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, according to early results of a study.
The research into repurposing the immunosuppressant rapamycin has been hailed as a “paradigm shift” in how menopause is studied.
The Validating Benefits of Rapamycin for Reproductive Ageing Treatment (Vibrant) study is designed to measure whether the drug can slow ovaries ageing, thereby delaying menopause, extending fertility and reducing the risk of age-related diseases.
The study, which will eventually include more than 1,000 women, now has 34 participants aged up to 35, with more women joining every day.
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Yousin Suh, a professor of reproductive sciences and professor of genetics and development at Columbia University and Zev Williams, associate professor of women’s health and the chief of the division of reproductive endocrinology and infertility at Columbia University Irving Medical Center, co-led on the study.
Suh said early results suggested it was realistic to hope the drug could decrease ovary ageing by 20 per cent without women experiencing any of the 44 side effects rapamycin can have, which range from mild nausea and headaches to high blood pressure and infections.
In fact, Suh said, participants in the randomised, placebo-controlled study had self-reported improvements in their health, memory, energy levels and in the quality of their skin and hair: health improvements consistent with other studies into rapamycin that have suggested the medication can increase lifespan by 9-14 per cent while revitalising the immune system and organs that deteriorate in old age.
“The results of this study – the first in human history – are very, very exciting. It means that those with age-related fertility problems now have hope when before, they didn’t,” said Suh.
“These early results mean we now have a clear shot at our ultimate goal: using rapamycin to extend the lifespan of the ovary and thereby delaying the menopause, while also extending the lifespan of the woman and improving her health and quality of life.”
Suh said the team of at least 12 scientists working on the study, which will cost more than $1m (€920,000) in total, had “great confidence in the results being just as exciting when we scale the study up”.
“In a way, our results are too good to be true – except, because rapamycin is so well-studied, we know they are true,” she said. “These results are like a dream come true.”
It is the first study to look at the core of ovarian ageing and trying to slow down the rate at which that occurs. Previous research on menopause has only targeted it at a symptomatic level.
“Ovarian ageing is the fundamental driver of ageing in women,” said Suh. “HRT is a Band-Aid for ageing that has already taken place but if women take rapamycin in their 30s, when their ovaries start to decline but there aren’t yet any symptoms, they can actually slow the whole ageing process.”
Ovaries release eggs continuously: women lose about 50 every month, with just one reaching ovulation. A small, weekly dose of rapamycin slows ovaries down, so they release only 15 eggs a month. Suh and Williams estimate this decreases the organs’ ageing by 20 per cent.
“We know this works with animals – and now we know it’s safe for humans,” said Williams. “Now we just need a bigger study to put both parts together.”
Because rapamycin is a cheap, generic drug already widely used, once the evidence is established, progress will be fast, he said.
“The very features of the drug that make it so promising and give it such great potential for having a quick and major impact for women are, ironically, the very factors that make it hard to find funders for the study,” he said.
“That’s why this hasn’t been done before: it’s an expensive study and a lot of women will benefit from it – but there’s no motivation for pharmaceutical companies to invest because there’s no possibility of making money from an off-patent drug.”
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A clinical trial of rapamycin in humans has also been considered impossible because it would take decades to detect any longevity effects. Ovaries, however, age so quickly that change can be measured over six months .
The level of rapamycin used is small: women are given 5mg a week for three months compared with the 13mg a day that transplant patients can be prescribed for years. But doses are critical: too much rapamycin could stop ovulation completely and it is yet unknown whether the quality of the follicles will deteriorate over the extra time ovaries will live, thereby producing eggs more likely to contain genetic abnormalities.
Another exciting outcome of the study is that all the women have continued to menstruate as normal, said Williams. “The implication of that is that we’ve hit on the perfect dose: if we were giving too much, menstruation would become irregular or stop.”
Vibrant will report in two years and be followed up by a much bigger, “phase 2” study. “Our vision is women in their 30s and older can make a simple visit to their family doctor if they want to have more freedom over when they have babies,” said Suh.
Women could stop taking rapamycin after menopause but the wider health benefits the medication seems to provide might make it beneficial for them to continue, she added.
The findings have been celebrated by Dr Jennifer Garrison, a neuroscientist at the Buck Institute for Research on Aging and the founder of the Global Consortium for Reproductive Longevity and Equality.
“This research is remarkable and marks a paradigm shift in biomedical research for women,” she said. “It is the very first in what needs to be many studies to solidify the idea that we can prolong ovarian function.
“What we can definitely take from the results so far is that keeping the endocrine function of ovaries intact with age is now within our grasp.” – Guardian