Can low DHEA-S align with low testosterone in postmenopausal women?

In postmenopausal women, the adrenal glands assume a dominant role in maintaining androgen levels. As ovarian function declines, the systemic availability of testosterone becomes increasingly dependent on the peripheral conversion of adrenal precursors.

Adrenal origin and precursor function

The adrenal glands, specifically the zona reticularis of the adrenal cortex, are the near-exclusive source of circulating dehydroepiandrosterone sulfate (DHEA-S), accounting for 90–100% of its production. DHEA-S acts as a massive circulating reservoir—with levels significantly higher than downstream androgens—that peripheral tissues can draw upon for local hormone synthesis.

• Mechanistic pathway: The conversion of DHEA-S to testosterone is a multi-step enzymatic process known as intracrinology. It begins with the hydrolysis of DHEA-S into free DHEA by steroid sulfatase (STS). DHEA is then converted into androstenedione by 3β-hydroxysteroid dehydrogenase (3β-HSD), which is finally reduced into testosterone by 17β-hydroxysteroid dehydrogenase (17β-HSD).
• Tissue-specific production: This pathway allows tissues such as the skin, bone, and adipose tissue to synthesize active androgens independently of direct glandular secretion.

Alignment in postmenopausal physiology

In the postmenopausal period, the relationship between DHEA-S and testosterone becomes more pronounced as the adrenal contribution to the total androgen pool reaches approximately 50%.

• Concomitant trajectories: Data from the Study of Women’s Health Across the Nation (SWAN) indicate that DHEA-S and testosterone follow similar longitudinal trajectories during the menopausal transition, often showing parallel fluctuations.
• Substrate availability: Clinical evidence from DHEA supplementation studies confirms that increasing DHEA-S levels directly raises circulating testosterone. Conversely, low DHEA-S levels limit the substrate available for peripheral conversion, frequently resulting in a corresponding decline in testosterone.

Bottom line

Low DHEA-S levels in postmenopausal women are strongly associated with low testosterone because DHEA-S serves as the primary adrenal substrate for peripheral androgen synthesis. When this precursor reservoir is depleted, the body’s ability to maintain testosterone levels through intracrine conversion is significantly diminished.