Ray Peat, PhD on the Menstrual Cycle

Also see:
Light is Right
Hot flashes, energy, and aging
SOS for PMS
Collection of Ray Peat Quote Blogs by FPS
Progesterone Decreases Aromatase Activity
Quotes: Thyroid, Estrogen, Menstrual Symptoms, PMS, and Infertility
Estrogen Stimulates Insulin, Promotes Weight Gain
Possible Indicators of Excess Estrogen
Progesterone: Essential to Your Well-Being
Plasma Estrogen Does Not Reflect Tissue Concentration of Estrogen
Estrogen and PCOS
Shock Increases Estrogen
Autoimmune Disease and Estrogen Connection
Hormonal profiles in women with breast cancer
PUFA Increases Estrogen
PUFA Inhibit Glucuronidation
PUFA Promote Cancer
Maternal PUFA Intake Increases Breast Cancer Risk in Female Offspring
Vitamin A: Anti-Cancer and Anti-Estrogen
Toxic Plant Estrogens
The Dire Effects of Estrogen Pollution
Alcohol Consumption – Estrogen and Progesterone In Women
Estrogen, Endotoxin, and Alcohol-Induced Liver Injury
Estrogen Levels Increase with Age
Fat Tissue and Aging – Increased Estrogen
Estrogen Related to Loss of Fat Free Mass with Aging
Bisphenol A (BPA), Estrogen, and Diabetes
PUFA, Estrogen, Obesity and Early Onset of Puberty
Estrogen Related to Loss of Fat Free Mass with Aging
Nutrition and Brain Growth in Chick Embryos
The Brain: Estrogen’s Harm and Progesterone’s Protection
Estrogen Increases Serotonin
Estrogen, Serotonin, and Aggression
Women, Estrogen, and Circulating DHA
PUFA, Fish Oil, and Alzheimers
Estrogen, Glutamate, & Free Fatty Acids
Phospholipases, PUFA, and Inflammation
Estrogen’s Role in Seizures
Benefits of Aspirin
Estrogen’s Role in Asthma
Menstrual Cycle Related Epilepsy (Catamenial Epilepsy)

“Women’s monthly cycles, in which a brief estrogen dominance is followed by sustained exposure to progesterone, are probably an important factor in the renewal of the cells of the brain and other organs, as well as those of the reproductive organs. The daily rhythms of hormones and metabolism are known to be involved in the regulation of cell renewal.”

“Cells respond to stimulation by estrogen by producing a variety of molecules, including the “progesterone receptor” protein. When progesterone enters the cell, binding to these proteins, the estrogenic stimulation is halted, by a series of reactions in which the estrogen receptors disintegrate, and in which estrogen is made water soluble by the activation of enzymes that attach sulfate or a sugar acid, causing it leave the cell and move into the bloodstream, and by reactions that prevent its reentry into the cell by inactivating another type of enzyme, and that suppress its de novo formation in the cell, and that oxidize it into a less active form. Progesterone terminates estrogen’s cellular functions with extreme thoroughness.”

“In polycystic ovaries, menopausal symptoms, arthritis, angina pectoris, multiple sclerosis, some kinds of dementia, migraine, and emphysema, the relief achieved with a simple improvement of cellular energy can be rapid and complete.”

“For example, the follicular phase is a time of low steroid production by the ovary, until near the end of the phase, just before ovulation, when estrogen rises. The luteal phase is a time of high estrogen and high progesterone synthesis. Many publications describe the follicular phase as a time of high estrogen, and the luteal phase as a time of low estrogen, roughly the opposite of the actual situation. And an even larger number of studies get the results they want by using a short exposure to estrogen to study something which takes a long time to develop.”

“The normal cyclic function of the ovaries is a model for the potentially creative role of an inflammation-like stress. Every month (in a rhythm influenced by many cues), a productive crisis comes to a focus in the ovary, with the formation of estrogen, prostaglandins, carbon monoxide, and other signal substances, causing rapid changes both locally and systemically, with water, hormones, and nutrients gathering around the ovum (as well as in other parts of the body, such as the feet). Then as the follicle ruptures with the release of an ovum, the excitatory, inflammation-like state is resolved, with a massive increase in the production of antiinflammatoy, antistress substance, progesterone, leading to the suppression of the excitatory substances. These monthly processes are developmental, they are part of the epigenetic development of the organ.

