- As women age, the number and quality of their eggs reduces, leading to a decline in fertility.
- At menopause, which generally occurs at about the age of 51, ovulation stops, and a woman can no longer conceive a child.
- Alongside this, the risk of several health conditions, including cardiovascular disease, osteoporosis, cognitive decline and dementia, increases.
- Now, a pilot study has found that a common drug, rapamycin, may delay ovarian aging, extending fertility and delaying the onset of menopause.
- The research suggests that the treatment might even have other anti-aging benefits.
Many people are now delaying having children until they are in their 30s. However, decreasing fertility at this age means that those above the age of 35 may find it more difficult to get pregnant than younger people.
Women are born with around 2 million immature eggs in their ovaries. Starting at puberty, one or more of these eggs will mature each month, and be released at ovulation. Menopause occurs when no more immature eggs mature and ovulation ceases.
A woman in her 20s has an 85% chance of conceiving within one year; by the age of 35, that chance has declined to 66%, and by 40 to 44%. These changes are due to the effects of aging on the ovaries and eggs.
Rapamycin, also known as sirolimus and sold under the brand name Rapamune, is a drug that is currently approved as an anti-rejection treatment after transplants and as an anti-cancer therapy. However, it is now also being hailed as a potential anti-aging drug. Studies in mice have shown that rapamycin both increases lifespan and delays the onset of many age-related diseases.
Other studies in mice have shown that short-term treatment with the drug can increase the lifetime of the ovaries, both by preserving the follicles and improving the quality of the ova.
Now, a pilot study in 50 women, that has not been peer-reviewed, has reported that a weekly dose of rapamycin could delay ovarian aging by as much as 20%. The researchers are now continuing the study with a larger cohort of women.
“The findings from the pilot study are promising, suggesting that rapamycin could decrease ovarian ageing by 20% without side effects. This is potentially beneficial as it could extend fertility by up to five years, addressing the fertility decline that many women face after the age of 35. However, concerns include the small sample size and the need for further research on larger scales to confirm these results and ensure long-term safety and efficacy.”
— Dr. Meltem Özkan Girgin, obstetrician and gynaecologist specialist at the London Regenerative Institute.
Rapamycin inhibits the mTOR signaling pathway which regulates cell growth and metabolism. It was approved by the Food and Drug Administration (FDA) for use as an anti-rejection treatment following kidney transplants in 1999, and has since been authorised for use against some cancers.
There is growing evidence that it may also have some potential in treatment of neurological and metabolic disorders. A 2024 review of studies in people found that rapamycin treatment has beneficial effects on the immune and cardiovascular system and the skin, but no effects on learning, memory or neurodegeneration.
Mouse studies have shown that rapamycin can increase lifespan and health span and delay ovarian aging.
In this latest pilot study, 50 women aged 35-45 who were in the stage 3a of reproductive aging, just before the onset of perimenopause, took 5mg of rapamycin or 5mg of placebo orally once a week for 12 weeks.
The researchers then assessed their ovarian reserve by transvaginal ultrasound, and used blood tests to detect a number of ovarian hormones.
“The ultimate goal of this work is to be able to extend the time when the ovary can provide its many health benefits and thereby extent the healthspan and lifespan of women,” Dr. Zev Williams, one of the study authors, and Director of Columbia University Fertility Center, told Medical News Today.
The researchers say that their early results suggest that this weekly dose of rapamycin could delay ovarian aging by as much as 20%, giving women a potential 5 extra fertile years.
They also found that there were no side effects at this low dosage — after kidney transplant, patients usually need 2–5mg per day, compared with 5mg per week in this study.
In addition, the researchers said that participants reported improvements in their general health, memory, energy levels and skin and hair quality while taking rapamycin.
“Rapamycin appears to slow down the rate at which eggs in the ovary are lost. Normally, dozens of eggs are lost every month. By slowing the rate at which eggs are lost, we hope to be able to extend the ovaries’ lifespan and delay menopause.”
— Dr. Zev Williams
However, Özkan Girgin, who was not involved in the study, sounded a note of caution about extending the years of fertility, telling MNT:
“Delaying menopause could pose several risks to women. Menopause naturally decreases the risk of hormone-related cancers such as breast and ovarian cancer. Prolonging ovarian activity might increase exposure to oestrogen, potentially raising these cancer risks.”
“Rapamycin may boost fertility by improving ovarian function, but its effects on pregnancy outcomes and birth warrant careful consideration. As age increases for women, so does the probability of foetal abnormality concerns including structural chromosomal and genetic abnormalities,” she added.
“The re-purposing of rapamycin for ovarian aging is an innovative approach that could offer significant benefits for women delaying childbirth. However, it is crucial to balance optimism with caution, ensuring comprehensive evaluation of both short-term and long-term effects.”
— Dr. Meltem Özkan Girgin
Encouraged by the results of this pilot study, the researchers are now recruiting up to 1,000 women to engage in their full study.
Özkan Girgin told MNT what she would like to see from the study:
“To verify the early findings, the clinical trial should demonstrate consistent results across a larger, more diverse cohort and more human studies. Desired outcomes include a statistically significant decrease in ovarian ageing, no serious side effects, maintained or improved overall health and confirmation that the extended fertility results in successful pregnancies,” she told MNT.
