An interesting article in nature examined this issue.  Zondervan published her view on 4th August 2021.  

Menopause as we know is the permanent cessation of menstrual cycles in women following the loss of ovarian function.  On average it occurs between 47 and 52 years old globally but around 4% of women undergo the menopause before the age of 45 and this is called an early menopause or even 40 and this is known as primary ovarian insufficiency. 

Being able to predict when the menopause will occur would give women and their partner’s greater flexibility in choosing when to have a child.  This knowledge and treatments to delay menopause, might be particularly welcomed by women at a high risk of early menopause or primary ovarian insurgency.  

Researchers now report genetic identity that could bring us closer to predicting and treating early menopause. 

They found genetic variants that influenced age at natural menopause.  The results indicated mechanisms such as DNA damage repair and gave insight into the potential for predicting and treating the early menopause. 

Age at natural menopause is determined by a complex interaction of both non genetic and genetic factors.  

Non genetic factors associated with the early age of natural menopause include poor childhood nutrition and smoking, whereas being overweight is associated with a later age of natural menopause.  

Genetic factors are thought to account for about 50% of the variation in menopausal timing.  

Previous genetic studies have implicated a role for DNA damage response mechanisms at the timing of menopause.  DNA damage response 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 smoking.  

Ruth and others conducted the largest genetic analysis so far in women whose age of natural menopause has occurred between the age of 40 and 60.  It tested millions of common genetic variants from across the genome for an association with age of natural menopause.  They found 290 independent areas of the genome that contained common genetic variants associated with the age of natural menopause, a fivefold increase from previous results.  

They found that many of the variants implicated in their analysis affected genes involved in DNA damage response including the genes BRCA1 and CHEK2, which have been suggested to previously affect age of normal menopause.  

They found that the age for normal menopause associated genes were preferentially expressed in blood derived stem cells, the cell types that had a high turnover and therefore depended heavily on the DNA damage response.  

Earlier research had shown that feeding pregnant mice a high fat, high sugar diet resulted in the female offspring having a lowered reproductive potential as in a reduced ovarian reserve.  

What can be inferred from this research?  They found that each year of a genetically delayed age phenomenal menopause increased the risk of hormone dependent cancers such as endometrial cancer 5% and oestrogen receptor positive breast cancer 3.8% consistent with epidemiological evidence.  

By contrast, genetic variants that delayed the age of normal menopause were inferred to increase bone density and reduce the risk of factors and not to affect the risk of cardiovascular disease or Alzheimer’s disease, lipid levels, body mass or longevity. 

For women at risk of early menopause and premature ovarian insufficiency, the benefits might be more likely to outweigh the risks, although caution should be exercised in translating the findings into genetic tests for early menopause and premature ovarian insufficiency.  

This research paves the way for far more detailed studies that could lead to women being able to predict their menopausal age and to consider options to extend their reproductive age span.

Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed

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