Family history as a predictor of early menopause

To determine the relative importance of family history as a predictor of early menopause.

Case-control study. From a population-based survey of 10,606 women between 45 and 54 years of age, we selected 344 cases with early menopause (average age 42.2 years) and 344 age-matched controls who were still menstruating or who had a menopause after age 46 years. 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.

Overall 129 (37.5%) of the early menopause cases reported a family history of menopause before age 46 years 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 40 years, 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.

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.