Fetal environment and early age at natural menopause in a British birth cohort study

Abstract

background: Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study.methods: Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44 -45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44 -45 years, with and without adjustments for confounding factors.results: There was a U-shaped association between birthweight and menopausal status at 44-45 years: women at either extremes of birthweight (,2.5 and 4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0-3.49 kg [odds ratio (OR) ¼ 1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44-45 years (OR for fastest quarter versus second fastest quarter ¼ 1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives.conclusions: These findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further.

What influences the age of menopause?

“…In a study of over 2000 premenopausal women, alcohol, socioeconomic status, exercise and body composition appeared to play no role in determining age of menopause. Very low (52.5 kg) or high (44 kg) birth weight has been associated with an earlier than average menopause but breast-feeding or weight at age 2 years has no impact 6 . Use of the contraceptive pill and longer cycles have been linked with a later age at menopause but the effect of parity remains controversial.…”

Is in utero exposure to maternal socioeconomic disadvantage related to offspring ovarian reserve in adulthood?

“…The inclusion of these biomarkers offers a unique opportunity to examine prenatal exposures in relation to variability in ovarian aging among younger women when fertility preservation may still be possible. Although there are prior studies of prenatal adversity exposures, none have considered SES exposures in particular [40][41][42][43][44][45] and only one examined a biomarker of ovarian reserve [46]. Lastly, the current study drew from a large, well-characterized group of reproductive age participants in the OVA Study.…”

“…Notably, because the ovarian follicle pool is established in utero, exposures during this time may be especially relevant. In fact, a range of prenatal exposures (e.g., famine exposure, maternal pre-pregnancy diabetes, maternal smoking during pregnancy, multiple birth status, and both low and high birthweight) has been shown to predict earlier menopause in adult offspring [40][41][42][43][44][45] and, in the only study to examine a biomarker of ovarian aging (antimullerian hormone [AMH]), prenatal paternal smoking and maternal gestational weight gain were related to lower AMH (indexing lower ovarian reserve) while pre-pregnancy maternal history of menstrual cycle irregularity was related to higher AMH (indexing higher ovarian reserve) in adolescent offspring [46]. To date, however, no studies have examined prenatal SES-related exposures in particular.…”

“…To date, the methodological challenges of studying ovarian follicle formation and loss have been a barrier to understanding how particular exposures may influence the size and health of the initial follicle endowment as well as the rate of ovarian follicle loss over time. As evidenced by the literatures described above, the majority of studies of prenatal exposures have been limited to the examination of ovarian aging as indexed by markers of menopausal timing [40][41][42][43][44][45], with only one study examining prenatal exposures in relation to AMH, a biochemical marker of ovarian reserve [46]. Building on the literatures described above, the current study focused on the sensitive period of follicle formation in utero by examining adverse prenatal exposures related to maternal SES.…”

The Effect of Benign Gynecologic Procedures on Ovarian Reserve: A Prospective Study

“…It has been correlated with fecundity, time of menopause, as well as a predictor of the success of infertility treatment. Many factors determine ovarian reserve including genetic endowment, fetal environment, external environment (smoking, disease states), and iatrogenic interventions such as surgery, and medications (Tom et al, 2010). Oocyte related decline in ovarian function is referred to as decreased ovarian reserve.…”