Most, if not all, of the substances involved in ovarian physiology are involved in the disease of stress and degeneration, which progress in proportion to the inability to produce the resolution of inflammation and restoration of the stable condition. The ovary is a major source of estrogen which can produce the excited, activated, inflammatory, and proliferative state in any tissue of the body, though it acts mainly on the uterus, breasts, and pituitary. But the ovary is also, in response, able to produce massive amounts of the protective progesterone, which interrupts the inflammatory effects of estrogen on the various tissues and organs, largely by suppressing the proteins that hold estrogen within cells (especially the “estrogen receptor”), but also by changing the activities of many enzymes away from the estrogen-controlled, inefficient pattern. The developmental actions of the ovary cause continuing epigenetic process in other organs, causing noticeable changes in their structure every month.”

“The estrogen dominance which is needed to start the reproductive cycle, with cell proliferation in the endometrium, breast, and pituitary, is not otherwise useful to the organism, and is controlled and opposed during pregnancy by a constantly rising production of progesterone. The state of estrogen dominance is essentially unstable.”

“Minks that have mated in the winter don’t implant the fertilized ovum in the uterus until the spring equinox, when progesterone rises suddenly, and allows both the uterus and the embryo to begin the process of pregnancy and gestation. Progesterone provides the oxygen needed for the successful implantation of the embryo, while estrogen and serotonin lower the intrauterine oxygen.

Under good conditions, the (premenstrual) luteal phase of the monthly cycle resembles pregnancy, as a period of progesterone dominance, in which the abundance of progesterone causes cells to decrease their estrogen content. The luteal phase is actually the first stage of pregnancy, and if there is implantation of an embryo all of the processes that begin at ovulation progress continuously until childbirth occurs. When there is no implantation, the luteal phase progesterone dominance is terminated, allowing estrogen to enter tissues and producing menstruation. The sudden decrease of progesterone production before menstruation is similar to the decrease of hormone production just before childbirth. The same conditions that produce the premenstrual syndrome, if they aren’t corrected by the placenta’s massive production of progesterone, will produce preeclampsia, toxemia of pregnancy, eclampsia, and postpartum depression. They are also related to the problems that become so common at menopause. Whenever the production of progesterone falls, tissues are susceptible to estrogen.

There are several common causes of a progesterone deficiency. Deficiencies of thyroid, vitamin A, and cholesterol are often responsible for a progesterone deficiency. Inadequate light exposure can cause it. Excess polyunsaturated fats, interfering with gonads and thyroid, can cause it. And excess serotonin can cause it.”

“In the ovary and uterus, the healthy alternation of excitation and quiescence usually continues for many years, and in rodents it often ends in a state of “persistent estrus,” in which the excitatory state can’t be terminated in the usual way, by the production of progesterone. In humans, menopause is analogous, because the excitatory FSH hormone from the pituitary becomes excessive, with the ovary continuing to produce estrogen but failing to produce progesterone, sometimes with the pituitary failing to shift from FSH to LH. In rodents, it’s recognized that persistent estrus is caused by chronically elevated estrogen, but in humans there has been tremendous resistance to the recognition of estrogen’s central role in menopause and senescence. An excess of the basic promoter of inflammation, serotonin, which is closely associated with estrogen’s influence, can have similar effects on the reproductive cycle (Cooper, et al., 1986). The industry has devoted the necessary funding to making the easily manipulated medical culture, and the public, believe the opposite, i.e., that reproductive aging is mainly caused by estrogen deficiency.”

“Stress uses progesterone and can cause menstrual periods to stop. Girls who begin regular exercise (such as dancing) before puberty have later sexual development.”

