Researchers at Oregon Regional Primate Research Center have demonstrated that natural progesterone - but not medroxyprogesterone acetate (MPA), the most widely prescribed synthetic progesterone in the US - may help prevent heart attacks.1 As reported by primate scientists in Nature Medicine, when given to menopausal women as part of a hormone replacement program, Provera® (MPA) may increase their risk of heart failure.

The team of researchers gave estrogen (estradiol) to a group of rhesus monkeys whose ovaries had been removed to induce menopause. In addition to estrogen, some of the monkeys received Provera, and some received natural progesterone. Four weeks later the animals were injected with two chemicals released by platelets when a heart attack occurs in order to simulate a heart attack.

Those monkeys receiving Provera and estrogen experienced constriction of the coronary arteries, which cut the blood supply to their hearts so severely that they would have died within minutes had the researchers not treated them with an emergency rescue medication.

However, those monkeys receiving natural progesterone plus estrogen, or estrogen alone, were found to recover rapidly without the use of emergency drugs. In the judgement of the researchers, Provera (but not natural progesterone) increases the risk of coronary vasospasm.

The conclusion: synthetic progestin is clearly inferior to natural, unpatented progesterone, which is identical to the hormone naturally produced in the human body. In the words of researcher Kent Hermsmeyer, PhD, "The big surprise is that [Provera] poses such a huge risk. This is really a dangerous drug."2

An editorial comment in the same issue of Nature Medicine by Dr. J. Koudy Williams, a scientist from Wake Forrest University, who is also conducting research on monkeys, indicated less of a surprise at this result.3 Based on his own research with monkeys, Williams agreed that Provera can wipe out the beneficial effect of estrogen therapy in heart disease.

Other scientists doing research in this area have long suspected a negative influence of Provera on coronary function.4 A group of scientists at London's National Heart and Lung Institute have concluded that natural progesterone has a direct impact on reducing platelet aggregation through its ability to enhance endothelium-derived relaxing factor (nitric oxide).5

The bottom line with regard to Provera, warns Dr. Williams: "It's worse than no treatment at all." These studies reinforce the belief held by a growing number of researchers who have studied hormone replacement that natural progesterone is far superior to any synthetic progesterone in terms of both its safety and effectiveness in protecting menopausal women against heart disease and osteoporosis. (See LEN Issue #29, January 1997.)


1. Miyagawa K, Rssch J, Stanczyk F, Hermsmeyer K. Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nature Med. 1997;3:324-327.
2. Raloff J. Hormone Therapy: Issues of the Heart. Science News. 1997;151;140. 3. Williams JK, Adams MR. Estrogens, progestins and coronary artery reactivity. Nature Med. 1997;3:273-274.
4. De Ziegler D. Cardiovascular effects of the ovarian hormones. Arch Malad Coeur Vais 1996;89(suppl):9-16.
5. Jiang C, Sarrel PM, Lindsay DC, Poole-Wilson PA, Collins P. Progesterone induces endothelium-independent relaxation of rabbit coronary artery in vitro. Eur J Pharmacol. 1992;211:163-167.

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