Does declining ovarian reserve during perimenopause reduce ovarian androgen production?

Anti-Müllerian hormone (AMH) is a validated biomarker for the quantitative assessment of the ovarian reserve, but the relationship between this reserve and androgen production during perimenopause is often misunderstood.

Clinical evidence on AMH and ovarian reserve

AMH is a gold-standard marker for assessing the functional ovarian reserve in clinical practice. Unlike Follicle-Stimulating Hormone (FSH), AMH levels are cycle-independent and reflect the pool of preantral and small antral follicles.

• Follicular Tracking: Research consistently shows that serum AMH levels correlate strongly with the number of primordial follicles remaining in the ovary. In a 44-year-old female, declining AMH levels serve as a precise indicator of the natural depletion of the follicle pool associated with reproductive aging.
• Diagnostic Utility: Longitudinal studies demonstrate that AMH begins to decline years before the final menstrual period (FMP), making it a superior early indicator of the menopausal transition compared to estrogen, which typically remains stable until about two years before the FMP.

Endocrine dynamics and androgen production

While the decline in ovarian reserve leads to a significant reduction in estrogen and inhibin, the same does not apply to ovarian androgens. Longitudinal data, such as those from the Study of Women’s Health Across the Nation (SWAN), show that testosterone levels remain remarkably stable through the perimenopausal transition.

• Theca Cell Persistence: The depletion of the follicular pool primarily affects granulosa cells (the source of estrogen). However, the ovarian stroma and theca cells, which produce androgens, persist and remain functionally active well into the postmenopausal years.
• Gonadotropin Stimulation: During perimenopause, as FSH rises, Luteinizing Hormone (LH) also increases. This elevated LH continues to stimulate the remaining theca cells, maintaining or even slightly increasing androgen synthesis via cAMP-dependent pathways.
• Adrenal Buffering: Adrenal androgens (DHEA and androstenediol) also provide a significant contribution to the total androgen pool, further decoupling androgen levels from the exhaustion of the follicular reserve.

Bottom line

While AMH is a highly accurate marker for the declining follicular reserve, this decline does not cause a corresponding reduction in ovarian androgen production. Testosterone levels generally remain stable during the perimenopausal transition due to persistent androgenic activity in the ovarian stroma and elevated LH stimulation.