Matthew Nudy, MD, on hormone therapy and cardiovascular effects

In an interview, Matthew Nudy, MD, discussed the results of a study analyzing cardiovascular biomarkers in participants of the Women's Health Initiative hormone therapy clinical trials. The research focused on 2 groups: women who had undergone hysterectomies and received estrogen therapy, and women with intact uteruses who received a combination of estrogen and progestin. The objective of the study was to evaluate how these hormone therapies influenced cardiovascular biomarkers over a 6-year period.

"We were able to look at the effect of hormone therapy on these different cardiovascular biomarkers out to six years," said Nudy. This long-term perspective allowed the researchers to assess changes in a range of biomarkers, including low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, lipoprotein(a) (Lp(a)), and markers of insulin resistance like glucose and insulin concentrations. They also explored coagulation factors, such as fibrinogen, as secondary endpoints.

One of the key findings was that both hormone therapy formulations—estrogen alone and estrogen plus medroxyprogesterone—reduced LDL cholesterol levels over time. "We found that both conjugated equine estrogen and conjugated equine estrogen plus medroxyprogesterone reduced LDL concentrations over the long term," Nudy explained. Additionally, the therapies had generally positive effects on several cardiovascular biomarkers, such as increasing HDL cholesterol and reducing total cholesterol, Lp(a), insulin, glucose concentrations, and insulin resistance (measured by Homa IR).

Despite these favorable results, the study also identified some drawbacks. Both hormone therapy formulations increased triglyceride concentrations and elevated factor VII antigen concentrations, which are linked to blood clotting. "Both formulations increased triglyceride concentrations and did increase factor seven antigen concentrations," Nudy acknowledged, highlighting the need for patients and clinicians to be aware of these potential changes when considering long-term hormone therapy.

An intriguing and somewhat unexpected finding was that both formulations of hormone therapy reduced Lp(a) concentrations. High levels of Lp(a) are associated with an increased risk of atherosclerotic cardiovascular disease and aortic stenosis. Nudy emphasized, "Right now, there are no FDA-approved medications to reduce Lp(a) concentrations... we found it interesting and somewhat of a surprising finding that hormone therapy was able to reduce concentrations of LP."

However, Nudy was careful to place these findings in the broader context of the original Women's Health Initiative hormone therapy trials. "In the original hormone therapy clinical trial, both formulations of hormone therapy did not reduce coronary heart disease events, and both formulations of hormone therapy increased the risk of stroke," he noted. This disconnect between the biomarkers' positive outcomes and the lack of observed heart disease benefits led the researchers to explore possible explanations. One theory is that hormone therapy may increase coagulation factors early on, creating a prothrombotic state soon after patients begin treatment. "One potential explanation is that potentially, thrombosis forms on subclinical plaques early after starting hormone therapy, and we may not see the beneficial effects of hormone therapy on cardiovascular biomarkers until many years have passed," Nudy explained.

Ultimately, while the study's findings on cardiovascular biomarkers are encouraging, they raise important questions about the clinical implications of hormone therapy in the long term. The reduction in Lp(a) is promising, but the increased risk of stroke and early thrombotic activity remain significant concerns. Dr. Nudy's research contributes to a better understanding of the complex interactions between hormone therapy and cardiovascular health, offering valuable insights for both clinicians and patients navigating hormone therapy options.