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Age At Menopause and Type 2 Diabetes Risk

Early onset menopause linked to increased risk of type 2 diabetes in a cohort study.

Menopause is a universal phenomenon that all women will eventually experience after a certain age. This major life transition is due to the ovaries cessation of estrogen and progesterone production. The age at which menopause occurs varies greatly from woman to woman, however the age of final menstruation is key to predicting health outcomes. Later age of natural menopause is associated with reduced morbidity and mortality, reduced risk of cardiovascular disease and complications, reduced risk of osteoporosis and fracture and overall better quality of life. The average age of menopause in the United States is 51 years old, with premature menopause being defined by final menstruation before the age of 40. Menopause is associated with weight gain, impaired glucose homeostasis, and an increase in visceral fat; all major risk factors for the development of type 2 diabetes.

Type 2 diabetes is a major risk factor for cardiovascular disease, however, it is unclear if menopause is associated with the risk of developing type 2 diabetes. Animal studies have shown that estradiol decreases the amount of adipose tissues and has a protective role in the metabolism of glucose. Other trials have also shown that postmenopausal women on oral estrogen therapy have a decreased risk of developing type 2 diabetes. Therefore, the aim of this study was to investigate the association between age at natural menopause and the risk of developing type 2 diabetes.

This project was initiated in 1990 and researchers held two more allocation rounds in 2000-2001 and 2006. Follow-up examinations were scheduled every 3-5 years and participants gave researchers full access to their medical records. In total, 3,639 women out of the 6,816 eligible women were included in the final analysis. Women were excluded if their menopause status was unknown, the age at menopause was unknown, they had a previous diagnosis of type 2 diabetes, they experienced a non-natural menopause or if the type of menopause was unknown. Age at menopause was assessed by a home interview questionnaire or through correspondence with the participant’s healthcare provider. Researchers accounted for current health status, medical history, smoking status and socioeconomic status. Cox proportional hazards models were used to evaluate whether age at natural menopause, continuous or categorical, was associated with type 2 diabetes. To determine whether age was independent of the development of diabetes, researchers further accounted for other factors including: metabolic risk factors, systolic BP, alcohol intake, parental diabetes status, use of hormone replacement therapy, activity level and use of lipid-lowering medications. The mean age of entry into the study was 66.9 years old, and the mean age of natural menopause was 50 years old with 2.3% of women experiencing menopause before age 40 and 8.2% of women experiencing menopause between the ages of 40 and 44. The median time since onset of menopause was 15 years. The hazard ratios for the association between age at natural menopause and type 2 diabetes were 3.65 (95% CI 1.76, 7.55), 2.36 (95% CI 1.30, 4.30) and 1.62 (95% CI 0.96, 2.76) for women who experienced menopause at ages <40, 40–44 and 45–55 years, respectively.1

These results demonstrated that the earlier the onset of natural menopause the greater the risk of developing type 2 diabetes, independent of risk factors such as BMI, glucose levels, genetic factors and levels of endogenous sex hormones. However, lifestyle factors such as alcohol and tobacco use, negatively impact the age at which a woman experiences menopause with women who smoke reaching menopause an average of 2 years earlier than women who do not smoke. Researchers accounted for both variables, and after restricting their research to women who do not smoke, but achieved menopause at the same age, still yielded the same results. The mechanism by which type 2 diabetes develops and the age at onset of menopause is still unclear and future studies are required to determine which biological pathways may be responsible for this association.

Practice Pearls:

  • Early onset of menopause is linked to increased risk of developing type 2 diabetes.
  • Later age of natural menopause is associated with reduced morbidity and mortality, reduced risk of cardiovascular disease and complications, reduced risk of osteoporosis and fracture, and overall better quality of life.
  • Smoking and regular alcohol consumption results in women experiencing menopause an average of 2 years earlier.

References:

Muka, Taulant, et al. “Age at natural menopause and risk of type 2 diabetes: a prospective cohort study.” Diabetologia (2017): 1-10.

Gold, Ellen B. “The Timing of the Age at Which Natural Menopause Occurs.” Obstetrics and Gynecology Clinics of North America 38.3 (2011): 425–440. PMC. Web. 11 Aug. 2017.

Jessica Lambert R.Ph., PharmD. Candidate, USF College of Pharmacy