Testosterone Therapy in Women: Clinical Considerations Beyond the Number

Testosterone's physiologic role in women

Testosterone is often discussed as a "male hormone," but it is a normal, physiologically important hormone in women as well — described in current clinical guidance as "a metabolic, vascular, and reproductive hormone in women."^[2] Its physiologic roles include contributions to libido, energy, mood and cognition, though — as detailed under "Where evidence is strongest," below — the evidence-based therapeutic indication for testosterone is considerably narrower than this list of physiologic roles. Circulating testosterone concentrations in women are far lower than in men. One cited clinical reference range places premenopausal total testosterone at roughly 45.5–57.5 ng/dL for women aged 20–29, declining to roughly 27.0–38.6 ng/dL by ages 40–49.^[2] These figures are illustrative reference values from one cited source, not a universal treatment target or an "optimal" level — the reference range used for interpretation should come from the patient's own laboratory. These low absolute concentrations have real implications for how testosterone is measured and interpreted in women, discussed further below.

Ovarian and adrenal contributions

In women, testosterone and its precursors are synthesized by the ovaries and adrenal glands, with roughly half of circulating testosterone arising from peripheral conversion of precursor androgens (such as androstenedione and DHEA) in tissues outside the ovary and adrenal gland directly.^[2] Because production is split across multiple sources and pathways, testosterone levels in women don't fall in a single sharp cliff at one life event the way estradiol does at menopause. Cross-sectional studies of healthy women show a substantial decrease in androgen levels across the reproductive years, but current guidance specifically notes no significant further change across the menopausal transition itself (roughly ages 45–54) — a more nuanced pattern than a single decline timed to menopause.^[2]

Total testosterone, free testosterone and SHBG

Most circulating testosterone is bound to sex hormone-binding globulin (SHBG), with a smaller fraction bound to albumin and a small free fraction that is considered the biologically active portion. Total testosterone measures all of it; free testosterone (measured directly, or calculated from total testosterone and SHBG) attempts to estimate the active fraction. Current clinical practice guidance specifically recommends total testosterone as the best available routine measure, rather than free or bioavailable testosterone or the free androgen index (FAI), for both baseline assessment and ongoing monitoring.^[2] SHBG is still measured alongside total testosterone as context — a change in SHBG can shift the clinically active fraction even when total testosterone looks stable — but in current practice it informs interpretation of the total testosterone result rather than anchoring a separately-reported "free" number for routine decision-making.

Laboratory limitations in women

This is one of the more important technical points in this article: assay methodology matters more for women than for men, because female concentrations sit at the low end of what some platforms were originally designed to measure precisely. Current guidance describes total testosterone as measurable "with high accuracy and reproducibility" using liquid chromatography/gas chromatography or LC-tandem mass spectrometry (LC-MS/MS) assays — while also noting that these methods have not themselves been internationally standardized.^[2] Where LC-GC or LC-MS/MS is not available, measurement using the direct assays routinely used in clinical laboratories is considered an appropriate alternative, not a disqualifying limitation on its own.^[2] That said, this appropriateness is specific to total testosterone measurement — it does not extend to direct-immunoassay measurement of free testosterone, which is a separate and more specifically discouraged practice (see above).

Symptoms vs. laboratory values

Because of the assay considerations above, and because there is no single, validated "low testosterone" laboratory threshold that diagnoses a clinical condition in women, testosterone therapy decisions are guided by clinical assessment rather than a lab cutoff. Current guidance is explicit on this point: "there is no absolute level of any androgen that signals" hypoactive sexual desire disorder, and "a total testosterone level should not be used to diagnose" it.^[2] Diagnosis instead relies on structured clinical assessment tools and a detailed history, not a laboratory value.^[2] A low-normal or borderline-low level in a woman without relevant symptoms is a different clinical picture than the same level in a woman with significant, otherwise-unexplained symptoms — but neither the presence of symptoms alone, nor the lab value alone, establishes a diagnosis on its own.

