Krina T. Zondervan is in the Nuffield Department of Women’s and Reproductive Health, University of Oxford, Women’s Centre, John Radcliffe Hospital

Genomic analysis identifies variants that can predict the timing of menopause

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2021-08-05 15:30:04

Krina T. Zondervan is in the Nuffield Department of Women’s and Reproductive Health, University of Oxford, Women’s Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK, and at the Wellcome Centre for Human Genetics, University of Oxford, UK.

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Menopause is the permanent cessation of menstrual cycles in women following the loss of ovarian function1. It occurs, on average, between 47 and 52 years of age globally2, but around 4% of women undergo it before the age of 45 (early menopause) or even 40 (primary ovarian insufficiency; POI)3. Being able to predict when menopause will occur would give women and their partners greater flexibility in choosing when to have a child. This knowledge, and treatments to delay menopause, might be particularly welcomed by women at high risk of early menopause or POI. Ruth et al.4 now report genetic findings that could bring us a step closer to predicting and treating early menopause.

Age at natural menopause (ANM) is determined by the complex interaction of both non-genetic and genetic factors. Non-genetic factors associated with earlier ANM include poor childhood nutrition and smoking, whereas being overweight is associated with later ANM1,2. Genetic factors are thought to account for about 50% of the variation in menopausal timing5. Previous genetic studies6,7 have implicated a role for DNA-damage-response (DDR) mechanisms in the timing of menopause. DDR is a molecular process that is crucial for the error-free replication of cells, including the generation of egg cells in the ovary, and for the repair of DNA damage caused by environmental factors such as cigarette smoke8.