Biology and sexual orientation
The relationship between biology and sexual orientation is a subject of ongoing research. While scientists do not know the exact cause of sexual orientation, they theorize that it is caused by a complex interplay of genetic, hormonal, and environmental influences. However, evidence is weak for hypotheses that the postnatal social environment impacts sexual orientation, especially for males.
Biological theories for explaining the causes of sexual orientation are favored by scientists. These factors, which may be related to the development of a sexual orientation, include genes, the early uterine environment, and brain structure. While the evolutionary explanation for heterosexuality in organisms that reproduce sexually is straightforwardly understood to be a psychological adaptation resulting from greater reproductive success, evolutionary explanations for homosexuality rely upon other mechanisms of evolution such as kin selection and inclusive fitness, or antagonistic pleiotropy that favors heterozygotes causing homosexuality among homozygotes as a by-product.
Scientific research and studies
Fetal development and hormones
The influence of hormones on the developing fetus has been the most influential causal hypothesis of the development of sexual orientation. In simple terms, the developing fetal brain begins in a "female" state. Both INAH3 area on the left side of the hypothalamus, which stores gender preference, and the center area of the bed stria terminalis area on the right side of the hypothalamus, which stores gender identity, are undeveloped and function as female. The action of the SRY gene in the Y chromosome in the fetus prompts the development of testes, which release testosterone, the primary androgen receptor-activating hormone, to allow testosterone to enter the cells and masculinize the fetus and fetal brain. If a sufficient amount of testosterone is received by INAH3 at 12 weeks following conception, the testosterone stimulates the enlargement of INAH3, which is known to be involved in directing typical male sex behavior, such as attraction to females. If INAH3 does not receive enough testosterone to override the circulating estrogen, it may not grow to the size typically observed in males. Subsequently, INAH3 may function as female or partially female, potentially causing same-sex attraction to males. Although the size of INAH3 in homosexual men compared to heterosexual men may not be statistically different, homosexual men may have a greater cell density than heterosexual men, though a similar total number of INAH3 neurons.Studies have shown that INAH3 in gay men has likely been exposed to lower levels of testosterone in the brain compared to straight men, or had different levels of receptivity to its masculinizing effects, or experienced hormone fluctuations at critical times during fetal development. In women, if INAH3 receives more testosterone than is normal for females, INAH3 may enlarge somewhat or even to the size that is normal for males, increasing the likelihood of same sex attraction. Supporting this are studies of the finger digit ratio of the right hand, which is a robust marker of prenatal testosterone exposure. Lesbians tend to have significantly more masculine digit ratios, a finding which has been replicated in numerous cross-cultural studies. Controlled experiments in animals, where scientists manipulate exposure to sex hormones during gestation, can also induce lifelong male-typical behavior and mounting in females, and female-typical behavior in males.
2D:4D ratio correlation with sexual orientation has been recently researched. In a meta-analysis, digit ratios were more masculine in lesbians and more feminine in gay men. Gay men had more feminine digit ratios on both the right and left hands, contrary to previous analyses, such as Grimbos et al. which found “no association of 2D:4D with male sexual orientation”. Although previous studies tended to group bisexual and homosexual individuals as "non-heterosexual", or left them out completely, the Swift-Gallant meta-analysis found that bisexual individuals were more similar to heterosexual individuals in their digit ratios.
Maternal immune responses during fetal development are strongly demonstrated as causing male homosexuality and bisexuality. Research since the 1990s has demonstrated that as a woman has more sons, there is a higher chance of later born sons having same-sex attraction. During pregnancy, male cells enter a mother's bloodstream, which provoke an immune response to neutralize them. These antibodies are then released on future male fetuses and may neutralize Y-linked antigens, which play a role in brain masculinization, leaving areas of the brain responsible for sexual attraction in the female-typical default position, i.e. expressing attraction to men. Each subsequent son will increase the levels of these antibodies, creating the observed fraternal birth order effect. Biochemical evidence to support this effect was confirmed in a lab study in 2017, finding that mothers with a gay son, particularly those with older brothers, had heightened levels of antibodies to the NLGN4Y Y-protein than mothers with heterosexual sons. This effect is estimated to account for between 15 and 29% of gay men, while other gay and bisexual men are thought to owe sexual orientation to genetic and hormonal interactions.
Socialization theories, which were dominant in the 1900s, favored the idea that children were born "undifferentiated" and were socialized into gender roles and sexual orientation. This led to medical experiments in which newborn and infant boys were surgically reassigned into girls after accidents such as botched circumcisions. These males were then reared and raised as females without telling them, but contrary to expectations, this did not make them feminine nor attracted to men. All published cases providing sexual orientation grew up to be strongly attracted to women. The failure of these experiments demonstrate that socialization effects do not induce feminine sexual behavior or psychology in males, and that the organizational effects of hormones on the fetal brain prior to birth have permanent effects. These indicate the primary role of nature, not post-birth nurture, in the development of male sexual orientation.
