Around two per cent of women with primary ovarian insufficiency – the medical term for a permanent halt in menstruation occurring naturally before the age of 40 – are affected by changes to a particular gene, a study has shown.

The study, led by Dr Anna Murray at the University of Exeter and including researchers from The Institute of Cancer Research, London, found that changes to the gene FMR1 are responsible for a smaller proportion of cases of primary ovarian insufficiency than some previous studies had suggested. This was the first study of women from the general population rather than specifically selected women and therefore provides a more accurate estimate of the true prevalence of the genetic change.

However, the results, published in the journal Genetics in Medicine, also show testing women for changes in FMR1 could be a useful option to use in diagnosing the cause of primary ovarian insufficiency.

The researchers used the Breakthrough Generations Study database – which is funded by Breakthrough Breast Cancer – to help calculate the chance that 254 women with primary ovarian insufficiency carried so-called ‘pre’-mutations in FMR1. Premutations in FMR1 are multiple short repeats of DNA code which affect the FMR1 gene without inactivating it.
By analysing the DNA of the women with primary ovarian insufficiency, the study found that around two per cent of the women had premutations inFMR1. Although only a small proportion of the total number, it is the most common known genetic cause of primary ovarian insufficiency.

For women with it, knowing that FMR1 was the cause is important because the premutation could be carried by other members of their family and women with a premutation are at risk of having children with the full mutation version of the gene, which can causes learning disability. At risk individuals can be offered prenatal testing once the gene mutation has been identified in them.

The researchers also looked at the genetic profiles of 1,881 women who underwent early menopause, between the ages of 40 and 45. They found the FMR1 premutation in 0.7 per cent of the women.
The authors of the study note that FMR1 testing is a possible option for women who have primary ovarian insufficiency or have an early menopause.

Professor Anthony Swerdlow, Professor of Epidemiology at the ICR, who co-led the study, said: “In most women with premature menopause, the cause is not known. It is important, where we can, however, to give women information about their causes.

“This study shows the prevalence of changes to the FMR1 gene as a cause of premature menopause. It also shows the importance of large studies that gather detailed participant data – like the Breakthrough Generations Study – in investigating the causation of many conditions and diseases.”