Volume 33, Number 5, September/October 2001
Multiple Factors, Including Genetic and Environmental Components, Influence When Menopause Begins
Half of women reach natural menopause (i.e., not resulting from surgery) by 51.4 years of age, according to a large, multicenter study.1 Women who smoke, who have not graduated from college, who are formerly married, who are unemployed and who have had heart disease all reach natural menopause sooner than other women. On the other hand, women who have taken the pill, Japanese American women and women who have ever given birth all experience a delay in reaching natural menopause relative to other women. This study of roughly 15,000 women from five racial and ethnic groups, which controlled for a wide range of potentially confounding variables, represents the largest such study to be conducted so far in the United States.
The data come from the cross-sectional component of the Study of Women's Health Across the Nation, which was conducted in 1995-1997 at seven clinic sites--in Boston; Chicago; Detroit; Los Angeles; Newark, New Jersey; Oakland; and Pittsburgh. The researchers recruited women aged 40-55 from five ethnic or racial groups: blacks, non-Hispanic whites, Chinese Americans, Japanese Americans and Hispanics.
Participants were divided into five menstrual-status categories--four specific menopausal categories (surgical amenorrhea, natural postmenopause, perimenopause and premenopause) and a fifth category that included women whose menopausal status could not be determined because they were currently taking hormones. The investigators compared these groups according to a range of demographic, lifestyle and health factors,* and conducted bivariate analyses and multivariate proportional hazards regression analyses to determine how these factors affected the risk of reaching natural menopause.
Of the 15,154 women whose menstrual status was known, the majority--58%--were still menstruating: Thirty percent were premenopausal (i.e., they had menstruated predictably in the past three months), and 28% were perimenopausal (had menstruated within the past year, but not predictably in the past three months). Fourteen percent were naturally postmenopausal (had stopped menstruating for at least one year without surgery), 20% had had surgery that ended menstruation (either hysterectomy or oophorectomy) and 7% were currently taking hormones.
Since in the bivariate analyses women's menstrual status varied significantly by all 13 demographic, lifestyle and health factors examined, these variables--along with the woman's current age and the specific clinic site--were entered in the multivariate analysis. As data were missing on some covariates, the final sample size for multivariate analysis was 14,620 women.
Once all potentially confounding variables were controlled for, the overall median age at natural menopause was 51.4 years. Five factors were significantly and independently associated with a lower age at menopause--smoking more than 10 cigarettes a day; not having graduated from college; being separated, widowed or divorced; being unemployed; and having a history of heart disease. For example, net of all factors, women who had a history of heart disease reached meno-pause 1.4 years earlier than those without such a history (median age of 50.0 years vs. 51.4), and women who smoked 10-19 cigarettes a day reached menopause sooner than those who had never smoked (50.2 years vs. 51.4 years).
Three factors were significantly and independently associated with a later age at natural menopause. Japanese American women were 0.4 years older than white women at the time of natural menopause (median of 51.8 years vs. 51.4). Women who had taken the pill reached natural menopause later than those who had never used the pill (51.6 vs. 51.0), and women who had had a live birth stopped menstruating later than women who had never had a child (51.3 vs. 51.2). The researchers theorize that oral contraceptive use and childbirth may delay age at menopause by reducing ovulatory cycles earlier in life, thus preserving oocytes and leading to later menopause; age at menopause was not affected by the duration of pill use, however.
The amount of physical activity women engage in, a history of diabetes or high blood pressure, body mass index and current economic hardship (i.e., inability to pay for basics) did not affect the age at which women reach natural menopause, once all demographic, lifestyle and health factors were considered in the analysis.
Results of the proportional hazards analysis indicated the extent to which women's characteristics affected their risk of having reached natural menopause in any given period of time. The largest differentials found were associated with smoking and educational attainment: Women who smoked 10 or more cigarettes a day were nearly twice as likely to have stopped menstruating as those who had never smoked (adjusted hazard ratio, 1.7), and women who had gone no further than high school were 1.5 times as likely to have reached menopause as those who had gone to graduate school. Other factors that increased women's likelihood of having reached menopause were having attended but not graduated from college, being formerly married, being unemployed and having a history of heart disease (1.2-1.4). The risk of having reached menopause was reduced by about 20-30% among ever-users of the pill, women who had had a live birth and Japanese Americans (0.7-0.8).
The researchers acknowledge that their study is limited by the time constraints of a cross-sectional survey, which prevented women from giving more complete details, especially regarding the precise timing of major events, such as the month of their final menstrual period (data were available on the year of that event only); thus, estimates of age at menopause may be inaccurate by up to one year in either direction. Another shortcoming is the study's need to use a variety of sampling techniques to achieve sufficient samples of minority women.
Despite these limitations, however, the investigators assert that their study represents one of the largest conducted to date among a multiethnic, community-based sample of women. They conclude that their robust findings suggest that multiple factors, including possible genetic and environmental components, contribute to a "likely complex mechanism" that determines the onset of menopause.--L. Remez
1. Gold EB et al., Factors associated with age at natural menopause in a multiethnic sample of midlife women, American Journal of Epidemiology, 2001, 153(9):865-874.