Ray Peat on Progesterone and Heart Health: What He Argued and What Trials Show

Peat's argument The trials How progesterone acts Men and menopause Supporting progesterone FAQ

For most of the twentieth century, estrogen was sold as the hormone that protects women from heart disease. Dr. Ray Peat, an endocrine physiologist, spent decades arguing the reverse: that estrogen stresses the heart and blood vessels, and that progesterone is the hormone responsible for the lower heart attack rates seen in women before menopause.¹ This article lays out his reasoning, checks it against the randomized trials that reshaped hormone therapy after 1998, and marks where the evidence supports him, where it is mixed, and where it does not.

Key takeaways

• Peat's central claim: progesterone, by opposing estrogen, protects the heart and blood vessels. Estrogen promotes clotting, vein relaxation, and fluid retention.¹
• Two large randomized trials (HERS in 1998, the Women's Health Initiative in 2003) found that estrogen plus a synthetic progestin did not prevent heart disease in postmenopausal women and raised the rate of blood clots.^{2, 3}
• Cell and animal studies show progesterone lowers nitric oxide production and prevents hypoxia-induced coronary constriction. These are mechanistic findings, not human outcome data.^{7, 8}
• Studies on men's estrogen levels and heart attacks disagree. Two older studies found higher estradiol in men with heart disease; a 2023 UK Biobank analysis did not.^{9, 10, 11}
• Wild yam does not raise progesterone in the body. Chasteberry has trial support for PMS symptoms, not for heart outcomes.^{13, 15}

This article is educational and does not diagnose, treat, or replace medical care. I am a certified clinical herbalist, not a physician. Do not start, stop, or change any hormone therapy, prescription, or supplement based on what you read here. Hormones interact with many medications and conditions, including blood clotting disorders, liver disease, hormone-sensitive cancers, pregnancy, and upcoming surgery. Responses to hormones vary from person to person. If you are in crisis, contact your local emergency number or a crisis line.

What Ray Peat argued about progesterone and the heart

Evidence: expert opinion. This section summarizes Peat's published position.

Peat's article on coronary protection makes one claim and builds everything else on it: "Progesterone, by opposing estrogen, is universally protective against vascular and heart disease."¹ He describes estrogen as a hormone that changes the liver's production of clotting proteins, relaxes the large veins so blood pools and slows, raises growth hormone, and increases the free fatty acids circulating in the blood. In his view each of these effects pushes toward clots, swelling of tissue (edema), and a weaker heartbeat.¹

Progesterone, he wrote, does the opposite on each point. It reduces nitric oxide formation, which lowers edema, and it improves the return of blood to the heart so each beat moves more blood. At the same time it relaxes the arteries, which lowers the resistance the heart pumps against.¹ He closed the article with a line that the old version of this page quoted often: "Rather than being 'heart protective,' estrogen is highly heart-toxic."¹

Peat did not present this as settled science. He presented it as a reading of the endocrine literature that the pharmaceutical industry had reasons to ignore. That framing matters for how the rest of this article treats his claims: each one gets checked against what has been measured in people.

Where the idea came from

Peat traced his thinking to the 1940s, when Hans Selye reported that estrogen could produce shock in animals while progesterone protected against stress-related damage.¹ By that decade, he wrote, estrogen was already known to cause excess clotting, miscarriage, and varicose veins, yet it was being promoted for hundreds of uses. He also pointed to the DES episode, in which a synthetic estrogen sold to prevent miscarriage was later shown to cause harm, and to an early trial in which men given estrogen to prevent heart attacks had more of them.¹

In the 1970s, after reading Albert Szent-Gyorgyi's description of how estrogen and progesterone act in opposite directions on the heart, Peat ran his own experiments showing that progesterone increases muscle tone in the walls of veins.¹ That observation became the physical basis for his argument that progesterone helps blood return to the heart.

What the hormone trials found

Evidence: strong. Randomized, placebo-controlled trials in postmenopausal women.

Before 1998, the belief that estrogen protected the heart rested on observational studies: women who chose to take estrogen had fewer heart attacks than women who did not. The first large randomized test of that belief was the Heart and Estrogen/progestin Replacement Study (HERS). It enrolled 2,763 postmenopausal women who already had coronary disease and gave half of them conjugated equine estrogen plus medroxyprogesterone acetate, a synthetic progestin, for an average of 4.1 years. There was no reduction in heart attacks or coronary deaths. The hormone group had more cardiac events in the first year and nearly three times as many venous blood clots, even though its LDL cholesterol was 11 percent lower.²

The Women's Health Initiative tested the same combination in 16,608 healthy postmenopausal women. The trial was stopped early. Women taking the hormones had a 24 percent higher rate of coronary heart disease than women on placebo, with the excess concentrated in the first year.³ Both trials fit the pattern Peat predicted: cholesterol went down, clotting went up, and the heart was not protected.

