Nexuses
HormonalPulse+ — every 6 months

Testosterone

Total Testosterone, Free Testosterone & SHBG

What it is

Testosterone is the primary androgen in humans, produced predominantly by the Leydig cells of the testes in males and, in substantially smaller quantities, by the ovaries and adrenal glands in females. In the bloodstream, testosterone circulates in three fractions: free testosterone (biologically active, approximately 2–3% of total), albumin-bound testosterone (loosely bound and largely bioavailable), and testosterone bound tightly to sex hormone-binding globulin (SHBG), which is not directly available to tissues. Total testosterone — the sum of all three — is the standard clinical measure, but it can be misleading. Elevated SHBG (which rises with ageing, liver disease, hyperthyroidism, and oestrogen exposure) can produce a normal total testosterone alongside a markedly reduced bioavailable fraction. The Blueprint protocol tests total testosterone, free testosterone, and SHBG together, providing the information needed to distinguish true androgen sufficiency from laboratory artefact.

Why we measure it

Testosterone exerts effects across virtually every tissue system. In males, it regulates skeletal muscle mass and strength, bone mineral density, erythropoiesis, libido, cognitive function, mood, and insulin sensitivity. In females, it plays important roles in libido, body composition, bone density, and general wellbeing at much lower absolute concentrations. The cardiometabolic consequences of androgen deficiency are substantial and increasingly well-characterised. A systematic review and meta-analysis published in the Journal of Clinical Endocrinology & Metabolism, pooling data from longitudinal cohort studies including over 1.7 million patient-years of follow-up, found that low endogenous testosterone in men was independently associated with increased all-cause mortality, cardiovascular mortality, and incidence of type 2 diabetes and metabolic syndrome — effects that persisted after adjustment for age, BMI, and pre-existing conditions. The physiological mechanism is partly direct (testosterone promotes insulin-sensitising lean mass and suppresses visceral adiposity) and partly a self-reinforcing cycle: low testosterone promotes fat gain, which increases aromatase activity converting testosterone to oestradiol, which further suppresses gonadotropin-driven testosterone production. Testing total and free testosterone with SHBG allows the protocol to detect this declining trajectory before symptoms reach clinical threshold, and to assess whether lifestyle interventions are producing measurable androgenic benefit.

Why every 6 months

Testosterone levels exhibit a diurnal rhythm, peaking in the morning (typically 7–9 am) and declining by 25–40% by the evening — which is why the protocol specifies a morning, fasting draw for consistency. On this timescale, single measurements are noisy. On a six-monthly timescale, testosterone captures the meaningful trajectory: the slow age-related decline of approximately 1–2% per year in males, and the impact of changes in body composition, sleep quality, stress load, and training on the hormonal milieu. For males investigating androgen deficiency or monitoring a therapeutic response, the six-month interval provides two data points per year — enough to confirm a trend, assess an intervention, and detect the gradual progression that annual testing would miss entirely.

What movement means

The Endocrine Society's 2018 clinical practice guideline defines male hypogonadism as total testosterone consistently below 300 ng/dL (10.4 nmol/L) on two morning draws, supported by signs and symptoms. The guideline-defined normal adult male range is approximately 300–1,000 ng/dL (10.4–34.7 nmol/L), though what is optimal within this range is age-dependent — a 65-year-old at 310 ng/dL is technically within normal limits but at a level the literature associates with metabolic vulnerability. Female reference ranges are substantially lower, typically 15–70 ng/dL (0.5–2.4 nmol/L), and clinical guidelines for female androgen insufficiency remain less standardised than male hypogonadism criteria. Across both sexes, the number in isolation is less informative than the number in context — of age, SHBG, free testosterone, symptoms, and trend.

Hypogonadal (Male)

< 300 ng/dL (< 10.4 nmol/L)

Below the Endocrine Society's defined threshold for male hypogonadism. Associated with increased risk of metabolic syndrome, cardiovascular disease, impaired body composition, and reduced quality of life. Confirmatory morning draw and assessment of free testosterone and SHBG are recommended before clinical classification.

Endocrine Society Clinical Practice Guideline — Bhasin et al., J Clin Endocrinol Metab, 2018 — doi:10.1210/jc.2018-00229

Normal (Male)

300 – 1,000 ng/dL (10.4 – 34.7 nmol/L)

Endocrine Society-defined normal range for adult males. The clinically meaningful level within this range depends on age, SHBG, free testosterone, and individual context. Upper-normal values are associated with favourable body composition and cardiometabolic markers across most age groups.

Endocrine Society Clinical Practice Guideline — Bhasin et al., J Clin Endocrinol Metab, 2018 — doi:10.1210/jc.2018-00229

Normal (Female)

15 – 70 ng/dL (0.5 – 2.4 nmol/L)

Standard clinical laboratory reference range for adult premenopausal females. Levels vary across the menstrual cycle and decline significantly after menopause. Clinical guidelines for female androgen insufficiency are less standardised than male hypogonadism criteria.

Standard laboratory reference ranges — vary by institution and assay method

References

  1. 1.

    Bhasin S, Brito JP, Cunningham GR, et al.. “Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline.” Journal of Clinical Endocrinology & Metabolism. 2018.

  2. 2.

    Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. “Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-analysis.” Journal of Clinical Endocrinology & Metabolism. 2011.

  3. 3.

    Yeap BB, Alfonso H, Chubb SAP, et al.. “In Older Men, Higher Plasma Testosterone or Dihydrotestosterone Is an Independent Predictor for Reduced Incidence of Stroke but Not Myocardial Infarction.” Journal of Clinical Endocrinology & Metabolism. 2014.

  4. 4.

    Grossmann M, Matsumoto AM. “A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.” Journal of Clinical Endocrinology & Metabolism. 2017.

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