Does age-related decline in ovarian androgens affect sexual desire and energy in midlife women?

The physiological transition of midlife involves a gradual and significant shift in androgen production, which can influence sexual health and vitality in women.

Clinical evidence

• Androgen Decline: Longitudinal data, such as from the SWAN study, confirm that ovarian and adrenal androgen production (specifically testosterone and androstenedione) declines gradually across the female lifespan. This decline is distinct from the abrupt cessation of estrogen during menopause.
• Sexual Health: There is a well-established association between testosterone levels and sexual desire. Meta-analyses of randomized controlled trials (RCTs) involving hundreds of postmenopausal women show that testosterone therapy significantly improves sexual desire compared to placebo (OR 3.18), leading clinical guidelines to recognize it as a treatment for Hypoactive Sexual Desire Disorder (HSDD).
• Energy and Well-being: While the link between endogenous testosterone levels and overall vitality is less consistent in the general population, clinical trials suggest a benefit in symptomatic subsets. Approximately 47% of women reported improved mood and 39% reported improved cognitive function after four months of transdermal testosterone therapy.

Mechanistic explanations

• Receptor Signaling: Testosterone acts as a primary ligand for the androgen receptor (AR). This receptor functions as a transcription factor in brain regions that govern sexual motivation and reproductive behavior.
• Ovarian Changes: The decline in production is driven by the aging of ovarian theca-interstitial cells, which produce androgens under the regulation of luteinizing hormone (LH). As follicle numbers decrease, the ovary’s contribution to the circulating androgen pool diminishes.
• Cellular Energy: Mechanistically, testosterone may influence "energy" levels by supporting mitochondrial biogenesis and increasing ATP production. It acts via pathways such as PGC-1α to enhance mitochondrial function and reduce oxidative stress, which may explain the reported improvements in vitality in some clinical settings.

Bottom line

The claim is strongly supported regarding the age-related decline of androgens and their link to sexual desire. The association with energy and well-being is plausible and observed in clinical treatment settings, though it is more multifactorial than the direct link to libido.