A number of genetic signals have been identified that influence the age at which women begin menopause, which could pave the way for fertility treatment that could extend women’s natural reproductive lives.
The researchers scanned the genes of more than 200,000 women and found nearly 300 genetic cues that the researchers say could help identify why some women are predisposed to early menopause, the health consequences of going through early menopause, and whether These signals can be manipulated to improve fertility.
The study, led by scientists from the universities of Cambridge, Exeter and Copenhagen and still in its early stages, found that two genes called CHEK1 and CHEK2 were key to understanding the difference between these women.
When CHEK2 was inhibited in mice, their offspring had a longer reproductive life.
Similarly, when CHEK1 was overexpressed in mice, it extended the reproductive life of the offspring by improving the initial number of eggs in fetal life.
Their data suggested that women who lacked sufficient CHEK2 protein experienced menopause more than three years later than those who had normal CHEK2 levels.
The researchers also examined certain health impacts of having an earlier or later menopause.
They genetically found that earlier menopause increased the risk of type 2 diabetes and was linked to poorer bone health and an increased risk of fractures.
But they also found that earlier menopause reduced the risk of some types of cancer, such as ovarian and breast cancer.
Study co-author Dr Katherine Ruth from the University of Exeter said: “We found that earlier menopause was causally associated with a lower risk of hormone-sensitive cancers.
“We think this is probably because the exposure to high levels of sex hormones (which are at higher levels while the woman is still menstruating) is shorter.”
Ruth added: “We hope that our work will help open up 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 begin to predict which women might have earlier menopause and therefore struggle to get pregnant naturally.
“And since we are born with our genetic variations, we could offer this advice to young women.”
Professor Eva Hoffmann from the University of Copenhagen, also a co-author of the study, said her findings “provide potential new direction for therapeutic approaches that could seek to treat infertility, particularly in the treatment of IVF.”
He added: “Of course, there are a number of scientific issues and safety concerns that need to be addressed before trying it on humans.
“But what our studies show is that it is possible that short-term, targeted inhibition of these pathways during IVF treatment could help some women respond better.”
Female reproductive life expectancy begins with puberty and ends with menopause, but the time of menopause varies considerably among women: most women go through menopause between the ages of 40 and 60 (about 1% are menopause before age 40). As with almost all health conditions, this time is determined by genetics along with environmental and lifestyle factors.
These environmental factors, such as smoking and BMI, are well studied, but the genetic basis for menopause has been relatively opaque. These genetic foundations have been difficult to investigate because, although women’s egg supply is determined in the womb before birth, throughout their reproductive life, some are lost due to cell death caused by DNA damage.
“We found five times more genetic factors than were previously known,” said study author Dr. John Perry of the University of Cambridge. “In terms of what we know about the genetics of menopause, it’s a big step forward.”
One of the key goals of the study was to help predict a woman’s natural fertility window. There are some tests that can measure the hormones that indicate that a woman has a low ovarian reserve, but when it is detected, the decline has already begun; there is no long-term predictor of when the decline will begin, Perry said.
Additional research could help identify some women who are at relatively high risk compared to others, he added.
“Ultimately, we are working towards this kind of predictive test where you can analyze someone’s DNA and then try to infer what their natural fertility window would be … then women can make more informed reproductive decisions.” He said.
Based on the genetic variants identified, the researchers also developed a risk score to assess whether it was possible to determine which women were likely to reach menopause early.
“We compared the predictive ability of our genetic risk to the best non-genetic predictor that we knew about, which was smoking,” Perry said.
“It turns out that our genetic risk score has not yet reached the level of clinical utility, but it is a better predictor than smoking.”
George is Digismak’s reported cum editor with 13 years of experience in Journalism