In the brain, the sexually dimorphic nucleus of the preoptic area is a key region which differs between males and females in humans and a number of mammals, and is caused by sex differences in hormone exposure. Also, the INAH-3 region is bigger in males than in females, and is known to be critical for sexual behavior. Dissection studies found that gay men had significantly smaller INAH-3 than heterosexual men, a shift in the female direction, as first demonstrated by neuroscientist Simon LeVay, which has been replicated. Dissection studies are rare, however, due to lack of funding and brain samples.
Long-term studies of homosexual behavior in domesticated sheep led by Charles Roselli have found that 6-8% of rams have a homosexual preference through their life. Dissection of ram brains also found a similar smaller structure in homosexually oriented rams in the brain region equivalent to human SDN, the ovine sexually dimorphic nucleus. The size of the sheep oSDN has also been demonstrated to be formed in utero, rather than postnatally, underscoring the role of prenatal hormones in masculinization of the brain for sexual attraction.
Other studies in humans have relied on brain imaging, such as research led by Ivanka Savic which compared hemispheres of the brain. This research found that straight men had right hemispheres 2% larger than the left, described as modest but "highly significant difference" by LeVay. In heterosexual women, the two hemispheres were the same size. In gay men, the two hemispheres were also the same size, or sex atypical, while in lesbians, the right hemispheres were slightly larger than the left, indicating a small shift in the male direction.
A model proposed by evolutionary geneticist William R. Rice argues that a misexpressed epigenetic modifier of testosterone sensitivity or insensitivity that affected development of the brain can explain homosexuality, and can best explain twin discordance. Rice et al. propose that these epimarks normally canalize sexual development, preventing intersex conditions in most of the population, but sometimes failing to erase across generations and causing reversed sexual preference. On grounds of evolutionary plausibility, Gavrilets, Friberg and Rice argue that all mechanisms for exclusive homosexual orientations likely trace back to their epigenetic model. Testing this hypothesis is possible with current stem cell technology.
Isolated GRH Deficiency
Isolated GRH deficiency also provides evidence of the influence of estrogen on androphilia. Shirazi et al. found that women with IGD reported lower male attraction than typical females. However, IGD did not lead to a complete decrease in attraction to males, possible leading to an elevated proportion of participants with IGD to identify as bisexual in comparison to unaffected females. IGD did not directly decrease libido or other sexual desire. Males with IGD did not differ in sexual orientation from typical males.Prenatal thyroid theory
Prenatal thyroid theory of same-sex attraction/gender dysphoria has been based on clinical and developmental observations of youngsters presenting to child psychiatry clinics in Istanbul/Turkey. The report of 12 cases with same-sex attraction/gender dysphoria born to mothers with thyroid diseases was first presented in EPA Congress, Vienna and published as an article in the same year. The extremely significant relationship between the two conditions suggested an independent model, named the Prenatal Thyroid Model of Homosexuality. According to Turkish child & adolescent psychiatrist Osman Sabuncuoglu, who generated the theory, maternal thyroid dysfunction may lead to abnormal deviations from gender-specific development in the offspring. Autoimmune destructive process as seen in Hashimoto's thyroiditis, diminished supply of thyroid hormones, and impacts on prenatal androgen system were all considered as contributing mechanisms. In a follow-up theoretical paper, previous research findings indicating higher rates of polycystic ovary syndrome in female-to-male transsexuals and lesbian women were conceived as an indication of Prenatal Thyroid Model since PCOS and autoimmune thyroiditis are frequently comorbid diseases. Likewise, increased rates of autism spectrum disorder in children born to mothers with thyroid dysfunction and overrepresentation of ASD individuals in gender dysphoria populations suggest such an association. A second group of young children with this pattern were presented in IACAPAP Congress, Prague. Furthermore, 9 additional cases were reported in the IACAPAP Congress.The findings from previous research in LGBT populations had called for attention to be paid to the thyroid system. A commentary by Jeffrey Mullen, published shortly after the 2015 article, underlined the importance of Prenatal Thyroid Model and supported developments in this field. Afterwards, several authors have emphasized the role of thyroid system in sexuality while citing the Prenatal Thyroid Model. Among them, Carosa et al. concluded that thyroid hormones, affecting the human sexual function strongly, the thyroid gland must be considered, along with the genitals and the brain, a sexual organ. As a tertiary source, an authoritative book on the subject of interplay between endocrinology, brain and behavior has also cited the thyroid-homosexuality proposal article in the latest edition.