Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women’s Health Initiative Hormone Trial

Abstract

Aims/hypothesis. Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance. Methods. The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years.

Heterogeneity of genetic associations of CDKAL1 and HHEX with susceptibility of type 2 diabetes mellitus by gender

“…10 The genetic heterogeneity by gender might be attributed to sexual hormones which considerably influenced insulin sensitivity and secretion. 20,21 Especially, as estrogen could affect the susceptibility of T2DM 22 and regulate the activity of cdk5 in adult rat uterus, 23 it could serve as an important candidate resulting in the gender-specific effect of CDKAL1 on T2DM susceptibility. Also, estrogen could enhance serum level of thyroid hormone 24 whose production was regulated by HHEX, a crucial transcription factor.…”

Understanding of diabetes prevention studies: questionnaire survey of professionals in diabetes care

“…Results of four publications formed the basis of the questionnaires [10,12,17,18]. Articles were selected according to their clinical and public impact and their appropriateness for data extraction for different presentations of study results.…”

“…Results of the lifestyle intervention arms were used [10,12]. The third study, the Women's Health Initiative (WHI), described the effects of combined oestrogen plus progestin or placebo on metabolic parameters and the self-reported incidence of diabetes over more than 5 years of follow-up [17]. The fourth article was the main publication of the United Kingdom Prospective Diabetes Study (UKPDS), a landmark study on secondary prevention in persons with newly diagnosed type 2 diabetes [18].…”

“…The questionnaire with an explanation on how alternative presentations were derived is available as electronic supplementary material (ESM). Corresponding study results were used in items 1 and 4 [10], items 2, 3, 5 and 9 [17], and items 7 and 8 [12]; item 6 was not based on real data, but displayed relative risk reductions that were comparable to item 1 but at lower absolute risks. In item 10, the main results of the UKPDS on the primary endpoint were used to evaluate understanding of natural frequencies [18].…”

Does WHI tell us how to prevent diabetes?

“…This issue of the journal features a report from the Women's Health Initiative (WHI) that offers new insights into how diabetes may be prevented in women [7]. The study was designed to examine the effect of post-menopausal hormone replacement on a number of health outcomes, with a primary endpoint of coronary heart disease death or non-fatal myocardial infarction.…”