Menopause and testosterone

Testosterone is not a standard, universal component of menopausal hormone therapy the way estrogen (and, for women with a uterus, progesterone) can be, and menopause itself — on its own — is not a therapeutic indication for testosterone. Current international guidance limits the evidence-based indication specifically to postmenopausal women who experience a decline in sexual desire causing personal or interpersonal distress, evaluated with a biopsychosocial assessment^[1][2] — not simply the fact of having gone through menopause, and not fatigue, weight, cognition, mood, or general wellness considered in isolation. It is not something every woman going through menopause needs or is a candidate for, and it is not part of a default hormone therapy regimen.

Where evidence is strongest

The area of testosterone therapy in women with the most substantial supporting evidence is treatment of hypoactive sexual desire disorder (HSDD) in postmenopausal women. The 2019 Global Consensus Position Statement on the Use of Testosterone Therapy for Women — endorsed by multiple international societies — and the 2021 International Society for the Study of Women's Sexual Health (ISSWSH) Clinical Practice Guideline both describe this as the sole evidence-based indication for testosterone therapy in women.^[1][2] Evidence in premenopausal women is more limited: a small number of placebo-controlled trials suggest favorable effects, but with small sample sizes, and a more recent meta-analysis found the evidence insufficient to establish efficacy in this population, calling for further research before it can be considered an established indication.^[2] Evidence for other proposed benefits — such as mood, cognition, energy, or musculoskeletal outcomes — is comparatively less robust and is not an endorsed treatment indication.^[1][2]

Routes of administration and monitoring

Because no testosterone product is FDA-approved specifically for women in the United States, prescribers generally choose between off-label dosing of an approved male-labeled transdermal product (commonly around one-tenth of a typical male dose) and a compounded preparation.^[2] Current guidance describes transdermal delivery (patch, gel or cream), at an appropriately controlled dose, as "the most physiological form of replacement therapy."^[2]

On compounded formulations specifically, the 2021 ISSWSH guideline does not recommend compounded testosterone products for HSDD, citing a lack of efficacy and safety evidence specific to compounded formulations and the potential for variability in delivered concentration; it similarly does not recommend testosterone pellets/implants, noting they can produce supraphysiologic levels and do not allow for dose titration.^[2] This is a guideline preference reflecting the evidence base available for compounded products specifically — not an assertion that individualized, prescriber-directed compounded therapy is inherently unsafe or inappropriate for a given patient. The same guideline notes that where a compounded product is used, the compounding pharmacy should meet industry standards for purity.^[2] Whichever formulation is chosen, monitoring typically includes periodic total testosterone testing alongside clinical assessment of symptom response and side effects, with an initial follow-up test around 3–6 weeks after starting therapy and roughly every 4–6 months once a stable dose is reached.^[2]

Androgenic adverse effects

Because testosterone is androgenic, potential adverse effects include acne/oily skin, hirsutism (increased facial or body hair), and androgenic alopecia (scalp hair thinning). A meta-analysis cited in current guidance found an increased risk of acne (hazard ratio 1.41) and hair growth (hazard ratio 1.56) with testosterone therapy, without evidence of alopecia, clitoromegaly, or voice deepening in the randomized-trial data reviewed^[2] — findings that specifically apply when testosterone is kept within the premenopausal physiologic reference range. Voice change and clitoral enlargement remain recognized risks of supraphysiologic (above premenopausal-range) testosterone exposure, and are not reliably reversible if they occur; guidance is explicit that therapy should not target testosterone concentrations exceeding the upper limit of the premenopausal reference range, and that the dose should usually be decreased if androgenic side effects appear.^[2] Liver function and a fasting lipid profile are typically checked before starting therapy; liver disease and hyperlipidemia are considered contraindications to treatment.^[2] Long-term safety data remain limited — randomized controlled trial safety data are not available beyond 24 months of treatment, so long-term safety has not been established.^[2]

Contraindications and precautions

As with any hormone therapy, testosterone therapy in women requires an individualized risk assessment by a prescriber, taking into account personal and family history, current health status, and other medications. This article does not enumerate a complete contraindications list because that determination belongs with a licensed prescriber reviewing an individual patient's history — not a general educational article.