Genes and timing of menopause

An international team of researchers has discovered 13 new regions of the genome associated with the timing of menopause. These genes shed light on the biological pathways involved in reproductive lifespan and will provide insights into conditions connected to menopause, such as breast cancer and heart disease.

Menopause is a major hormonal change that affects most women when they are in their early 50s. The timing of menopause can have a huge impact on fertility, as well as influencing the risk of a range of common diseases such as breast cancer. It has been known for some time that genetic factors influenced the onset of menopause, however until recently very few genes had been identified.

In the new study, published in the journal Nature Genetics on 22 January 2012, Dr Anna Murray, University of Exeter, Peninsula College of Medicine and Dentistry (PCMD) Dr John Perry, PCMD and WTCHG, University of Oxford, and dozens of international collaborators, examined the genomes of over 50,000 women. They identified 13 novel gene regions associated with menopause onset, and confirmed four previously identified. Most of the 17 regions include genes related to DNA damage/repair or the immune system, whilst others are linked to hormonal regulation.

Dr Perry said: “The new findings highlight biological pathways not previously associated with reproductive lifespan, and may provide insights into the other conditions connected with menopause age, such as cardiovascular disease and breast cancer.”

The association with breast cancer is related to the length of time a woman menstruates in total and is thought to be related to oestrogen exposure over a lifetime - in fact earlier menopause is protective for breast cancer. Cardiovascular risk is increased in post-menopausal women compared to pre-menopausal and reduced oestrogen is thought to be a key component of this increased risk. Genetic studies will be beneficial in working out exactly what the relationships are between these conditions.

There are many myths and misconceptions about menopause, but not a lot of solid menopause facts.  The most inspiring fact is that women of the new millennium going through menopause are much more youthful than women of the past.  The majority of women of menopausal age - I purposely did not say menopausal women, because it seems a limiting label-are active, employed or in business, energetic, and in top shape; indicating through their personal stories that they are happier and more productive than ever before in their lives.

Women entering their forties want answers to simple questions: What will be different when I am in menopause?  How will I know when it starts? The fact is, you might not now when it begins.  Other than a change in your periods, you may not feel any different.  Each woman experiences it differently.  In pre or peri-menopause, you may start to have irregular periods - heavy bleeding or light bleeding one month and then no periods for several months, or a light period every month (or any combination of these).

Then, at some point, you will stop having periods, a menopause fact that is cause for celebration.  Free from worry about accidents, free of PMS, free of cramps…what could be better!  There are some typical symptoms, however you may have none, some or different symptoms than the typical ones. Some but not all unhappy menopause facts, i.e. symptoms some but not all women experience, are:

  Mood swings and swings from low to high energy, general irritability

  Drop in serotonin in the brain, or feel-good chemicals, which may cause loss of interest in previously enjoyable activities, aka depression

  Hot flashes.  Suddenly feeling the need to get outdoors (if it is cool) and get some air, having night sweats.  This may or may not be accompanied by irritability.

  Decrease in female hormones leading to a possible change in libido - this is not always the case. Some women even report a greater desire for sex.

  Reduction of vaginal secretions, along with general dryness, thinning and/or loss of elasticity of skin, sometimes causing painful intercourse

Dr. Murray added: “Menopause is a process most women go through, yet we know very little about what governs the timing of this key event in a woman’s life. By finding out which genes control the timing of menopause we hope to be able understand why this happens very early to some women, reducing their chances of having children naturally.”

The authors said they expected further research will identify additional genes, and also assess the impact of these genetic regions on related reproductive disorders. The research team are currently investigating women who had very early menopause, before 45 years, to determine whether the new menopause genes play a role in this clinically important condition which affects over five per cent of women.

How does the menopause start?

Many women experience symptoms of the menopause and irregular periods for several years up to the menopause itself.

This is called the climacteric, or ‘perimenopause’, and represents the gradual decline in the normal function of the ovaries.

One of the common problems of the climacteric is that periods become erratic both in spacing and amount. Until the periods peter out altogether, heavy bleeding can cause plenty of problems.

Besides Dr Murray and Dr Perry, senior authors on the study include Professor Kathryn Lunetta and Dr Joanne Murabito at the Boston University schools of Public Health and Medicine, and Jenny A. Visser, a scientist at Erasmus Medical Center in Rotterdam (Netherlands).


Andrew Gould
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The Peninsula College of Medicine and Dentistry

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