Genetic profile affects age of menopause

The average age of menopause in the UK is 51 years. This is partly determined by your lifestyle but recent scientific research is revealing the genes that account for a 50% link with your mother’s age of menopause.

The onset of menopause is associated with various health risks, such as cardiovascular disease, osteoporosis and breast cancer, increasingly important as the population ages. In 1900 the life expectancy for a women in the UK was 50, so many women would not have reached menopause before they died. In 2017, the life expectancy for a women is in the late 80s, at least 35 years after the onset of menopause.

Women are born with a finite number of eggs in their ovaries. During the monthly menstrual cycle, an egg is realised from the ovaries. If no fertilisation takes place, the lining of the uterus is shed in the monthly period. As the levels of fertility hormones change with increasing age, egg production and monthly periods gradually cease, often with accompanying symptoms such as hot flushes.

Menopause is said to have occurred when a woman has not had a period in the preceding 12 months. Natural menopause happens between the age of 40 and 60, with the average at 51 years. Premature menopause, occurring before the age of 40, is also of concern as women have children later in life. It is estimated that 1-5% of women have a premature menopause; in some cases, this is associated with surgery and/or the treatment of cancer. Studies of populations who use no birth control have also shown that fertility wanes significantly about 10 years before menopause occurs.

If you smoke around the time of the menopause, it will hasten its onset by 2 years. This only appears to apply if you smoke 14 or more cigarettes a day; the association does not hold up if you’re a light smoker or smoked in the past.

Although the evidence is clear cut with smoking, the jury is still out on other environmental influences. These include: race, education, BMI, number of children, age of first menstrual cycle, oral contraceptive use, breast feeding, alcohol consumption, altitude and even exposure to sunlight.  Reports are conflicting, partly because of the difficulties of studying menopause, which is defined retrospectively.

The age at which your mother or sister had their last period plays a large part in the timing of your menopause. Studies in twins and in mothers and daughters have revealed that approximately 50% of the timing of your last period is governed by your genetic inheritance. A Danish research team found that women whose mothers had an early menopause had significantly fewer eggs in their ovaries than those whose mothers had a later menopause.

Now scientists are beginning to dissect the genes involved. One gene which has emerged is carried on the X sex chromosome (women have two X chromosomes and men an X and a Y chromosome). Men who carry a particular form of this gene develop Fragile X syndrome with severe learning difficulties. Female relatives of Fragile X individuals do not tend to have developmental problems, but are at a 25% risk of menopause before the age of 40.

With the latest technologies techniques that scan the entire genome, containing all our genes, large numbers of people can be studied. Similar research has been done for genetic markers of obesity for example. “One thing that intrigues scientists is whether different genes act at different ages to explain the huge range in natural age of menopause,” says Dr Anna Murray (Lecturer in Human Genetics, Peninsula University Medical School, Exeter, UK). In the latest research, published in Nature Genetics, 56 genetic variants were identified from a cohort of 70,000 women. These variants were enriched in genes involved in repairing damaged DNA and in genes linked to delayed puberty, suggesting potential molecular links between the onset and end of the female reproductive lifespan. In addition, the study also found evidence that genetic variants leading to later menopause also increase breast cancer risk.

Understanding the genes that influence the age of menopause, and how defective DNA repair mechanisms affect the quality and release of eggs, may help the treatment of infertility and influence treatments for heart disease and breast cancer. This will be increasingly relevant as, with an ageing population, women can except to live approximately 40% of their lives after the menopause.