Hormonal and Genetic Effects on Sexual Orientation and Gender Identity

Hormonal Effects

• Hormonal effects are split into two types: activation and organizational.
  • Activation: Effects due to current hormone levels in the bloodstream.
  • Organizational: Effects due to hormonal differences during embryonic development or puberty.
• Activation effects: Vary when hormone levels vary; the effect is present when the hormone is present and absent when the hormone is absent.
  • Example: Testosterone levels correlate with sexual motivation in both men and women.
    • Higher testosterone leads to more interest in sex.
    • Lower testosterone leads to less interest in sex.
    • Anti-testosterone drugs are used to reduce sex drive in sex offenders.
  • However, testosterone changes interest but not sexual orientation.
  • Estrogen levels: People don't change sexual orientation during menopause or when treated to reduce estrogen levels.
  • Menstrual cycle: Hormone levels fluctuate, but sexual orientation doesn't change.
• Activation of hormones doesn't seem to influence sexual orientation, but it influences other things, like interest in sex and some behavioral sex differences.

Origin of Sexual Orientation

• Activation of hormones doesn't seem to influence sexual orientation.
• No correlation between testosterone levels and sexual orientation.
• Other sex differences may be caused by genetics and organizational hormonal effects, but not the sex differences in sexual orientation.

Organizational Hormonal Effects

• Usually refers to early development, specifically embryonic development.
• Two periods of high testosterone in males compared to females:
  • Weeks 8-24 of pregnancy:
    • External genitalia are formed.
    • Brain differentiation takes place; the brain is sensitive to early testosterone effects.
  • Just after birth (mini-puberty):
    • Short period of testosterone peak.
    • May influence brain differentiation.
• Sexual orientation might be set up during these periods if early testosterone predicts sexual orientation in adulthood.
  • Cannot check sexual orientation in young children.
• Ideal: Look for actual measures of prenatal hormones, but it's hard due to risks associated with sampling amniotic fluid.
• Indirect evidence: Look at things known to be influenced by early testosterone and see if they correlate with sexual orientation.
• Populations with atypical early hormone levels:
  • 46XX individuals with congenital adrenal hyperplasia (high testosterone during embryonic development).
  • 46XY individuals with androgen insensitivity syndrome (do not respond to testosterone).

Correlates Dependent on Prenatal Hormones

• Three correlates with small, replicable effects:
  • Cognitive performance
  • 2D:4D ratios (ratio of index finger to ring finger length)
  • otoacoustic emissions

Cognitive Performance

• Small differences in cognitive performance exist (spatial abilities in males, verbal abilities in females).
• Some evidence that sexual orientation varies with these, and early testosterone influences them.
• Verbal abilities:
  • Generally better in females.
  • Also slightly better in androphilic men.
• Visual-spatial performance:
  • Generally better in males.
  • Worse in androphilic men; gynophilic women are faster at mental rotation.

2D:4D Ratios

• Ratio of the length of the second digit (index finger) to the fourth digit (ring finger).
• On average, men have a slightly shorter index finger relative to their ring finger compared to females.
• Consistent results have been found in gynophilic women.
• Masculine presenting gynophilic women tend to have more masculine 2D:4D ratios, men that presented feminine as children have more feminine ratios.
• This occurs in other species as well, indicating it might be an indicator of early testosterone exposure.

Otoacoustic Emissions

• A click next to the ear elicits a response; stronger in females.
• Depends on low testosterone levels during development.
• Gynophilic women have more masculine otoacoustic emissions.

Atypical Hormone Levels

Androgen Insensitivity Syndrome (46 XY Individuals)

• Present as female from birth, often don't know they are XY until puberty.
• Tend to be androphilic.
• Suggests not responding to testosterone might make you more androphilic.

Congenital Adrenal Hyperplasia (46 XX Individuals)

• Exposed to high testosterone during embryonic development.
• Higher proportion identify as gynophilic or bisexual compared to the general 46 XX population.
• Suggests early testosterone exposure biases towards being gynophilic.

Conclusion on Hormones

• Early testosterone is a factor in the development of sexual orientation.
• Most males have higher early testosterone and identify as gyno-acidic.
• Females with higher testosterone are more likely to identify as gynophilic.
• Correlates with prenatal and postnatal indicators of prenatal testosterone.
• Early testosterone might be one factor, but not the only one.
• Still unknown when in embryonic development this happens.

Questions Regarding Hormones

• Not aware of any studies relating hormone levels with bisexuality and asexuality.
• Females' 2D:4D are closer in length while male's index finger is a bit shorter.
• If organizational, predictability of sexual orientation would be possible if it was the only factor, the levels were able to measured correctly, and right timing.
• Possibility of predicting sexual orientation better than completely random odds if biological mechanisms are tapped into, but not enough is known yet.
• Biological perspective: Possibility of being both androphilic and gynophilic due to separate masculine and de-feminization processes during early development.
• Manipulating early testosterone in mice to see their sexualities is possible, assuming similar mechanisms, with careful timing.

Genetic Effects on Sexual Orientation

• Twin studies, genetic mapping, evolutionary concerns, and the fraternal birth order effect.

Twin Studies

• Monozygotic twins (genetically identical) vs. dizygotic twins (similar to any other siblings).
• Monozygotic twins grow up in similar environment, dizygotic twins are no different from any other two siblings with the same two parents in terms of their similarity.
• Look for concordance: Monozygotic twins are more likely to be alike than dizygotic twins.
• Studies look at minority sexual orientations
• Estimates vary widely in the studies.
• Higher concordance in monozygotic twins: Indicates a genetic component to sexual orientation.

