Women who had their first menstrual period when they were aged 11 or younger have an increased risk of an early or premature menopause and if they remain childless the risk is increased even more, according to results from the first large scale, multi-national study to investigate the links between age at puberty and menopause and whether or not a woman has had children.

The study, which is published in Human Reproduction, one of the world's leading reproductive medicine journals, looked at 51,450 women who had agreed to take part in nine studies in the UK, Scandinavia, Australia and Japan that contribute to the Life course Approach to reproductive health and Chronic disease Events (InterLACE) international collaboration.

It found that women who started their menstrual periods aged 11 or younger had an 80% higher risk of experiencing a natural menopause before the age of 40 (premature menopause) and a 30% higher risk of menopause between the ages of 40-44 (early menopause), when compared with women whose first period occurred between the ages of 12 and 13. Women who had never been pregnant or who had never had children had a two-fold increased risk of premature menopause and a 30% increased risk of early menopause.

The risk increased even further for women whose periods started early if they had no children: the risk of premature or early menopause increased five-fold and two-fold respectively compared to women who had their first period aged 12 or older and who had two or more children.

In the general population of women in high-income countries (and also in this study) the prevalence of premature menopause is 2% and early menopause 7.6%. Therefore, the combination of starting periods early and having no children, means that the absolute risk of premature or early menopause for these women is 5.2% and 9.9% respectively.

The lead researcher for the study, Professor Gita Mishra, Professor of Life Course Epidemiology and Director of the Australian Longitudinal Study on Women's Health at the University of Queensland, Australia, said: "If the findings from our study were incorporated into clinical guidelines for advising childless women from around the age of 35 years who had their first period aged 11 or younger, clinicians could gain valuable time to prepare these women for the possibility of premature or early menopause. It provides an opportunity for clinicians to include women's reproductive history alongside other lifestyle factors, such as smoking, when assessing the risk of early menopause, and enables them to focus health messages more effectively both earlier in life and for women at most risk. In addition, they could consider early strategies for preventing and detecting chronic conditions that are linked to earlier menopause, such as heart disease."

Most of the women in the study were born before 1960, with two-thirds born between 1930 and 1949. During these years contraception was less widely available, there were no advanced treatments for infertility, and women tended to start their first period (menarche) at a slightly older age than in more recent years (14% had reached menarche by age 11, compared to approximately 18% for women born after 1990). This means that some caution is needed when applying these findings to the current generation of young and middle-aged women.

However, Prof Mishra said: "We expect that the underlying relationship between these reproductive characteristics across life is still present, but it may be that our definition of early menarche would be revised. It is also possible that we will see a higher prevalence of premature menopause for the current generation of women. Another change worth considering is that fertility treatments today can enable women to have children, whereas previously they would have been childless."

In this study only 12% of the women remained childless and it is possible that they may have remained childless due to ovarian problems, which may or may not have been detected, and which might also be implicated in the early onset of menopause. (Women who had their menopause as a result of an intervention, such as removal of the womb or ovaries, were excluded from the study).

Prof Mishra said: "In this study, women were of reproductive age when fertility rates were still relatively high, so we can speculate that childlessness may reflect underlying fertility problems, which might then lead to early menopause. In general, we know that women who do not become pregnant have an earlier menopause than women with children. It is also the case that common factors could explain the relationship and influence fertility, the timing of the first period and menopause; these range from genetics factors to environmental factors in childhood such as obesity, psychosocial stress and the social environment.

"The message for everyone to take on board from this and other similar studies is to think of the timing of menopause as a biological marker of reproductive ageing, which has implications for health and the risk of chronic diseases. So if we want to improve health outcomes in the later life, we need to be thinking about the risk factors through the whole of a woman's life from the early years and the time of their first period through to their childbearing years and menopause."

Menopause was defined as menstrual periods having ceased for at least a year.

Article: Early menarche, nulliparity and the risk for premature and early natural menopause, Gita D. Mishra et al., Human Reproduction, doi: 10.1093/humrep/dew350, published online 24 January 2017.