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Nearly 300 gene variations that influence menopause age identified

The findings could lead to improved infertility treatments as well as increase the natural reproductive lifespan of women, researchers say.
The findings could lead to improved infertility treatments as well as increase the natural reproductive lifespan of women, researchers say. The findings could lead to improved infertility treatments as well as increase the natural reproductive lifespan of women, researchers say.

Scientists have identified nearly 300 gene variations that influence menopause age which, they say, could lead to improved infertility treatments in the future and increase the natural reproductive lifespan of women.

UK researchers have found that these genetic variants are able to roughly predict the age at which some women will stop having periods, and thus identify those at risk of early menopause.

The team said its findings, published in the journal Nature, could also lay the groundwork for future research on preventing certain types of cancer associated with hormones, such as ovarian and breast cancer, as well as type 2 diabetes.

Study co-author Dr Katherine Ruth, of the University of Exeter, said: “We hope our work will help provide new possibilities to help women plan for the future.

“By finding many more of the genetic causes of variability in the timing of menopause, we have shown that we can start to predict which women might have earlier menopause and therefore struggle to get pregnant naturally.

“And because we are born with our genetic variations, we could offer this advice to young women.”

For the study, the researchers looked at genetic data gathered from 201,323 women of European ancestry and an additional 80,000 women of East Asian ancestry from the UK Biobank, which has health and genetic information on around half a million people, as well as 23andMe, a consumer DNA testing company.

They also designed mouse models to examine the effects of some of the genes on the reproductive lifespan of the rodents.

In mice, the researchers found two particular genes, Chek1 and Chek2, to affect fertility and reproductive lifespan.

The team found that inactivating Chek2 so that it no longer functions while over-expressing Chek1 to enhance its activity increased reproductive lifespan in mice by around 25%.

Meanwhile, in women who naturally lack an active Chek2 gene, the scientists found they reach menopause on average 3.5 years later than women with a normally active gene.

Professor Eva Hoffmann, of the University of Copenhagen, who is also a co-author on the study, said their findings “provide potential new direction for therapeutic approaches that might seek to treat infertility, particularly, in IVF treatment”.

She said: “IVF relies on hormone stimulation of women.

“We found that in one of our mouse models, Chek2, the female mice there had an improved response to hormone stimulation, which means that more eggs were obtained for actual IVF treatment.

“There are, of course, a number of scientific questions and safety concerns that have to be addressed before this is attempted in humans.

“But what our studies show is that it is possible that targeted short-term inhibition of these pathways during IVF treatment could help some women respond better.”

The researchers also examined certain health impacts of having an earlier or later menopause.

They found genetically that earlier menopause increased the risk of type 2 diabetes and was linked to poorer bone health and increased risk of fractures.

But they found earlier menopause to decrease the risk of some types of cancer, such as ovarian and breast cancer.

Dr Ruth said: “We found that earlier menopause was causally associated with a lower risk of hormone-sensitive cancers.

“We think this is probably due to having a shorter lifetime exposure to high levels of sex hormones (which are at higher levels while a woman is still menstruating).”