Note: hormone therapy (HT) may also be referred to as hormone replacement therapy (HRT).

Expert analysis from The Jean Hailes Foundation on Manuscripts pertaining to findings of the Women’s Health Initiative Estrogen plus Progestin Study, published in the New England Journal of Medicine August 7 2003.

Key Statements

Two papers addressing the effects of postmenopausal hormone therapy on coronary heart disease risk have been published this week in the New England Journal of Medicine.

The first paper provides more details of the results of the Women’s Health initiative Trial published in JAMA in July 2002, and the findings are unchanged¹. Oral oestrogen plus progestin does not provide cardiac protection and may increase the risk of cardiac events in postmenopausal women.

A number of sub group analyses are presented in this week’s paper, ie risk by age, years since menopause, cholesterol levels and so forth. However the authors and the editorial commentary caution against conclusions being drawn from these analyses. This is because many of the subgroups only included a small number of women and thus lack statistical power. Furthermore, as so many different subgroups were evaluated there is a risk that just by chance one would be positive, rather than the finding being a “ true” effect.

It was previously believed that hormone therapy would protect against coronary heart disease because it lowers LDL (bad) cholesterol and increases HDL (good) cholesterol. These favourable effects of hormone therapy on cholesterol levels were also seen in this study and highlight the fact that cholesterol levels are not the main predictors of cardiac events. We now know that inflammation and thrombosis (formation of a blood clot) are key events in the development of a heart attack, and that oral oestrogen increases the tendency towards thrombosis. Whether oestrogen given in other ways, as a skin patch or gel etc, conveys the same risk is not yet known.

The second paper reports on the effects of oestradiol alone, oestradiol with medroxyprogesterone acetate or placebo on change in the diameter of coronary arteries in women known to have coronary artery narrowing due to plaque (cholesterol buildup)². The findings were that neither oestrogen alone or with progestin had any effect on the progression of coronary artery narrowing over a median follow up time of 3.3 years.

Neither of these trials addressed the role of oestrogen plus progestin for the treatment of menopausal symptoms. Women using hormone therapy for this purpose need to discuss the possibility of a small increase in overall cardiovascular risk with hormone therapy with their prescribing physician.

Reference List

1. Manson JE, Hsia J, Johnson K et al. Estrogen plus progestin and the risk of coronary heart disease. N Eng J Med 2003;349:523-34.

2. Hodis H, Mack W, Aznar S et al. Hormone therapy and the progression of coronary artery atherosclerosis in postmenopausal women. N Eng J Med 2003;349:535-45.

Content updated August 07, 2003