopted in 2015 by the International Olympic Committee (IOC). Those 2015 guidelines required trans women to suppress their testosterone levels below 10 nmol/liter for 12 months prior to being allowed to compete in women’s events, while earlier requirements that trans women undergo gender reassignment surgery were dropped. But that testosterone level is still six times higher than is typical of non-transgender female athletes, and thus allows a distinctly non-level playing field, as has been claimed by many non-transgender athletes, prominently including former tennis champion Martina Navratilova, who has consequently been subjected to labeling as a “transphobe.”

As Debra Soh points out: “Identifying as female doesn’t negate the advantages an individual has gained from undergoing male puberty, including those related to greater height, upper body strength, wrist size, hand size, muscle mass, lung capacity and bone density. Males are, on average, stronger, larger, and faster than females. Testosterone increases muscle mass, leading to greater strength and endurance. Putting estrogen in a person’s body – even if they have removed their testes – doesn’t override the benefits of having this structural foundation.” Her claims here are backed up by quantitative analyses of the physical advantages post-puberty men (see Fig. VIII.4) and trans women (Fig. VIII.5) have over non-transgender women for sport activities. The analyses are reported in Fair Game: Biology, Fairness, and Transgender Athletes in Women’s Sport, by Jon Pike, Emma Hilton and Leslie Howe. The trans women included in their charts have had cross-sex hormone therapy and have all brought their testosterone levels below the 2015 IOC requirement of 10 nmol/L for at least one year.

Figure VIII.4. A chart showing sports-relevant average physical, functional and performance differences between male and female bodies. Positive differences (bars to the right) indicate male advantages, while negative differences (bars to the left) indicate female advantages.
Figure VIII.5. A chart showing the percentage losses (bars to the left) of lean body mass, muscle and/or strength in transgender women who have suppressed testosterone for at least 12 months, and their retained advantages (bars to the right) over non-transgender females in the same cohort. The references on the right side indicate the metrics and sources of the measurements.

Pike, Hilton and Howe reach the following conclusion: “Thus, the most recent analyses generate a consensus that testosterone suppression in transwomen who meet the central IOC criteria adopted by most sporting federations induces only small amounts of muscle/strength loss, and does not remove the male athletic advantage acquired under high-testosterone conditions at puberty. Male musculoskeletal advantage is retained, and this raises obvious concerns about fairness and safety within female categories when transwomen are included. In the face of this evidence, the IOC has publicly made it clear that the guidance it offered in 2015 is ‘not fit for purpose.’ Rather than tightening the policy, though, the IOC has passed the task on to International Federations and Governing Bodies” for individual sports competitions. In the U.S. the National Collegiate Athletics Association (NCAA) followed the IOC’s lead on Jan. 19, 2021, adopting guidelines according to which “transgender participation for each sport will be determined by the policy for the sport’s national governing body, subject to review and recommendation by an NCAA committee to the Board of Governors.”

The specific recommendation that Pike, Hilton and Howe offer is the following: “We advocate, therefore, a change in the conceptualization of the categories. This reinforces and clarifies their point – that they are categories based on physiological advantage. Because the issues are asymmetrical, there is not a fairness issue in the inclusion of transmen in male competition, though there is often a safety issue…For this reason, it seems to us that fairness in sport can be achieved with the removal, as far as is possible, of gender identifiers in sport, and the reconceptualization of the male category as ‘Open’ and the women’s category as ‘Female’ where female refers to the sex recorded at birth.” It is unlikely that this suggestion will be welcomed by trans activists or by intersex individuals, so the controversy is sure to continue.

More generally, trans activists often claim that transgender women are the same as birth females. But this is certainly not true biologically. Transgender individuals are not – even after surgery – biologically identical to people of the sex they’ve transitioned to. Beyond the physical differences noted in Fig. VIII.5, for example, trans women still have a much greater risk of prostate cancer than born females, and cannot get pregnant, while trans men can (and in some cases have) get pregnant. Trans individuals who have not had so-called “bottom surgery” as part of their gender reassignment have genitals corresponding to their birth sex, rather than to their transitioned gender. These biological differences must be taken into account in any sensible policies regarding transgender rights.

IX. summary

Public discussions and controversies surrounding human sexuality often appear to be carried out on a plane separated from that in which the biological sciences reside. Sex and gender are both biologically determined, but distinct. Sex is determined by the reproductive organs a person is born with, while gender identity depends on characteristics of an individual’s brain. Men and women have different brains, on average, strongly influenced by exposure of the fetus and the newborn to surges in testosterone and estrogen. But individual variations among genes and hormone secretion can produce intermediate brains and a spectrum of male and female behavior and sexual orientation. Extremes on that spectrum often lead to gender dysphoria and possible surgical transitioning to the opposite gender from one’s birth sex.

Scientific research into the genetic and epigenetic origins of gender dysphoria and homosexuality is at an early stage. Results to date indicate that gender identity and sexual orientation are distinct but related characteristics, with some gene variations contributing to each having been identified. Gender dysphoria often first shows up in childhood, but must be treated carefully before children’s brains develop further during the hormone surges at puberty. The use of puberty blockers on children expressing gender dysphoria is a hotly debated subject. In the light of the growing cultural acceptance, and even celebration, of “non-binary” genders, a rapidly growing number of adolescent girls are now self-identifying with rapid-onset gender dysphoria, but it is not clear that gender identity is the real issue in many of these cases.

The final stage of treatment for severe cases of gender dysphoria is often gender reassignment surgery. But even after undergoing such surgery, trans women are not biologically the same as birth females and trans men are not biologically the same as birth males. It is important to take those biological differences into account in public policies to ensure transgender rights without impinging on the rights of cisgendered (gender the same as birth sex) people. Attaining that balance is challenging and is threatened by passionate, but unscientific, activism on all sides of the issues.


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