Background--Abnormal glucose tolerance (AGT; diabetes or impaired glucose tolerance) is associated with increased risk of cardiovascular disease, especially in women. Cardiovascular disease rates in women increase after menopause. The Women’s Health Initiative found that postmenopausal hormone therapy (PHT) increased the risk of cardiovascular disease and that effects in diabetic women did not differ from those in women without diabetes. In this study, we hypothesized that PHT would have a worse effect on disease among women with AGT.

Methods and Results--We randomly assigned 423 postmenopausal women with angiographically defined atherosclerosis (321 women had exit angiograms) with (n=140) or without (n=181) AGT to receive estrogen, estrogen plus progestin, or a placebo for 2.8±0.9 years. LDL was lower and HDL and triglycerides were higher after PHT in non-AGT and AGT women, but more adverse changes occurred in C-reactive protein and fibrinogen in women with AGT (P=0.11 and P=0.02 for interactions). PHT had no effect on fasting glucose or insulin concentrations in women without AGT, but in women with AGT, fasting glucose levels, insulin concentration, and insulin resistance as assessed by the HOMA (homeostasis model) calculation decreased slightly (P=0.28, P=0.25, P=0.14 for interaction, respectively). Atherosclerotic progression was greater in women with AGT. Atherosclerotic progression in previously nondiseased segments was enhanced by PHT to a greater extent in women with AGT (P=0.11 for interaction).

Conclusions--PHT is associated with a worsening of coronary atherosclerosis and exacerbation of the profile of inflammatory markers in women with AGT. Therefore, PHT is not warranted for use in diabetic women. Further study is needed to explore the improvement in insulin resistance and glycemia that appears to occur with PHT in women with AGT.