New research brings into question the current understanding of genetic factors behind early menopause

The genetic causes of very early menopause will have to be reconsidered after researchers found that nearly all women who carried variations thought to cause the condition in fact had their menopause at an older age.

Until now, variants in any one of more than 100 genes were thought to cause premature ovarian insufficiency (POI), which results in menopause before the age of 40 and affects around one per cent of women, making it a leading cause of infertility. Under current guidance, a variation in one of these genes is cause for clinicians to consider a genetic diagnosis of POI.

Now, in the largest study to date, published in Nature Medicine, a team led by the University of Exeter and the University of Cambridge analyzed genetic data from more than 104,733 women in UK Biobank, of whom 2,231 reported experiencing menopause before the age of 40.

The study found evidence that 98 percent of women carrying variations in the genes that were previously considered to be causes of premature menopause in fact had menopause over 40, the Reference ore ruling out a diagnosis of POI in these women.

Reference: Penetrance of pathogenic genetic variants associated with Premature Ovarian Insufficiency, Nature Medicine, DOI 10.1038/s41591-023-02405-5