Spanish scientists may have found the key to delaying the menopause

RESEARCHERS from Spain have joined an international study which could predict the lifespan of women's fertility, and even prolong it.

The findings could be equally helpful for women who do not want to have children, since increasing egg reserves delays the menopause and the health and wellbeing issues that come with it.

A 'map' has identified 290 gene variants – 56 of which were already known – which enable scientists to work out more precisely when a woman may hit the menopause.

The team, made up of Barcelona Autonomous University (UAB), Copenhagen University (Denmark), and the British universities of Cambridge and Exeter recalls that, although life expectancy has increased dramatically in the last 150 years and is already around 86 for women in Spain, with living to 100 or beyond no longer as ground-breaking as it was even in the mid-to-late 20th century, reproductive life expectancy has not moved; women continue to be at their most fertile between 17 and 25, when the majority are still at school or college or have not yet 'found their feet' with a career, own home and steady relationship, and the menopause still comes at an average age of 50.

Even before then, the 'perimenopause' can start as young as the early 30s, by which time fertility is already in freefall; from about 27 to 30, the chances of a live birth – not even a pregnancy – are lower than those of a non-pregnancy or a miscarriage; by around 40, they are roughly 20% and by the mid-40s, lower than 5% - typically just as women become 'settled' into life and in a position where having a baby might be feasible.

Fertility clinics will perform insemination, or embryo transfer using either a woman's own eggs or donor eggs, until age 50 inclusive, even if the woman has already menopaused; and in the case of the latter option – given that donors are typically at the younger end of the stipulated 18-35 age group – the chances of a live birth are around 80% irrespective of the mother's own age, but insemination even in much younger women only has about a 15% chance of success and costs in region of €1,000 for each attempt.

The research team recalls that 'natural' fertility declines dramatically some years before the menopause, since women are born with all the eggs they are ever going to produce and the better-quality ones are released early in her reproductive years, with the poorer-quality ones left to the end.

Health issues associated with the menopause include depression and a greater risk of type II diabetes and osteoporosis, the UAB explains.

Genes that manage repair of age-damaged DNA

The team analysed data from over half a million women's genetic bases – the majority of whom were of European origin but of whom 80,000 were of east Asian extraction, and all of whom had hit the menopause between age 40 and 60.

Results were very similar in European – Nordic and Mediterranean – and east Asian women, and after examining around 13.1 million genetic variants, scientists identified 290 linked to 'ageing of the ovaries'.

Most of them were connected to DNA repair processes – it is damage to DNA which causes ageing, as the 'tails', or telomeres, become shorter with the passage of years, and this phenomenon accelerates when the organism is exposed to environmental stressors, such as pollution, alcohol, smoking and poor diet.

Mechanisms that control DNA quality and regulate its repair when it becomes damaged are 'fundamental' in maintaining egg numbers and ovarian function, says Dr Ignasi Roig, one of the research report authors and head of the UAB's Biotechnology and Biomedicine Institute.

The menopause is associated with a reduction in egg quantity, meaning that the longer eggs stay in the ovaries, the longer it will be before the menopause arrives.

Two main genes were found which regulate a vast variety of DNA-repair processes – the CHEK1 and CHEK2.

In tests on mice, scientists found that when they eliminated the CHEK2, or when the CHEK1 levels were higher, reproductive life extended by 25% and eggs took longer to run out.

Although experiments on mice are not conclusive, since this species does not go through a menopause, mice do in fact go through an ovarian function ageing process very similar to those of humans.

Also, the meta-analysis of genetic data in human females found that those who do not, naturally, have an active CHEK2 gene went through the menopause on average 3.5 years later than those whose CHEK2 showed normal activity.

Women carrying the gene mutation BRCA1, associated with hereditary breast cancer, were found to go through the menopause earlier – approximately 2.63 years earlier on average.

Dr Katherine Ruth of Exeter University says: “We hope our work will offer new possibilities to help women plan their future.”

Extending egg-production years to put off the menopause

Although the researchers, studying the impact of the menopause, found that this increased the risk of type II diabetes and osteoporosis or, at least, poorer bone health, they also found that the end of menstruation came with a reduced risk of certain types of cancer, such as some breast cancers and ovarian tumours.

This is an area that will require further study, since breast cancer is statistically more frequent in post-menopausal women, although strains suffered by much younger women tend to be more aggressive.

“This research is really exciting,” said John Perry of Cambridge University, “although there's still a long way to go.

“We now know more about the mechanisms that regulate the reproductive ageing process in women, and slowing it down can help prevent, or reduce the risk, of certain health problems.”

The next step, says Dr Roig, is to work out, using animals such as mice, how to extend the 'ovarian reserve', or level of egg production, using pharmaceutical drugs. 

Enabling a woman to continue producing eggs could keep her fertile for longer, but would also put off the menopause for a few more years.

Eventually, it could even mean that a woman gets to choose when her menopause happens – opting to delay it if she has care duties whilst still working, for example, and putting it off until she is nearer retirement.

It seems unlikely at this stage that science will enable women to be producing eggs for the rest of their natural lives, but it may be able to predict when a female is facing an early menopause and help delay it if she wants to have children.