In recent years, many people have chosen to delay having children until they are in their 30s. The trend, however, comes with challenges, as fertility tends to decrease with age. Women over the age of 35 often find it more difficult to conceive than their younger counterparts. This decline in fertility is primarily due to the natural aging process that affects the ovaries and the eggs they contain.
Women are born with approximately 2 million immature eggs in their ovaries. From puberty onward, one or more of these eggs mature each month and are released during ovulation. As a woman ages, the number and quality of these eggs decrease, leading to a decline in fertility. Menopause occurs when no more eggs mature, and ovulation ceases altogether.
Statistics illustrate this decline in fertility. A woman in her 20s has an 85% chance of conceiving within one year. By the age of 35, this probability drops to 66%, and by the age of 40 to 44, it decreases even further. The reasons for this decline are tied to the natural aging process, which affects the health and viability of the ovaries and eggs.
Rapamycin: A Drug with Potential Beyond Its Original Use
Rapamycin, also known as sirolimus and sold under the brand named Rapamune, is a drug initially approved for us as an anti-rejection treatment after organ transplants. It is also used as a therapy for certain types of cancer.
However, recent research has revealed that rapamycin may have potential as an anti-aging drug. Studies conducted on mice have shown that rapamycin can increase lifespan and delay the onset of many age-related diseases, including those affecting the ovaries.
In these animal studies, short-term treatment with rapamycin was found to increase the lifespan of the ovaries by preserving the follicles and improving the quality of the eggs. These findings have sparked interest in exploring whether rapamycin could have similar effects in humans, particularly in delaying ovarian aging and extending fertility.
Promising Results from a Pilot Study
Recently, a pilot study involving 50 women provided preliminary evidence that rapamycin might be able to delay ovarian aging in humans. The study, which has not yet been peer-reviewed, reported that a weekly dose of rapamycin could delay ovarian aging by as much as 20%. If these findings are confirmed, rapamycin could potentially extend a woman’s fertility by up to five years, addressing the fertility decline that many women face after the age of 35.
“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 larges scales to confirm these results and ensure long-term safety and efficacy,” says Dr. Meltem Özkan Girgin, an obstetrician and gynecologist specialist at the London Regenerative Institute.
Understanding How Rapamycin Works
Rapamycin works by inhibiting the mTOR signaling pathway, a critical regulator of cell growth and metabolism. This pathway has been linked to the aging process and is a target for anti-aging therapies.
Rapamycin was approved by the U.S. Food and Drug Administration (FDA) for use as an anti-rejection drug following kidney transplants in 1999, and it has also been authorized for use in treating some types of cancer.
There is a growing body of evidence suggesting that rapamycin may have additional benefits, including potential applications in treating neurological and metabolic disorders. A 2024 review of studies involving human subjects found that rapamycin treatment had beneficial effects on the immune and cardiovascular systems, as well as on the skin. However, the review did not find significant effects on learning, memory, or neurodegeneration.
In the recent pilot study on ovarian aging, 50 women aged 35-45, who were in the stage 3a of reproductive aging (just before the onset of perimenopause), took either 5 mg of rapamycin or a placebo orally once a week for 12 weeks. The researchers then assessed the participants’ ovarian reserve using transvaginal ultrasound and measured various ovarian hormones through blood tests.
“The ultimate goal of this week is to be able to extend the time when the ovary can provide its many health benefits and thereby extend the health span and lifespan of women,” Dr. Zev Williams, one of the study’s authors and Director of Columbia University Fertility Center, told Medical News Today.
The Potential Impact of Delaying Ovarian Aging
The researchers behind the study believe that their early results suggests that a weekly dose of rapamycin could delay ovarian aging by as much as 20%, potentially giving women five extra fertile years. They also found that the low dosage used in the study (5 mg per week) did not cause any side effects. In contrast, patients undergoing kidney transplants typically require a daily dose of 2-5 mg of rapamycin.
Moreover, the study 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,” says Dr. Zev Williams.
However, not everyone is convinced that delaying menopause is without risks. Dr. Özkan Girgin, who was not involved in the study, cautions that extending the years of fertility could pose several risks.
“Delaying menopause could pose several risks to women. Menopause naturally decrease the risk of hormone-related cancers such as breast and ovarian cancer. Prolonging ovarian activity might increase exposure to estrogen, potentially raising these cancer risks,” she explains.
“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 fetal abnormality concerns including structural chromosomal and genetic abnormalities,” she adds.
The Future of Rapamycin Research
Encouraged by the promising results of this pilot study, the researchers are now expanding their research to include up to 1,000 women in a full-scale study. This larger study aims to verify the initial findings and provide a more comprehensive understanding of rapamycin’s effects on ovarian aging and fertility.
“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,” says Dr. Özkan Girgin.
As the research progresses, Dr. Özkan Girgin highlights the importance of consistent results across a larger and more diverse cohort.
“To verify the early findings, the clinical trials 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 concludes.
The potential of rapamycin to delay ovarian aging and extend fertility represents an exciting development in reproductive health. However, further research is necessary to fully understand the long-term implications and to ensure the safety and efficacy of this treatment for women who choose to delay motherhood.
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