Anti-Müllerian hormone and somatic ovarian function: a new perspective

Area of Science:

• Reproductive biology
• Endocrinology
• Gerontology

Background:

• Anti-Müllerian hormone (AMH) is traditionally viewed as a marker of ovarian reserve, reflecting the number of remaining oocytes.
• However, AMH is produced by granulosa cells of growing follicles, suggesting it may reflect somatic follicular activity rather than dormant oocyte quantity.

Purpose of the Study:

• To propose a conceptual framework redefining ovarian aging as influenced by progressive somatic ovarian dysfunction.
• To reframe Anti-Müllerian hormone (AMH) as a biomarker of ovarian functional capacity rather than solely a quantitative reserve marker.

Main Methods:

• The study proposes a model where granulosa cells, stromal integrity, vascular support, immune regulation, and metabolic environment form a somatic support network for follicular health.
• Evidence from granulosa cell biology, controlled ovarian stimulation, ovarian surgery, autoimmune disease, chemotherapy, and fertility outcomes was reviewed.

Main Results:

• Circulating AMH levels decline in response to somatic ovarian injury, indicating AMH reflects the functional cohort of supported follicles, not total ovarian reserve.
• Primordial follicle depletion does not directly correlate with continuous AMH decline.
• Ovarian reserve markers, including AMH, have limited predictive value for natural fecundability.

Conclusions:

• Introducing the concept of somatic ovarian function provides a new framework for interpreting AMH.
• Reframing AMH as a functional systems biomarker reflecting granulosa cell integrity, metabolic health, and environmental influences can reconcile clinical paradoxes.
• This reframing opens avenues for fertility preservation, ovarian aging research, and therapeutic interventions.