432. Meditations on Women’s Hormone Replacement Therapy and Ray Peat’s Legacy

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This post is dedicated to our wonderful menopausal women. I spent a quarter of my career trying to help you, but most of you DFL to me.

Editor’s introduction by Jim Arnold of Liar’s World Substack

I like this post. It is specialized, but motivated readers will learn a lot. It gives an inside view into Dr. Yoho’s medical knowledge and his discernment in sorting through conflicting information.

Ray Peat came from an atypical background for a healthcare authority, and he made important contributions to thyroid therapy. He also gave misleading guidance on estrogen and progesterone. Since no one has his hands on the entire healthcare elephant, there is no shame in making a few mistakes. The trouble is that his zealous followers are preserving his bathwater along with his baby. The key theme of Dr. Yoho’s Substack is that you must do your research and not place blind faith in any guru or institution.

Author’s Introduction

This post took weeks of research, thought, and editing. It is the start of my rewrite of Hormone Secrets, and the key takeaways are more about hormone therapy than Ray Peat. Even if you have no great interest in this subject, scan past the first few sections to find the video interview of two women who were thoughtlessly castrated by their gynecologist. This event happens daily in every major city in the United States, and it is a testimony to how aggressively dysfunctional this specialty is.

Although I always recommend obtaining provider help if you can find a good one, the appendix has information on where to obtain hormones without a prescription. Most of the field, with the exception of thyroid, is driven by simple protocols, and a DIY approach is far better than doing without hormone health-improving and protective effects as a senior. Although there are a few simple caveats, the risk-to-reward ratio is infinitesimally small. I would go a step further and say that hormones should be over-the-counter, and that scheduling testosterone was political rather than designed for patient protection. Hormone Secrets has more about that.

Summary

· Ray Peat was a PhD biologist and theoretician with a destroyed thyroid who became an underground hormone authority without ever treating a patient in person.

· His bioenergetic framework, with mitochondria at the center, thyroid as the master switch, carbohydrates as the preferred fuel, and polyunsaturated fats as metabolic poisons, is largely correct.

· His thyroid work is his strongest contribution. It updates the temperature-and-pulse diagnostic tradition of Broda Barnes, a Fort Collins, Colorado, physician who treated tens of thousands of hypothyroid patients in the mid-20th century.

· His estrogen position generalized from synthetic carcinogen data in rats to bioidentical estradiol in women, and it is wrong.

· The Women’s Health Initiative (WHI), launched in 1991 and reported in 2002, was captured science. Between 2002 and 2011, somewhere between 18,600 and 91,000 American women died prematurely as a result. The historical record is incomplete, but the study’s structural flaws appear intentional.

· Bioidentical hormone therapy started within the menopausal window, balanced with progesterone and testosterone, is safe and life-enhancing.

A roadmap before we begin

I reached a split verdict on Peat. He was right about the thyroid and the bioenergetics of cell metabolism. He was wrong about estrogen. The error came from generalizing rat studies done with diethylstilbestrol (DES), a synthetic carcinogen, to bioidentical estradiol in women. The mistake was honest, not corrupt, but his followers and sympathetic figures like Joe Mercola have amplified it in ways that have hurt women.

The 2002 Women’s Health Initiative report did similar damage from inside the medical establishment. Both errors share the same shape: synthetic hormones are not bioidentical hormones, and treating them as identical kills people.

I have a firm rule. If a topic is confusing, it is not because I am out of my intellectual depth. The problem is usually inconsistencies or falsehoods. For some lawyers or salespeople, these are purposeful. I felt a sense of bewilderment about the Peat material, and I will explain the analysis I worked out after studying it.

I have a deep background in hormone therapy. I worked full-time for a year and spent at least 1,000 hours reviewing the academic literature and writing Hormone Secrets. My hormone clinical experience and training, combined, total at least another 1,000 hours.

I expand on these subjects in the new edition of my book, which will be available soon. The first edition is excellent, and you download it here for free.

Players in this drama

Hormone specialists

They prescribe bioidentical hormones that are chemically indistinguishable from the body’s. This is safe with a few caveats. The field is not complicated, and many physician’s assistants or nurse clinicians do a good job if they have proper training.

Gynecologists

They are rarely well-informed about up-to-date menopause treatment because they focus on profitable hysterectomies and cesarean sections. These procedures are performed at least 50% more often than they should be for the best patient outcomes. Things have gotten so bad that 41.8% of women aged 75 and older and roughly 35% of women aged 65 to 74 have had a hysterectomy.

Some gynecologists do a great job, and others casually mutilate their patients. The hormone-prescribing logic of many of them is broken. When a woman has had a hysterectomy, they prescribe estrogen alone. The reasoning: progesterone is needed only to protect the uterus from cancer, so a woman without a uterus does not need it. This ignores progesterone’s many benefits for sleep, mood, bone, breast tissue, and the cardiovascular system.

Endocrinologists

They claim to know more about hormones and thyroid disease than other specialists. Their success at treating the most common thyroid disorder, hypothyroidism, is hampered by their compulsory use of TSH (thyroid-stimulating hormone) to measure the condition and direct therapy. This measure is indirect and imprecise.

They are aggressively anticompetitive and sometimes try to intimidate their colleagues by reporting them to the medical board for practicing outside the Endos’ purported “gold standards.” In their defense, endocrinologists are the most sophisticated physicians when it comes to a far rarer problem: Graves’ disease.

Ray Peat (1936-2022)

He was an academic, not a clinician. He wrote and spoke widely about menopause and related issues. His work was imperfect but widely respected in some circles. He advocated for the long-established but partly forgotten approach to hypothyroidism that uses body temperature and careful symptom monitoring. His signature position, that estrogen is commonly a health problem, is 180 degrees wrong, and that error makes it difficult to take the rest of his platform seriously.

Comment: Criticizing anyone retrospectively, after they have died, is an easy project. Peat’s legacy holds many intellectual triumphs and good works, and I do not want to pretend otherwise. The point of this essay is to keep what he got right and walk away from what he got wrong.

