Androgen Hormone Levels and Your Genetics

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

Androgens — testosterone, dihydrotestosterone, and related steroid hormones — govern a broad range of physiological functions across the lifespan. Circulating androgen concentrations are substantially heritable, with SHBG, JMJD1C, and FAM9B among the genetic loci contributing to testosterone and DHT variance in population-scale genome-wide research.^[1] Below: how inherited variation in these genes shapes androgen biology, what the evidence reveals about the genetics of circulating androgen levels, and what the research means for understanding this trait.

What are androgen hormone levels?

Androgens are a class of steroid hormones produced primarily in the gonads — testes in men, ovaries in women — and the adrenal glands. Testosterone is the most abundant androgen and circulates in three forms: free testosterone (biologically active, approximately 2%), albumin-bound testosterone (partially bioavailable, approximately 38%), and sex hormone-binding globulin (SHBG)-bound testosterone, which is tightly sequestered and biologically inactive at tissue receptors. Dihydrotestosterone (DHT) is the more potent androgen converted from testosterone by 5-alpha reductase in peripheral tissues including the prostate, skin, and hair follicles.

SHBG — the sex hormone-binding glycoprotein produced in the liver — is the primary determinant of bioavailable androgen concentrations. SHBG binds both testosterone and DHT with high affinity, holding them in an inactive circulating reservoir. Genetic variants affecting SHBG production therefore have major downstream effects on androgen availability regardless of how much testosterone is produced by the gonads themselves.

Androgen levels vary substantially by sex, age, and health status. Men have substantially higher testosterone than women; both sexes show age-related decline — precipitous in women at menopause, more gradual in men across decades. Because androgens serve different biological functions at different life stages and in different tissues, the optimal level is context-dependent: there is no single universally favorable target that applies across sexes, ages, and health situations.

The genetics of androgen hormone levels

The genetic architecture of circulating androgen levels is anchored by three established loci: SHBG on chromosome 17, JMJD1C on chromosome 10, and FAM9B on the X chromosome — identified in genome-wide research as the primary heritable contributors to testosterone and DHT variance in men.^[1]

Three genetic loci — SHBG, JMJD1C, and FAM9B — were estimated to account for approximately 5.3% of serum testosterone variance and 4.1% of dihydrotestosterone variance in men in a genome-wide association study of 3,225 European-ancestry men from the REDUCE prostate cancer prevention study (Jin et al. 2012, Human Molecular Genetics).^[1]

SHBG (sex hormone-binding globulin) is the top-ranked genetic signal for circulating androgen levels. Variants at the SHBG locus that affect SHBG protein production or stability directly alter the bound-to-free ratio of both testosterone and DHT in circulation. Genetically higher SHBG reduces free and bioavailable androgens despite potentially normal total testosterone levels; genetically lower SHBG raises bioavailable androgens for the same total testosterone concentration. The SHBG genetic signal is the most mechanistically direct path from inherited variation to tissue-level androgen availability.

The SHBG locus showed genome-wide significant association with both testosterone and DHT concentrations in the same 3,225-man REDUCE cohort — confirming SHBG as the primary genetic regulator of circulating androgen levels in men, with its effect transmitted through alteration of the bioavailable fraction of both major androgens.^[1]

JMJD1C — jumonji domain containing 1C — is a histone demethylase containing a jumonji domain (the catalytic signature of H3K9me2 demethylase enzymes) that interacts with thyroid hormone receptors and functions as a coactivator for key transcription factors including the androgen receptor. Its appearance as a genome-wide significant androgen locus at 10q21 was a novel finding at the time of discovery, implicating epigenetic regulation of androgen-responsive gene programs as a heritable component of androgen level variation. ATP1B2, encoding the Na+/K+ ATPase beta-2 subunit, appears at the chromosome 17 region near SHBG, reflecting the genomic architecture of that locus rather than a direct independent androgen biology mechanism.

FAM9B — family with sequence similarity 9, member B — is an X-linked gene encoding a protein with nuclear localization signals. Its specific role in androgen regulation is not yet fully characterized; its emergence in androgen GWAS data suggests a regulatory contribution to gonadal or androgen-axis biology that warrants further investigation.

What the research says

Research base: Moderate. The genetic architecture of circulating androgen levels captured here is supported by a genome-wide association study of 3,225 European-ancestry men from the REDUCE prostate cancer prevention study (Jin et al. 2012, Human Molecular Genetics).^[1] Three genome-wide significant loci (SHBG, JMJD1C, FAM9B) emerged from this analysis. Moderate confidence reflects the limited sample size relative to current GWAS standards, the restriction to European ancestry, and the study being conducted exclusively in men. Larger, ancestry-diverse, and sex-inclusive studies are needed to fully characterize the genetic architecture of androgen levels across the full population. See our methodology page for how we evaluate and apply genetic evidence in your ExomeDNA profile.

An important note on scope: the research supporting this trait characterized testosterone and DHT levels in men specifically. The three loci — particularly SHBG — are broadly relevant to androgen biology across sexes, but genetic effect sizes and additional loci for women may differ and are less well characterized in this particular study.

How androgen levels affect health

Androgens influence a broad range of physiological systems, and the health implications of higher versus lower levels are fundamentally context-dependent: the relevant question is whether levels fall within a range appropriate to an individual's sex, age, and health status.

In men, adequate testosterone supports lean muscle mass and strength, bone mineral density, erythropoiesis, libido, energy, and aspects of cognitive function. Testosterone below the clinical normal range in men associates with fatigue, reduced muscle mass, bone density loss, metabolic changes, and sexual function changes. Very high testosterone in men carries its own risks including hematocrit elevation, potential sleep apnea effects, and suppression of endogenous production through HPG axis feedback. The SHBG genetic variation in this trait shapes the bioavailable fraction of whatever testosterone is produced — variants that reduce SHBG may raise free testosterone effects even when total testosterone appears normal on standard testing.

