Guideline Summary: Testosterone Assessment and Therapy in Women

Age‑Specific Reference Ranges

Total testosterone declines progressively with age in women, making age‑specific reference ranges more clinically relevant than a single universal cutoff. 1
In women aged 20–80 years, the reference range is 0.35–1.97 nmol/L when measured by LC‑MS/MS, the gold‑standard method. 1
For premenopausal women (approximately 30 years old), the 5th–95th percentile range is 0.52–1.60 nmol/L. 1
Postmenopausal women have lower median total testosterone values, but these overlap substantially with premenopausal ranges and show high inter‑woman variability. 1

Free testosterone is a more accurate indicator of biologically active hormone; calculated free testosterone is acceptable when validated formulas that incorporate total testosterone, SHBG, and albumin are used, although equilibrium dialysis or ultrafiltration remain the most reliable measurement techniques. 1

Testosterone levels exhibit modest but statistically significant variation across the menstrual cycle, with a small mid‑cycle peak that is minor relative to between‑woman variability. 1
When precise assessment is required, obtaining multiple samples or timing samples across the cycle improves clinical reliability. 1

Accurate measurement of low‑level testosterone in women requires LC‑MS/MS methodology; direct immunoassays (including traditional radioimmunoassays) are unreliable and should not be used. 1
All assays must be calibrated against Centers for Disease Control and Prevention (CDC) reference standards to ensure accuracy. 1
Even among mass‑spectrometry‑based methods, results can vary unless laboratories standardize against agreed‑upon reference materials. 1

In postmenopausal women with hypoactive sexual desire disorder—the only evidence‑based indication—testosterone therapy should aim to maintain serum levels within the physiologic premenopausal female range. 2
Baseline total testosterone should be measured before initiating therapy, repeated at 3–6 weeks, and then every 6 months to monitor for androgen excess. 2
Supraphysiologic concentrations delivered via pellets or injections are not recommended. 2
Therapy should be discontinued if no clinical benefit is observed by 6 months. 2

Direct immunoassays for free testosterone are seriously flawed and should be avoided despite their simplicity and low cost. 1
Routine diagnostic measurement of testosterone in women is discouraged because symptom‑level correlations have not been validated. 3
SHBG concentrations significantly influence free testosterone calculations, yet no universally accepted SHBG standard or dissociation constant exists. 1
Age is the strongest correlate of testosterone decline in women, more so than menopausal status per se; prospective studies show no significant change attributable solely to menopause. 1