Bioavailable Testosterone and Your Genetics

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

Bioavailable testosterone is the portion of circulating testosterone available for cellular uptake — the fraction not bound to sex hormone-binding globulin (SHBG). Genetic variants near enzymes involved in androgen synthesis and metabolism, including those near AKR1C2 and AKR1C3, are among the heritable signals for testosterone levels in large population studies.^[1] Research shows the health effects of testosterone vary substantially by sex and context. Below: the genetic architecture, the evidence base, and what research says about metabolic health and testosterone levels.

What is bioavailable testosterone?

Bioavailable testosterone is the fraction of circulating testosterone that is either free or loosely bound — and therefore biologically active at tissue level. The majority of testosterone in the bloodstream is tightly bound to SHBG, making it unavailable for cellular uptake. Total testosterone levels may not reflect how much is actually acting on tissues; bioavailable testosterone measures the active fraction more directly.

Testosterone is produced primarily in the gonads — testes in men, ovaries and adrenal glands in women — and its levels vary considerably between people due to both genetic and environmental factors. The genetic contribution to testosterone variation is substantial: twin and population studies estimate heritability at roughly 40 to 60 percent for total testosterone, with similar estimates for the bioavailable fraction. Variants affecting synthesis enzymes, SHBG levels, and androgen receptor sensitivity each contribute to where an individual's levels fall within the normal range.

The genetics behind bioavailable testosterone

The genetic architecture of bioavailable testosterone reflects the multiple biological steps involved in androgen production, transport, and metabolism. Loci near AKR1C2 and AKR1C3 — genes encoding aldo-keto reductase enzymes central to steroid hormone interconversion — are among the signals in this trait's evidence landscape.^[1] AKR1C3 catalyzes the conversion of androstenedione to testosterone in peripheral tissues, and AKR1C2 is involved in inactivating potent androgens. Variants in these loci can shift the equilibrium of androgen interconversion, influencing circulating testosterone levels.

In a genetic study of 425,097 UK Biobank participants, the health effects of testosterone were found to differ substantially by sex — genetically elevated testosterone increased type 2 diabetes risk in women while reducing it in men, with sex-specific patterns also seen for other cardiometabolic and hormonal outcomes.^[1]

The ADH6 locus, also in this trait's GWAS landscape, encodes an alcohol dehydrogenase expressed in liver and other tissues that can participate in steroid metabolism pathways. ADAMTS3, an extracellular matrix remodeling protease, appears among the signals — potentially reflecting gonadal or vascular biology relevant to hormone production. These associations are at the population/signal level; the mechanisms linking each individual locus to testosterone levels remain areas of active investigation.

A Mendelian randomization analysis of 306,248 men and women found little evidence that testosterone causally influences socioeconomic position, general health behaviors, or physical outcomes beyond direct hormonal pathways — suggesting that many previously observed associations between testosterone and behavioral traits reflect confounding rather than direct causal effects.^[2]

What the research says

Research base: Robust. Large genome-wide association studies and Mendelian randomization analyses have established the heritable basis of testosterone levels and begun to map the sex-specific causal effects of testosterone variation on health outcomes.^[1][2] The evidence is robust for the genetic architecture of testosterone levels; specific causal links between genetic testosterone variation and individual clinical outcomes are an active area of research with some findings already replicated across large independent cohorts. See our methodology page for how genetic association evidence is assessed and weighted in your ExomeDNA profile.

An important caveat on interpretation: testosterone biology is markedly sex-specific, and population reference ranges, genetic effect sizes, and health associations differ between sexes. Your ExomeDNA result for this trait is calibrated to ancestry-matched reference distributions; the health implications described below apply in the context of your sex as well.

How bioavailable testosterone affects you

Testosterone exerts effects on multiple organ systems — muscle, bone, fat distribution, cardiovascular tissue, and reproductive function all respond to androgen signaling. The direction of health associations with higher testosterone differs meaningfully by sex, as established in large Mendelian randomization analyses using genetic instruments for testosterone levels.^[1]

In men, genetically elevated testosterone has been associated with reduced type 2 diabetes risk and potentially favorable effects on body composition, alongside increased prostate cancer risk in some analyses. In women, genetically elevated testosterone is associated with increased type 2 diabetes risk, elevated polycystic ovary syndrome (PCOS) susceptibility, and altered cancer risk profiles. These sex-divergent effects reflect different hormonal contexts: testosterone operates within different baseline concentrations, receptor densities, and competing endocrine environments in men versus women.

For both sexes, the health implications of testosterone genetics are probabilistic, context-dependent, and modifiable by lifestyle factors including body weight, physical activity, and metabolic health. An ExomeDNA result for this trait reflects the inherited component of testosterone variation — not a clinical measurement of your current hormone levels.

