Women who enter natural menopause before 45 years old have increased risks of cardiovascular disease (CVD) and overall mortality compared with women whose onset of menopause is at 50-54 years of age. However, it remains uncertain whether early onset of menopause influences levels of CVD risk factors leading to increased CVD risk.
One of the major CVD risk factors is type 2 diabetes (T2D). Researchers at the Department of Epidemiology at Erasmus University Medical Center (Rotterdam, the Netherlands) set out to investigate the association between age at natural menopause and risk of developing T2D. They were also interesting in whether this association was independent of common risk factors of T2D (e.g., BMI, fasting insulin and glucose levels, and inflammatory markers).
Nearly 7,000 women from the prospective, population-based Rotterdam Study were initially included in the study, but those who had had T2D at baseline or experienced non-natural menopause were excluded. In the end, 3639 women were eligible. Questionnaires were used to identify age at menopause. Potential intermediate variables such as BMI, fasting insulin, fasting glucose, sex hormones, and inflammatory markers were assessed at baseline. Cases of incident T2D were ascertained during follow-up visits.
The researchers found that early onset of natural menopause was significantly associated with a higher risk of T2D. Using women with late menopause (after 55 years old) as the reference group, women with normal menopause (45-55 years), early menopause (40-44 years), and premature menopause (less than 40 years) had increased risks of T2D by 1.62, 2.36, and 3.65 fold, respectively. The association was not affected after adjusting for BMI, glycemic traits, metabolic risk factors, C-reactive protein and endogenous sex hormone levels. 
Although the association is statistically significant, the mechanisms linking age at menopause and T2D remain poorly understood. The cohort study also has limitations. For example, the retrospective self-reporting of age at menopause is subject to faulty memory. The assessment of BMI and other biomarkers and lifestyle factors was done years after menopause and not at the start of menopause. Further, the study population was comprised of 98% European ancestry and therefore the finding may not extend to other ethnicities.
The study results were published in the journal Diabetologia (July 2017)
Why is this Clinically Relevant?
- Because women with early onset of menopause are at increased risks of developing T2D and CVD, clinicians should inquire about the age at which patients entered menopause
- Clinicians should encourage exercise and healthy nutrition for heart health and glycemic control in this patient population
- Clinicians should assist younger patients to avoid risky lifestyle behaviors that trigger early onset menopause (e.g., smokers reach menopause on average 2 years earlier than non-smokers) 
 Muka, T., et al., Age at natural menopause and risk of type 2 diabetes: a prospective cohort study. Diabetologia, 2017.
 Sun, L., et al., Meta-analysis suggests that smoking is associated with an increased risk of early natural menopause. Menopause, 2012. 19(2): p. 126-32.