Testosterone Level and Your Genetics

Written by Scott Peeples, BS Biomedical Sciences · ExomeDNA Founder Reviewed by ExomeDNA Editorial Process Last reviewed: May 26, 2026

Testosterone levels in the general population vary substantially between individuals — and a meaningful fraction of that variation is inherited. Large genome-wide association studies involving hundreds of thousands of participants have identified loci distributed across the genome influencing testosterone concentrations, revealing a highly polygenic genetic architecture that differs substantially between sexes.^[1][5] This trait covers the broad population genetics of testosterone variation — distinct from the specific questions of bioavailable testosterone fractions or susceptibility to clinically low levels. Below: how inherited factors shape testosterone levels, what population-scale research shows, and how genetics fits alongside clinical hormone assessment.

What influences testosterone levels?

Testosterone is a steroid hormone synthesized primarily in the gonads — testes in men, ovaries in women — with smaller contributions from the adrenal glands in both sexes. Its production is tightly regulated by the hypothalamic-pituitary-gonadal (HPG) axis: the hypothalamus releases GnRH, triggering LH secretion from the pituitary, which in turn stimulates gonadal testosterone production. A negative feedback loop regulates this system, with testosterone and estradiol (in men, via aromatization of testosterone) suppressing GnRH and LH as levels rise.

Once in the bloodstream, most testosterone is bound to proteins — primarily sex hormone-binding globulin (SHBG) and albumin. Tightly SHBG-bound testosterone is biologically inactive at tissue level; the free fraction and albumin-bound fraction constitute the bioavailable portion. Total testosterone measurements capture both bound and free fractions, making total levels a composite that reflects both production and transport biology.

Heritability estimates from twin studies place the inherited contribution to testosterone levels at roughly 40–60%, indicating that genetics substantially shapes where an individual falls within the population distribution while leaving meaningful room for environmental and lifestyle influences. Age, body composition, sleep, metabolic health, and physical activity all contribute to where actual levels fall relative to the inherited set point.

The genetics of testosterone variation

The genetic architecture of testosterone levels is highly polygenic — distributed across many hundreds of common variants, each with small individual effects that aggregate into meaningful differences between people. Crucially, this architecture differs substantially between men and women: genetic signals influencing male testosterone are enriched in HPG-axis regulatory genes and hormonal feedback mechanisms, while female testosterone shows a largely non-overlapping genetic pattern driven by distinct biological pathways.^[5]

363,228 individuals from the UK Biobank contributed to a large-scale genetic study of 35 blood and urine biomarkers including testosterone, identifying 1,857 independent loci and enabling polygenic risk prediction that improved disease risk stratification across multiple conditions.^[4]

Early foundational research established that the SHBG locus carries some of the strongest common-variant signals for testosterone levels in men, reflecting the critical role of this binding protein in determining circulating testosterone. Variants at the SHBG locus affect how the protein binds testosterone, influencing what the standard total testosterone assay detects and driving a wide range in testosterone susceptibility between individuals carrying different numbers of risk alleles.^[1]

Men carrying three or more testosterone-lowering risk alleles at the SHBG locus showed a 6.5-fold higher risk of low serum testosterone compared with men carrying no risk alleles, in a meta-analysis across 8,938 men from seven independent cohorts.^[1]

ADH4, present in this trait's genetic landscape, encodes an alcohol dehydrogenase expressed in the liver. Alcohol dehydrogenase enzymes participate not only in alcohol metabolism but also in oxidoreduction reactions involving steroid hormones, illustrating the overlap between hepatic metabolism and androgen processing. ABCA8 and ABCC10 — ATP-binding cassette transporters present among the GWAS signals — reflect the broad membrane transport and cellular metabolism biology that underlies circulating hormone variation across large populations. Cross-ancestry genome-wide analyses in pre- and postmenopausal women have further broadened the evidence base beyond European-ancestry populations, identifying sex hormone associations in more diverse cohorts.^[6] At the reproductive extreme, testosterone-lowering genetic variants have been linked to infertility outcomes in women, connecting population-level testosterone genetics to clinically significant reproductive endpoints.^[7]

What the research says

Research base: Robust. The genetics of testosterone levels is supported by multiple large-scale genome-wide studies across independent cohorts, including sex-specific and combined-sex analyses in European, multi-ancestry, and female-focused populations.^{[1][2][4][5][6]} Associations have been replicated across studies, and Mendelian randomization analyses have extended findings to downstream health outcomes in cardiometabolic, reproductive, and musculoskeletal biology.^[3][7] See our methodology page for how we evaluate and apply genetic evidence in your ExomeDNA profile.