Working with your testosterone result

What research suggests about factors influencing testosterone levels

• Resistance training and regular physical activity consistently associate with higher testosterone in men and favorable sex hormone profiles in both sexes — exercise is among the most effective lifestyle modulators of androgen levels.^[1]
• Body weight management is relevant because excess adipose tissue converts androgens to estrogens via aromatase activity, reducing bioavailable testosterone — particularly in men with higher body fat.
• Sleep quality and duration influence testosterone production, which follows a circadian pattern with peak secretion during sleep. Chronic sleep restriction is associated with reduced testosterone levels in clinical studies.
• Dietary patterns influence testosterone indirectly through their effects on body composition, insulin sensitivity, and stress hormone levels. Mediterranean-pattern diets are associated with favorable sex hormone profiles in population studies.
• Alcohol consumption can impair testosterone production; ADH6 — present in this trait's genetic landscape — encodes an enzyme involved in both alcohol and steroid metabolism, illustrating the overlap between these pathways.
• Clinical testing (serum testosterone and SHBG measurement) is the appropriate route when symptoms of hormone imbalance are present; genetic estimates complement but do not replace clinical measurement.

Related traits and genes

Bioavailable testosterone connects to several related traits in your ExomeDNA hormonal and metabolic profile. Within metabolism and hormones, SHBG Levels is directly coupled — SHBG is the binding protein that determines what fraction of testosterone remains bioavailable, and variants influencing SHBG strongly affect this trait. Estrogen Metabolism shares the same steroid hormone synthesis pathway; the AKR1C enzymes relevant to this trait also participate in estrogen interconversion. PCOS Risk is biologically adjacent for women: testosterone elevation is both a marker and a driver of PCOS biology, and the genetic signals for both traits partially overlap.

Across categories, Lean Muscle Mass is directly relevant: testosterone is a primary anabolic hormone, and genetic variation in testosterone levels influences muscle quantity independently of training. Bone Density shares androgen dependence — testosterone supports cortical bone formation in both sexes, and lower bioavailable testosterone is a known contributor to bone density decline.

Frequently asked questions

Is bioavailable testosterone the same as total testosterone?

No. Total testosterone measures all circulating testosterone, including the majority that is tightly bound to SHBG and therefore biologically inactive at tissue level. Bioavailable testosterone measures only the free and loosely-bound fraction that cells can actually use. Two people with identical total testosterone can have different bioavailable levels depending on their SHBG concentrations — which are themselves heritable.

Does higher testosterone genetics mean better health outcomes?

Not universally. Research shows the health effects of testosterone are sex-specific and context-dependent. In men, some analyses show metabolic benefits from higher testosterone; in women, higher genetically-predicted testosterone is associated with increased type 2 diabetes and PCOS risk. Neither higher nor lower testosterone is categorically better — the relevant question is whether levels are in a range appropriate for your sex, age, and individual health context.

Can lifestyle changes significantly affect testosterone levels?

Yes. Physical activity — especially resistance training — is among the most evidence-backed lifestyle interventions for testosterone modulation. Body weight, sleep quality, stress, and diet all influence androgen levels meaningfully. Genetics set a baseline range, but lifestyle factors can shift levels substantially within that range and sometimes beyond it.

What is the role of AKR1C3 in testosterone?

AKR1C3 encodes an enzyme (aldo-keto reductase family 1 member C3, also known as 17β-HSD type 5) that converts androstenedione to testosterone in peripheral tissues — particularly in adipose, breast, and prostate tissue. Variants near this gene influence how efficiently the body produces testosterone outside the gonads, which is especially relevant for bioavailable testosterone since peripheral production bypasses some of the SHBG binding that total testosterone measurements reflect.

Should I get a clinical testosterone test based on my genetic result?

A genetic result for bioavailable testosterone reflects inherited variation in population-level testosterone regulation — it does not measure your current hormone levels. When symptoms may relate to hormone imbalance (fatigue, changes in libido, mood changes, irregular cycles, or changes in body composition), a serum testosterone and SHBG measurement is the appropriate next step. Discuss the interpretation of your genetic result alongside clinical findings with a clinician familiar with endocrine health.

References

1. Ruth KS, et al. (2020). Using human genetics to understand the disease impacts of testosterone in men and women. Nat Med. PMID: 32042192. DOI: 10.1038/s41591-020-0751-5.
2. Harrison S, et al. (2021). Testosterone and socioeconomic position: Mendelian randomization in 306,248 men and women in UK Biobank. Sci Adv. PMID: 34321204. DOI: 10.1126/sciadv.abf8257.

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.