Rapamycin: a new treatment to delay menopause?

The menopause marks the end of the fertility period in women. It occurs when the ovaries stop producing estrogens, causing the cessation of menstrual cycles. This process may appear sudden. It begins years earlier. At birth, the ovaries contain about one million oocytes, which falls to 600,000 or 700,000 by the start of puberty. Their number decreases with each menstrual cycle, falling below 1,000 at menopause. Each cycle recruits several follicles, but only one reaches ovulation. The rest degenerate, reducing the ovarian reserve over time.

Menopause occurs between ages 45 and 55, according to World Health Organization data.

Menopause is not always a calm process. For some women, it brings symptoms that can affect quality of life. The most common symptoms, such as hot flushes, night sweats, vaginal dryness, and sleep disturbances, can last for several years. The menopause affects the skin. The drop in estrogen levels leads to a drastic decline in fibroblast activity, the dermal cells that produce collagen, elastin, and hyaluronic acid, resulting in skin sagging and more pronounced wrinkles.

Early menopause, defined as onset before age 45, is associated with an increased risk of osteoporosis, leading to a higher fracture risk. Inserm estimates osteoporosis is two to three times more common in postmenopausal women than in men of the same age. Menopause also increases women's cardiovascular risk. Delaying its onset may offer medical benefits.

Slowing the ovarian biological clock—Is it possible? This question is raised by rapamycin, also known as sirolimus. This molecule, isolated in 1975 from the filamentous bacterium Streptomyces hygroscopicus, it was used as an immunosuppressant after organ transplants before being studied for its effects on longevity. Studies showed rapamycin could extend mouse lifespan by 10 to 15%. A 2023 trial assessed its safety in 333 individuals taking low doses of 1 to 15 mg per week. Few side effects were reported, though the risk of bacterial infections increased. Patients noted symptom relief in conditions from arthritis to mood disorders and long COVID. This study, based on participant reports without medical evaluation of benefits or side effects, does not offer sufficient evidence of rapamycin’s efficacy or safety. It supports further research into this molecule’s role in senescence.

Rapamycin could help preserve ovarian function.

Rapamycin inhibits the mTOR protein (mechanistic target of rapamycin), an enzyme that regulates many cellular metabolism pathways. When mTOR is active, it promotes cell proliferation and function. Inhibition by rapamycin slows these processes. This resembles cellular rest, which may extend cell lifespan. In the ovaries, the mTOR pathway plays a key role in the activation of primordial follicles, the structures containing immature oocytes. Over time, some of these follicles activate, mature, then degenerate if they do not lead to ovulation. This repeated monthly cycle accelerates ovarian reserve depletion.

A double-blind clinical trial is under way to evaluate rapamycin’s effects. Participants receive a 5 mg oral dose per week for 12 weeks, compared with placebo. 50 women aged 35 to 45 take part. The goal is to slow activation of primordial follicles by blocking the mTOR pathway, to preserve the oocyte reserve, and delay menopause. According to initial results, rapamycin would slow ovarian aging by 20%. The compound would reduce the number of eggs released each month to 15 instead of 50.

These early results are encouraging but warrant caution. The clinical trial is ongoing and expected to conclude in September 2026.

Definitive data are needed to confirm whether low-dose, short-term rapamycin can slow activation of primordial follicles without causing major adverse effects. If final data confirm preliminary observations, the implications may be significant: rapamycin may help slow depletion of the follicular reserve and extend female fertility.

Rapamycin does not appear to act directly on estrogen secretion. Its primary benefit lies in its ability to preserve ovarian follicles, and thus delay their premature activation. Fertility and menstrual cycle regularity depend on both follicle presence and cyclic estrogen and progesterone production. If rapamycin preserves follicles that remain hormonally inactive, its impact on fertility may be limited. We need the study’s final results to determine whether preserving the follicle reserve maintains ovarian hormonal function. Without this data, the clinical value of rapamycin to extend fertility or delay menopause remains uncertain.