Predictors of the age at which natural menopause occurs in women with type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study

Abstract

Objective: Women with type 1 diabetes (T1D) are thought to experience menopause earlier than women without diabetes, although not all studies agree. We assessed metabolic predictors of the age at which natural menopause occurs among women with T1D participating in the Epidemiology of Diabetes Complications study. Methods: Women with childhood-onset (<17 y) of T1D who underwent natural menopause without use of hormone therapy during their menopausal transition were included in the analysis (n = 105; mean baseline age, 29.5 and diabetes duration, 20.2 y). Self-reported reproductive history and the Women's Ischemia Syndrome Evaluation hormonal algorithms were used to determine menopause status. Linear regression was used to ascertain whether time-weighted metabolic factors (eg, BMI, lipids, HbA1c, insulin dose, albumin excretion rate [AER]) were associated with age at natural menopause. Results: Univariately, only insulin dose (β = −4.87, P = 0.04) and log (AER) (β = −0.62, P = 0.02) were associated (negatively) with age at natural menopause. Adjusting for BMI, smoking status, lipids, HbA1c, number of pregnancies, and oral contraceptive use, each 0.1 unit increase in the daily dose of insulin per kilogram body weight was associated with 0.64 years younger age at natural menopause (P = 0.01), while for every 30% increase in AER, age at natural menopause decreased by 0.18 years (P = 0.03). Conclusion: Higher average levels of insulin dose and AER over time were significantly associated with a younger age at which natural menopause occurred among women with T1D. The biologic mechanisms underlying the observed associations between exogenous insulin dose and AER on reproductive health should be investigated among women with T1D.

Metabolic hormones are integral regulators of female reproductive health and function

“…Abnormal insulin levels—relatively common with metabolic disorders—are linked to impaired reproductive health. For instance, women with Type 1 diabetes (typically treated with exogenous insulin) are more likely to exhibit ovarian dysfunction, and those taking a higher daily dose of insulin have an increased chance of earlier menopause [ 261 , 262 ]. An early diagnosis of Type 2 diabetes, which is closely tied to obesity and high endogenous insulin, is also predictive of earlier menopause [ 261 , 263–265 ].…”

Type 1 diabetes and reduced ovarian life span: ovotoxicity, increased follicle throughput, or both?

“…It is against this backdrop that the interesting findings of Yi et al, 4 require interpretation. The authors sought to identify the determinants of earlier age at menopause among a cohort of 105 of 325 female T1DM participants in the Pittsburgh Epidemiology of Diabetes Complications Study.…”