The association of elective hormone therapy with changes in lipids among glucose intolerant postmenopausal women in the diabetes prevention program

Abstract

Objective: It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones.

Materials/methods: We performed a secondary analysis of a randomized controlled trial of 342 women who used HT at baseline and year 1 and 382 women who did not use HT at either time point. Interventions included intensive lifestyle (ILS) with goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, or metformin or placebo administered 850 mg up to twice a day. Women were not randomized to HT. Main outcome measures were changes between baseline and study year 1 in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.

Results: Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin. In contrast, DPP interventions had no effect on LDL-C and HDL-C among non-HT users. ILS significantly lowered triglycerides among non-users but did not significantly change triglycerides among HT users. Metformin did not significantly change triglycerides among non-users but increased triglycerides among HT users.

Conclusions: The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use.

Keywords: 5′ adenosine monophosphate-activated protein kinase; AMPK; BMI; DHEA; DPP; Diabetes Prevention Program; E2; FHS; FPG; HDL-C; HOMA-IR; HT; Hormone therapy; ILS; LDL-C; Lifestyle intervention; Lipids; OGTT; SD; SHBG; Sex hormones; T; VLDL; Women; apoB; apolipoprotein B; body mass index; dehydroepiandrosterone; estradiol; fasting plasma glucose; follicle stimulating hormone; high-density lipoprotein cholesterol; homeostatic model assessment of insulin resistance; hormone therapy; intensive lifestyle therapy; low-density lipoprotein cholesterol; oral glucose tolerance test; sex hormone binding globulin; standard deviation; testosterone; very low-density lipoprotein.

Figure 1

Secondary analysis design. We conducted an analysis of the effectiveness of interventions in a randomized trial (the Diabetes Prevention Program), among postmenopausal women who were either 1) oral estrogen users at baseline and at 1-year follow-up or 2) non-estrogen users at baseline and at 1-year follow-up. Adapted from: Kim C et al. Reduction in Glucose Among Postmenopausal Women Who Use and Do Not Use Estrogen Therapy. Menopause, 2012, In press.