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IMS Menopause Live

Age at Natural Menopause and Burden of Chronic Disease

27 April, 2020

Summary

Using data from women who were 45 – 50 years old in 1996 followed through the Australian Longitudinal Study of Women’s Health (ALSWH) [1]. Xu et al. studied the association between age at natural menopause and the burden of chronic disease assessed by prevalence in 2010 and incidence from 2010 through 2016 [2]. Participants provided data at 3-year intervals in the ALSWH. After exclusions for missing eligibility data, and loss to follow-up prior to 2010, 11258 women were available for the study. Of those, 4196 were excluded for surgical menopause, and 1420 were excluded for missing outcome data, leaving 5107 women for analysis. Age at natural menopause (ANM) was categorized as < or = 40, 41-45, 46-49, 50-51, 52-53 and > or = 54 years. Premature menopause was defined as natural menopause at the age of < or = 40, and the prevalence was 2.3% (N=119). Multi-morbidity was defined as the occurrence of 2 or more of the following chronic conditions: diabetes, hypertension, heart disease, stroke, arthritis, osteoporosis, asthma, chronic obstructive pulmonary disease, depression, anxiety and breast cancer. Using ANM of 50-51 as the reference group, women with premature menopause had a crude Odds Ratio (OR) for the prevalence of multimorbidity of 3.57; 95% CI 1.39 – 9.19 that was reduced to 1.98; 95% CI 1.31 – 2.98, after adjusting for a variety of confounders including parity, education, BMI, physical activity, smoking status and ever use of menopausal hormone therapy (MHT). In the adjusted model, the OR for the incidence of multimorbidity during the 6-year follow-up was 3.03; 95% CI 1.62 – 5.64 in women with premature menopause. Of the 11 conditions, women with premature menopause had significant increased risks for diabetes, stroke, osteoporosis and COPD, but not for hypertension, heart disease, arthritis, asthma, depression, anxiety or breast cancer. The association between ANM and multimorbidity was not linear, and significant findings were limited to the women with ANM < or = 40 compared with women having ANM at 50-51 years.

Commentary

While considerable literature exists regarding associations with individual chronic diseases in women with early menopause due to premature ovarian insufficiency (POI) or surgery,[3] the study by Xu is unusual in reporting on multiple disease associations in women experiencing natural menopause at early ages. Despite relatively small numbers (N=119, 2.3% of the cohort), the authors found relatively robust estimates for the co-occurrence of at least 2 major chronic diseases in women with ANM < or = 40. That subgroup was also an outlier in several risk factors: having the lowest rate of 2 or more children, the poorest educational level, and the highest rates of obesity, sedentary lifestyle, and smoking. Nonetheless, the elevated risk remained after adjustment for these factors plus ever use of MHT. Importantly, the investigators tested for a linear association between ANM and multimorbidity, including by use of a quadratic term in their model. There was none, and ORs for categorical comparisons for all other age groups were not statistically significant, so that women with ANM at 41-49 years, or ANM at 52 years or older, were similar in regard to multimorbidity to women with ANM at 50-51. The findings in Xu et al. are consistent with the literature on early surgical menopause and POI, including studies evaluating associations with a single chronic disease.[4-9] POI is not discussed in the Xu paper and, given the need for laboratory confirmation, it is likely that data on that condition were not available. Coefficients for the associations of individual comorbidities, or information on interactions across comorbidities in the fully adjusted model, are not provided, so it is not clear to what extent the individual risk factors might explain these findings, or if MHT mitigates the increased risk in women with premature menopause. Evidence demonstrating that MHT reduces the incidence of many of the individual diseases included in this analysis among women with premature or early menopause suggests that MHT should reduce the co-occurrence of those diseases.[10] Further evaluation of that association would be informative.

Robert Langer

Jackson Hole Center for Preventive Medicine, Jackson, Wyoming, USA

References

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