“Stress, trauma, and shock start an inflammatory process, that can cause progressive damage to the organs, including the liver. Giving progesterone following the injury protects against the increase of TNF, IL-6, and leakage of liver enzymes (Kuebler, et al., 2003). It has similar protective effects in the brain, lungs, and other organs. During the normal menstrual cycle, IL-6 is inversely related to the level of progesterone (Angstwurm, et aI., 1997).”

“Dr. Peat’s (Progesterone) Dosage Recommendations
For topical treatment of sun damaged skin, or acne, wrinkles, dark marks, the oil can be applied directly to the affected areas.

Since progesterone has none of the harmful side effects of other hormones (except the alteration of the menstrual cycle if taken at the wrong time of the month), the basic procedure should be to use it in sufficient quantity to make the symptoms disappear, and to time its use so that menstrual cycles are not disrupted. This normally means using it only between ovulation and menstruation unless symptoms are sufficiently serious that a missed period is not important to you.

If a person has an enlarged thyroid gland, progesterone encourages secretion and unloading of the stored colloid and can bring on a temporary hyperthyroid state which is a corrective process. A thyroid supplement, like Thyodine may be used to shrink the goiter before progesterone is given.

Normal amounts of progesterone promote thyroid secretion, while a deficiency, especially when too much estrogen is present, causes the thyroid to enlarge. Some mention euphoria as a “side-effect” of progesterone usage, but euphoria is simply an indication of good physiological state. To avoid unexpected anesthesia, the correct dose should be determined by taking about 10 mg (3-4 drops) at a time, allowing it to spread into the membranes of the mouth, and repeating the dose after 10 minutes until the symptoms are controlled.

An excessive estrogen/progesterone ratio (should be 1 part to 10 parts, estrogen to progesterone), is involved in producing aggravating symptoms such thin, bluish skin. Low thyroid is one cause of excess estrogen, and when high estrogen is combined with low thyroid function, the skin can look relatively bloodless.

Symptoms in cycling women are most common around ovulation and in the premenstrual week, when the estrogen/progesterone ratio is normally highest. At puberty, in the early twenties and in the late thirties and menopause are the ages when the ratio is most often disturbed – and these are also the ages when thyroid disorders are most common.

The individual who suffers from one aspect of progesterone (and/or thyroid) deficiency will tend to develop other problems at varying times. With cyclic depression or migraine headaches at 22, there will possibly be breast disease after, and often there will be problems with pregnancy. These people with a history of severe symptoms are the ones most likely to have problems around menopause. Prenatal exposure to poorly balanced hormones seems to predispose children to later hormone imbalances.

Excess stress (which can block progesterone synthesis and elevate estrogen) may being on symptoms in someone who never had them. As well as darker days without sun, toxins and nutritional deficiencies. A very common cause of an estrogen excess is a dietary protein deficiency because the liver cannot detoxify estrogen when it is under nourished.

With a diet high in protein and vitamin A, progesterone can usually be reduced each month. Using thyroid supplementation will also usually reduce the amount of progesterone needed. Occasionally, a women won’t feel any effect even from 100 mg of progesterone and this may indicate they need to use thyroid supplementation and diet changes to normalize their estrogen, prolactin and cortisol levels.

Progesterone stimulates the ovaries and adrenals to produce progesterone, and it also activates the thyroid. It shouldn’t be necessary to use progesterone indefinitely unless the ovaries have been removed. In slender post-menopausal women, 10 mg per day is usually enough to prevent progesterone deficiency.

Ina 10% solution of progesterone in vitamin E, one drop contains about three milligrams of progesterone. Normally the body produces 10 to 20 milligrams per day. A dose of 3 or 4 drops usually brings the blood levels up to normal range, but this dose can be repeated throughout the day to control symptoms.

For general purposes, it is most economical and effective to take progesterone dissolved in vitamin E orally, for example taking a few drops on the lips and tongue, or rubbing it into the gums. (It is good for the general health of the gums, too.) These membranes are very thin and hence the progesterone can easily and quickly enter the blood. when swallowed, the vitamin E allows it to be absorbed through the walls of the stomach and intestine.

