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Lower premenopausal hormone levels associated with diabetes risk

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January 9, 2017

Premenopausal women with higher endogenous estradiol levels have a lower risk for developing type 2 diabetes in midlife as they transition through menopause vs. women with lower endogenous estradiol levels, according to an analysis of data from the SWAN study.

“Although it is well known that women’s risk for type 2 diabetes increases after menopause, this study shows women with lower premenopausal estradiol levels and a slower rate of change in follicle-stimulating hormone during the menopausal transition, phenomena also associated with obesity, are at increased risk of developing diabetes during this life phase,” Sung Kyun Park, ScD, MPH, assistant professor in the departments of epidemiology and environmental health sciences at the University of Michigan School of Public Health, told Endocrine Today.

Sung Kyun Park
Sung Kyun Park

Park and colleagues analyzed data from 1,407 women without diabetes at baseline who experienced natural menopause while participating in the Study of Women’s Health Across the Nation (SWAN; mean age, 46 years; mean age at final menstrual period, 52 years). Researchers measured serum glucose, estradiol and follicle-stimulating hormone (FSH) at follow-up visits. Within the cohort, 13,122 hormone measurements were collected during the 12-year follow-up period (mean, 9.3 measurements per woman). Researchers used Cox proportional hazards regression to evaluate the associations of incident diabetes with three components of the rate of change in hormones: the intercept (premenopausal levels) and two piece-wise slopes representing change during the early and late transition, respectively.

During a mean of 11 years’ follow-up, 132 women developed type 2 diabetes in late perimenopause or postmenopause. Researchers found that women who developed diabetes during follow-up had lower baseline estradiol levels vs. women who did not develop diabetes (mean estradiol level, 160.4 pmol/L vs. 213.6 pmol/L). Women who developed type 2 diabetes were also more likely to be black or Hispanic, early perimenopausal, have obesity and be current smokers at baseline.

Researchers found that each interquartile range increase (comparing the 25th percentile with the 75th percentile) in the estradiol intercept (75.2 pmol/L) was borderline associated with a lower risk for developing type 2 diabetes (HR = 0.53; 95% CI, 0.27-1.06). In addition, a greater rate of increase in FSH levels in the 2 years before the final menstrual period (early transition) was associated with a lower risk for developing type 2 diabetes, but baseline FSH level or the rate of change in FSH between 2 years before and 2 years after the final menstrual period were not associated with diabetes risk. For an interquartile range increase of 5.9 IU/L per year during early menopause transition, the HR for developing diabetes was 0.31 (95% CI, 0.1-0.94).

“We need to focus on what modifiable factors can reduce diabetes risk and may also affect the levels and rate of changes in estradiol and FSH over the menopause transition,” Park said. “In a previous study of SWAN [participants], the same cohort in this paper, obesity was associated with lower estradiol levels prior to menopause and slower rates of change in steroid hormones. It is well known that obesity also plays a critical role in diabetes risk. Therefore, weight control in [women aged 40 to 49 years] may be a key strategy to prevent development of diabetes.” – by Regina Schaffer

For more information:

Sung Kyun Park, ScD, MPH, can be reached at the University of Michigan School of Public Health, Building-2 M5541, 1415 Washington Heights, Ann Arbor, MI 48109; email:

Disclosure: The researchers report no relevant financial disclosures.

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