The Ray Peat acolytes

I call them this because Peat was apparently so charismatic that his followers behaved like religious disciples. They had unreasoning faith in the supposed problems with estrogen.

One of them asked me a naive question: “Do you have personal experience prescribing estrogen alone?” The implication was that since I always paired estrogen with progesterone, I had no way to separate the effects of estrogen by itself.

I told him I had not, and explained why. Bioidentical prescribing pairs the two hormones because unopposed estrogen raises the risk of uterine cancer in women with an intact uterus. Adding progesterone drops the cancer rate below the baseline of untreated women. The follower had stumbled into a serious practice question without realizing it. There is a whole specialty, gynecology, that does prescribe estrogen alone after a hysterectomy. Their reasoning is illogical: they assume progesterone’s only function is uterine protection, so a woman without a uterus needs no progesterone. They miss progesterone’s benefits everywhere else in the body.

This Peat fan also seemed unaware of the hundreds of studies and millions of patient experiences that show the benefits of estradiol after menopause. The cardiovascular protection studies alone would fill a large book. Opinions like his are what you get when you set somebody up as a guru and study a single source.

I have been guilty of this several times: with Mercola, with Dr. Peter Breggin about methylene blue, and with Dr. Neal Rouzier about progesterone usage for men. The last two ran down the utility of these agents, and they were wrong. For whatever weaknesses I have, one strength is that I change my mind. I also walk away quickly from people who give me false information.

The stars of this show are our precious and often troubled menopausal women.

This section is excerpted from Hormone Secrets.

A lovely interview with two women who were castrated during their thirties by their gynecologists.

Castration in a woman means the surgical removal of both ovaries. It is the female equivalent of removing a man’s testicles, and the hormonal consequence is the same: an abrupt collapse of sex hormone production with body-wide effects. Castration is not the same as a hysterectomy, which removes only the uterus. The two surgeries often happen together because that brings in a second professional fee for the surgeon and makes the procedure technically simpler.

Yes, this is a thing, it is legal, and the surgery was done here in California, not Pakistan. The women below were crashed into severe premature menopause, which would have ended their lives prematurely. I treated them with bioidentical hormones, and they describe their recoveries in the video. Identical but less dramatic scenarios happen as hormonal secretion declines during normal menopause.

Both had hysterectomies for excessive uterine bleeding, sometimes done as a convenience rather than taking the time to administer high-dose progesterone or other restorative procedures. The destructive part of these surgeries was not the removal of the uterus but the removal of the ovaries. Even when the ovaries are preserved, their function is often destroyed by a disrupted blood supply.

How I got involved in hormone therapy for women, and how it works

Doctors tend to treat patients of similar age to them, and as my cosmetic practice and I matured, so did my patients. One day 20 years ago, I looked around, and almost all were postmenopausal women. Most had significant symptoms. I was sympathetic, and I was on hormone replacement therapy myself. My friend, Dr. Neal Rouzier, had become an international authority on HRT, so I started attending his seminars.

When I began treating patients, I decided to charge them only a nominal fee or make it free if they had cosmetic surgery from me. Their only cost was the price of their medications at the pharmacy.

Some clinicians check labs before starting, but many hormone doctors, including me, treat symptoms before getting bloodwork. A 55-year-old with hot flashes, crashed libido, broken sleep, and vaginal dryness got estrogen, progesterone, and testosterone in physiologic replacement amounts. The doses are stereotyped and easy to adjust. Thyroid therapy requires lab work that my patients often did not pay for and is more complicated, so I never prescribed it. This was a consequential mistake because the thyroid is the driver of all hormones and energy in the human body.

After therapy is established, a single blood test documents that hormones are present in protective concentrations. The American College of Gynecology and the Mayo Clinic both say that no testing is needed before prescribing hormones to menopausal women. It is that safe.

I prescribed bioidentical hormones to hundreds of patients using this approach. I checked blood levels later for the women who paid for it. With estradiol levels around 75 to 150 pg/ml using oral micronized estradiol and progesterone in the middle of the second half of the cycle for menstruating women (10 to 20 ng/ml), their symptoms went away. I would push progesterone higher to suppress bleeding when needed. Testosterone in the 250 to 300 ng/dL range, by cream or, rarely, injection, restored the patient’s vitality. Hot flashes stopped. Vaginal atrophy resolved. Libido came back. Mood stabilized. Sleep normalized. Skin improved.

These events happened routinely in my hormone practice, and each one seemed like a miracle to both the patient and me.

Three principles I learned in practice

The most common failure in hormone therapy is not too much hormone but too little. Doses creep down, patients skip doses, prescribers undertreat to avoid blame, and the woman never gets the relief the therapy delivers. Symptom resolution requires getting enough of the right hormone inside the body and keeping it there.

Within a range the clinician sets, the patient should adjust her dose. She knows her sleep, her libido, her hot flashes, her energy, and her mood better than the office or the lab does. Give her the range, the ceiling, the warning signs, and let her run the dial.

A blood test drawn after therapy has settled confirms that hormones are present in the protective range. The number tells whether the cardiovascular and bone-preserving effects are being delivered, and it tells the prescriber what to change when a patient is not responding.

How I got interested in Ray Peat

A brilliant reader, whom I will call Jane, generously sent me a set of Peat references along with her sharp commentary. Jane has been hypothyroid for more than 50 years. She has central hypothyroidism, which means her pituitary does not make TSH, so her thyroid gland does not get the signal to produce thyroid hormones. She has been adjusting her thyroid therapy using pulse, temperature, and blood testing for decades. She is not a doctor, but she is smarter about thyroid issues than most of them.

Peat was associated with Joe Mercola, who was my primary mentor for nearly a decade. Mercola adopted Peat and his signature position that estrogen is toxic. This contradicts everything I learned in my years of study and prescribing bioidentical hormones to hundreds of menopausal women whose lives visibly improved. I watched estrogen resolve vaginal atrophy, restore libido, sharpen cognition, and improve sleep. Academic evidence shows it also reduces the risk of heart disease.

