Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative

Abstract

Objective To understand the association between women’s reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk. Methods Prospective cohort analysis of 124,379 postmenopausal women aged 50–79 from the Women’s Health Initiative. We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes. Results In age-adjusted models, women with the shortest (<30 years) reproductive periods had a 37% (95% CI = 30–45%) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36 to 40 years). Women with the longest (45+ years) reproductive periods had a 23% (95% CI = 12–37%) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR of 1.07 [1.01, 1.14] for shortest and HR of 1.09 [0.99, 1.22] for longest, compared to medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04, 95% CI 0.99, 1.09 and HR 1.08, 95% CI 1.01, 1.14, respectively) compared to those with age of final menstrual period between 46 and 55. Timing of menarche and cycle regularity were not associated with risk after full adjustment. Conclusions Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

Age at natural menopause and risk of diabetes in adult women: Findings from the China Kadoorie Biobank study in the Zhejiang area

“…Consistent with previous studies showing that late menopause can increase the diabetes risk, the present findings also showed that the age at natural menopause affected type 2 diabetes risk even after adjustment for age, BMI and other potential confounders, though the cut‐off points for menopausal age differed from the previous studies. Another two studies involving menopausal age ≥53 years, which was in line with our cut‐off point for later age at menopause in the present study, showed that the association was not statistically significant after multivariable adjustment.…”

“…Both the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in Europe 11 and Dongfeng-Tongji cohort study in China 12 have found that early menopause is associated with a greater risk of type 2 diabetes. Several other studies from the USA and China [13][14][15] reported that women with late menopause had an increased diabetes risk. Meanwhile, three studies from Italy, Japan and China found no effects of age at menopause on diabetes risk [16][17][18] .…”

Impact of age at menarche on obesity and glycemic control in Japanese patients with type 2 diabetes: Fukuoka Diabetes Registry

“…One of the mechanisms that has been proposed to explain the association between early age at menarche and obesity is that earlier‐onset menarche might result in longer exposure to estrogen25 and adrenal steroids26, which tend to maintain adiposity. Furthermore, an overlap between single‐nucleotide polymorphisms implicated in the timing of puberty and in determining BMI in adulthood has been reported25. These single‐nucleotide polymorphisms include TCF , which was shown to be a risk factor for obesity and type 2 diabetes27, and LIN28B , which is associated with insulin sensitivity and oxidative stress‐related β‐cell apoptosis28.…”

“…The association between age at menarche and BMI was observed in both the <65 years and ≥65 years age groups. One of the mechanisms that has been proposed to explain the association between early age at menarche and obesity is that earlier-onset menarche might result in longer exposure to estrogen 25 and adrenal steroids 26 , which tend to maintain adiposity. Furthermore, an overlap between single-nucleotide polymorphisms implicated in the timing of puberty and in determining BMI in adulthood has been reported 25 .…”

“…Obesity is a global health problem. Although the prevalence of obesity is lower in Japan than Western populations generally (prevalence of body mass index [BMI] ≥30: 3.7% in Japan vs 38.2% in the USA 19 ), there has been an increase in the level of obesity in patients with type 2 diabetes in Japan (mean BMI increased from 24.1 kg/m 2 in 2002 to 25.0 kg/m 2 in 2013 20 ).…”