Genetic Mapping

• Map sexual orientation onto a family tree.
• Men have androphilic maternal uncles (mother's brother is also gay). The X chromosome can be mapped in these families.
• Three out of four studies have found association of a region on the X chromosome androphilic sexual orientation in males.
• The region on the X chromosome inherits with the trait.
• Genes there are biasing towards the direction of sexual orientation.
• Other potential sites on other chromosomes have also been linked to sexual orientation.
• Probabilities, not one-to-one.
• Evidence: There is some amount of genetic component involved.

Evolutionary Perspective

• How can there be a genetic basis for sexual orientation if same-sex attraction leads to lower fertility?
• Natural selection favours individuals with more offspring.
• Plenty of scenarios can keep those genes in the population, even if these specific individuals don't have children of their own.
  • These include kin selection, genes with different functions in males/females and heterozygote advantage.

Kin Selection

• Gene influences sexual orientation in men.
• Sisters could be carriers of that gene.
• Man helps his sister's offspring.
• Genes go to the next generation through sister, not him.
• If that gene also makes that person more likely to help his siblings, um, have good offspring and have them survive the next generation, etc. that's the one way in which a gene could be maintained in the population.
• Males with that gene wouldn't have any offspring themselves.

Genes Don't Always Do The Same Thing In Males And Females

• Gene makes a male more likely to be androphilic + gene makes a female more likely to have more children = The same gene stays in the population through the female line.
• Evidence exists showing that maternal relatives of male homosexuals have more children.

Heterozygote Advantage

• Sickle cell anemia is an example of heterozygote advantage. If you have two copies of the mutant haemoglobin gene you will have sickle cell anemia. However, If you only have one copy of the mutant gene, you have some protection from dying by malaria.
• Used as argument for sexual orientation. If a gene in a homozygous state makes you homosexual and therefore reproductively disadvantageous, maybe the heterozygous state gives an advantage, ie. more offspring, longer survival etc.

Fraternal Birth Order Effect

• The odds of a boy being gynophilic increase the more older brothers by the same mother there are.
• Study baseline: half homosexual, half heterosexual.
• Effect has been replicated several times.
• Hypothesis:
  • Due to the fact this has to be male older siblings (female doesn't have influence,) hypothesis came up maybe it has something to do with the mother.
  • Mother response over repeated male pregnancies = maybe an immune response occurs.
• Male embryos express genes, that female embryos don't express, so maybe the mother starts making antibodies against male specific proteins.
• Evidence: In 2017, they showed there is such an immune response.
• Mothers who had multiple Sons build up this immune response to a particular protein called neuro ligand four Y linked.
• It is a Y linked gene, so she herself does not express this protein, so her male embryo does. But what does the protein do? + What is the connection to sexual orientation?
  • Rank:
    • Mothers who have multiple sons and the gay son. One of whom is gay, will have the highest immune response.
    • Those who have gay sons of the next. Those who have sons will still have a higher one than people.
    • Women who have never had sons and assume abilities had daughters, so that they have been pregnant.

Conclusion on Sex Differences

• How to go about looking for causes of sex differences.
• Evidence suggests biological developmental influences that combined genetics and some early testosterone effects.
• Not a yes/no switch, but a combination of processes.

Gender Identity

• Gender identity may be an even larger sex difference.
• Binary and non-binary identities exist.
• Mixed literature on gender dysphoria.
• Only 40% of children with gender dysphoria are still gender dysphoric after they went through puberty, the current stats show.
• Gender identity may not be a single phenotype.
• Evidence for genetic predispositions.
• Genetic mapping on a large study and looking at trans individuals shows particular alleles maybe somewhat correlated with gender dysphoria.

Genetic Mapping of Gender Identity

• Study:
  • 599 male to female transgender individuals (trans women).
  • 434 female to male (trans men).
  • 599 cis females, 728 cis males.
• Genetic mapping:
  • Trans men (46, start off with ovaries and oestrogens): having the LONG version of the oestrogen receptor beta and the adenosine version of the oestrogen receptor alpha made them slightly more likely.
  • Trans women (male-to-female-46 XY). They obviously are why they have testes less as they make testosterone, but if the LONG version of the androgen receptor in this case, the SHORT version of the oestrogen receptor beta and the same as receptor alpha biases them towards being, um, trans women.
  • Links with genes involved in sex hormone signaling, suggesting potential role of early sex hormone levels and their interaction with receptors.

Brain Differences and Gender Identity

• Brains differences of somebody with a female brain in a male body or a male brain in a female body. Is it that simple?
• If we look at people before they transition, because we know hormones can have organizational effects, can have, um, activation of effects.
• Brain volumes larger in males than females in line for natal/chromosomal sex.
• Trans women showed more feminine cortical thickness and white matter and men show more masculine basil ganglia and other white matter tracts.
• Some aspects are more similar among trans people than either cisgender people.
• Brain changes in trans individuals:
  • People live unhappily with their gender dysphoria for a good part of childhood.
  • Difficulties with living as a pre-transindividual can cause differences in the train.
• Reminder: Main takeaway = it very complicated!
• Hints shown are transitioning to different genders even before biologically/hormonally transitioning.
• Real brain differences in brain of people that are gender dysphiric.

Final Conclusion

• Genetic factors cause are involved in sexual differentiation.
• You can have masculinized feminisation, de-masculinized feminisation in different traits at different times.
• No male/female phenotype due to lots of variations.