Based on Peat’s work, Jane is doubtful about the importance of estrogen. I view her as a serious intellect, but as I have written before, no one has his hands on the entire healthcare elephant.

Who was Ray Peat?

Raymond Franklin Peat was born in Santee, California, in 1936 and died in November 2022 at 86. He attended Southern Oregon University, transferred to the University of Oregon as a humanities student, and did residency coursework in philosophy of language at Ohio State before finishing a master’s thesis titled “William Blake and the Mysticism of Sense and Non-Sense” in 1960.

He started as a literature student and a Blake scholar. In 1961, he taught intro biology at Urbana College. In 1962, he founded Blake College, a tiny liberal arts school in Valle de Bravo, Mexico, described by one source as “a school with a critical attitude rather than a curriculum.” He ran it for most of the decade. Only in 1968 did he return to the University of Oregon, this time for a PhD in biology-biochemistry with a focus on physiology. He finished in 1972 with a dissertation titled “Age-Related Oxidative Changes in the Hamster Uterus.”

Everything Peat wrote for the next 50 years flowed out of that dissertation. The central claim: aging is a pro-oxidative, pro-inflammatory, estrogen-dominant process, and the preservation of youthful structure and function requires mitochondrial energy output, adequate thyroid hormone, abundant progesterone, and protection from the things that degrade mitochondrial function: polyunsaturated fats, chronic stress, excess serotonin, and unopposed estrogen.

He taught at the University of Oregon, Urbana College, Montana State University, the National College of Naturopathic Medicine, Universidad Veracruzana in Mexico, Universidad Autonoma del Estado de Mexico, and Blake College. In 1984, he patented a formulation described in his article “Treatment of progesterone deficiency and related conditions with a stable composition of progesterone and tocopherols.” This was the progesterone-in-vitamin-E combination he later commercialized as Progest-E.

What nobody tells you about Peat

Multiple Peat followers report that his thyroid gland was destroyed in childhood by radiation from a miscalibrated fluoroscopy. This aligns with Peat’s lifelong self-experimentation with desiccated thyroid and his insistence that hypothyroidism is the master dysfunction underlying most chronic illnesses. A boy whose thyroid was wrecked by medical incompetence before he was a teenager, and who lived to 86 on his hormonal regimen, is not a man whose thyroid opinions should be dismissed.

It also frames his estrogen phobia. Radiation was the original carcinogen to which he was exposed. In the 1930s and 1940s, Alexander Lipschutz demonstrated that small continuous doses of diethylstilbestrol (DES), a synthetic estrogen-mimicking carcinogen, produced cancer in every animal he studied. Peat read this literature at a time when the dominant message was “estrogen is a feminine hormone, give it freely.” He was watching a scientific error, but he interpreted the mistake as corruption.

Was Peat a clinician?

Not in any sense recognizable to a practicing physician. He ran what he called “private nutritional counseling”: phone consultations, newsletters, and emails from correspondents around the world. This was an early form of telemedicine, and he did take histories by phone. Yet he never did a physical exam, never ordered a lab as a treating clinician, never saw the same patient over months and adjusted her dose, and never watched a 55-year-old woman with hot flashes go from miserable to flourishing on bioidentical hormones.

A theoretician reads the animal literature and concludes that all estrogen is carcinogenic. He cannot then compare that conclusion to the physiologic levels restored by a 1 to 2.5 mg oral estradiol capsule in a 55-year-old woman whose ovaries made the same compound at higher concentrations for 40 years without giving her cancer.

Peat compounded this by staying mostly within the Oregon alternative-medicine ecosystem. His readers and correspondents were the tip of the iceberg of people whose medicine had failed them, or who had been harmed by synthetic progestins or equine estrogens. The feedback he got was authentic but filtered. He did not see the millions of women for whom proper bioidentical hormone therapy, started in the menopausal window, transformed their health and well-being.

The bioenergetic framework: where Peat got it mostly right

Energy is the organizing principle. Mitochondria are not only the cell’s energy factories; they are the main regulator of cell structure, signaling, and adaptive response. If you lose mitochondrial output, you lose the capacity to maintain structure, repair damage, and resist stress. Aging is largely a story of progressive mitochondrial failure.

The thyroid is the master regulator of mitochondrial output. T3 (triiodothyronine) is the active thyroid hormone. T4 (thyroxine) is the less active storage form the body converts to T3. T3 controls the rate at which mitochondria burn fuel and produce heat and energy. The critical measure is T3, not TSH or T4 (my group uses free T3 rather than the other thyroid hormones). Measuring TSH to diagnose hypothyroidism is like checking the wall thermostat to determine whether the furnace is working. The pituitary hormones from the brain influence thyroid hormone production, but they do not have effects at the tissue level.

Carbon dioxide is protective, not a waste product. Peat was one of the few physiologists writing for a popular audience about how carbon dioxide stabilizes proteins, supports oxygen delivery to tissues, and reduces lactic acid buildup. When cells burn glucose properly with oxygen, they put out carbon dioxide. When they cannot burn glucose properly, they make lactic acid, the same compound that gives muscles a burn during heavy exercise. Lactic acid pile-up is a sign that the cell has run out of oxygen or that its energy machinery is broken.

Polyunsaturated fats destabilize membranes and poison mitochondria. This is now mainstream, at least outside the corrupt American Heart Association’s guidelines. Linoleic acid from seed oil sources like nuts and corn oil oxidizes inside cells, produces reactive molecules that damage tissue, binds up the inner mitochondrial membrane, and interferes with energy production. Saturated and monounsaturated fats, like animal fats, coconut oil, and olive oil, are stable. Peat wrote about this in the 1970s, when the official position was that polyunsaturated fats were heart-healthy. Chris Knobbe, Cate Shanahan, Peter Attia, and most of the serious metabolic-health community have caught up with him.

Serotonin is a stress hormone, not the happiness hormone. For decades, doctors and patients have been told that depression results from low serotonin and that raising serotonin levels with drugs like Prozac (fluoxetine) and Zoloft (sertraline) corrects the problem. This was a marketing fiction. The serotonin-deficit theory was never proven. The drug companies needed a story to sell the SSRIs (selective serotonin reuptake inhibitors), so they invented one and the medical establishment accepted it.