As was mentioned previously, topical application of this oil aids sun damaged skin. For topical treatment of arthritis, osteoporosis, tendinitis, bursitis, or varicose veins, to speed absorption it is best to apply a few drops of olive oil to the area, and then to rub the progesterone -vitamin E solution into and around the affected area.”

“PROGESTERONE SUPPLEMENTATION
SYMPTOMATIC: For tendonitis, bursitis, arthritis, sunburn, etc., progesterone in vitamin E can be applied locally after a little olive oil has been put on the skin to make it easier to spread the progesterone solution. For migraines, it has been taken orally just as the symptoms begin.

FOR PMS: The normal pattern of progesterone secretion during the month is for the ovaries to produce a large amount in the 2nd two weeks of the menstrual cycle, (i.e., day 14 through day 28) beginning at ovulation and ending around the beginning of menstruation, and then to produce little for the following two weeks. An average person produces about 30 milligrams daily during the 2nd two weeks. The solution I have used contains approximately 3 or 4 milligrams of progesterone per small drop. Three to four drops, or about 10 to 15 milligrams of progesterone, is often enough to bring the progesterone level up to normal. That amount can be taken days 14 through 28 of the menstrual cycle; this amount may be repeated once or twice during the day as needed to alleviate symptoms. Since an essential mechanism of progesterone’s action involves its opposition to estrogen, smaller amounts are effective when estrogen production is low, and if estrogen is extremely high, even large supplements of progesterone will have no clear effect; in that case, it is essential to regulate estrogen metabolism, by improving the diet, correcting a thyroid deficiency, etc. (Unsaturated fat is antithyroid and synergizes with estrogen.)

PERIMENOPAUSAL: The symptoms and body changes leading up to menopause are associated with decreasing production of progesterone, at a time when estrogen may be at a lifetime high. The cyclic use of progesterone, two weeks on, two weeks off, will often keep the normal menstrual cycle going. Three to our drops, providing ten or twelve milligrams of progesterone, is typical for a day, but some women prefer to repeat that amount. Progesterone is always more effective when the diet contains adequate protein, and when thee isn’t an excessive amount of unsaturated fat in the diet.

POSTMENOPAUSAL: Some women continue the cyclic use of progesterone ater menopause, because the pituitary gland and brain may continue to cycle long after menstruation has stopped, and progesterone is an important regulator of pituitary and brain function. The cycling pituitary affects the adrenal glands and other organs, and progesterone tends to protect against the unopposed actions of prolactin, cortisol, and adrenal androgenic hormones. Progesterone’s effects on the pituitary apparently contribute to its protective effect against osteoporosis, hypertension, hirsutism, etc. But some women prefer to use progesterone without interruption after the menopause, for its protective antistress effects. Slender people usually find that two or three drops are enough, but this amount may be repeated once or twice as needed to relieve symptoms. Adequate protein in the diet and good thyroid function help the body to produce its own progesterone; even if the ovaries have been removed, the adrenal glands and brain continue to produce progesterone.

DOSAGE OF PROGESTERONE
Since progesterone has none of the harmful side effects of other hormones (except for alteration of the menstrual cycle if it is taken at the wrong time of month), the basic procedure should be to use it in sufficient quantity to make the symptoms disappear, and to time its use so that menstrual cycles are not disrupted. This normally means using it only between ovulation and menstruation unless symptoms are sufficiently serious that a missed period is not important. The basic idea of giving enough to stop the symptoms can be refined by some information on a few of the factors that condition the need for progesterone.

An excessive estrogen/progesterone ratio is more generally involved in producing or aggravating symptoms than either a simple excess of estrogen or a deficiency of progesterone, but even this ratio is conditioned by other factors, including age, diet, other steroids, thyroid, and other hormones. The relative estrogen excess seems to act by producing tissue hypoxia (as reported in my dissertation, University of Oregon, 1972), and this is the result of changes induced by estrogen in alveolar diffusion, peripheral vascular changes, and intracellular oxygen wastage.