An important caveat on interpretation: while the genetic architecture of testosterone is robustly characterized at the population level, translating GWAS findings into individual-level predictions carries inherent uncertainty. Testosterone levels are highly dynamic — varying with age, season, time of day, body weight, and health status. Genetic variants capture tendencies across populations; clinical assessment captures the current state of an individual.

How testosterone genetics affects your health

The health implications of testosterone variation are sex-specific and context-dependent, making this trait one where the direction of associations differs meaningfully between men and women. In men, testosterone influences muscle mass, bone density, fat distribution, erythropoiesis, libido, and mood. In women, testosterone operates at much lower concentrations but still influences bone density, muscle maintenance, and reproductive function.

Genetic studies using steroid hormone variants as instruments have established causal relationships between testosterone variation and specific health outcomes: associations with cardiometabolic risk, body composition, and musculoskeletal traits have been tested through Mendelian randomization in large population datasets.^[3] Genetic variants influencing steroid hormone levels more broadly show enrichment among known cardiovascular risk loci, suggesting shared biology between androgen regulation and cardiometabolic pathways — a relationship that differs in direction between sexes.^[3]

At the reproductive level, rare testosterone-lowering variants in specific genes associate with infertility risk in women, while population-level testosterone genetics correlates with indices of reproductive function.^[7] These connections across cardiometabolic and reproductive biology reflect the wide tissue distribution of androgen receptors and the hormone's role as a cross-system metabolic signal, not merely a reproductive hormone.

Working with your testosterone genetics result

What research suggests about testosterone-influencing lifestyle factors

• Resistance training consistently raises testosterone in men and favorably modulates sex hormone profiles in both sexes — it is among the most evidence-backed lifestyle modulators of androgen levels.^[1]
• Body composition management is relevant because adipose tissue aromatizes androgens to estrogens via aromatase activity, reducing total circulating testosterone particularly in men with higher body fat.
• Sleep quality and duration directly affect testosterone production, which follows a circadian pattern with peak secretion during sleep; chronic sleep restriction measurably reduces morning testosterone concentrations.
• Alcohol metabolism intersects with androgen biology through the ADH enzyme family present in this trait's genetic signals — alcohol consumption can suppress HPG-axis function and reduce testosterone production over time.
• Dietary and metabolic health influence testosterone indirectly through body composition, insulin sensitivity, and liver function, each of which modulates the hormonal environment that genetic susceptibility operates within.
• Serum hormone testing — total testosterone and sex hormone-binding globulin — is the appropriate route for assessing current hormone status; genetic results reflect inherited population-level tendency, not a measurement of current levels.

Related traits and genes

Testosterone levels connects to several related traits in your ExomeDNA hormonal and metabolic profile. Bioavailable Testosterone covers the specific question of what fraction of total testosterone is available for cellular uptake — a related but distinct trait where SHBG genetics play a particularly prominent role. Low Testosterone Risk focuses specifically on susceptibility to falling below clinical androgen thresholds, with its own evidence base. SHBG Levels is directly coupled — SHBG variants are among the strongest signals for total testosterone levels and are the primary determinant of the bound-versus-bioavailable split.

Across categories, Lean Muscle Mass is directly relevant since testosterone is the principal anabolic hormone influencing muscle quantity across the lifespan. Estrogen Metabolism shares steroid synthesis biology; aromatization of testosterone to estradiol in peripheral tissues links these two hormonal profiles. Bone Density is affected by androgen levels in both sexes, as testosterone supports cortical bone formation and its decline is a recognized contributor to bone density loss over time.

Frequently asked questions

How heritable are testosterone levels?