In women, androgens in the normal range contribute to bone density, muscle mass, libido, and energy. Elevated androgens above normal female ranges — particularly in premenopausal women — associate with polycystic ovary syndrome, hirsutism, acne, and menstrual irregularity. Very low androgens in women associate with reduced libido and bone density decline.

JMJD1C's role as a histone demethylase coactivator links androgen genetics to epigenetic regulation of androgen-responsive gene programs — connecting inherited chromatin biology to the downstream expression of androgen effects across tissues.

Working with your androgen hormone result

What research suggests about lifestyle factors and androgen levels

• Resistance training: the most evidence-supported lifestyle factor for testosterone in men; strength exercise directly stimulates HPG-axis androgen production and androgen receptor sensitivity.^[1]
• Body weight management: excess adiposity increases aromatase activity, converting androgens to estrogens and elevating SHBG through hepatic signaling — both of which reduce free testosterone availability in men.
• Sleep quality: testosterone production follows a circadian rhythm with peak secretion during sleep; chronic sleep restriction measurably reduces morning testosterone concentrations.
• Alcohol moderation: alcohol suppresses HPG-axis signaling at multiple levels, reducing LH-driven testosterone production and increasing aromatase activity.
• Metabolic health: insulin resistance, elevated fasting glucose, and liver dysfunction alter SHBG production, with direct consequences for bioavailable androgen levels — metabolic health is one of the most impactful modifiable determinants of SHBG and free androgen availability.
• Clinical assessment: serum total testosterone, free or bioavailable testosterone, and SHBG together provide the complete hormonal picture — genetics identifies susceptibility patterns but does not replace clinical measurement of actual circulating concentrations.

Related traits and genes

Androgen hormone levels connect to several adjacent traits in your ExomeDNA hormonal profile. Total Testosterone and Testosterone Levels cover sex-specific testosterone GWAS with larger and more recent datasets than the androgen study underlying this trait. SHBG Levels covers the mechanically central SHBG gene's role in androgen bioavailability as a standalone trait with dedicated analysis.

Within metabolism, Type 2 Diabetes Risk connects through androgen-insulin interactions — insulin resistance alters both SHBG production and androgen output, creating bidirectional relationships between androgen genetics and metabolic health. PCOS Risk is directly relevant for women, where androgen elevation is a defining feature of PCOS biology. Lean Muscle Mass and Bone Density are downstream androgen-sensitive physiological traits shaped in part by the bioavailable androgen biology captured here.

Frequently asked questions

What is SHBG and why does it matter for androgen levels?

SHBG (sex hormone-binding globulin) is a liver-produced glycoprotein that binds testosterone and DHT with high affinity, rendering the bound fraction biologically inactive at tissue receptors. Only the free testosterone fraction (approximately 2%) and albumin-bound testosterone (approximately 38%) are bioavailable for tissue effects. Genetic variants at the SHBG locus that reduce SHBG production raise free androgen availability for equivalent total testosterone; variants that raise SHBG reduce it. SHBG is the primary genetic determinant of circulating androgen levels because it controls the bioavailable fraction downstream of hormone production.

Why is this trait context-dependent rather than higher-is-better?

Optimal androgen levels vary by sex, age, and health status. In men, low testosterone associates with fatigue, muscle loss, bone density decline, and sexual dysfunction, while very high levels carry risks including hematocrit elevation and HPG-axis suppression. In women, low androgens reduce libido and bone density; elevated androgens above normal female ranges associate with PCOS, hirsutism, and menstrual irregularity. There is no universal directionality — optimal levels are individual, sex-specific, and age-dependent. A genetic result indicating higher androgen tendency is not categorically favorable or unfavorable.

What is JMJD1C and how does it relate to androgen levels?

JMJD1C encodes a jumonji domain histone demethylase that removes methyl groups from histone H3K9, altering chromatin accessibility and gene expression programs. It functions as a coactivator for androgen receptor-driven transcription, influencing the downstream gene expression response to androgens in target tissues. Its emergence as a genome-wide significant locus for both testosterone and DHT levels in men suggests that epigenetic regulation of androgen-responsive gene programs is a heritable component of circulating androgen variation, connecting chromatin biology to the hormonal phenotype.

How does SHBG variation affect the interpretation of total testosterone results?

Total testosterone measures all circulating testosterone regardless of binding status. When SHBG is genetically elevated, a large proportion of total testosterone is bound and biologically inactive, so total testosterone overstates androgen effect at tissue receptors. When SHBG is genetically reduced, more testosterone is free and bioavailable, so total testosterone understates tissue-level androgen activity. This is why SHBG must be considered alongside total testosterone for accurate interpretation — genetics, liver function, and metabolic health all shape SHBG levels and the bioavailable fraction.

Can androgen genetics change over a lifetime?

The genetic variants themselves are fixed, but the hormonal context in which they operate changes substantially. Puberty initiates gonadal testosterone production; reproductive years establish sex-specific ranges; age-related decline shifts the baseline over decades. The genetic contribution to androgen levels — particularly SHBG variants shaping bioavailability — expresses within whichever hormonal context is current. The same genetic profile can produce different functional androgen outcomes at different life stages as the hormonal and metabolic environment shifts around it.

References

1. Jin G, et al. (2012). Genome-wide association study identifies a new locus JMJD1C at 10q21 that may influence serum androgen levels in men. Hum Mol Genet. PMID: 22936694. DOI: 10.1093/hmg/dds361.

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.