Hypoxia in turn produces edema (as can be observed in the cornea when it is deprived of oxygen, as by a contact lens) and hypoglycemia (e.g., diminished ATP acts like insulin), because glycolysis must increase greatly for even a small deficiency of oxygen. Elevated blood lactic acid is one sign of tissue hypoxia. Edema, hypoglycemia, and lactic academia can also be produced by other “respiratory” defects, including hypothyroidism, in which the tissue does not use enough oxygen. In hypoxia, the skin will be bluer (in thin places, such as around the eyes), than when low oxygen consumption is the main problem. Low thyroid is one cause of excess estrogen, and when high estrogen is combined with low thyroid, the skin looks relatively bloodless.

Symptoms in cycling women are most common around ovulation and in the premenstrual week, when the estrogen/progesterone ratio is normally highest. At puberty, in the early twenties and in the late thirties and menopause are the ages when the ratio is most often disturbed–and these are also the ages when thyroid disorders are commonest in women.

The individual who suffers from one aspect of the progesterone (and/or thyroid) deficiency will tend to develop other problems at different times. With cyclic depressions or migraine headaches at age 22, there will possibly be breast disease later, and often there will be problems with pregnancy. These people with a history of sever symptoms are the ones most likely to have severe problems around menopause. Prenatal exposure to poorly balanced hormones seems to predispose the child to later hormone problems.

Excess stress (which can block progesterone synthesis and elevate estrogen) may bring on symptoms in someone who never had them. Spending a summer in Alaska, with an unusually long day, may relieve the symptoms of a chronic sufferer. Dark cloudy winters in England or the Pacific Northwest are powerful stressors, and cause lower production of progesterone in women, and testosterone in men. Toxins can produce similar symptoms, as can nutritional deficiencies. A very common cause of an estrogen excess is a dietary protein deficiency–the liver simply cannot detoxify estrogen when it is under-nourished.

With a diet high in protein (e.g., at least 70-100 grams per day, including eggs) and vitamin A (not carotene), I have found that the dose of progesterone can be reduced each month. Using thyroid will usually reduce the amount of progesterone needed. Occasionally, a woman won’t feel any effect even from 100 mg. of progesterone; I think this indicates that they need to use thyroid and diet, to normalize their estrogen, prolactin, and cortisol.

Progesterone stimulates the ovaries and adrenals to produce progesterone, and it also activates the thyroid, so one dose can sometimes have prolonged effects. It shouldn’t be necessary to keep using progesterone indefinitely, unless the ovaries have been removed. In slender post-menopausal women, 10 mg. per day is usually enough to prevent progesterone deficiency symptoms.

In a 10% solution of progesterone in vitamin E, one drop contains about three milligrams of progesterone. Normally, the body produces 10 to 20 milligrams per day. A dose of 3 or 4 drops usually brings the blood levels up to the normal range, but this dose can be repeated several times during the day if it is needed to control symptoms.

For general purposes, it is most economical and effective to take progesterone dissolved in vitamin E orally, for example taking a few drops on the lips and tongue, or rubbing it into the gums. (It is good for the general health of the gums.) These membranes are very thin, and the progesterone quickly enters the blood. When it is swallowed, the vitamin E allows it to be absorbed through the walls of the stomach and intestine, and it can be assimilated along with food, in the chylomicrons, permitting it to circulate in the blood to all of the organs before being processed by the liver. These droplets are smaller than red blood cells, and some physicians seem to forget that red blood cells pass freely through the liver.

For the topical treatment of sun damaged skin, or acne, wrinkles, etc. the oil can be applied directly to the affected area.”

“I have observed the use of progesterone transdermally (applied to the skin in about 400 women suffering from the full range of peri-menstrual symptoms, including migraine, acne, depression, mastalgia (breast pain), edema (water retention and swelling), and lethargy. I found that nearly all the women who apply the lotion themselves, are able to find the appropriate dosage for controlling their symptoms. Occasionally, thyroid therapy, weight reduction: or change in some aspect of lifestyle is necessary for complete relief from symptoms. When some women said the progesterone had no effect, it turned out that they were applying it as sparingly as they would a rare perfume-just touching it to their wrists.

