Researchers find candidate gene for premature menopause

November 29, 2000

Researchers from New Zealand have identified a gene which may be implicated in premature menopause, also known as premature ovarian failure (POF)*, a condition affecting one in a hundred women under the age of 40 and one in a thousand under the age of 30.

Women as young as teenagers can suffer this distressing condition and although some retain a measure of ovarian function and even become pregnant, most suffer premature menopause with loss of fertility and the symptoms and side-effects of low oestrogen levels.

A team from the University of Auckland based at the National Women's Hospital, collected medical histories and analysed DNA from women who had undergone premature menopause. They found that the inhibin alpha gene (one of three inhibin genes) was mutated in three of the 43 women they studied (7%), compared with only one out of 150 (0.7%) in an ethnically matched control group. Their findings are reported today (Thursday 30 November) in Human Reproduction**.

Lead researcher Dr Andrew Shelling, from the National Women's Hospital, said that while the results are preliminary and need substantiating, their findings suggest that inhibin and a pathway of co-operating genes may be at fault in premature menopause.

"We think that mutations in the inhibin alpha gene may be responsible for premature menopause in very young women, but that more subtle changes in gene function could cause premature menopause in the older women," he said.

The identification of the mutant gene highlights the importance of inhibin (a glycoprotein involved in regulating follicle stimulating hormone) in the normal functioning of women's reproductive system. The three women with the mutant gene had relatively severe symptoms of POF with their menstrual periods ceasing at the ages of 16, 20 and 24 respectively.

If these women, who made up 7% of the study group, were an accurate indication of the number of cases of POF caused by the mutation, then it could be responsible for around a quarter of under 25s affected by POF. There would be thousands of these women worldwide, according to Dr Shelling. Verification of the research team's work should ultimately lead to the development of a standard genetic test.

Another member of the research team, Dr Ingrid Winship, from the University of Auckland School of Medicine's Department of Molecular Medicine, said: "Initially, those who would benefit most from a test would be women with a family history of the condition. These could account for between 10% and 30% of all POF cases. If the mutation is found in a family with a history of premature menopause, screening younger women members would provide valuable information to help them plan their families."

The researchers are expanding their investigations to include more samples, to look at other similar genes in the inhibin pathway and at other reproductive disorders involving inhibin such as polycystic ovarian syndrome and ovarian cancer.

Dr Shelling said: "To verify our findings there needs to be more good biochemical research and population studies from different parts of the world with ethnically matched controls. If that research also turns out to be significant then we will definitely have identified a new molecule involved in premature menopause and possibly other reproductive disorders. That could lead to new treatments in the future, either by replacing the defective inhibin molecule through some form of hormone replacement therapy or possibly even by gene therapy."

He added: "As women in developed countries delay motherhood into their thirties it may even be that one day women in their early 20s could take a genetic test to confirm that they weren't at risk of premature menopause. If there were indications that they were at risk of premature menopause they may want to rethink their reproductive plans. But that is highly speculative for now."
*Premature ovarian failure is generally defined as the occurrence of menopause before the age of 40. It is characterised by loss of periods, low oestrogen and elevation of reproductive hormones such as follicle stimulating hormone (FSH). POF is becoming a challenging issue for couples, particularly as women delay having families until later in life. It can be emotionally distressing: the premature loss of ovarian function is unexpected, unwelcome and disrupts a couple's life plans. Most of the emotional distress is related to infertility and grief at loss of what is supposed to be one of the normal stages in a woman's life. For some women it is also perceived as loss of femininity or youth. A specific cause is found only in one third of women. For most of these known causes the pathway of molecular events leading to ovarian failure is unclear, but the condition is most likely to result from either a decreased number of follicles being formed during development or an increased rate of follicle loss during reproductive life.

** Inhibin: a candidate gene for premature ovarian failure. Human Reproduction. Vol 15. No 12. pp 2644-2649.

1. Full text of the paper with participating research teams can be found starting 09.00hrs GMT Thursday 30 November on website:

2 Human Reproduction is a monthly journal of the European Society of Human Reproduction and Embryology. Please acknowledge Human Reproduction as a source.

3 Faxed text available on request from Margaret Willson (details below) or Dr Helen Beard, Managing Editor Tel: 44-1954-212404 or email:

Margaret Willson (media relations officer, Human Reproduction)
Tel: 44-1536-772181
Fax: 44-1536-772191 Mobile: 0973-853347
Home tel: 44-1536-770851
Email: or
Karyn Clare (communications officer)
Faculty of Medical and Health Science, University of Auckland
Tel : 64-9373-7599 ext 4919
Fax: 64-9373-7143
Mobile: 64-921-664100
Home tel: 649-360-5385

For further information on premature menopause, send a large S.A.E. to: The Daisy Network, P.O. Box 392, High Wycombe, Bucks HP15 7SH, England.

European Society of Human Reproduction and Embryology

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