The non-heterosexual orientation of an individual is a topic on which society has a distinctly divided opinion. While part of the human population still believes that this is just a phase or desire to stand out, today a considerable amount of research supports the fact that there is a biological basis that can affect an individual’s sexuality.

Effect of serotonin on sexuality

Serotonin is a hormone that plays an important role in emotions, motivation and cognitive functions. In the 1960s and 1970s, research was done on p-chlorophenylalanine (pCPA), an irreversible tryptophan hydroxylase inhibitor that quite selectively depletes serotonin in the brain. PCPA was found to cause hypersexuality in cats, while in rats and rabbits pCPA administration led to homosexual behaviors. A similar result was found after exposing animals to a diet low in tryptophan, which in turn led to a decrease in tryptophan levels and thus serotonin in the brain.

For females, a similar study in which female rats lacked central serotonergic transfer from embryogenesis to adulthood found that they preferred female genital odors when they had a choice and showed an increased preference for females when offered a choice of male and female partners.

Another study in rats supports the involvement of the serotonergic system in the development of same-sex predisposition, and that is the effect of fluoxetine – an antidepressant from the SSRI group (selective serotonin reuptake inhibitors). This drug increased homosexual tendencies in acute treatment in males who were not prenatally treated with any other agents.

In humans, however, a single oral administration of fluoxetine resulted in metabolic differences in some regions of the brain between homosexual and heterosexual men. Thus, using positron emission tomography (PET), it was found that after administering fluoxetine in homosexual men, for example, the hypothalamus shows less activation compared to heterosexuals, while in the prefrontal cortex of homosexual men was higher metabolism than in heterosexuals.

However, in rats and humans, chronic administration of fluoxetine did not produce different effects according to sexual orientation/preference.

It’s not all serotonin’s “fault”

Some studies suggest that changes in the dopaminergic system may alter sexual preferences in animals and humans. Dopamine may be involved in the formation of sexual preference during development in Drosophila melanogaster. Using genetic and pharmacological approaches to reduce dopamine levels has shown increased homosexual attraction.

In humans, there is one study that addresses the effect of dopamine on sexual orientation. The study reports a case of a male patient diagnosed with schizophrenia who, after starting aripiprazole therapy (an antipsychotic with action on dopamine D2 and D3 receptors), claimed to have gone from a heterosexual with poor sexual activity to a hypersexual homosexual. Interestingly, two weeks after stopping taking aripiprazole, the patient stopped compulsive sexual behavior and reported a return to heterosexual orientation.

In addition to the serotonin and dopamine systems, the GABAergic system could also be partially involved in the formation of sexual preference. There is also some circumstantial evidence on the effect of oxytocin on sexuality, although solid evidence has not been found so far.

What about genes?

Genetic studies have revealed a link between catechol-O-methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) with sexual orientation. COMT is an enzyme that regulates the catabolism of neurotransmitters such as dopamine, norepinephrine, and epinephrine, while the MTHFR enzyme may affect methylation and COMT function. To some extent, these studies suggest a possible link between sexual orientation and genes involved in the regulation of neurotransmitters.

Furthermore, a study conducted on over 400,000 people based on genome research revealed 5 loci that could be associated with homosexuality. Although this shows that there is not just one, often called “gay gene” in layman’s terms, it is important to emphasize that many loci with individually small effects, spread throughout the genome, together contribute to individual differences in predisposition to same-sex sexual behavior. Therefore, it is currently impossible to predict an individual’s sexuality based on a genetic map.

Interestingly, research on families and twins has shown that homosexuality is more common in identical twins than in fraternal twins.

Gray sexuality

In a study conducted by Votinov et al. the difference in gray matter volume in homosexual and heterosexual people of both biological sexes was investigated. Hole-brain analyses revealed an increased volume of gray matter in the thalamus, postcentral gyrus, middle occipital gyrus, precentral gyrus, middle temporal gyrus, and cerebellum in homosexual participants, and a smaller volume in the putamen compared to heterosexual participants. The results of the study show that sexual orientation has unique effects on brain morphology and that these effects are dependent on biological sex.

Putamen has also emerged as one of the regions with increased gray matter volume in homosexual, as opposed to heterosexual individuals. An increased volume of gray matter putamen among homosexual women could be a sign of masculinization, as a higher volume was previously observed in men than in women, the authors say. The limitation of this conclusion lies in the fact that not all lesbians are masculine (so-called “butch”), but there are also feminized ones (so-called “femme”).

The authors of this paper also explain the possible influence of differences in the volume of gray matter of the thalamus on sexual preferences. Namely, the thalamus is, among other things, responsible for the so-called “Reward” behaviors, and the authors believe that differences in the volume of gray matter in the region can change the tendency to reward by weighing stimuli related to one’s preferred sex. Although they suggest that hypothalamic activation has effects on visual perception that are likely to influence partner selection, the findings also support the role of the thalamus in signaling sexual arousal.

All in all

It is known that non-heterosexuality is not a product of a single factor, but it is the result of a combination of several different factors, from genetic, hormonal to prenatal stress, etc. To find out exactly what impact human biology has on sexuality, additional preclinical and clinical research needs to be done. The disadvantage of previous research definitely lies in the fact that most of it was conducted on male individuals and that sexual fluidity was not taken into account, since human sexuality is not expressed in a binary way.



  1. Ganna A et all. Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior. Science. 2019. 365
  2. Li H, Fernández-Guasti A, Xu Y, Swaab D. Sexual orientation, neuropsychiatric disorders and the neurotransmitters involved. Neuroscience & Biobehavioral Reviews. 2021. 131. 479-488,
  3. Balthazart J. Minireview: Hormones and human sexual orientation. Endocrinology. 2011. 152. 2937–2947.
  4. Votinov M et all. Brain structure changes associated with sexual orientation. Scientific reports. 2021. 11. 5078. 

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Ena Penić