Endocr Rev. 2017 Mar 8. doi: 10.1210/er.2016-1146.

Author
Mauvais-Jarvis F¹, Manson JE², Stevenson JC³, Fonseca VA¹

Author information
1  Department of Medicine, Division of Endocrinology and Metabolism, Tulane University Health Sciences Center, School of Medicine, New Orleans, LA, USA.
2  Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
3  National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK.

Abstract

Type 2 diabetes has reached epidemic proportions in the US. Large randomized controlled trials suggest that menopausal hormone therapy (MHT) delays the onset of type 2 diabetes in women. Still, the mechanisms and clinical implications of these associations are a matter of controversy. This review provides an up-to-date analysis and integration of epidemiological, clinical and basic studies, and proposes a mechanistic explanation for the effect of menopause and MHT on type 2 diabetes development and prevention. We discuss the beneficial effects of endogenous estradiol in insulin secretion, insulin sensitivity and glucose effectiveness, as well as energy expenditure and adipose distribution that are lost at menopause and improved by MHT, which decreases the incidence of type 2 diabetes. We reconcile differences among studies of the effect of menopause and MHT formulations on type 2 diabetes. We argue that discrepancies arise from physiological differences in methods used to assess glucose homeostasis, ranging from clinical indices of insulin sensitivity to steady state methods to assess insulin action. We also discuss the influence of the route of estrogen administration and the addition of progestogens. We conclude that, although MHT is not approved or appropriate for the prevention of type 2 diabetes due to its complex balance of risks and benefits, it should not be withheld from women with or at increased risk for type 2 diabetes who seek treatment for menopausal symptoms.