Peat’s framework gets it right. Serotonin is elevated in sepsis, in shock, in gut-derived endotoxemia, and in carcinoid tumors. Raising it chronically with SSRIs produces the flattened, dissociated, sexually-blunted patient with the thousand-yard stare we recognize as another antidepressant casualty. Sixteen percent of US residents take these drugs.

Comment: Peat’s framework predicted the damage SSRIs have been proven to cause. Beyond the disorders above, they produce violence and suicide. This was known to the researchers before they released the drugs. The mass murders we have seen are nearly all associated with antidepressant usage. The double-blind, placebo-controlled trials supposedly underpinning the SSRIs were ruined by fake controls. For more, see Robert Whitaker’s books and madinamerica.com.

Sugar is not the enemy. The body’s preferred fuel is glucose, burned aerobically in mitochondria. Fructose from fruit and honey spares liver glycogen, supports thyroid conversion, and fills the 3 a.m. cortisol trough that wakes so many perimenopausal women. The demonization of sugar in the last 20 years has been driven in part by the low-carb industry and is not fully supported by physiology. The damage attributed to sugar has mostly been done by sugar delivered alongside industrial polyunsaturated fats: a donut, a corn chip, a fried potato. The sugar does less damage than the oil it is fried in. Peat is right about this.

None of this is new if you have been following the metabolic health movement. But Peat was saying it 40 years earlier.

Thyroid: where Peat is strongest

Peat wrote “Thyroid: Therapies, Confusion, and Fraud” in 2006, and it is the single most useful short document on hypothyroidism I have ever seen. To make sense of his claims, you need to know who Broda Barnes was. Barnes was a Fort Collins, Colorado, physician who treated tens of thousands of hypothyroid patients from the 1940s through the 1980s. He used basal body temperature on waking, resting pulse, and clinical signs to diagnose, then prescribed natural desiccated thyroid (NDT) to almost universal benefit. His 1976 book “Hypothyroidism: The Unsuspected Illness” is still the best general treatment of the topic. Peat’s ideas match Barnes’s almost exactly:

1. TSH is a pituitary signal, not a thyroid hormone, so it is a poor measure of function that fails most hypothyroid patients.

2. T4 is a storage hormone, and T3 is the active hormone. If the liver cannot convert T4 to T3 due to low selenium, low carbohydrate intake, chronic cortisol elevation, estrogen excess, gut endotoxin, or mercury exposure, prescribing more T4 will not help.

3. Morning body temperature below 98 degrees Fahrenheit and a resting pulse under 80 beats per minute in a sedentary adult are better diagnostic signs of hypothyroidism than any blood test.

4. Natural desiccated thyroid, or NDT (Armour, NP Thyroid, ThyroVanz), supplies both T4 and T3 in a physiologic ratio. Synthetic T4 alone does not.

5. Older testing methods using body temperature in the first half of the 20th century identified about 40% of Americans as hypothyroid. Family physicians prescribed desiccated thyroid and cured a wide range of diseases with it: cold hands, infertility, depression, high cholesterol, and even some cancers. This did not fit the business model of the American Thyroid Association, whose guidelines card is, as Jane puts it, “pocket-sized scripture for the white-coated brain-dead zombies.”

I tried this older approach myself. Using a grain of NP Thyroid plus 5 mcg of T3, I watched my basal temperature climb from 96.4 to 97.8. I had a general uptick in energy and better sleep. Jane’s account of adjusting her NP Thyroid over nine months, with blood tests every six to eight weeks, shows the same pattern from a far harder starting point.

Bovine-sourced desiccated thyroid (ThyroVanz and others) is available without a prescription. T3 is available from research peptide suppliers and Mexican pharmacies. Neither requires a licensed prescriber (See the appendix for purchasing details). Combined with the temperature-and-pulse protocol, this is the best system for basic hypothyroid patients, who are the vast majority of thyroid cases. For complicated thyroid issues like Hashimoto’s with high antibodies, central hypothyroidism like Jane’s, pituitary problems, and thyroid cancer, a licensed physician with lab access is the right choice.

The American Thyroid Association advocates a narrow TSH reference range (0.5 to 2.5 mIU/L), refuses to accept TSH values below 0.5, persecutes family physicians who prescribe desiccated thyroid, and guards its prescribing authority from other specialties with cartel-like rigidity. They are among the sharpest examples of medical capture I have studied. Jane is right: much of medicine is a criminal enterprise, and the Medicare Part D insurers who send warning letters to patients telling them to get their doctors to “take them off this dangerous drug” (referring to NDT) are accessories.

If Peat had done nothing else, his hypothyroid work alone would secure his legacy. He took a partly forgotten diagnostic tradition from Broda Barnes, updated it with enzymology and selenium biochemistry, and made it available to a generation of patients who were being failed by endocrinologists. Jane’s case, central hypothyroidism with a pituitary that does not make TSH, diagnosed and managed over 50 years with temperature, pulse, blood testing, and desiccated thyroid, is a living refutation of the TSH-only paradigm.

Estrogen: where Peat went wrong

Peat’s estrogen position is laid out in his book, “Not the ‘female hormone,’ but the shock hormone.” He claims that estrogen, unopposed by relatively high progesterone levels, creates the conditions of aging. These include interference with oxidative metabolism, formation of lipofuscin, iron retention, free radical production, excitotoxic cell death, elevated prolactin, thymic atrophy, increased blood clotting, and susceptibility to a wide variety of cancers.

We hormone clinicians know now that estrogen should never be prescribed without progesterone. If the uterus is intact, unopposed estrogen slightly increases the chances of uterine cancer. When the two are prescribed together, uterine cancer rates drop below the baseline of untreated patients. Women who have had a hysterectomy should take progesterone anyway because of its many benefits. The gynecologists’ claim that, if you do not need progesterone to prevent uterine cancer, you do not need it at all, is moronic.

