Do adrenal DHEA-S precursors maintain androgen signaling as ovarian androgen production declines during the menopausal transition?

The menopausal transition is defined by a profound shift in the endocrine landscape, characterized by both increased variability in ovarian output and a transition in the primary sources of androgenic signaling.

Clinical and effectiveness evidence

Research, including longitudinal data from the Study of Women's Health Across the Nation (SWAN), confirms that the menopausal transition is marked by extreme instability in ovarian hormone production.

• Hormonal Variability: As the primordial follicle pool depletes, the hypothalamic-pituitary-ovarian (HPO) axis becomes dysregulated. This leads to erratic fluctuations in estradiol and progesterone, often with unpredictable spikes in follicle-stimulating hormone (FSH).
• Androgen Decline: Total systemic androgen levels, including testosterone and androstenedione, decline longitudinally. While the drop in estrogens is precipitous, the decline in androgens is more gradual and is influenced by both chronological aging and the menopausal stage.
• Shift in Ratios: Despite the absolute decline in androgens, the faster rate of estrogen loss often results in a state of "relative hyperandrogenism," where the ratio of androgens to estrogens increases, contributing to clinical symptoms like metabolic changes and shifts in body composition.

Mechanistic explanations

The body maintains androgen signaling during this transition through a process known as intracrinology, shifting reliance from systemic ovarian secretion to peripheral conversion of adrenal precursors.

• Adrenal Contribution: Dehydroepiandrosterone sulfate (DHEA-S), produced by the adrenal zona reticularis, becomes the critical reservoir for androgen production. In early perimenopause, DHEA-S levels may show a temporary stabilization or even a slight positive inflection, contrasting with the declining ovarian output.
• Intracrine Conversion: Peripheral tissues—including the skin, bone, adipose tissue, and vagina—possess the enzymatic machinery (such as 3β-hydroxysteroid dehydrogenase and 17β-HSD) to convert circulating DHEA-S into potent androgens like testosterone and dihydrotestosterone (DHT) directly within the target cells.
• Signaling Maintenance: It is estimated that approximately 66% of total androgens in postmenopausal women are derived from these adrenal precursors via local intracrine pathways. This localized conversion allows tissues to maintain essential androgenic functions even when systemic levels of ovarian hormones are low.

Bottom line

The claim is supported by scientific evidence. During menopause, the ovaries provide a highly variable and ultimately declining supply of hormones, leading the body to rely predominantly on adrenal-derived DHEA-S for peripheral conversion into active androgens to maintain cellular signaling.