A drug that could extend women’s fertility by five years – and help them live longer in better health – is safe for a young, healthy population, early results from a study suggest.
The research into the repurposing of the immunosuppressant rapamycin is being hailed as a “paradigm shift” in the way menopause is studied.
The Validating Benefits of Rapamycin for Reproductive Aging Treatment (Vibrant) study is designed to measure whether the drug can slow ovarian aging, thereby delaying menopause, prolonging fertility and reducing the risk of age-related diseases.
The study, which will eventually involve more than 1,000 women, currently includes 34 women under the age of 35. And more women are joining every day.
Yousin Suh, professor of reproductive sciences and professor of genetics and development at Columbia University, and Zev Williams, associate professor of women’s health and chief of the division of reproductive endocrinology and infertility at Columbia University Irving Medical Center, both led the study.
Suh said early results suggested it was realistic to hope the drug could slow ovarian aging by 20 percent without women experiencing the 44 side effects rapamycin can have, ranging from mild nausea and headaches to high blood pressure and infections.
Suh said participants in the randomized, placebo-controlled trial self-reported improvements in their health, memory, energy levels, and the quality of their skin and hair. Those improvements are consistent with other studies of rapamycin, which have shown the drug can extend life by 9-14% while revitalizing the immune system and organs that decline with age.
“The results of this study – the first in human history – are very, very exciting. It means that people with age-related fertility problems now have hope, where they didn’t before,” Suh said.
“These early results mean that we now have a clear chance of achieving our ultimate goal: using rapamycin to extend the lifespan of the ovaries and thereby delay menopause, while also extending a woman’s lifespan and improving her health and quality of life.”
Suh said the team of at least 12 scientists working on the research, which will cost more than $1 million (£750,000) in total, are “very confident that the results will be just as exciting as we scale up the research”.
“In some ways, our results are too good to be true — except we know they are true, because rapamycin has been studied so well,” she said. “These results are like a dream come true.”
It is the first study to look at the core of ovarian aging and attempt to slow the rate at which it occurs. Previous research into menopause has focused only on the symptomatic level.
“Ovarian aging is the fundamental driver of aging in women,” Suh said. “HRT is a Band-Aid for aging that has already occurred, but if women take rapamycin in their 30s, when their ovaries are starting to decline but there are no symptoms yet, they can actually slow the entire aging process.”
Ovaries release eggs continuously: women lose about 50 each month, only one of which reaches ovulation. A small, weekly dose of rapamycin slows the ovaries down so that they release only 15 eggs each month. Suh and Williams estimate that this reduces the aging of the organs by 20 percent.
“We know this works in animals — and now we know it’s safe for humans,” Williams said. “Now we just need a larger study to put both parts together.”
Because rapamycin is a cheap, generic drug that is already widely used, progress will be rapid once the evidence is known, he said.
“The very features of the drug that make it so promising and give it such great potential to have such rapid and large effects on women are, ironically, the very factors that make it difficult to find funding for the research,” he said.
“That’s why this hasn’t been done before: it’s an expensive study and many women will benefit from it – but pharmaceutical companies have no incentive to invest because there’s no way to make money on an off-patent drug.”
A human clinical trial of rapamycin is also considered impossible because it would take decades to detect effects on lifespan. However, ovaries age so quickly that change can be measured over six months.
The amount of rapamycin used is low: women are given 5 mg a week for three months, compared with the 13 mg a day that transplant patients may be prescribed for years. But doses are crucial: too much rapamycin can stop ovulation altogether, and it’s not yet known whether the quality of the follicles will deteriorate as the ovaries live longer, increasing the risk of eggs with genetic abnormalities.
Another exciting finding from the study is that all of the women continued to menstruate as normal, Williams said. “The implication of that is that we found the perfect dose: If we gave too much, the periods would become irregular or stop.”
Vibrant will report in two years and will be followed by a much larger, “phase 2” study. “Our vision is that women 30 and older can have a simple visit to their primary care physician if they want more freedom over when they have children,” Suh said.
Women could stop taking rapamycin after menopause, but the broader health benefits the drug appears to offer might make it wise for them to continue, she added.
The findings have been celebrated by Doctor Jennifer Garrisonneuroscientist at the Buck Institute for Research on Aging and founder of the Global Consortium for Reproductive Longevity and Equality.
“This study is remarkable and marks a paradigm shift in biomedical research for women,” she said. “It is the very first of what will be many studies to confirm the idea that we can extend ovarian function.
“What we can certainly take away from the results so far is that it is now within our reach to keep ovarian endocrine function intact as we age.”