Peat’s main animal evidence came from Alexander Lipschutz’s 1930s and 1940s studies in hamsters and rats. Those studies proved that continuous low-dose synthetic estrogen causes cancer. The finding does not generalize to bioidentical hormones in humans because Lipschutz used DES, a transplacental synthetic carcinogen and one of the worst drugs approved in the 20th century. The wrong type of estrogen, given at the wrong dose, in the wrong species, says nothing about a 55-year-old woman taking 1 to 2.5 mg of oral bioidentical estradiol to replace what her ovaries produced for 40 years.

Peat is right about the hazards of synthetic progestins and equine estrogens. Premarin is a chaotic mixture of conjugated equine estrogens harvested from the urine of pregnant horses. It contains equilin, equilenin, and other estrogens foreign to the human body. Medroxyprogesterone acetate, sold as Provera and used as the “progestin” (imitation progesterone) component of Prempro, is not progesterone but a synthetic steroid with partial glucocorticoid, androgenic, and antiprogestogenic activity. It does not act like progesterone at the receptor. Synthetic progestins have strong associations with breast cancer in the studies.

Peat’s central error was conflating bioidentical estradiol with synthetic and equine analogs at supraphysiologic doses. He called all of it “estrogen” and treated chemicals that bind the estrogen receptor as the same molecules the human ovary makes. Other medical providers, including many gynecologists, make the same conceptual error: bucketing synthetic, equine, and bioidentical hormones under a single term.

Peat never engaged the bioidentical HRT (hormone replacement therapy) community on its evidence. Millions of women on compounded or FDA-approved bioidentical estradiol, progesterone, and testosterone, started within 10 years of menopause (the clinical window now confirmed repeatedly), do not develop the cancers he predicted. On average, they live longer, maintain bone and cognitive health, keep their hearts healthy, and enjoy their lives. JoAnn Manson, a Harvard professor and one of the original WHI principal investigators, has led the long-term mortality follow-ups, with her 2017 paper in JAMA the most prominent. She has cried “nonsense” about the original 2002 interpretation of the trial.

Peat’s nutritional and hormonal work was never peer-reviewed. His dissertation and two papers from 1971-1972 in Physiological Chemistry and Physics are the only formal scientific publications he produced. Peer review is corrupt, but the absence of any adversarial process meant that nothing challenged his weaker positions. The mainstream medical establishment did little to engage him, and his reach stayed mostly inside alternative-medicine.

Progesterone: sorting out the claims

Where I disagree most with the Peat orthodoxy is the claim that oral micronized progesterone does not work well.

For women who need progesterone supplementation, Peat recommended progesterone dissolved in vitamin E, applied to the gum mucosa or vaginally. He invented that formulation. He says oral micronized progesterone (Prometrium or its generics) is “subject to first-pass liver metabolism, which reduces potency.”

Katharina Dalton was a British physician who treated severe premenstrual syndrome, postpartum depression, and postpartum psychosis with progesterone starting in the 1950s. Dalton treated thousands of patients over four decades, wrote several books, coined the term “premenstrual syndrome” (or PMS), and testified in British criminal cases where severe premenstrual hormonal collapse was accepted as a mitigating circumstance for violent acts, including at least one murder. Her work is the answer to anyone who claims progesterone’s benefits are speculative. Dalton put progesterone into practice for thousands of women and documented the results decades before the synthetic-progestin controversy obscured the picture.

Oral progesterone has low bioavailability measured against an intravenous baseline, but a 200 mg oral dose still produces peak serum levels of about 38 ng/ml at three hours, well above the 10 to 20 ng/ml range that supports the protective clinical effects. Levels decline overnight, which is fine for a bedtime dose. Vaginal and buccal progesterone reaches measurable serum levels and has been used successfully in the European literature.

Transdermal progesterone creams, by contrast, do not produce sustained blood levels. Dr. Neal Rouzier, a hormone expert who has trained many thousands of physicians, drew blood from himself and his patients after using progesterone creams and found that progesterone levels declined within about an hour. The gold standard in our prescribing community is a sustained blood level, because that is what produces the cardiovascular protection, the bone maintenance, and the symptom relief that hormone therapy is prescribed for. The uterine and ovarian cancer prevention from progesterone is also likely tied to sustained levels.

Progest-E bypasses first-pass liver metabolism to reach the bloodstream. Comparative head-to-head data against oral micronized progesterone are nonexistent. What we have is Peat’s assertion that oral is inferior, set against a vast body of clinical data supporting oral for the endpoints that matter.

The clinical question is: Does the patient feel better, sleep better, and avoid endometrial cancer? The data strongly support the use of oral micronized progesterone.

Endometrial protection is proven. The KEEPS (Kronos Early Estrogen Prevention Study) trial used 200 mg of oral micronized progesterone for 12 days per month alongside estrogen and demonstrated adequate endometrial protection, with no increase in endometrial or breast cancer incidence across the study period. Other studies show breast and uterine cancer reduction. This is the standard many menopausal medicine specialists use today. Neil Rouzier’s group uses continuous daily progesterone, which he believes has a better protective anti-cancer effect on the uterine endometrium.

Sleep is substantially improved. Oral progesterone, because it goes through the liver, produces large amounts of allopregnanolone, a neurosteroid that acts on GABA (gamma-aminobutyric acid) receptors like a gentle sedative. Patients fall asleep and stay asleep. This has transformed my sleep. The “liver metabolism” Peat views as a liability is the source of the benefit for sleep disturbance, the most important symptom most perimenopausal women bring to the doctor.

Old bioavailability numbers are partly an artifact of old methods. The older radioimmunoassays cross-reacted with progesterone metabolites, yielding inflated readings. Modern LC-MS (liquid chromatography-mass spectrometry) methods show the parent compound circulating in the blood is lower than previously thought. A large share of progesterone’s clinical effect is produced by its neuroactive metabolites, not the parent compound, so the LC-MS number understates clinical potency.

Few women have trouble tolerating the oral route’s sedation when it is taken at bedtime, and most of them view it as a plus. If the goal is symptom control for a perimenopausal woman with wrecked sleep, night sweats, and anxiety, oral micronized progesterone at bedtime is superior.

