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Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on hormones and fertility. Browse all Hormones & Fertility education

At least six genes directly shape how testosterone is produced, bound, converted, sensed, and cleared in the male body. No single gene tells the complete story — testosterone biology is a multi-gene system, and understanding which variants you carry is what separates personalized hormone strategy from one-size-fits-all guesswork. Here is the complete genetic answer to the question "what genes affect testosterone levels?" — and what the PlexusDx Precision Peptide Genetic Test analyzes across 14 pathways, 49 peptides, and 150+ genetic insights.

The Six Genes That Affect Testosterone in Men

1. SHBG — Sex Hormone Binding Globulin
SHBG is the protein that binds testosterone in circulation, making it biologically inactive. SHBG variants that produce elevated expression or higher binding affinity reduce the free testosterone fraction — the bioavailable portion that actually reaches tissues and receptors. A man can have a clinically normal total testosterone reading while carrying substantially lower free testosterone because of SHBG genetics. SHBG variants don't change how much testosterone is made; they determine how much of it the body can use. SHBG Genetics: Why Your Free Testosterone Varies covers this in depth.

2. CYP19A1 — Aromatase
CYP19A1 encodes aromatase, the enzyme that irreversibly converts testosterone to estradiol. High-activity CYP19A1 variants accelerate this conversion, reducing available testosterone while simultaneously raising estrogen. This is not a protocol problem — it's a genetic baseline that operates continuously, becoming more consequential when testosterone levels are elevated through any androgen-pathway strategy. CYP19A1 and Estrogen Conversion in Men explains the aromatization dimension fully.

3. AR — Androgen Receptor (CAG Repeats)
The androgen receptor, encoded by the AR gene, is the cellular destination for testosterone. CAG repeat length in the AR gene directly determines receptor transactivation efficiency — how powerfully the receptor converts a testosterone signal into cellular action. Longer repeats mean reduced sensitivity; shorter repeats mean higher sensitivity. The same testosterone level produces a meaningfully different biological effect depending on where a man sits on the AR CAG repeat spectrum. Androgen Receptor CAG Repeats: Sensitivity Explained covers this receptor layer in full.

4. SRD5A2 — 5-Alpha Reductase
SRD5A2 converts testosterone to dihydrotestosterone (DHT) — the more potent androgen that drives the signal at prostate, hair follicle, and certain other androgen-sensitive tissues. SRD5A2 variants determine what fraction of available testosterone is converted to DHT and what fraction remains as testosterone. High-activity SRD5A2 amplifies the androgen signal at DHT-sensitive tissues; lower-activity variants reduce it. SRD5A2 and 5-Alpha Reductase Genetics covers the DHT dimension in full.

5. LHCGR — LH Receptor
LHCGR encodes the LH (luteinizing hormone) receptor on Leydig cells in the testes — the receptor that receives the pituitary signal to produce testosterone. LHCGR variants affect how sensitively Leydig cells respond to LH stimulation: different men require different LH signal strengths to drive equivalent testicular testosterone output. LHCGR genetics also shape how deeply the HPTA axis suppresses under negative feedback and how readily testicular function recovers when protocols change. HPTA Axis Genetics: LH, FSH, and Fertility Preservation covers LH receptor genetics in full.

6. CYP17A1 — 17α-Hydroxylase / 17,20-Lyase
CYP17A1 governs adrenal DHEA production — the upstream steroid precursor that feeds into testosterone synthesis through the adrenal androgen pathway. Specifically, CYP17A1's 17,20-lyase activity determines how efficiently pregnenolone is converted to DHEA, and from there to androstenedione and testosterone. Lower-activity CYP17A1 variants reduce the adrenal precursor contribution to total androgen output — a supply-side variable most hormone assessments never measure. DHEA and Pregnenolone Pathway Genetics covers the upstream precursor layer in full.

A Seventh Variable: MTHFR and Methylation

Beyond the six primary genes above, MTHFR (C677T and A1298C variants) affects testosterone metabolism indirectly through the methylation cycle. Impaired MTHFR activity reduces SAMe production, which limits COMT enzyme activity — slowing the methylation-dependent clearance of catechol estrogens. In men, this means impaired methylation can compound estrogen accumulation on top of aromatase genetics, affecting the net androgen-to-estrogen balance even when testosterone production itself is normal. MTHFR and Methylation: How They Shape Male Hormone Optimization covers this connection in full.

What "Affecting Testosterone" Actually Means

The phrase "genes affect testosterone levels" covers at least four distinct mechanisms, and different genes act at different points:

Production: LHCGR and CYP17A1 affect how much testosterone is made — through testicular LH-stimulated synthesis and adrenal precursor supply respectively.

Binding: SHBG variants determine how much of that testosterone circulates free vs. bound — directly shaping bioavailability independent of production.

Conversion: CYP19A1 (to estradiol) and SRD5A2 (to DHT) determine how the available testosterone is metabolized — reducing or amplifying the androgen signal at different tissues in different ways.

Sensing: AR CAG repeats determine how efficiently the androgen receptor reads the testosterone signal that does reach it — making receptor sensitivity as consequential as the level itself.

A serum testosterone measurement captures none of these four dimensions. It reports a single number upstream of the most genetically variable parts of the entire cascade. That's why Why TRT Works for Some Men and Not Others: The Genetic Answer is still the most important question in this space — and why genetics is the answer to that question.

How the Precision Peptide Genetic Test Maps Your Testosterone Genetics

The Precision Peptide Genetic Test analyzes all six of the genes above — plus MTHFR and FSH receptor variants — as part of 6 Reproductive Health insights within a 14-pathway panel. Results are delivered through the secure PlexusDx Results Portal on the Illumina Global Screening Array from CLIA-certified labs, analyzing 57 unique SNPs across 48 unique genes. The complete framework for how these insights work together is covered in the Complete Guide to Genetic Men's Hormone Testing.

The Precision Peptide Genetic Test analyzes how your genes influence hormone-related biological pathways. It does not recommend, prescribe, or determine which peptides you should use. Consult a qualified healthcare provider before beginning any peptide protocol.

Ready to see exactly which testosterone-related gene variants you carry? Take the Precision Peptide Genetic Test

Frequently Asked Questions About Genes and Testosterone Levels

What is the most important gene for testosterone levels?

No single gene dominates testosterone levels — at least six interact to shape how it is made, bound, converted, and sensed. SHBG governs free availability, CYP19A1 controls aromatization, AR CAG repeats determine receptor sensitivity, and LHCGR drives testicular production. The Precision Peptide Genetic Test analyzes all 6 Reproductive Health insights together.

Can a genetic test tell me what my testosterone level will be?

No — genetic testing reveals variables that shape how testosterone is produced, bound, converted, and sensed, not what your number will measure. SHBG, CYP19A1, AR, and LHCGR genetics define the biological terrain. Actual levels require blood testing. The Precision Peptide Genetic Test gives providers the genetic context to interpret those numbers more accurately.

Does SHBG genetics affect total testosterone or free testosterone?

SHBG genetics primarily affect free testosterone — the bioavailable fraction not bound to proteins. High-SHBG variants can produce normal total testosterone with significantly reduced free availability, meaning less androgen signal reaches target tissues. The Precision Peptide Genetic Test analyzes SHBG variants as one of 6 Reproductive Health insights within 14 pathways, 150+ genetic insights.

This article is part of the PlexusDx Education Hub. Browse all Hormones & Fertility education

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.