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Progesterone vs. Progestin:
Vive La Différence!

Clara Felix
Reprinted with permission from
The Felix Letter: A Commentary on Nutrition

(The following article about Dr. John Lee's use of Pro-Gest refers to his book, Natural Progesterone: The Multiple Roles of a Remarkable Hormone. See also: What Your Doctor May Not Tell You About Menopause.)

In simpler times, 'female complaints' were treated with special foods, herbs and tonics. Nowadays, powerful synthetic hormones are dispensed freely if not cheaply to women all over the globe. Medical and popular media wage a phenomenally successful campaign to make these products appear as benign as sunlight. (Don't bother reading the fine print on the package inserts, ladies, it's just a silly legal requirement.)

The hormone era came into its own with The Pill. Taken on a cyclical schedule monthly, synthetic estrogen plus synthetic progesterone, or synthetic progesterone alone, send signals to the master controller - the pituitary and hypothalamus - to shut down ovulation. If no egg is release from the ovary, there's no pregnancy. Presto! - sexual freedom without paying the piper! Fantastically convenient and safe.

Try telling that to Mother Nature. Ask epidemiologists who chart the steady rise of breast cancer rates in the U.S. while other cancers, except lung cancer in women, have decreased. Look up the manufacturers' product information for any well-known oral contraceptive in the Physicians' Desk Reference. Pages of tiny print list Cautions, Contraindications, and Adverse Reactions that include life-threatening pulmonary embolism, cerebral thrombosis, and cerebral hemorrhage. Never mind the 'milder' patient complaints such as nausea and vomiting, migraine, mental depression, gallbladder disease, enlargement of uterine fibroid tumors, and loss of scalp hair! (Just a sample, believe me.)

First, the young women were snookered on a grand scale into accepting without a fuss the havoc The Pill makes of their natural functions. The Pill's success ($$) and safety record (hah!) helped launch the next campaign, Hormone Replacement Therapy (HRT) for the disease of aging in women - medical salvation for a tragic medical condition! The goal appears to be pharmaceutical control over every woman's 'female' functions, beginning with puberty and stopping only with her obituary.

Besides generating monumental windfalls for the drug firms, it makes steady work for journalists, ad-makers, medical experts, etc. whose job it is to terrify women (and physicians) about the horrors of menopause, decrepitude, bone loss, etc. - avoidable, they say, only through HRT. Skeptical doctors, slow to prescribe it, risk an exodus of patients who turn to more caring physicians. Scan the magnificent HRT ads in any medical journal, or read standard medical texts on menopausal symptoms and treatment, if you think I'm overstating the case.

Each of the scores of synthetics developed for oral contraceptives and HRT is patentable, unlike real hormones, creating the profit incentive. Most important in terms of convenience, they work when taken orally. Natural hormones are commercially extracted easily from plants but lose some effectiveness when swallowed. So, what's wrong with making powerful hormones that work by mouth?

The answer lies in the story of progesterone. In John R. Lee M.D.'s Natural Progesterone: The Multiple Roles of a Remarkable Hormone (1993), the good doctor from Sebastopol tells what happens to women who use the true hormone. The contrast between its benign effects and the hair-raising ones caused by synthetics was a revelation to me. Like most people, clinicians included, I didn't know about the difference*.

The synthetic analogues of progesterone are call progestins - a term designed to blur the distinction. Another term is "progestogens". No wonder doctors, patients, journalists - everyone but the drug makers - seldom know the difference. Dr. Lee writes: "Gail Sheehy, in her popular 1991 book The Silent Passage, for instance, admits to being so confused about the names that she decided to call all of them 'progesterone' throughout the book even though she is generally writing about the synthetic progestins."

The lists in Physicians' Desk Reference of 'adverse reactions' for Provera and the other progestins are very long and very scary. For starters, they're known to increase the risk of birth defects, of breast cancer, and of runaway blood clots (embolisms) that lodge in the lungs or the brain.

Natural progesterone doesn't have any harmful side effects even during pregnancy, and actually protects against breast cancer and abnormal clotting.

Swallowed as a pill, however, it goes through metabolic passes by the liver, losing some of its effectiveness. Earlier preparations of natural progesterone needed to be injected, or were made for vaginal or rectal insertion - not very convenient. (More recently, good absorption has been achieved from oral preparations that deliver the desired doses.) Also, as we observed, the natural is not patentable. The drug makers got busy. Starting with the real hormone, they did a little snipping here, a bit of tailoring there - creative organic chemistry stuff! The reformulated molecules were powerful inhibitors of ovulation, making them the drug of choice (along with synthetic estrogens) for contraception.

The other beckoning market was the menopausal woman on estrogen replacement therapy (ERT). Alas, these ladies were getting too many cancers of the uterus. Back to the drawing board! Progestins saved the day. Taken cyclically, they tend to cause bleeding that sheds the cancer-promoting buildup (stimulated by ERT) of tissues lining the uterus. Wunderbar! Mostly male doctors now have restored to us older females the privilege of having monthly periods till we totter to the grave. Thanks a heap.

Question: Why is true progesterone good for us and the synthetic analogs not so good?

Progesterone is the master 'starter' hormone from which the other great steroid hormones are made, i.e., testosterone, estrogens, and the adrenal corticosteroids. We're talking basic.** For example, Dr. Lee explains how cortisone's unique anti-arthritic, anti-inflammatory effects can take place only if enough progesterone is available as precursor to cortisone synthesis by the body.

Progesterone's second indispensable function is the survival and development of the fertilized ovum. Ample amounts made by the placenta and ovary are essential for a full-term pregnancy.

