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IMS Menopause Live

Age at natural menopause and risk of type 2 diabetes: a prospective cohort study

10 July 2023

Summary

Recently, Muka et al. [1] carried out a prospective cohort study that aimed at examining the association between the age at natural menopause and the risk of developing type 2 diabetes. For this, 3,639 postmenopausal women of the Rotterdam population based study were included. Age of natural menopause was retrospectively self-reported and was treated as a continuous variable and in categories: premature < 40 years, early 40-44 years, normal 45-55 years, and late > 55 years. Other potential mediators such as obesity, C-reactive protein (CRP), blood glucose, insulin level, total estradiol, and androgens were also included. Women were followed for a period of 9.2 years, time in which 348 women who developed type 2 diabetes were identified. After adjusting for the data, the results showed a hazard ratio (HR) of 3.7 (95% CI: 1.8, 7.5), 2.4 (95% CI: 1.3, 4.3), and 1.60 (95% Cl: 1.0, 2.8) for women with premature, early, and normal menopause, respectively, in developing type 2 diabetes, in comparison to those with late menopause. The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98). Further adjustment for body mass index, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association. The authors conclude that early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women.

Commentary

Menopause is defined as the end of the ovarian function evidenced by the cessation of menstruation. When it occurs prematurely, women experience menopause before the age of 40. Diabetes, on the other hand, is a chronic disease that affects the body's ability to regulate blood glucose levels. Although early menopause and diabetes are distinct conditions, they may be related in some cases [2]. Menopause in women is a complex process that involves various hormonal and metabolic changes, in addition to a decrease in estrogen levels. Endogenous estrogens can be beneficial for glucose homeostasis and help prevent diabetes. Therefore, estrogen deficiency in early menopause or the prolonged decrease of ovarian functioning is associated with an increased risk of developing type 2 diabetes. Different clinical studies have shown that hormone replacement therapy has a positive impact on the prevention of type 2 diabetes. Studies such as PEPI, HERS, and WHI support the idea that hormone replacement therapy can reduce the incidence of diabetes and improve glycemic control in postmenopausal women. Therefore, early menopause is related to the risk of developing type 2 diabetes due to early exposure to decreased estrogen levels [3-5].
 
In the present commented study [1] the authors conclude that there is a significant association between early onset of menopause and an increased risk of developing type 2 diabetes in postmenopausal women. This association persisted even after adjusting for genetic and environmental factors, suggesting that other biological mechanisms are involved in this relationship. It is important to consider the age of menopause onset as an independent marker of type 2 diabetes risk in postmenopausal women, as evidenced by Muka et al. [1] where the HRs for type 2 diabetes were 3.7 (95% CI: 1.8, 7.5), 2.4 (95% CI: 1.3, 4.3), and 1.60 (95% CI: 1.0, 2.8) for women with premature, early, and normal menopause, respectively. These findings have important implications for the prediction and prevention of type 2 diabetes, as early onset of menopause can be an additional risk factor to consider in the metabolic evaluation of mid aged women [6].

Camilo Rueda-Beltz, MD
Universidad de la Sabana, Chía, Colombia
Clínica del Country-La Colina
Bogotá, Colombia
 
Alejandra Prieto-Guerrero, MD
Universidad de la Sabana, Clínica Universidad de La Sabana
Chía, Colombia

References

  1. Muka T, Asllanaj E, Avazverdi N, et al. Age at natural menopause and risk of type 2 diabetes: a prospective cohort study. Diabetologia. 2017;60(10):1951-1960.
    https://pubmed.ncbi.nlm.nih.gov/28721436/
  2. Mauvais-Jarvis F. Menopause, Estrogens, and Glucose Homeostasis in Women. Adv Exp Med Biol. 2017;1043:217-225.
    https://pubmed.ncbi.nlm.nih.gov/29224097/
  3. Grady D, Herrington D, Bittner V, et al.; HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288(1):49-57.
    https://pubmed.ncbi.nlm.nih.gov/12090862/
  4. Greendale GA, Espeland M, Slone S, Marcus R, Barrett-Connor E; PEPI Safety Follow-Up Study (PSFS) Investigators. Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study. Arch Intern Med. 2002;162(6):665-672.
    https://pubmed.ncbi.nlm.nih.gov/11911720/
  5. Chlebowski RT, Hendrix SL, Langer RD, et al.; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003;289(24):3243-3253.
    https://pubmed.ncbi.nlm.nih.gov/12824205/
  6. Jiang J, Cui J, Wang A, et al. Association Between Age at Natural Menopause and Risk of Type 2 Diabetes in Postmenopausal Women With and Without Obesity. J Clin Endocrinol Metab. 2019;104(7):3039-3048.
    https://pubmed.ncbi.nlm.nih.gov/30896740/