After menopause, do adrenal and residual ovarian stromal androgens contribute more to testosterone availability?

Following menopause, follicular depletion halts ovarian estrogen production, and overall circulating androgen pools decline by approximately 50%. Consequently, the body undergoes a significant endocrine shift, relying on alternative pathways to maintain systemic testosterone availability.

Clinical evidence and quantitative contributions

• Direct ovarian secretion: The postmenopausal ovary is not hormonally inert; its residual stromal tissue continues to synthesize and directly secrete testosterone and androstenedione, accounting for approximately 40% to 50% of circulating testosterone.
• Impact of oophorectomy: The clinical significance of this residual function is demonstrated by surgical studies showing that postmenopausal women who undergo bilateral oophorectomy experience a rapid, permanent 30% to 50% reduction in circulating testosterone levels compared to naturally postmenopausal counterparts with intact ovaries.

Mechanistic pathways and adrenal conversion

• Adrenal precursor conversion: The adrenal zona reticularis secretes primary androgenic precursors, specifically dehydroepiandrosterone (DHEA), DHEA-S, and androstenedione. These precursors are subsequently converted in peripheral tissues, such as adipose tissue and skin, to supply the remaining half of circulating active testosterone.
• Gonadotropin stimulation: Mechanistically, the loss of follicular negative feedback in the postmenopausal state leads to elevated luteinizing hormone (LH) levels. This elevated LH directly stimulates specialized residual ovarian-stromal, hilar, and theca-like cells to maintain direct testosterone and androstenedione synthesis.

Bottom line

• Postmenopausal testosterone availability is maintained by a dual system where the LH-stimulated residual ovarian stroma directly secretes 30% to 50% of the circulating pool, while peripheral conversion of adrenal precursors (DHEA, DHEA-S, androstenedione) supplies the remaining half.