Genetic variations give insight into the age women start menopause

Hundreds of genetic variations may influence the age at which menopause starts, researchers have discovered.

Scientists have uncovered hundreds of genetic variations linked to reproductive lifespan, which has previously been most strongly linked to environmental and lifestyle factors. These insights could help both predict response to fertility treatments such as IVF, and potentially even extend fertility.

'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,' explained co-author Dr Katherine Ruth, of the University of Exeter.

The study was jointly led by the University of Exeter, the University of Cambridge, the Universitat Autònoma de Barcelona, Spain, and the University of Copenhagen, Denmark. The researchers looked for an association between specific genes and the age of menopause onset in over 200,000 women. They found hundreds of genes implicated in reproductive ageing, increasing the total number of known involved genes from 56 to 290.

Many of the genes are involved in repairing damaged DNA within cells – most significantly, the CHEK1 and CHEK2 genes. Whereas CHEK1 works to repair damaged DNA, CHEK2 produces a 'checkpoint' protein responsible for triggering cell death when DNA cannot be repaired. The research team studied genetically modified mice and found that mice with no functioning copy of CHEK2 had a longer reproductive lifespan, as measured by the rate of egg cell death. They confirmed that within human genetic datasets, women with a non-functional copy of CHEK2 had a delay in menopause onset of over three years.

Fertility can dramatically decline up to a decade before a woman begins menopause, but there is currently no reliable predictor of when this will be. Menopause occurs due to the loss of immature egg cells, present at birth, as DNA damage accumulates and repair machinery becomes less efficient.

The researchers suggested that their findings could be used to find treatments for delaying menopause to improve fertility treatment success – by blocking function of genes such as CHEK2.

'I think that enhancing DNA repair has very high promise in delaying menopause,' Professor Kutluk Oktay, fertility specialist at Yale University, Connecticut, not involved with the study, commented, 'But abolishing checkpoints that get rid of damaged oocytes might be a risky proposition'.

Dr John Perry of the University of Cambridge and co-author of the study summarised: 'This research is incredibly exciting. Although there's still a long way to go... we now know a lot more about human reproductive ageing.'

The results of the study were published in the journal Nature.