Predicting the biological clock

The Daily Mail today reports on, “the blood test that will set a date for your menopause.” They say scientists are developing a "simple and cheap" test that will measure the level of anti-Müllerian hormone (AMH, involved in the development of ovarian follicles that release eggs) in your blood and be able to “predict within two or three years when the menopause will happen,” the newspaper says.

This news will receive a lot of interest, particularly among career women who may prefer to wait until starting a family or those who fear that the biological clock is ticking. Increasingly, women are waiting until they're over 30 before starting a family. However, although the news of this test is promising, this is only early research and this test has not previously been used to indicate menopause.

In this Dutch study, the test was trialled in a small group of women who had not yet reached menopause, so there is no way of knowing how accurate the test predictions for their age at menopause were. Much more research is needed into the use of AMH testing and it is likely to be some time before it is clear whether this test could be incorporated into general healthcare, who it would be used for and how it would be made available.

Where did the story come from?

Dr Jeroen van Disseldorp of Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, The Netherlands, and colleagues of Erasmus Medical Center, Rotterdam and Queensland University of Technology, Australia, carried out this research. The study was funded by the European Commission: Public Health and Consumer Protection Directorate 1993–2004; the Dutch Ministry of Health; the Dutch Cancer Society; ZonMw the Netherlands Organisation for Health Research and Development and the World Cancer Research Fund. It was published in the peer-reviewed medical journal: Journal Clinical Endocrinology and Metabolism .

What kind of scientific study was this?

This was a cross-sectional study in which the researchers tested anti-Müllerian hormone (AMH) levels in healthy female volunteers, and combined these with data from another population-based study (the Prospect-Epic Cohort) to see how levels of AMH relate to age and reproductive events such as the onset of menopause.

The researchers recruited 144 healthy, predominantly Caucasian, women between the ages of 25 and 46 years. All women had to be menstruating regularly and have proven natural fertility (having carried at least one baby to full term with conception being achieved within one year of withdrawing contraception). They also had to have natural two-phase fluctuation of body temperature through the menstrual cycle (which suggests ovulation), no evidence of body hormonal imbalance, no ovarian abnormalities or previous ovarian surgery and all needed to stop taking hormonal contraception at least two months before entering the study. In all women, a blood test was taken to measure AMH on day three of their menstrual cycle.

In order to look at the range of ages at menopause, the researchers used data from the Prospect-EPIC cohort study that had recruited 17,357 women between the ages of 50 and 70 years for a breast cancer screening programme. All women had provided data on reproductive history through a questionnaire. The researchers took a cross-sectional sample of 3,384 of these women (aged over 58 years) who had gone through their natural menopause and had conceived at least one child to compare with the women in their sample.

The researchers plotted the AMH levels of the healthy women against their ages and used statistical methods to draw a smooth line through the centre of the scattered points to represent the mean estimated level of AMH at different ages. Making the assumption that menopause is triggered by AMH falling below a certain level, they used their graph to predict the distribution of the women’s ages at menopause. They then matched this to the EPIC data on actual age at menopause to see how well the predicted age distribution based on AMH levels matched the actual distribution of age of menopause. Using each volunteer’s data on age and AMH level, they then placed them in a percentile band (ranging from the lowest 5% of levels for her age to the highest 5%) and used this to predict the woman’s age at menopause.

What were the results of the study?

Average age of the women volunteers was 38 years. AMH levels generally began to decline after age 30, but there was wide variation in individual women of the same age, i.e. the plotted points of the AMH level were spread widely about the central line representing average levels. The EPIC data showed that average age of menopause was 50.4 years, but ages were widely distributed, similar to the varied distribution found with the AMH levels.

From the distribution of age at menopause, the researchers predicted from their graph the estimated AMH threshold level for menopause. They found from putting the women into percentile categories according to their age and AMH level that the predicted ages of menopause correlated quite well with the distribution of ages at menopause among the EPIC cohort women. In general, a woman with an AMH level low for her age could expect to go through an earlier menopause, conversely a woman with an AMH level that was high for her age could expect to go through a later menopause.

There were significant differences in the characteristics of the women volunteers and the EPIC cohort, with the EPIC cohort women generally having more children, having their first child at an earlier age, and having slightly higher body mass index (BMI).

What interpretations did the researchers draw from these results?

The researchers conclude that there was good conformity between the predicted age at menopause from the AMH levels and that actually seen in the cohort of older women. They say this supports the hypothesis that AMH levels are related to the onset of menopause and suggest that they may be able to give a more specific indicator of a woman’s reproductive age than her chronological age alone can.

What does the NHS Knowledge Service make of this study?

While this study suggests that AMH levels may be a predictor for menopause, this is a very early hypothesis-generating study and its results must be considered in context.

• AMH has never before been used as a test to predict menopause or fertility and much further research would be needed in other groups of women to see whether it is reliable considering the wide distribution of AMH levels seen among the individual women and the many factors that may affect when a woman goes through the menopause.
• None of the women in the volunteer group tested for AMH levels have actually undergone menopause, therefore it is not possible to tell whether the predicted ages of menopause according to their current age and AMH levels will actually be accurate. Although the predicted age distribution of menopause was similar to the age distribution among the EPIC cohort, the researchers demonstrated that there were significant differences between the women, which may affect age at menopause. Other factors that may have an effect upon menopausal age, e.g. age at which their periods started and mother’s age at menopause, were not compared between the volunteers and the EPIC cohort and may have also been different between the groups.
• The women whose AMH levels were tested were a very select group of women all with healthy reproductive cycles, e.g. having regular periods and ovulation, and having successfully completed a pregnancy without needing fertility assistance. Therefore, these results cannot be generalised to mean that testing AMH levels would be predictive among women having trouble conceiving, whose menstrual cycle is irregular, those with other hormonal problems or those with any ovarian abnormality; i.e. all groups of women who may have a particular interest in this research. Results may also not be representative of non-Caucasian women.

Much more research is needed into the use of AMH testing and it is likely to be some time before it is clear whether this test could be incorporated into general healthcare, who it would be used for, and how it would be made available.

Sir Muir Gray adds...

Simply knowing you have a problem earlier can sometimes do more harm than good unless there is an effective treatment or something you can do better as a result of knowing earlier. In this case, a stitch in time does not always save nine.