The available oocyte pool is determined before birth, with the majority of oocytes lost before puberty. We hypothesised that events occurring before birth, in childhood or in adolescence ( early-life risk factors ) could influence the size of the oocyte pool and thus the timing of menopause. We included cross-sectional data from 273,474 women from the UK Biobank, recruited in 2006 2010 from across the UK. We analysed the association of early menopause with events occurring before adulthood in 11,781 cases (menopause aged under 45) and 173,641 controls (menopause/pre-menopausal at =45 years), in models controlling for potential confounding variables. Being part of a multiple birth was strongly associated with early menopause (odds ratio = 1.42, confidence interval: 1.11, 1.82, P = 8.0 10-9, fully-adjusted model). Earlier age at menarche (odds ratio = 1.03, confidence interval: 1.01, 1.06, P = 2.5 10-6) and earlier year of birth were also associated with EM (odds ratio = 1.02, confidence interval: 1.00, 1.04, P = 8.0 10-6). We also confirmed previously reported associations with smoking, drinking alcohol, educational level and number of births. We identified an association between multiple births and early menopause, which connects events pre-birth, when the oocyte pool is formed, with reproductive ageing in later life.
Genetic factors associated with being at different extremes of the reproductive lifespan
We aim to shed light on the processes which govern female reproduction throughout life.
Female reproductive life begins at puberty when women start menstruating and ends at menopause when a woman?s supply of eggs becomes exhausted. On average most women start menstruating at about 13 years old, a process called menarche and go through menopause at about 50 years. Both of these processes are controlled jointly by genes and environmental factors. To date we have only identified a small proportion of the genetic influences and the environmental factors are not well understood. The length of reproductive lifespan impacts many aspects of female health, particularly fertility, breast cancer risk and osteoporosis.
We aim to better understand the factors governing timing of menarche and menopause. In addition we will investigate the interaction of menopause risk factors and their impact on common diseases that have been linked to age at menopause, eg. heart disease and cancer. The study requires access to data only from female participants. We intend to make a subsequent linked application for access to genetic data when available. The long term impact of a better understanding of the processes that determine ovarian development and function may well lead to new methods of contraception, assisted fertility and fertility preservation.
|Dr Anna Murray
|University of Exeter
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|Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause and impact female reproductive health
|4 Jul 2018