T2D Risk Prediction in Women With Premature or Early Onset Menopause

Age at menopause affects T2D risk
Age at menopause affects T2D risk
Data from the Rotterdam Study were used to assess the relationship between age at menopause onset and type 2 diabetes risk.

Age at menopause onset can act as an independent predictor of type 2 diabetes (T2D) risk in postmenopausal women, according to research published in Diabetologia.1

Taulant Muka, MD, PhD, MPH, of the Department of Epidemiology at Erasmus Medical Center in Rotterdam, The Netherlands, and colleagues evaluated the intersection between age at natural menopause and T2D risk using data from the prospective, population-based Rotterdam Study cohort.2


More than 6800 women were eligible for analysis; however, 2053 women were excluded due to missing information, unknown age at menopause onset, or lack of data on incident T2D. Ultimately, 3639 women (mean age, 66.9 years; mean age at menopause onset, 50.0 years) were included in the final analysis.

Baseline data were collected for all participants; during follow-up, investigators collected cases of both prevalent and incident T2D via general practitioner records, discharge letters, and Rotterdam Study visits. 

Of all study participants, 348 women developed incident T2D (median follow-up, 9.2 years). Women who experienced premature menopause or early onset of natural menopause (<40 years, 40-44 years, and 45-55 years) had a higher risk of developing T2D; hazard ratios [HR] for these groups were 3.65, 2.36, and 1.62, respectively (95% CI, 1.76-7.55; 1.30-4.30; and 0.96-2.76, respectively; P trend <.001).

Dr Muka and colleagues performed adjusted analyses, controlling for body mass index (BMI), glycemic traits, metabolic and lifestyle risk factors, inflammatory markers, and prevalent cardiovascular disease; these adjustments did not affect participants’ risk for developing T2D. Results were similar when the analysis was restricted to women who were not current smokers or were not undergoing hormone replacement therapy. Ultimately, the researchers found that the association between early age at menopause (either natural or non-natural) and T2D risk was significant.

“Early onset of natural menopause has been suggested to increase the risk of cardiometabolic diseases, including type 2 diabetes, due to early cessation of the protective effects of endogenous oestrogen,” the researchers wrote. “In postmenopausal women, higher endogenous oestradiol levels have been associated with higher levels of glucose and insulin, and an increase rather than decrease in diabetes risk.”

“This evidence … suggests that other menopause-related factors may explain the association between age at menopause and risk of type 2 diabetes,” they concluded.

Study Limitations

  • The study relied on retrospective self-reporting of age at onset of natural menopause, which is subject to faulty memory and reporting bias.
  • T2D status was assessed prospectively, so the subjective measure of natural age at menopause onset may lead to nondifferential misclassification.
  • Despite the prospective design, researchers could not rule out the possibility that “observed associations may partly reflect unmeasured residual confounding [factors].” The researchers noted that survival bias may also exist.
  • Findings may not be generalizable to individuals who are not white.

Disclosures: Drs Muka, Jaspers, and Franco are employed at ErasmusAE, which is funded by Nestlé Nutrition, Metagenics Inc, and AXA. Drs Muka and Jaspers report receiving research support from Metagenics Inc. For a complete list of disclosures, please see the full study online

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  1. Muka T, Asllanaj E, Avazverdi N, et al. Age at natural menopause and risk of type 2 diabetes: a prospective cohort study [published online July 18, 2017]. Diabetologia. doi:10.1007/s00125-017-4346-8
  2. Hofman A, Brusselle GG, Darwish Murad S, et al. The Rotterdam Study: 2016 objectives and design update. Eur J Epidemiol. 2015;30(8):661-708. doi:10.1007/s10654-015-0082-x