Testosterone and pre-androgens by age and menopausal stage at midlife: findings from a cross-sectional study.

Background: Whether testosterone and the pre-androgens, androstenedione and dehydroepiandrosterone (DHEA) change at menopause remains uncertain.

Methods: The Australian Women's Midlife Years Study recruited a nationally representative sample of 8096 women aged 40-69 years, between 27th October 2023 and 19th March 2024. Participants were excluded from providing a blood sample if pregnant, breastfeeding, using medications that affect sex hormone concentrations, or living over 100 km from a collection centre. Sex steroids were measured by liquid chromatography-tandem mass spectrometry and menopausal status was determined by the Stages of Reproductive Ageing Workshop (STRAW) + 10 criteria.

Findings: Blood samples were provided by 1435 of the 5031 invited participants. After excluding participants with no menopause stage classification, abnormal thyroid function, hyperprolactinemia, bilateral oophorectomy, and an unreported pregnancy, 1104 participants, mean (SD) age 56.5 (8.5) years, were included in the main analysis. Median testosterone concentrations declined between the ages of 40-44 and 55-59 years (median (interdecile range) 0.56 (0.29-1.01) nmol/L vs 0.42 (0.21-0.79) nmol/L, p = 0.001 adjusted for BMI and smoking), reached a nadir at the age of 58-59 years, followed by a modest increase, and did not differ between the youngest group and participants aged 60-64 or 65-69 years. Median androstenedione and DHEA concentrations declined from the age of 40-44 years to 65-69 years, by 51% and 33%, respectively. Testosterone and DHEA concentrations did not vary by menopausal stage in participants aged 48-53 years, whereas androstenedione concentrations were significantly higher in premenopausal, compared with postmenopausal individuals (median (IQR) 1.94 (1.42-2.54) nmol/L vs 1.63 (1.01-2.02) nmol/L, p = 0.001).

Interpretation: Testosterone concentrations declined from the age of 40 years, reaching a nadir at approximately 58-59 years followed by a modest increase, with no impact of natural menopause. These data do not support menopause per se as an indication for testosterone supplementation.

Funding: This research was supported by a National Health and Medical Research Council (NHMRC) Leadership 3 Investigator Grant award SRD (2016627).