Premature Menopause May Increase Risk of Type 2 Diabetes: Study of 1.1 Million Women

Premature and early menopause were associated with a higher risk of developing type 2 diabetes (T2D) according to results of new research from Korea that evaluated data from more than 1.1 million women. Women with onset of menopause at ages younger than 40 years and between ages 40 and 44 years were more likely to develop T2D than those who experienced the change at age 50 years and older, study authors wrote in JAMA Network Open.¹

They also reported that earlier age of menopause was associated with greater risk of T2D in a dose-dependent manner (P _trend <.001). The risk remained after multivariable adjustment including for conventional cardiovascular risk factors.¹

Given that premature menopause is already considered a risk factor associated with cardiovascular disease in the recent cholesterol guidelines from the American College of Cardiology and American Heart Association,² the investigators suggest that the climacteric should also be recognized as a risk factor associated with T2D in diabetes management guidelines.¹

Lead study author Ga Uen Nam, MD, PhD, Department of Family Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea, and colleagues point to previous research that has examined potential links between reproductive factors such as breast feeding and parity and T2D. Studies that have looked at connections between age at menopause and T2D have been small and cross sectional, however, leaving open a wide gap in evidence.

Nam et al culled data from the Korean National Health Insurance Service (NHIS) of over 3 million women over age 30 years who underwent NHIS screening in 2009 and reported age at menarche. After applying inclusion and exclusion criteria, the cohort numbered 1,125,378 participants (mean age, 61.2 years at enrollment and 50.0 years at menopause) who were followed until December 31, 2028, a median of 8.4 years.

The study’s primary end point was the occurrence of new-onset T2D at any time from the index date to the end of the study period. Researchers followed participants until they received a T2D diagnosis, they died, or the study period ended.

Age at menopause stratified into 4 groups:

• younger than 40 years: 19,311
• ages 40 to 44 years: 64,700
• ages 45 to 49 years: 310,772
• age 50 years and older: 730,595

Of the final study population, 113,864 individuals (10.1%) were diagnosed with T2D.

In subgroup analyses, Han et al found that body mass index (BMI), depressive disorder, and prediabetes modified the association between early menopause and risk for T2D. For individuals with premature menopause vs those with menopause at ages 50 years or older, HRs were 1.54 (95% CI, 1.14-2.06) for a BMI less than 18.5 and 1.14 (95% CI, 1.00-1.30) for a BMI of 30 or greater (P < .001), 1.28 (95% CI, 1.12-1.45) for individuals with depression and 1.11 (95% CI, 1.07-1.16) for those without depression (P = .01), and 1.25 (95% CI, 1.18-1.33) for individuals who were not prediabetic and 1.04 (95% CI, 0.99-1.11) those who were prediabetic (P < .001).

In addition to including premature menopause as a risk factor for developing T2D in diabetes management guidelines, the researchers add that the history of premature menopause might be used to screen for, treat, and potentially prevent T2D in at-risk groups.

“These findings suggest that premature menopause should be emphasized and considered an emerging risk factor in the management of T2D to delay disease progression and inform therapeutic strategies,” concluded the authors.

References
1. Ko B, Jung J, Han K, et al. Age at menopause and development of type 2 diabetes in Korea. JAMA Netw Open. 2025;8(1):e2455388. doi:10.1001/jamanetworkopen.2024.55388
2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ ACPM/ ADA/ AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350. doi:10.1016/j.jacc.2018.11.003