Anesthesia (or drunkenness) from a very large overdose is the only negative side effective reported in the literature. Experimenting with very large doses of natural progesterone on myself, for migraine, I found that there is a temporary antagonism to testosterone, causing small symptoms, including a slight sense of gregariousness, an urge to socialize. However, synthetic progestins do have harmful side effects including breast tumors. Unfortunately, most physicians do not yet know the difference between natural progesterone and synthetic progestins.”

“Estrogen’s name, derived from the gadfly, accurately suggests its role as an excitant, getting things started. Progesterone’s name, relating to pregnancy, is compatible with thinking of it as an agent of calming and fulfillment. But these properties show up in every aspect of physiology, and the special cases of female estrus and pregnancy can be properly understood only in the larger context, in which, for example, progesterone is a brain hormone in both sexes and at all ages, and estrogen is an essential male hormone involved in the sperm cell’s function and male libido.”

“Sometimes progesterone can cause an underactive enlarged thyroid gland to begin secreting, temporarily producing mild hypothyroidism while the gland returns to a normal size. Supplemental progesterone can reduce excessive cortisol production.

Since progesterone helps the thyroid to secrete, and helps the liver to regulate glucose and convert T4 to T3, women who are low in progesterone usually have hypothyroid symptoms (because of insufficient T3), including high cortisol, which promotes the synthesis of estrogen (in several ways, but never from progesterone). Cortisol is made from progesterone, but increasing the supply of progesterone reliably lowers cortisol synthesis, acting on the brain, pituitary, and adrenal glands. Progesterone, by many mechanisms, including its antagonism to cortisol, lowers the amount of estrogen in cells (causing the estrogen-binding proteins to be degraded, inhibiting the enzymes that release estrogen from the sulfates and glucuronides, and activating the enzymes that detoxify estrogen). So I think the symptoms of increased estrogen and cortisol are the result of either extraneous ingredients in the creams, or from using it at the wrong time, for example, too early, triggering premature ovulation. Supplementing a small amount of T3, Cytomel or Cynomel, usually stops symptoms such as breast pain, irritability, and restless energy, in less than an hour.”

“(progesterone) Protection against hypoglycemia is probably the main mechanism. Diabetic mothers often have precocious children, if they aren’t damaged by drugs and irrational diets. Ten to 15 grams per pregnancy, at increasing dosage, seems to be the optimal amount, when there is some sign of excessive estrogen or unexpected toxemia.”

“In good health, an animal’s systems are designed so that certain tissues will be intensely but briefly stimulated by estrogen.”

“It [progest-e] can help with cramps, but it would probably take a lot; I think it’s better to use thyroid (including T3) to solve the basic problem, since it will let you regulate the balance between estrogen and progesterone, while allowing your cells to balance the minerals, retaining the magnesium needed to prevent cramping. Increasing your intake of all the main minerals, calcium, sodium, potassium, and magnesium usually helps in the short term, but the balance isn’t stable if your thyroid is low. Milk, orange juice, coffee (even decaffeinated coffee is a good source of magnesium), and well salted foods, support thyroid functions. Aspirin helps with thyroid function and mineral balance, even helps to prevent excessive estrogen production.”

“More recently, it has been discovered that progesterone inhibits the expression of the enzyme nitric oxide synthase while estrogen stimulates its expression. At the time of ovulation, when estrogen is high, a woman breathes out 50% more nitric oxide (“NO”) than men do, but at other times, under the influence of increased progesterone and thyroid, and reduced estrogen, women exhale much less NO than men do. (Nitric oxide is a free radical, and it decomposes’ into other toxic compounds, including the free radical peroxyrutnle} which damages cells, including the blood vessels, brain, and heart. Carbon dioxide tends to inhibit the production of peioxynitrile.)”

“When estrogen is given to an animal, it almost instantly causes capillaries to become leaky, allowing water to move out of the blood stream, and at the same time, estrogen causes cells to take up water. Both of these processes are the same as the early effects of oxygen deprivation. In the normal reproductive cycle, the surge of estrogen lasts only a few hours, and normal permeability is quickly restored by increasing progesterone. During those intermittent short exposures to estrogen, there isn’t a massive leakage of serum proteins into the tissues. During the time of estrogenic influence, all kinds of cells are influenced, with the excitatory equilibrium of nerve cells, glandular cells, and immune system cells being shifted, lowering the threshold of excitation, or prolonging the excited state.”

