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This article reviews methodologic and clinical aspects of predicting age at menopause. Lifetable methods or logistic models applied to a perimenopausal population represent the most feasible and the least biased methods for estimating the probability of menopause by age. Information is emerging about risk factors besides age which influence risk for an earlier menopause and include a variety of medical, demographic, environmental, and genetic factors. The concept of menopause as a consequence of depleted oocytes suggests that the estimated number of ovulatory cycles might also be a useful predictor. Using these variables in a logistic model yields estimated probabilities of menopause for various risk profiles. Smokers who have accumulated more than 10 pack-years, women estimated to have had more than 300 ovulatory cycles, women with a history of depression, women who have lost one ovary at an early age, and women who have a family history of early menopause have earlier menopause and the greatest shift in the cumulative probability of menopause occurs in women with multiple risk factors.

To examine potential confounders and dose-response data for the association between smoking and menopause, we used both a cross-sectional and case-controlled approach. In total, 10,606 middle-aged women residing in eastern Massachusetts were surveyed about their age at menopause and smoking history; 344 women (cases) with natural menopause prior to age 47 and 344 age-matched women (controls) who were still menstruating or who had a menopause after age 46 were selected for further study. Risk for menopause was assessed by Kaplan-Meier, Cox proportional hazards, or logistic regression models. From cross-sectional data on 8657 women aged 45-54, the hazards odds ratio for a natural menopause among women who ever smoked compared to non-smokers was 1.31 (95% C.L. 1.21-1.42) and among women who had accumulated 30 or more pack-years was 1.87 (95% C.L. 1.67-2.04) after adjustment for parity and weight. An additional potential confounder from the case-controlled study was lower educational attainment, and after adjustment for this variable, significant trends persisted for risk of early menopause associated with age began smoking (P = 0.03), years of smoking (P = 0.01) and pack-years of smoking (P = 0.03). This study demonstrates an association between smoking and early menopause in both cross-sectional and case-controlled data that is not confounded by parity, weight, socio-economic status, or nutritional variables.

Objective To determine the relative importance of family history as a predictor of early menopause. Design Case-control study. From a population-based survey of 10,606 women between 45 and 54years of age, we selected 344 cases with early menopause (average age 42.2years) and 344 age-matched controls who were still menstruating or who had a menopause after age 46years. Subjects were interviewed about their medical and family history and blood was drawn for identification of women who were carriers for the classic or Duarte variant of galactosemia, a potential hereditary factor for early menopause. Logistic regression analysis was used to estimate the risk of an early menopause in women with and without a family history of early menopause. Results Overall 129 (37.5%) of the early menopause cases reported a family history of menopause before age 46years in a mother, sister, aunt, or grandmother compared to 31 (9.0%) of controls yielding an odds ratio (OR) of 6.1 (95% confidence interval [CI] of 3.9 to 9.4) after adjustment for smoking history, education, parity, and body mass index. Risk for early menopause associated with family history of same was greatest: for family history in a sister, OR=9.1 (95% CI 3.1 to 26.5); multiple relatives, OR=12.4 (95% CI 4.4 to 34.2); and cases menopausal before age 40years, OR=8.4 (95% CI 2.5 to 31.2). Cases with a family history of early menopause were not more likely to have errors of galactose metabolism compared with cases without a family history or to all controls, nor did they possess Turner's stigmata such as short stature, but they were less likely to have brothers in their sibships. Conclusions Although preferential recall of family history by women with early menopause could contribute to the association between family history and early menopause observed in this study, a genetic factor is also plausible including partial deletions of the X chromosome compatible with the deficiency of male siblings in cases with family history of early menopause.