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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

Two men can have identical testosterone lab values and radically different experiences — one with energy, drive, and recovery, the other exhausted, stalled in the gym, and questioning everything. The gap almost always lives in genetics: how efficiently testosterone binds to carrier proteins, converts to estrogen, activates androgen receptors, and clears through Phase 2 detox. The Precision Peptide Genetic Test analyzes the genes that govern each of those steps — part of a broader panel spanning 14 pathways, 49 peptides, and 150+ genetic insights. This pillar guide walks through what each gene measures, why "normal" lab values can still feel terrible, and how to translate your results into an informed hormone conversation with a qualified healthcare provider.

The Four Systems That Shape Male Hormone Biology

Testosterone isn't a single variable — it's the output of four interconnected systems. Binding and bioavailability (how much T is actually free to do work) is governed by SHBG. Aromatization (how much T converts to estrogen) runs through CYP19A1. Receptor sensitivity (how your tissues hear the androgen signal) lives in the AR gene. And potent metabolite formation (T to DHT conversion) is controlled by SRD5A2. Upstream of all four, the HPTA axis — LH and FSH signaling from the pituitary to the testes — sets the production side of the equation. Your 6 Reproductive Health insights map onto each of these systems.

SHBG — Why Your Free Testosterone Can Diverge from Your Total

SHBG (sex hormone binding globulin) is the carrier protein that binds roughly 98% of circulating testosterone. Only the unbound fraction — free testosterone — can enter cells and activate receptors. Common variants in the SHBG gene influence baseline SHBG levels, which means two men with identical total testosterone on a lab report can have dramatically different free T — and dramatically different symptoms. High SHBG means less bioavailable testosterone, often despite "normal" total levels. Low SHBG means more free T and sometimes more aggressive responses to hormone support.

CYP19A1 — Aromatase and the Testosterone-to-Estrogen Conversion

CYP19A1 encodes aromatase, the enzyme that converts testosterone into estradiol. Some men carry high-activity variants that aromatize testosterone aggressively — these men often experience more estrogen-related symptoms (water retention, emotional volatility, nipple sensitivity) at the same total T level. Others carry lower-activity variants and skew toward lower estrogen, which carries its own tradeoffs for bone density, libido, and cognitive function. CYP19A1 insights are particularly relevant for anyone considering an androgen replacement pathway, because aromatase management is typically a central part of the protocol.

AR — The Androgen Receptor and CAG Repeat Length

The AR gene encodes the androgen receptor — the molecular lock that testosterone and DHT bind to. The gene contains a stretch of repeating CAG triplets, and the length of that stretch influences receptor sensitivity. Shorter CAG repeats correlate with more sensitive receptors: the same testosterone level produces a stronger androgen signal. Longer CAG repeats correlate with less sensitive receptors: "normal" testosterone may not translate into normal androgen signaling. This is one of the cleanest answers to "why do I feel off with normal labs?" — a question that drives millions of men into hormone clinics every year.

SRD5A2 — 5-Alpha Reductase and the Conversion to DHT

SRD5A2 encodes 5-alpha reductase type 2, the enzyme that converts testosterone into dihydrotestosterone (DHT). DHT is significantly more potent than testosterone at the androgen receptor and drives some of the strongest androgenic effects — libido, hair patterns, prostate activity. Variants in SRD5A2 influence baseline DHT formation. High-activity variants produce more DHT-driven effects; low-activity variants produce less. Relevant for anyone dealing with DHT-sensitive symptoms or weighing the tradeoffs of 5-alpha reductase modulation.

LH and FSH Receptors — The HPTA Axis at the Genetic Level

Testosterone production doesn't start in the testes — it starts in the brain. The hypothalamus releases GnRH, which prompts the pituitary to release LH and FSH, which signal the testes to produce testosterone and sperm. Variants in the LH and FSH receptors influence how efficiently those signals translate into output. This is foundational for understanding fertility preservation, HPTA restoration strategies after hormone therapy, and the broader question of whether your low T is a production issue, a signaling issue, or a receptor sensitivity issue.

Beyond Men's Hormone: How Your Panel Connects

Male hormone biology doesn't live in one pathway. Your 6 Reproductive Health insights intersect with the 12 Energy Metabolism insights (testosterone is deeply entangled with mitochondrial function), the 15 Muscle Growth insights (androgen signaling drives hypertrophy), the 34 Weight Management insights (body fat raises aromatase activity, lowering T), and the 6 Inflammation insights (chronic inflammation suppresses HPTA output). For a full overview of what the Precision Peptide Genetic Test covers, see our guide to genetic peptide testing. The Peptide Pathways Report synthesizes these cross-pathway findings into a single actionable roadmap.

Genetics as a Guide, Not a Guarantee

Your results don't diagnose low testosterone, and they don't prescribe a protocol. What they do is reveal the biological terrain your hormone strategy has to operate on. A fast-aromatizing CYP19A1 variant means estrogen management will carry more weight in any plan. A long-CAG AR variant means "normal" T levels may not feel normal until the conversation shifts toward receptor sensitivity. The real win is replacing generic hormone advice with decisions calibrated to your actual biology — the premise of testing before you invest in a hormone protocol.

The Precision Peptide Genetic Test analyzes how your genes influence men's hormone 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 your men's hormone genetic profile? Take the Precision Peptide Genetic Test

Frequently Asked Questions

How many genes does men's hormone testing cover in the PlexusDx panel?

The Precision Peptide Genetic Test analyzes men's hormone genetics as part of 6 Reproductive Health insights across 14 total pathways, 49 peptides, and 150+ genetic insights. Core genes include SHBG, CYP19A1 (aromatase), AR (androgen receptor), SRD5A2 (5-alpha reductase), and LH/FSH receptor variants. Processed via Illumina Global Screening Array at CLIA-certified labs.

Why do two men with the same testosterone level feel different?

Genetics. The AR gene determines how sensitively your tissues respond to testosterone — CAG repeat length is the key variant. SHBG determines how much testosterone is bioavailable versus bound. Identical total T levels produce different experiences depending on receptor sensitivity and binding. Part of 6 Reproductive Health insights in the Precision Peptide Genetic Test.

Can genetic testing tell me if TRT will work for me?

No — genetic testing informs the conversation, not the prescription. Your 6 Reproductive Health insights reveal how aggressively your body aromatizes testosterone to estrogen (CYP19A1), how sensitive your androgen receptors are (AR), and how your HPTA axis signals. These shape how a qualified healthcare provider approaches hormone optimization — the protocol is theirs to make.

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.