Where Peat is most correct is that bioidentical progesterone, not the synthetics, is protective, anti-inflammatory, antiestrogenic, and radically underprescribed. He was one of the few people in the second half of the 20th century who understood that progesterone and synthetic progestins are not interchangeable. That distinction has saved incalculable numbers of women.

The Women’s Health Initiative: a ruined study

The Women’s Health Initiative was an ideological takedown operation, run from inside the National Institutes of Health (NIH) with the full complicity of the media and silence of most of the researchers involved.

The WHI was launched in 1991 by Bernadine Healy, a cardiologist appointed by George H. W. Bush and the first woman to direct the NIH. Her intent was corrective. Most prior clinical research had been done on men, and women’s health was seriously underfunded. The WHI budget was $625 million, and it was initially considered a good-faith effort.

By 2002, the trial was being run by Jacques Rossouw, a South African cardiologist who was not a neutral investigator. He had publicly called for “a halt to the HRT bandwagon” six years before the study was published. Other principal investigators, with Robert Langer at the forefront, later went on record that the interpretation of the data had been distorted for publicity. Rossouw told Tara Parker-Pope they wanted “high impact” to “change thinking about hormones.”

The study, as designed, had four structural flaws visible before it started:

1. It used Premarin, not bioidentical estradiol.

2. It used medroxyprogesterone acetate, not progesterone.

3. The average participant was 63 years old, more than 12 years past menopause. The “timing hypothesis,” that HRT started early protects the cardiovascular system while HRT started late might harm it, was known to the investigators but was not built into the design.

4. The investigators administered continuous combined therapy rather than cyclic, overriding the natural monthly rhythm of hormone variation. Peat himself had claimed this was critical.

Comment: Again, Dr. Neal Rouzier’s group, which includes me, does not believe cyclic dosing is important for the health of postmenopausal women. Cycling is important for reproduction.

When the data came in, the writing group withheld it from most WHI investigators and from the companies that made the drugs. They held a press conference before the paper was peer-reviewed, and stated that “the adverse effects of estrogen plus progestin applied to all women, irrespective of age, ethnicity, or prior disease status.” This was not what the data showed, and the age-stratified analysis was never released.

The consequences were devastating. Seventy percent of women on HRT stopped within a year of the 2002 announcement. Prescribing fell by half within months and dropped to about a quarter of pre-WHI levels by 2010. Philip Sarrel of Yale estimated that between 18,600 and 91,000 American women died prematurely between 2002 and 2011 because they were denied the cardioprotective and bone-preserving effects of estrogen. Wyeth lost billions on Prempro. Pharmaceutical marketing of compounded bioidentical hormones, which had not been studied in the WHI, filled the void with little oversight and has been largely responsible for the progress made since.

Was this a globalist operation? In the sense of a single, coordinated plot run by the Rockefeller Foundation, I have not found the evidence. It was a case of captured science, where an ideologically committed principal investigator pushed a rushed, misdesigned study into a media blitz to shift clinical practice in a specific direction, and a generation of women suffered because of it. That happens routinely inside the US government science. Look at what the CDC (Centers for Disease Control) did with Covid and what the NIH did with chronic Lyme. Look at what the EPA (Environmental Protection Agency) did with glyphosate. The WHI fits the pattern.

An ironic footnote: in April 2025, HHS (Health and Human Services) under RFK Jr. briefly tried to kill WHI funding, then reversed course within days under bipartisan pressure. The WHI is at once a cautionary tale about captured science and an irreplaceable long-term data resource on aging women. I am not sure whether RFK’s instincts were right or wrong on this one. The underlying data, fairly re-analyzed, has continued to produce useful results for 20 years, and cutting it off would be a loss.

For readers who want more, Avrum Bluming and Carol Tavris’s “Estrogen Matters” (2018) is the best account of the WHI debacle. I reviewed it in Hormone Secrets. Peter Attia has an excellent interview with them on his podcast.

Peat’s conflict of interest

In 1984, Peat patented the progesterone-in-tocopherol formulation and licensed it. The patent ultimately became Progest-E, sold through his followers’ websites and small distributors ever since. He also held a 1986 patent on DHEA and other anesthetic steroids for arthritis. These patents created a financial incentive to emphasize the formulations he had developed over competing ones. I cannot prove that this distorted his scientific judgment, but it is the sort of thing to keep track of when you read him on how to deliver progesterone. When Peat said oral micronized progesterone “does not work” and topical vitamin E progesterone is superior, he was selling a product he invented. I do not think this makes him a fraud, but it would be dishonest to pretend the conflict was not there.

For Peat, the conflict does not come close to what we see in mainstream medicine. Most endocrinologists are unwitting salespeople for Synthroid (levothyroxine), whose manufacturer derives $3.5 billion in revenue from the TSH-driven T4-only paradigm. Peat was a small independent theoretician with a tiny independent product. The asymmetry is enormous, and the reason you should still take Peat seriously is that his positions (anti-polyunsaturated-fat, pro-thyroid, pro-carbohydrate, anti-synthetic-progestin) cost him audience and career, and did not gain him either. A bought-off theoretician preaches consensus views. Peat did the opposite. That is evidence, though not proof, that he was calling what he saw.

Peat’s followers amplify his weaker positions

Peat was drawn to fringe theories, sympathetic to Project Blue Beam, UFOlogy, and other frameworks that cannot be discussed in polite scientific company. Much of this is trivial and separates cleanly from his metabolic work. His reliance on anecdote and single animal studies sometimes led him to state things as facts that were not.

He contradicted himself over the course of his career. RationalWiki documents numerous examples of him reversing positions on red light, methylene blue, and DHEA without acknowledgment. He was, by his description, a theoretician, and his output has the virtues and vices of theoretical work.

Mercola picked up Peat’s estrogen mistakes and relayed them to his enormous audience. I do not know what motivates Mercola, but his public biography is now that of a man who joined a cult, had a public psychological breakdown, fell under the influence of a “channeler” named “Bahlon,” and fired much of his company for refusing to submit to the channeler’s authority. I stopped trusting Mercola several years ago. Peat’s estrogen position is the part of his work Mercola has loudly amplified. That is the weakest part, and it has confused the community.

