CLINICAL STUDY: CORONARY ARTERY DISEASE
Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women
Giuseppe M. C. Rosano, MD, FACC*,
Carolyn M. Webb, PhD ,
Sergio Chierchia, MD, FACC*,
Gian Luigi Morgani, MD*,
Michele Gabraele, MD*,
Phillip M. Sarrel, MD ,
Dominique de Ziegler, MD and
Peter Collins, MD, FACC
* Department of Cardiology, Ospedale San Raffaele, Rome and Milan, Italy
Cardiac Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, and Royal Brompton and Harefield NHS Trust, London, United Kingdom
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA
Columbia Laboratories, Paris, France
Manuscript received October 28, 1999;
revised manuscript received July 6, 2000,
accepted August 18, 2000.
Reprint requests and correspondence: Dr. Peter Collins, Cardiac Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom
OBJECTIVES
We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both.
BACKGROUND
Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown.
METHODS
Eighteen postmenopausal women (mean ± SD age 59 ± 7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase.
RESULTS
Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina.
CONCLUSIONS
Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.
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Abbreviations and Acronyms
| | CAD | = coronary artery disease | | CI | = confidence interval | | ECG | = electrocardiographic | | FSH | = follicular stimulating hormone | | HERS | = Heart and Estrogen Replacement Study | | MPA | = medroxyprogesterone acetate |
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