Do ovarian androgens and testosterone fall during the menopausal transition?

The menopausal transition involves a significant reorganization of the endocrine system, characterized by diverging patterns between gonadotropins and androgens. While the rise in stimulatory hormones is a well-documented hallmark of this phase, the behavior of ovarian androgens is more complex than a simple decline.

Gonadotropin Dynamics

The transition to menopause is consistently marked by a progressive rise in follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

• Mechanism of rise: This elevation is driven by the depletion of ovarian follicles and a subsequent decline in inhibin B, a hormone that normally inhibits FSH. As this negative feedback loop weakens, the pituitary gland increases gonadotropin secretion in an attempt to stimulate the remaining follicles.
• Timeline: FSH levels begin to rise approximately 6 years before the final menstrual period (FMP), with levels above 13 mIU/mL being a strong indicator of incident menopause. Both FSH and LH peak several years after the FMP before slowly declining in late postmenopause.

Ovarian and Adrenal Androgen Production

Contrary to the sharp collapse seen in estradiol, ovarian androgen production does not necessarily decline during the transition.

• Sustained ovarian activity: While follicles are depleted, the ovarian stroma remains steroidogenically active. High circulating LH levels may actually maintain or slightly enhance androgen production from the remaining interstitial and theca cells.
• Adrenal contribution: Longitudinal data, such as the SWAN study, show that circulating androgens (testosterone and androstenedione) often remain stable or rise slightly due to a "positive inflection" in adrenal production (DHEAS) during early perimenopause. Consequently, the hormonal environment often becomes more androgenic relative to estrogen.

Testosterone Bioavailability

While total testosterone levels may remain stable, the clinical experience of lower testosterone often stems from changes in bioavailability.

• Bioavailable vs. total levels: The concentration of free (bioavailable) testosterone frequently declines during the transition. This is often due to fluctuations in Sex Hormone-Binding Globulin (SHBG), which can rise and sequester circulating testosterone, preventing it from reaching target tissues.
• Clinical implications: This reduction in free testosterone is linked to symptoms such as decreased libido, reduced energy, and changes in muscle mass, even when total testosterone levels appear within a standard reference range.

Bottom line

The claim is partially supported: while gonadotropins (FSH/LH) rise significantly and bioavailable testosterone often declines, ovarian androgen production itself does not typically fall. Instead, it remains stable or relatively increased compared to estrogen, supported by both adrenal output and sustained ovarian stromal activity.