Hormone Therapy Has Mixed Effects on Cholesterol

For the past few years, hormone therapy (HT) of oral estrogen with and without progesterone has been a moving target in postmenopausal women. While researchers have found favorable effects on cholesterol, as the therapy reduces LDL-cholesterol (LDL-C) and increases HDL-cholesterol (HDL-C), it also increases triglycerides and does not prevent cardiovascular disease or related events.

HT’s effects on women’s lipid profiles are complex. The therapy may act on enzymes in the lipid/lipoprotein metabolic pathway and raise sex hormone binding and lipoprotein or hepatic lipase. These effects suggest that manipulating serum sex hormones levels using interventions other than HT may alter the lipid profile in post-menopausal women, so researchers believe that lifestyle interventions such as physical activity and dietary changes may be able to create favorable lipid profile changes. However, past studies have delivered mixed findings.

Clinicians from the Division of Endocrinology and Metabolism at Johns Hopkins University School of Medicine examined the question of which interventions create favorable change in glucose intolerant and obese postmenopausal women. Using the randomized, controlled Diabetes Prevention Program involving 342 women who used HT and 382 women who did not, the researchers re-analyzed data collected in the late 1990s, before the Women’s Health Initiative recommended most women avoid HT.

The interventions were conventional and included:

• Intensive lifestyle modification (ILS) with goals of losing at least 7 percent of initial weight and 150 minutes of moderate intensity exercise per week, or
• Metformin or placebo administered in 850 milligram doses up to twice a day.

In the Diabetes Prevention Program, women were not randomized to HT, but in the re-analysis, the researchers identified each participant’s status with regard to HT. The study authors looked for changes in LDL-C, HDL-C, and triglycerides after one year.

ILS and metformin affected lipoprotein measures differently, though they generally improved LDL-C and HDL-C in HT users regardless of waist circumference changes or fasting insulin. Women who did not take HT didn’t reap those benefits, but they did have significantly lower triglyceride levels. However, HT users who engaged in ILS or took metformin generally had higher triglycerides.

The authors concluded that “the disparate effect of HT on LDL-C and HDL-C compared to triglycerides response to ILS and metformin might contribute to the failure to date of HT trials to demonstrate beneficial cardiovascular disease outcomes.”