Do DHEA-S and testosterone decline in women during aging and the menopausal transition?

Clinical evidence

• Longitudinal Cohort Data: Multi-ethnic cohort studies, such as the Study of Women's Health Across the Nation (SWAN), show that circulating levels of dehydroepiandrosterone (DHEA), DHEA-S, and testosterone decline progressively by approximately 1.5% to 3% per year as women age, starting as early as the third decade of life. By the age of 50, a woman's circulating DHEA-S level is typically reduced by 50% compared to her peak in early adulthood.
• The Menopausal Transition Dynamics: While overall aging is characterized by a steady decline in absolute androgen levels, the menopausal transition itself involves unique hormonal shifts. During this transition, estradiol levels drop precipitously (often by 90% or more), whereas testosterone declines at a much slower, gradual rate. This disparity creates a state of relative androgen excess (an elevated testosterone-to-estradiol ratio), which is strongly linked to clinical shifts such as increased visceral fat accumulation and metabolic syndrome.

Mechanistic explanations

• Intracrinology and Substrate Limitation: In women, the vast majority of active intracellular androgens are synthesized locally within peripheral target tissues (such as bone, muscle, brain, and adipose tissue) via the "intracrine" conversion of circulating adrenal precursors, principally DHEA-S. A decline in these circulating precursors directly starves the local tissue-specific enzymes (e.g., 3β-HSD and 17β-HSD) of the substrate necessary to synthesize testosterone and its highly active metabolite, dihydrotestosterone (DHT).
• SHBG Modulation of Bioavailability: Systemic androgen availability is also regulated by Sex Hormone-Binding Globulin (SHBG). Because SHBG binds testosterone with high affinity, only the unbound ("free") and weakly albumin-bound fractions are biologically active. Factors that alter SHBG levels further modulate the functional pool of circulating bioavailable testosterone.

Bottom line

Aging in women leads to a continuous, marked decline in circulating DHEA-S and testosterone levels, which directly reduces the precursor substrate available for both systemic circulation and local intracrine synthesis of active androgens in target tissues.