Far and beyond its role in pregnancy, Lee explains, are progesterone's multiple systemic functions, including these:

  • protects against breast fibrocysts

  • is a natural diuretic

  • helps use fat for energy

  • is a natural antidepressant

  • helps thyroid hormone action

  • normalizes blood clotting

  • restores libido

  • helps normalize blood sugar levels

  • normalizes zinc and copper levels

  • restores proper cell oxygen levels

  • protects against endometrial cancer

  • helps protect against breast cancer

  • stimulates bone building

The fakes - progestogens, progestins, etc. - do two things well: they prevent ovulation and they stop ERT-induced buildup of uterine lining (endometrium) to cancer-promoting levels. The following fatal flaws, however, make it impossible for them to take on most of progesterone's functions:
1) They can't be converted in the body into sex hormones and corticosteroids.
2) All progestins have powerful effects when taken orally because they're not readily metabolized (broken down) by the liver for excretion in bile and urine - unlike progesterone. Not only do they persist in the body abnormally long, they occupy progesterone receptor sites in tissues, taking over for the true hormone but not capable of doing most of its jobs.

Many of progestins' adverse effects are believed to arise from just this interference with highly complex natural processes. Reminds me of trans-fatty acids that get into our system after we eat foods prepared with margarine and other artificially hydrogenated oils. Trans fats displace vitally needed w3 and w6 fatty acids in the cell membrane, but then can't fish or cut bait!

Question: Why are so many women beset after menopause with stiff, aching joints, and loss of springiness and muscular strength, while men generally retain not just male virility but physical power and vitality?

Adrenal glands make progesterone for women and men both; but women depend on their ovaries for the main supply of progesterone (also estrogen). When at menopause the ovary's output of both drastically drops (but doesn't cease), the adrenal glands try harder but don't make up the difference. In contrast, older men maintain their usual progesterone levels, which in the U.S. tend to be much higher than in menopausal women!***

For women, progesterone loss means a big drop in corticosteroids, which protect against stiffness, soreness, and weakness in joints and muscles. Men, on the other hand, continue to maintain their corticosteroid levels.

Low progesterone also may lead to loss of bone density and ready fractures from physical exertions, so that many women fear to exercise or engage in sports, which only reinforces the stiffness, weakness, etc.

Question: Why do many pre-and postmenopausal women develop excess facial hair and male-pattern hair loss?

When a woman has too little progesterone with which to make the other steroids, the process has to proceed via an 'emergency' rerouting. This bypass relies more on androgenic (male type) hormones than the route where progesterone is the key precursor. Dr. Lee writes: "When this happens, the androgenic steroids along this pathway will become more dominant..." The good news is that with a number of patients "replacement of natural progesterone leads, in time, to disappearance of the facial hairs and the restoration of scalp hair."

Question: Can young women also experience low progesterone levels? What are the effects?

"...a good proportion of women in their 30's (and some even earlier) and long before actual menopause, will, on occasion, not ovulate during their menstrual month. Without ovulation, no corpus luteum results and no progesterone is made," Dr. Lee writes. Stress, poor nutrition, smoking, and toxic chemicals in the environment probably contribute to anovulatory periods. As these women approach the decade before menopause, "they are producing much less progesterone than expected but still producing normal (or more) estrogen."

Estrogen without progesterone's balancing effects are not as benign as we're led to believe. As a matter of fact, he's convinced the discomforts young women are most familiar with arise from unopposed estrogen in the face of a relative progesterone deficiency.

For example, "they retain water and salt, breasts swell and become fibrocystic, they gain weight (especially around the hips and torso), become depressed and lose libido, their bones suffer mineral loss, and they develop fibroids."

Natural progesterone, he and other doctors find, gives young and premenopausal patients relief from any or all of these symptoms. It also tones down sweets cravings!

The Felix Letter, P.O.B. 7094, Berkeley, CA 94707
is published independently by Clara Felix and supported solely by subscription.
Subscription $12/yr (6 issues), $22/2yrs (12 issues).

* I'm angry because I too was snookered long ago, when my doctor at the time prescribed Provera, a synthetic, that she called a "natural" progesterone. I stopped taking it after some years, and since menopause I've relied on good nutrition, ginseng, and plenty of omega-3 flax oil and fish oil to get me over the humps. (See my chapter in Women of the 14th Moon: Writings on Menopause, edited by Dena Taylor and Amber Coverdale Sumrall, 1991, preface by Grace Paley. The Crossing Press, Freedom ,CA, 95019). I wish I'd known about natural progesterone sooner as well! (back to where you were)

** The body makes progesterone and all steroids from its cholesterol, a small molecule with important stabilizing functions in every cell. The process can take place in the adrenal glands of both sexes and the testes in males. In women during their fertile years the ovaries are the major production site for progesterone. During the early phase of monthly preparation for ovulation, about 2 milligrams daily of progesterone are secreted. Starting around ovulation, progesterone increases to 25mg a day during the latter stage, then drops sharply unless the egg is fertilized. If fertilization occurs, ovaries and the placenta rapidly increase progesterone biosynthesis to 300 to 400 milligrams a day in order to maintain a healthy pregnancy.
The androgenic (male) hormones, testosterone and androstenedione, are made from progesterone. In turn, they can form the three estrogens: estrone, estradiol, and estriol. (D'you suppose that's where the story of Eve arising from Adam's rib came from???)
All the sex hormones and corticosteroids are small molecules shaped very much like one another and the parent molecule, cholesterol. Highly specific variation, created by natural enzymatic action, are responsible for their different roles in the body. (back to where you were)

*** Yes, men have female hormones and women have male ones! It's the balance that counts. By the way, a woman continues to produce estrogen after menopause not just in her ovaries but in her fat cells, from the male hormone androstenedione. (back to where you were)

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