One caution belongs here. Both trials used a synthetic progestin, not progesterone. Peat himself complained that researchers routinely labeled anti-progesterone compounds as "progesterone" and then reported that it failed.¹ So HERS and the WHI show that estrogen plus a progestin does not protect the heart. They do not test whether bioidentical progesterone does. No randomized trial has measured heart attack outcomes with progesterone alone.

The older signals

Framingham data published in 1978 showed no premenopausal woman in a cohort of 2,873 had a heart attack or died of coronary disease over 24 years, while rates more than doubled after menopause. Postmenopausal women taking hormones in that cohort had twice the coronary risk of those who did not.⁴ The same year, a case series of women under 46 hospitalized for heart attack found that 53 percent of the otherwise healthy patients were taking non-contraceptive estrogens, against 12 percent of controls.⁵ Nearly all were smokers, which limits how far the finding reaches.

The "healthy user" problem explains much of the earlier optimism. A 1996 analysis followed 541 premenopausal women and found that those who later chose estrogen therapy already had better cholesterol, lower blood pressure, lower weight, and more education before they ever took a pill.⁶ Comparing them to non-users made estrogen look protective when the protection came from the women, not the drug.

How progesterone acts on the heart and vessels

Evidence: mechanistic. Cell and animal studies, with limited human measurement.

Peat's most specific mechanism involves nitric oxide. Nitric oxide relaxes blood vessels, which is why drugs that raise it are used for chest pain and blood pressure. It is also a free radical, and it decomposes into peroxynitrite, a compound that damages cells.¹ Peat argued that estrogen raises nitric oxide production and progesterone suppresses it, and that the vessel relaxation credited to estrogen comes at the cost of oxidative damage and fluid leaking into tissue.

The suppression side has direct support. In 1996, researchers showed that progesterone reduced expression of the inducible nitric oxide synthase gene and cut nitric oxide output in mouse macrophages in a dose-dependent way. Estradiol did not have this effect.⁷ The same year, a study of healthy adults found men exhaled 50 percent more nitric oxide than women, which Peat used to make a simple point: if estrogen-driven nitric oxide protected the heart, men would have the advantage.¹²

A second line of evidence concerns coronary spasm. In isolated rat hearts, prolonged low oxygen caused the coronary arteries to constrict hard. Progesterone at physiological levels prevented the constriction. Estradiol and testosterone did not.⁸ Two surgeons at Tokyo Women's Medical College later proposed that estrogen activates a gene program in coronary smooth muscle that predisposes it to spasm, and that progesterone blocks it by reducing estrogen receptors.¹⁸ That paper is a hypothesis, not a result.

These studies describe what happens in cells and animal tissue. They are consistent with Peat's model, and they are the reason his argument cannot be dismissed. They do not measure heart attacks in people taking progesterone, and no study yet does.

Stroke volume and venous return

Peat's own experiments in the 1970s showed progesterone increases muscle tone in vein walls.¹ Tighter veins push blood back to the heart faster, which fills the ventricle more completely before each beat. He tied this to Szent-Gyorgyi's earlier finding that progesterone increases the volume of blood the heart ejects per beat, so the heart can meet demand without racing.¹ Estrogen, by relaxing veins, does the opposite: blood pools in the legs, which is the same mechanism behind estrogen's known links to varicose veins and to clots in the deep leg veins.

Menopause, men, and the estrogen question

Evidence: mixed. Observational studies that disagree with each other.

The menopause pattern is not in dispute. Women's heart attack rates are low before menopause and climb steeply after it.⁴ Peat's explanation is that progesterone, not estrogen, was doing the protecting: "Until menopause they have much higher levels of progesterone than men do. After menopause, women begin to have heart attacks at a rapidly increasing rate."¹ The conventional explanation credits estrogen. The two theories predict the same drop-off, because both hormones fall at menopause. What separates them is what happens in men.

Peat wrote that "men who have heart attacks have much higher levels of estrogen than men at the same age who haven't had a heart attack."¹ Two studies from the early 1980s support this. Klaiber and colleagues measured hormones in men admitted with heart attack, unstable angina, and non-cardiac critical illness. Estradiol was raised only in the men with confirmed or suspected coronary disease, and the five heart attack patients who died within ten days had markedly elevated levels.⁹ A Framingham analysis the following year reported an association between high estrogen and coronary heart disease in men.¹⁰

A much larger and more recent study points the other way. Researchers followed 479,797 UK Biobank participants for 12.5 years and recorded 10,517 heart attacks in men. After adjusting for standard risk factors, neither estrogen nor testosterone was associated with heart attack in either sex. In men, a higher ratio of estrogen to testosterone was associated with a 21 percent lower risk.¹¹ The Biobank measured hormones once at baseline in healthy people, while the older studies measured them at the time of a cardiac event, when stress raises estrogen on its own. That difference may explain the gap, but it does not resolve it. The literature on men's estrogen and the heart is unsettled.

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Frequently asked questions

Evidence: varies by question; each answer cites its source.

Did Ray Peat say estrogen causes heart disease?