Twin and family studies estimate heritability for testosterone levels at approximately 40–60%, meaning that roughly half of individual variation in testosterone is attributable to inherited genetic factors. The other half reflects environmental exposures, lifestyle, age, metabolic health, and other non-inherited influences. Large genome-wide studies have confirmed that this inherited component is distributed across many hundreds of genetic loci, each contributing small individual effects that collectively account for the observed heritability.

Why do the genetics of testosterone differ between men and women?

Male testosterone is primarily regulated through the hypothalamic-pituitary-gonadal axis, with genetic signals enriched in HPG-axis regulatory genes and testosterone feedback mechanisms. Female testosterone operates at much lower baseline concentrations within a different hormonal context — regulated by distinct feedback dynamics and interacting with estrogen and progesterone differently than in men. These different biological contexts produce largely non-overlapping genetic architectures, a finding confirmed by sex-stratified large-scale genome-wide analyses showing minimal genetic correlation between male and female testosterone loci.

What does it mean that testosterone genetics is highly polygenic?

Highly polygenic means the trait is influenced by many hundreds or thousands of genetic variants, each with very small effects individually, rather than a few variants with large effects. For testosterone, no single common genetic variant drives large changes in hormone levels — instead, the combined effect of many variants determines where an individual tends to fall in the population distribution. This is why polygenic risk scores that aggregate effects across many variants are necessary to capture the inherited contribution to testosterone levels in a clinically meaningful way.

How is this trait different from the Bioavailable Testosterone trait?

Total testosterone levels (this trait) measures all circulating testosterone, including the majority tightly bound to sex hormone-binding globulin. Bioavailable testosterone measures only the free and loosely-bound fraction that tissues can actually use. The two traits have overlapping but distinct genetic architectures: SHBG variants appear in both, but each trait also has unique signals. An individual can have normal total testosterone and lower bioavailable testosterone if SHBG is elevated, or vice versa — the two measurements reflect different aspects of androgen biology.

Do testosterone genetics predict specific health outcomes?

Genetic studies have used testosterone-associated variants as instruments to test causal effects on health outcomes through Mendelian randomization. Evidence supports associations with cardiometabolic traits, bone density, body composition, and reproductive outcomes. These are population-level probabilistic relationships — the genetic variants that influence testosterone levels contribute to health risk through multiple biological pathways, and individual outcomes depend on far more than androgen genetics alone.

References

1. Ohlsson C, et al. (2011). Genetic determinants of serum testosterone concentrations in men. PLoS Genet. PMID: 21998597. DOI: 10.1371/journal.pgen.1002313.
2. Prescott J, et al. (2012). Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. PLoS One. PMID: 22675492. DOI: 10.1371/journal.pone.0037815.
3. Pott J, et al. (2019). Genetic Association Study of Eight Steroid Hormones and Implications for Sexual Dimorphism of Coronary Artery Disease. J Clin Endocrinol Metab. PMID: 31169883. DOI: 10.1210/jc.2018-02460.
4. Sinnott-Armstrong N, et al. (2021). Genetics of 35 blood and urine biomarkers in the UK Biobank. Nat Genet. PMID: 33462484. DOI: 10.1038/s41588-020-00757-z.
5. Sinnott-Armstrong N, et al. (2021). GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background. eLife. PMID: 33587031. DOI: 10.7554/eLife.58615.
6. Haas CB, et al. (2022). Cross-ancestry Genome-wide Association Studies of Sex Hormone Concentrations in Pre- and Postmenopausal Women. Endocrinology. PMID: 35192695. DOI: 10.1210/endocr/bqac034.
7. Venkatesh SS, et al. (2025). Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum. Nat Genet. PMID: 40229599.

Data sources:

• GWAS Catalog (NHGRI-EBI, accessed 2026-05-26)
• Open Targets Platform (CC0 1.0, accessed 2026-05-26)
• ClinVar (NCBI, accessed 2026-05-26) — entries at ≥2-star review status
• ClinGen Gene-Disease Validity (CC0 1.0, accessed 2026-05-26)

This page is published by the ExomeDNA Research Team. Last reviewed: 2026-05-26.