Menopause is linked to unfavorable health effects in women with type 2 diabetes (T2D), but older age at menarche may be associated with a decrease in these adverse effects, including insulin resistance and elevated plasma glucose levels, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Many previous studies have explored the association between age at menarche and T2D with conflicting results, as several have reported that early menarche may be associated with an increased risk for T2D, while others reported no such association. Furthermore, early menopause has been found to increase the risk for osteoporosis, hypertension, and mortality, but little research has been conducted to investigate the interaction between age at menarche, menopausal status, and T2D.

The goal of the current study was to explore the effect of age at menarche on T2D and the interaction between age at menarche and menopausal status on glucose homeostasis in Chinese adults. The cross-sectional population-based study included 23,138 women (mean age, 54.9 years; 8010 premenopausal, 15,128 postmenopausal).

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The results showed an association between menarche age with fasting plasma glucose (FPG) levels and updated homeostatic model assessment of insulin resistance (HOMA2-IR) and β-cell function (HOMA2-β). After adjustment for multiple variables, each 1-year increase in age at menarche was associated with a 0.41 mg/dL lower FPG level (95% CI, -0.58 to -0.023; P <.001) and 1.0% lower HOMA2-IR (95% CI, -0.015 to -0.005; P <.001), but there was no significant association with HOMA2-β.

Furthermore, each 1-year increase in menarche age was associated with a 5.5% reduction in risk for T2D (95% CI, 0.924-0.966; P <.001) and the risk for T2D was 17.7% lower (95% CI, 0.712-0.951; P =.008) in women who experienced menarche at age ≥18 years. However, after adjustment for body mass index, this association was no longer significant (odds ratio, 0.884; 95% CI, 0.764-1.024; P =.099).

There was a significant interaction effect between age at menarche, menopausal status, and T2D (P =.004). For FPG, although there was no significant association with menarche age alone, there was a statistically significant association between the interaction of earlier menarche (age <18 years) and menopause with FPG (P =.002). For every 1-year increase in age at menarche, there was a 3.4% decrease in the adverse health effect of menopausal status on FPG. For later menarche (age ≥18 years), the effect of menopausal status on FPG was not statistically significant.

The adverse effect of menopausal status on HOMA2-IR also decreased with increasing menarche age but was only significant with menarche between ages 9 and 19 years.

The researchers acknowledged several study limitations, including its cross-sectional design, which precluded establishing causality. Furthermore, as the patients did not complete an oral glucose tolerance test, the prevalence of T2D may have been underestimated. In addition, age at menarche and menopausal status were based on recall, and therefore misclassification was possible.

“With increasing menarche age women are more likely to have a lower FPG, [body mass index,] and a later menopause age, which may decrease the unfavorable effect of menopause status on [T2D]. Further research is required to explore the related mechanisms of the menarche age menopause status interaction on [T2D],” wrote the researchers.

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Zhang L, Li Y, Dong X, et al. Effect of the age at menarche and menopause status interaction on type 2 diabetes: the Henan Rural Cohort Study [published online January 8, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz328

This article originally appeared on Endocrinology Advisor