Hormone replacement, Insulin sensitivity and Diabetes: Is there a critical window of opportunity?

This article is based on a commentary Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital and   a recent paper published in Journal of Clinical Endocrinology & Metabolism by Pereira R et al which concluded that there certainly is a time period in postmenopausal women when giving estrogen would alter the development of Insulin resistance and subsequent T2DM.

Pereira and colleague conducted a very small and short term RCT consisting of 46 postmenopausal women. Half of the subjects were less than 6 years into menopause and the other half were older and nearly 10 years past menopause.

All these women were given transdermal estradiol in high dose of 150 µg/day for a week.

After that they were given Glucose disposal rate ( GDR)  test which measures the rate of glucose uptake from the blood by the peripheral tissues, such as skeletal muscle with a hyperinsulinemic-euglycemic clamp.

There is no apparent time dependent decline in GDR with age or menopausal status per se. But, it was seen that after estrogen therapy  in younger women with less than 6 years into  menopause, a improvement in GDR and insulin sensitivity was observed , whereas those women who are older and further down the lane from menopause there was deterioration in GDR test and decrease in insulin sensitivity.

In the past there are several Randomized Control trials studying the effect of hormone therapy on diabetes in menopausal women. The data from the Heart and Estrogen/progestin Replacement Study (HERS), in which 2763 postmenopausal women with documented coronary heart disease (CHD) were randomly assigned to daily estrogen plus progestin therapy or to placebo showed that those assigned to hormone therapy had a 35% lower risk of diabetes.

Similarly two trials from the Women’s Health initiative also showed benefits, although the effect was smaller when using estrogen and progesterone as when using estrogen alone.

Now does that mean that HRT should be solely started to prevent the happening of diabetes? No, because HRT is associated with its own risks of venous embolism and stroke.

The study simply gives us one more reason to be optimistic and instrumental in starting HRT in those recently postmenopausal women who have other indications for hormone therapy, such as hot flashes and other symptoms where hormone therapy would be indicated. The study also points to important metabolic benefits of hormone therapy that should be studied in greater details with much larger trials. 

References:

Pereira RI, Casey BA, Swibas TA, et al. Timing of estradiol treatment after menopause may determine benefit or harm to insulin action. J Clin Endocrinol Metab. 2015;100:4456-4462. Abstract

Margolis KL, Bonds DE, Rodabough RJ, et al.; for the Women's Health Initiative investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative hormone trial. Diabetologia. 2004;47:1175-1187. Abstract

Kanaya AM, Herrington D, Vittinghoff E, et al.; for the Heart and Estrogen/progestin Replacement Study investigators. Glycemic effects of postmenopausal hormone replacement therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138:1-9.

http://www.ndei.org/Glossary/Glucose_disposal_rate/

http://care.diabetesjournals.org/content/30/5/1143.full