Recap and conclusion

On hypothyroid, Peat is essential. If you or someone you love has unexplained fatigue, weight gain, hair loss, cold intolerance, brain fog, or depression, and your doctor has told you your TSH is “normal,” read Peat’s thyroid article and find a provider who understands desiccated thyroid. Morning temperature and resting pulse cost nothing and tell you more than any blood test.

On carbohydrates, seed oils, and the basic bioenergetic framework, Peat is largely right. The body runs on glucose. Polyunsaturated fats accumulate in tissue, poison mitochondria, and take years to flush out after you change your diet. Saturated fats are stable. Sugar is not the enemy; industrial seed oils and chronic stress are. Eat fruit, drink milk if you tolerate it, use butter, coconut oil, and beef tallow, and avoid corn and canola oil.

On progesterone, Peat is mostly right, with one important caveat. Progesterone, the molecule and not the synthetics, is protective, anti-inflammatory, antiestrogenic, and dramatically underprescribed. Synthetic progestins are not equivalent and should be avoided. The claim that oral micronized progesterone does not work is wrong, because the liver metabolism Peat views as a liability produces the neurosteroid metabolites that deliver the most valuable clinical effect: sleep.

The hardest therapeutic problem in hormone therapy is getting enough hormone inside the body, so in many clinical situations, both oral and topical routes might be used together. For sleep and mood, oral is better. Topical progesterone cream works poorly enough that it should be abandoned except for symptom relief in people who have a superstitious dread of the oral version, or who choose to use both forms together.

On estrogen, Peat was half-right and dangerously overextrapolated. Premarin and medroxyprogesterone are toxic. Bioidentical estradiol, in physiologic replacement doses, started within the menopausal window, balanced with progesterone and often testosterone, is safe and life-enhancing for most women who use it. Peat did not see enough patients to appreciate the difference between bioidentical and synthetic hormones, and his followers amplified the error. Avrum Bluming and JoAnn Manson have the data on this.

On the WHI, Peat was gesturing at a scandal. The study was captured science run by an ideologically committed principal investigator who wanted “high impact” and got it at the cost of tens of thousands of American women’s lives. Peat’s suspicion of the whole thing was justified, even if his interpretive framework for why it happened was fuzzy.

On peripheral issues like UFOs, serotonin as a pure villain, and cholesterol as harmless at any level, Peat was unreliable. His followers have amplified the unreliability.

Peat was, in the end, a figure much like Broda Barnes, Hans Selye, Linus Pauling, Weston Price, and Denis Burkitt. An independent mind who worked largely outside the mainstream, published enormously, was right about more than he was wrong about, and left a body of work that rewards careful reading and careful filtering. He was not a prophet or a fraud. He was a good theoretician who understood mitochondria before most people had heard of them. If I were still in practice, my prescribing would change in small ways after this review. I would pay more attention to thyroid temperature data and give more aggressive carbohydrate and dairy advice for perimenopausal patients with 3 a.m. awakenings.

Three things worth repeating

The most common failure in hormone therapy is the prescriber giving too little, the patient taking too little, or both. Underdosing fails the woman more often than any side effect.

Within the safety range set by her clinician, the patient should turn the dial herself. She has the symptoms; she has the data that the lab cannot see.

Once dosing has settled, a blood level confirms that cardiovascular and bone protection are doing their work and indicates the next adjustment when a patient is not responding.

Many thanks to Jane, who supplied references and perspectives, and who sent me on this path to learn more about Ray Peat.

Where to obtain hormones without a prescription

What follows is informational. Hormones sold without a prescription move through grey-market channels, customs seizures happen, and vendors come and go. None of it replaces a licensed provider when one is accessible. The detail is here because readers have asked for it, and because the alternative, silence, leaves people at the mercy of whatever vendor ranks first on Google.

T3 (liothyronine)

Loti Labs sells 100 mcg/mL liquid in 30 mL bottles at about $38, with third-party testing and same-day US shipping. Products ship as “research use only,” so registration as a researcher on the site is required. For tablets, AllDayChemist ships generic liothyronine from India without a prescription, and Mexican pharmacies stock Cynomel (Sanofi, 25 mcg) over-the-counter. The FDA has stated it will not prosecute personal importation of small quantities.

Natural desiccated thyroid (NDT)

Two Thai brands, both porcine and both registered with the Thai FDA, ship worldwide without a prescription. Thyroid-S (Sriprasit Pharma) delivers 38 mcg T4 and 9 mcg T3 per 60 mg tablet, identical in ratio to Armour. Thyroids.shop sells 500-tablet bottles for about $170 shipped. Dose at 2 grains (two tablets) daily, split between morning and early afternoon to keep the T3 from interfering with sleep. Thiroyd by Greater Pharma is the porcine backup when Thyroid-S is out of stock; supply has come and gone over the years.

US bovine supplements are legal without a prescription, but hormone content is not standardized; JAMA flagged the variability decades ago. The Thai pharmaceuticals are the reliable choice.

Estradiol

For oral and transdermal (not recommended except for vaginal) estradiol, AllDayChemist (India), Inhousepharmacy.vu (Vanuatu), and IsraelPharm all ship worldwide without a prescription, carrying Progynova, Estrofem, Vagifem, and generics.

For injectable estradiol, the DIY HRT community, built to serve the trans population, compounds estradiol valerate, cypionate, and enanthate in oil. AstroVials is the reference vendor: EU-based, cryptocurrency payment, autoclave-sterilized, with one free resend on seized packages. DIYHRT.wiki and r/TransDIY track the active roster as vendors rotate.

Bulk powder (CAS 50-28-2) is available from Chinese API wholesalers. I would flag this route plainly as a legal and safety liability. Estrogens are not controlled substances in most countries, so legal risk on the finished-product routes is minimal.

