Follow Up from KEEPS trial confirms hormone therapy has no significant cardiac benefit

The cessation of menopausal hormone therapy (MHT), used for the treatment of menopausal symptoms, has no impact on the progression of carotid artery intima-media thickness (precursor of heart disease), according to a new study published in the journal Menopause. The results are a follow-up from Kronos Early Estrogen Prevention Study (KEEPS) trial.

There is a limited data on the progression of preclinical atherosclerosis upon cessation of MHT. Virginia M. Miller, Department of Surgery, Mayo Clinic, Rochester, MN, and colleagues conducted the study to evaluate changes in carotid artery intima-media thickness (CIMT) in a subgroup of participants during 4 years and 3 years after the KEEPS.

Hear disease is one of the leading causes of a large number of deaths worldwide. This drives a continued interest in the medical field to study risk factors that may affect the incidence of heart disease. This includes the ongoing debate regarding the effect of hormone therapy on the progression of cardiovascular disease.

The KEEPS study was designed for comparing the effects of either transdermal estradiol or oral conjugated equine estrogens (CEE) on the progression of atherosclerosis (thickening and hardening of arteries), leading cause of strokes and heart attacks. In this new study, a subgroup of KEEPS participants were further evaluated for 3 years after the initial study.

"In the KEEPS trial, low doses of hormone therapy (oral or transdermal) given for 4 years close to menopause did not improve carotid artery intima-media thickness (CIMT), and this study shows no rebound effect on progression of CIMT after stopping the hormones," says Dr. JoAnn Pinkerton, executive director of NAMS. "In contrast, the Early Versus Late Intervention Trial With Estradiol (ELITE) found benefits on CIMT when hormone therapy was given early but not when started more than 10 years from menopause. The primary indication for the use of hormone therapy should be for the relief of bothersome menopause symptoms or for those at elevated risk of bone loss. There may be beneficial effects on the reduction of heart disease, but it should not be used for its prevention."

"Cessation of MHT at the lower doses and formulations used in KEEPS did not appear to alter the trajectory of CIMT over a 3-year follow-up period. CIMT, however, increased in all groups over the entire 7-year timeframe as expected with age and timing of menopause possibly key contributors," concluded the authors.