“Our body controls estrogen’s effects by decreasing excitation while increasing efficient energy production.”

“Estrogen’s survival value exists only in the context of a whole organism with multiple ways for limiting estrogen’s destabilizing actions. Estrogen’s harmful effects occur when our systems for opposing it fail.”

“Women and other mammals that are deficient in progesterone, and/or that have an excess of estrogen, have a higher than average incidence of cancer. Animal experiments have shown that administering progesterone could prevent cancer. Cells in the most cancer-susceptible tissues proliferate in proportion to the ratio of estrogen to progesterone. When the estrogen dominance persists for a long time without interruption, there are progressive distortions in the structure of the responsive organs–the uterus, breast, pituitary, lung, liver, kidney, brain, and other organs–and those structural distortions tend to progress gradually from fibroses to cancer.

As a result of the early studies in both humans and animals, progesterone was used by many physicians to treat the types of cancer that were clearly caused by estrogen, especially uterine, breast, and kidney cancers. But by the 1950s, the drug industry had created the myth that their patented synthetic analogs of progesterone were medically more effective than progesterone itself, and the result has been that medroxyprogesterone acetate and other synthetics have been widely used to treat women’s cancers, including breast cancer.

Unfortunately, those synthetic compounds have a variety of functions unlike progesterone, including some estrogenic and/or androgenic and/or glucocorticoid and/or antiprogesterone functions, besides other special, idiosyncratic side effects. The rationale for their use was that they were “like progesterone, only better.” The unpleasant and unwanted truth is that, as a group, they are seriously carcinogenic, besides being toxic in a variety of other ways. Thousands of researchers have drawn conclusions about the effects of progesterone on the basis of their experiments with a synthetic progestin.”

“Each type of cell and organ is subject to injury, and in some cases these injuries are cumulative. In the healthy liver, which stores glycogen, toxins can be inactivated, for example by combining with glucuronic acid, derived from the stored glucose. With injury, such as alcoholism combined with a diet containing polyunsaturated fats, the liver’s detoxifying ability is reduced. Even at an early stage, before there is a significant amount of fibrosis, the reduced activity of the liver causes estrogen to accumulate in the body. Estrogen’s valuable actions are, in health, exerted briefly, and then the synthesis of estrogen is stopped, and its excretion reduces its activity, but when the liver’s function is impaired, estrogen’s activity continues, causing further deterioration of liver function, as well as injury of nerves such as Desjardins described, and the systemic energy shifts and stress activations mentioned above.

Besides lowering the liver’s detoxifying ability, stress, hypoglycemia, malnutrition, hypothyroidism, and aging can cause estrogen to be synthesized inappropriately and continuously. With aging, estrogen begins to be produced throughout the body–in fat, muscles, skin, bones, brain, liver, breast, uterus, etc. Polyunsaturated fats are a major factor in the induction and activation of the aromatase enzyme, which synthesizes estrogen.

Increased synthesis of estrogen, with aromatase, and decreased excretion of it, by the liver and kidneys, are only two of the processes that affect the influence of estrogen during aging. Cellular stress (chemical, mechanical, hypoxemic, hypoglycemic [Clere, et al., 2012; Aguirre, et al., 2007, Zaman, et al., 2006, Saxon, et al., 2007; Tamir, et al., 2002; Briski, et al., 2010]) increases estrogen receptors (which activate CRH and the stress response). The presence of estrogen receptors means that estrogen will be bound inside cells, where it acts to modify those cells. Before estrogen can reach the liver to be inactivated, it must be released from cells. Ordinarily, the cyclic production of progesterone has that function, by destroying the estrogen-binding proteins. Progesterone also inhibits the aromatase which synthesizes estrogen, and shifts the activities of other enzymes, including sulfatases and dehydrogenates, in a comprehensive process of eliminating the presence and activity of estrogen. At menopause, when the ovary fails to produce the cyclic progesterone, all of these processes of estrogen inactivation fail. In the absence of progesterone, cortisol becomes more active, increasing aromatase activity, which now becomes chronic and progressive. The decrease of progesterone causes many other changes, including the increased conversion of polyunsaturated fatty acids to prostaglandins, and the formation of nitric oxide, all of which contribute to the tendency to flush.”