Micronized progesterone

The cleanest path is Utrogestan (Besins Healthcare, France), molecularly identical to Prometrium, the proprietary pharma progesterone. Inhousepharmacy.vu ships 100 mg capsules at about $1.57 each, AllDayChemist stocks Susten 200 (the Indian equivalent), and Mexican chain pharmacies stock Utrogestan 100 mg and 200 mg over the counter. OTC transdermal creams (Emerita ProGest, Life-Flo Progesta-Care) are legal in all US states but produce erratic, low serum levels; they work for mild supplementation, not replacement.

The DIY powder route is also open. Lab Alley sells USP-grade micronized progesterone powder, yam-sourced, with 97-103% purity, direct to consumers. One gram equals ten 100 mg doses, so a 100 g jar covers roughly a year. A jeweler’s milligram scale at $30 gives accurate dosing, and size 0 gelatin caps filled with powder suspended in MCT or olive oil approximate commercial softgel pharmacokinetics. The oil carrier matters; dry powder has poor bioavailability.

Testosterone

Testosterone is Schedule III under the Controlled Substances Act, which makes importation legally riskier than the other hormones listed here. Much of the testosterone used in the United States is obtained through the grey market, sold at gyms and through fitness networks, with bodybuilders checking serum levels to confirm potency and titration. The market is vast, the batch-verification culture is mature, and quality ranges from pharmaceutical-grade to counterfeit.

Mexican chain pharmacies (Farmacias Guadalajara, Benavides, Similares, Costco Mexico, and Walmart Mexico) sell injectable testosterone without a prescription; Sostenon 250 (Organon, four-ester blend) and Primoteston Depot (Bayer, enanthate) are the reliable products. The FDA personal importation policy allows up to a 90-day supply to continue treatment.

Research-chemical liquid suppliers (Loti Labs, Behemoth Labz, Peptide Sciences) list testosterone enanthate, cypionate, and propionate at 200 to 250 mg/mL under “research use only” language; Schedule III status keeps this grey-legal at best, and listings come and go with enforcement pressure. EU DIY HRT vendors ship finished injectables alongside estradiol, cryptocurrency only. Underground labs on forums like Meso-Rx are the highest-legal-risk route; the bodybuilding community verifies batches through independent testing services like Janoshik.

Human Growth Hormone (HGH)

This is not a scheduled drug, so importing it is no more legally risky than progesterone. However, the problem with growth hormone is that it is so expensive that it is frequently counterfeited. If you can afford it, you are better off going to a prescribing physician inside the United States and getting it that way.

Unfortunately, this is not a perfect solution because gray-market pharmaceuticals flow back and forth among legitimate US compounding pharmacies, wholesale pharmacies, and retail pharmacies. Catherine Eban’s Bottle of Lies implies that the US drug distribution is one big gray market, just like the international one, only somewhat more reliable.

Dosing for hormone replacement or longevity typically ranges from 0.3 to 1 mg/day (1 to 3 IU/day), often on a 5-day-on, 2-day-off schedule. The IGF-1 blood test target in this protocol is high-normal for a younger reference range, generally 200 to 350 ng/mL. This produces meaningful effects on body composition, sleep architecture, and recovery without pushing IGF-1 into the supraphysiologic range, where the safety signal becomes concerning.

Norditropin and Omnitropin come in convenient pens for easy administration. The former requires no refrigeration, while the latter is heat-sensitive and half the price.

“Blue’s clues” about starting doses for hormone replacement

Read Hormone Secrets and see a knowledgeable provider for advice on these issues, but the following will give you an idea of what to do.

Oral estradiol for women is typically 1 to 2.5 mg capsules every morning.

Testosterone injectable for women is 1/10 to 2/10 of a 200-250 mg per cc oil preparation injected into fat. Testosterone cypionate or enanthate is used. The same drug for men is 1 cc, divided into one or two doses, injected into the muscle or sometimes fat over the course of a week.

Testosterone cream is more convenient and works as well for women as injectable. Twice-weekly dosing produces sustained levels. The creams are 25 to 50 mg per cc for women, with instructions to apply a quarter or half a cc several times a week. For men, the creams are 200 mg per cc, and the doses are 1 to 2 cc applied to the scrotal area twice a day, a lot more.

Oral micronized progesterone for women ranges from 50 to 800 mg at bedtime. For men, the dose is 50 to 400 mg at bedtime. These doses are based on symptom relief, and they are harmless. For more details on DHEA and Pregnenolone, see Hormone Secrets.

Monitor yourself and adjust dosing of everything based on how you feel. This is more important than blood levels or what the doctor says. The most typical mistake is not taking enough.

Disclaimers

None of the above is legal advice. Personal importation of prescription hormones occupies a grey zone, and Schedule III controlled substances carry more legal risk than the rest. Hormone therapy is straightforward when managed by an experienced provider. Find one if you can; WorldLinkMedical.com lists physicians trained in the Rouzier protocols. If you go it alone, get baseline blood work, start at the low end of the dose range, retest at eight to twelve weeks, and titrate primarily on how you feel rather than on numbers.

None of this is medical advice, and I am not responsible for your care. Please consult an experienced provider if you find one. Good luck on that one.

My editors did the heavy lifting on this post. You met Jim Arnold again in the introduction, and my attorney friend Elizabeth Cronin also provided counsel.

Selected references

Ray Peat, “Thyroid: Therapies, Confusion, and Fraud” (2006).

Ray Peat, “Not the ‘female hormone,’ but the shock hormone”.

Ray Peat, “Preventing and treating cancer with progesterone”.

Avrum Bluming and Carol Tavris, Estrogen Matters (Little, Brown, 2018).

Philip M. Sarrel et al., “The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years”, American Journal of Public Health 103, no. 9 (2013).

JoAnn E. Manson et al., “Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials”, JAMA (2017).

Katharina Dalton, Once a Month (multiple editions); Depression After Childbirth.

Derrick Lonsdale and Chandler Marrs, Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition(Academic Press, 2017).

My book, Hormone Secrets. Free download (covers physiologic blood-level targets, dosing, and clinical protocols in detail).

The Ray Peat complete collection at dokumen.pub.

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