Age at menopause and type 2 diabetes

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Later menopause is associated with a lower risk of type 2 diabetes mellitus (T2DM), according to a systematic review and dose-response meta-analysis of six cohort studies. Although early menopause has previously been linked to an increased risk of T2DM, the quantitative association between age at menopause and T2DM has been unclear, according to the Chinese review authors.

The meta-analysis in the journal Primary Care Diabetes consisted of studies from the PubMed, Embase and Web of Science databases through January 5, 2019, totalling 267,284 women and 19,654 cases of T2DM. Four studies were from Europe. The group with the latest age at menopause had a 36% lower of risk of T2DM (95% confidence interval [CI]: 0.44 to 0.94) as compared with those who had the earliest menopause. Risk of T2DM was reduced by 10% (RR 0.90; 95% CI: 0.84 to 0.98) with each 5-year increment in age at menopause.

“We found an inverse linear association between age at menopause and T2DM,” wrote the authors, adding that all the cohort studies were high quality, thus minimizing recall bias and obtaining sufficient statistical power to detect the association. The authors noted there has been debate about the connection between age at menopause and T2DM, and that epidemiological evidence remains inconsistent.

“Associations between age at menopause and risk of T2DM are usually attributed to the function of the reproductive system and changes in levels of hormones, including endogenous estrogen and androgen,” they wrote.

A mouse study published in 1980 found a decline in ovarian function that was linked to impaired pancreatic beta-cell function, which is closely associated with glucose metabolism and risk of diabetes.

In addition, both the Heart Estrogen Progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) concluded that estrogen therapy could significantly lower the prevalence of diabetes. A separate study indicates that estrogen plays a vital role in preventing diabetic peripheral vascular disease.

Also posing significant risk for diabetes are lipid metabolism, body composition, body mass index (BMI) and fat mass, all of which change rapidly in postmenopausal women. However, controlling the occurrence of diabetes is possible, as age at menopause is influenced by cigarette smoking, education level, and BMI.

Despite its many strengths, the meta-analysis is limited by inclusion of only six studies, all of them observational, for which the demonstrated intensity of causality is low. Furthermore, age at menopause was gleaned by self-reporting or interview, thus subject to recall error. The women in the included studies also had either natural, surgical or medical menopause. The review authors did not assess the effects of surgical or medical menopause on age at menopause and T2DM.

Two studies were of women with only natural menopause, one study of women with natural or surgical menopause, and the remaining studies did not mention the type of menopause.

Nonetheless, “the subgroup analysis by type of menopause and sensitivity analysis showed that the results of our meta-analysis were stable and have reference value for the target population to some extent,” they authors wrote.