“During the reproductive years, women’s cyclic production of large amounts of progesterone probably retards their aging enough to account for their greater longevity. Childbearing also has a residual antiestrogenic effect and is associated with increased longevity.”

“Estrogen blocks the release of hormone from the thyroid gland, and progesterone facilitates the release. Estrogen excess or progesterone deficiency tends to cause enlargement of the thyroid gland, in association with a hypothyroid state. Estrogen can activate the adrenals to produce cortisol, leading to various harmful effects, including brain aging and bone loss. Progesterone stimulates the adrenals and the ovaries to produce more progesterone, but since progesterone protects against the catabolic effects of cortisol, its effects are the opposite of estrogen’s. Progesterone has antiinflammatory and protective effects, similar to cortisol, but it doesn’t have the harmful effects. In hypothyroidism, there is a tendency to have too much estrogen and cortisol, and too little progesterone.

The blood tests can be useful to demonstrate to physicians what the problem is, but I don’t think they are necessary. There is evidence that having 50 or 100 times as much progesterone as estrogen is desirable, but I don’t advocate “progesterone replacement therapy” in the way it’s often understood. Progesterone can instantly activate the thyroid and the ovaries, so it shouldn’t be necessary to keep using it month after month. If progesterone is used consistently, it can postpone menopause for many years.

Cholesterol is converted to pregnenolone and progesterone by the ovaries, the adrenals, and the brain, if there is enough thyroid hormone and vitamin A, and if there are no interfering factors, such as too much carotene or unsaturated fatty acids. Progesterone deficiency is an indicator that something is wrong, and using a supplement of progesterone without investigating the nature of the problem isn’t a good approach. The normal time to use a progesterone supplement is during the “latter half” of the cycle, the two weeks from ovulation until menstruation. If it is being used to treat epilepsy, cancer, emphysema, migraine or arthritis, or something else so serious that menstrual regularity isn’t a concern, then it can be used at any time. If progesterone is used consistently, it can postpone menopause for many years.”

“Most people are aware of some of the variations of bleeding and clotting that occur commonly. Bleeding gums, nose-bleeds, menstruation and its variations, and the spontaneous bruising (especially on the thighs) that many women have premenstrually, are familiar events that don’t seem to mean much to the medical world. Sometimes nose-bleeds are clearly stress-related, but the usual “explanation” for that association is that high blood pressure simply blows out weak blood vessels. Bleeding gums are sometimes stress related, but high blood pressure is seldom invoked to explain that problem.”

“Menstrual bleeding is a good place to start the investigation of bleeding problems, since its relatively harmless abnormalities are physiologically related to some very serious health problems, such as pregnancy bleeding, abruptio placentae, and eclampsia. Women who die from eclampsia have been found to have massively clotted blood vessels in their brains, but the variety of names for the pregnancy disorders have prevented most people from thinking of pregnancy as a time when there is a high risk of the “thrombohemorrhagic disorders,” a time when the clotting system is under stress. (For about fifteen years after Selye coined the term, only he and some Russians were publishing research on it, and Americans still don’t show much interest in the subject.)

Women with a chronic menstrual problem resulting from progesterone deficiency often continue to bleed each month even when they are pregnant, and these women tend to develop toxemia, and to have a high incidence of pregnancy complications, and to deliver premature, poorly developed babies.

In 1933 James Shute was recommending the use of vitamin E for preventing the clotting problems associated with pregnancy, that often lead to miscarriage. He based his work on animal studies, that led to vitamin E’s being known as the “fertility vitamin.” Later, his sons Wilfred and Evan reported that vitamin E could prevent heart attacks, birth defects, complications of diabetes, phlebitis, hypertension, and some neurological problems.”