He said estrogen is heart-toxic and that its clotting, vein-relaxing, and fluid-retaining effects work against the heart.¹ He did not claim it was the only cause. He placed hypothyroidism, polyunsaturated fats, and low carbon dioxide alongside it.

Does progesterone protect the heart?

Cell and animal studies show progesterone lowers nitric oxide production and prevents coronary constriction under low oxygen.^{7, 8} No randomized trial has tested bioidentical progesterone against heart attack outcomes in people, so the human question is open.

What did the Women's Health Initiative find about hormones and the heart?

Healthy postmenopausal women taking conjugated estrogen plus a synthetic progestin had a 24 percent higher rate of coronary heart disease than women on placebo, and the trial was stopped early.³ HERS found no benefit and more blood clots in women who already had heart disease.²

Does wild yam raise progesterone?

No. The diosgenin in wild yam can be turned into progesterone in a laboratory, not in the body, and a placebo-controlled trial of wild yam cream found no change in hormone levels.^{13, 14}

Do men with heart attacks have higher estrogen?

Two studies from the 1980s found higher estradiol in men with coronary disease.^{9, 10} A 2023 analysis of nearly half a million UK Biobank participants found no association after adjustment.¹¹ The studies measured hormones at different times and the question is not settled.

Where this leaves Peat's argument

Evidence: summary of the sections above.

Peat predicted that estrogen given to postmenopausal women would lower cholesterol, raise clotting, and fail to protect the heart. Two large trials produced that result.^{2, 3} His mechanisms for progesterone have support in cells and animals.^{7, 8} The part of his argument that has weakened is the men's estrogen data, where the largest study to date does not agree with the older ones.¹¹ The part that has never been tested is the one that matters most to anyone reading this: whether progesterone itself, given to people, prevents heart attacks. If you want to follow his broader framework on thyroid, sugar, and fats, the Ray Peat guide is the place to start.

Sources

1. Peat R. Progesterone, not estrogen, is the coronary protection factor of women. RayPeat.com. raypeat.com/articles/aging/coronaryprogesterone.shtml
2. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women (HERS). JAMA. 1998;280(7):605-613. doi:10.1001/jama.280.7.605. Funded by Wyeth-Ayerst Research, the manufacturer of the study drug.
3. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349(6):523-534. PMID 12904517. Funded by the National Heart, Lung, and Blood Institute; study medication supplied by Wyeth-Ayerst.
4. Gordon T, Kannel WB, Hjortland MC, McNamara PM. Menopause and coronary heart disease: the Framingham Study. Ann Intern Med. 1978;89(2):157-161. PMID 677576
5. Jick H, Dinan B, Rothman KJ. Noncontraceptive estrogens and nonfatal myocardial infarction. JAMA. 1978;239(14):1407-1409.
6. Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P. Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol. 1996;143(10):971-978.
7. Miller L, Alley EW, Murphy WJ, Russell SW, Hunt JS. Progesterone inhibits inducible nitric oxide synthase gene expression and nitric oxide production in murine macrophages. J Leukoc Biol. 1996;59(3):442-450. PMID 8604025
8. Karmazyn M, Horrobin DF, Manku MS, et al. Changes in coronary vascular resistance associated with prolonged hypoxia in isolated rat hearts: a possible role of prostaglandins. Life Sci. 1979;25:1991-1999.
9. Klaiber EL, Broverman DM, Haffajee CI, Hochman JS, Sacks GM, Dalen JE. Serum estrogen levels in men with acute myocardial infarction. Am J Med. 1982;73(6):872-881. PMID 7148879
10. Phillips GB, Castelli WP, Abbott RD, McNamara PM. Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort. Am J Med. 1983;74(5):863-869. PMID 6837609
11. Harris K, Peters SAE, Woodward M. Sex hormones and the risk of myocardial infarction in women and men: a prospective cohort study in the UK Biobank. Biol Sex Differ. 2023;14(1):61. doi:10.1186/s13293-023-00546-3
12. Jilma B, Kastner J, Mensik C, et al. Sex differences in concentrations of exhaled nitric oxide and plasma nitrate. Life Sci. 1996;58(6):469-476.
13. Komesaroff PA, Black CV, Cable V, Sudhir K. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women. Climacteric. 2001;4(2):144-150.
14. Stanczyk FZ, Hapgood JP, Winer S, Mishell DR Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev. 2013;34(2):171-208. PMC3610676
15. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134-137. PMID 11157531. Funded by Bionorica, the manufacturer of the extract.
16. Muneyyirci-Delale O, Dalloul M, Nacharaju VL, Altura BM, Altura BT. Serum ionized magnesium and calcium and sex hormones in healthy young men: importance of serum progesterone level. Fertil Steril. 1999;72(5):817-822. PMID 10560984
17. Abraham GE. Nutritional factors in the etiology of the premenstrual tension syndromes. J Reprod Med. 1983;28(7):446-464. PMID 6684167
18. Kanda I, Endo M. Coronary artery spasm: a hypothesis on prevention by progesterone. Med Hypotheses. 1997;49(2):183-185.