Bio-Identical Progesterone
Bringing Your Life (and Hormones) Into Balance

What is progesterone?

Progesterone and estrogen are the two main hormones made by the ovaries of menstruating women. Progesterone is made in smaller amounts by the adrenal glands in both sexes, and by the testes in males. It is also produced in the brain and the peripheral nerves.1

Progesterone is manufactured in the body from the steroid hormone pregnenolone, and is a precursor to the estrogens and testosterone, and most of the other steroid hormones. These steroid hormones are essential for survival, stress response, sugar and electrolyte balance, and blood pressure.

During the childbearing years, progesterone’s main function is to prepare and maintain the uterus for pregnancy and to support the developing embryo. Every month, progesterone levels rise in anticipation of pregnancy, stimulating the thickening of the uterine lining. If pregnancy does not occur, progesterone (and estrogen) levels drop-off abruptly and menstruation begins; leading to a renewal of the entire menstrual cycle.

Progesterone is produced from a yellowish gland in the ovary called the corpus luteum at ovulation. The corpus luteum forms quickly in the small cyst-like structure left behind when a follicle ruptures. It produces 20 to 30 mg of progesterone daily during the luteal or fertile phase of the menstrual cycle.

But as a woman enters her mid-thirties to early forties, the follicle doesn’t always ovulate, which means the corpus luteum doesn’t form. Consequently, progesterone cannot be released at the appropriate time. This is called an anovulatory cycle and leads to a deficiency of progesterone.2 Unfortunately, it also leads to a myriad of health complaints, ranging from hot flashes and insomnia to depression and palpitations.

What are progestins?

The term progestin refers to a synthetic version of progesterone that has some biological activity similar to progesterone. These synthetic “progestins” were first developed in the 1950’s for use in oral contraceptives. Unlike natural progesterone, the synthetic progestins don’t have all the same biological effects of natural progesterone.

What does progesterone do?

Decades of research have shown that progesterone has a multitude of biological effects on many different parts of the body. These include effects on the cardiovascular system, endocrine system, nervous system, and skeletal system.

Progesterone and the cardiovascular system

One of the long believed benefits of hormone replacement was that it would protect the cardiovascular system from age-related negative changes. Unfortunately, recent research done by the National Institutes of Health (NIH) has shown that “traditional” synthetic hormone replacement actually can be detrimental to the cardiovascular system, resulting in a 29% increased risk of heart attack and a 41% increased risk of stroke.3 The findings were so worrisome that the NIH prematurely halted the planned long term study. However, natural progesterone replacement has been documented to have numerous beneficial actions on the cardiovascular system.

Natural progesterone has several positive effects that can be beneficial to the cardiovascular system. To begin with, progesterone has a mild diuretic effect due to its ability to increase sodium loss in the urine. Studies investigating this effect have shown the ability of progesterone to ease symptoms of water retention4, and even lower blood pressure in some patients with hypertension.5 Interestingly, this beneficial effect on blood pressure is not seen with most synthetic progestins that can actually increase blood pressure.6 Progesterone has also shown potential benefit in preventing one of the most perplexing of heart conditions, Coronary Vasospasm. This is when the coronary arteries spasm and close, often resulting in a sudden heart attack. Topical natural progesterone has shown the ability to inhibit this type of dangerous vasospasm in menopausal primates.7

A well-established side effect of estrogen replacement therapy is an increased risk of blood clots. This is because estrogens, especially oral and synthetic estrogens, increase the production of factors involved in blood coagulation and clotting.8 Because abnormal blood clot formation is believed to play the major role in adverse cardiovascular events in users of synthetic hormone replacement, researchers have compared the effect of natural progesterone and synthetic progestins on risk factors for clot formation. What they found was endothelial disruption, platelet activation, and clot formation was induced by synthetic progestins but not natural progesterone.9 In contrast to these negative effects of synthetic hormone replacement, the use of a progesterone cream was found to not have any negative effect on markers of blood clotting.10

Another finding in this same study was that progesterone could lower cortisol levels in women that had elevated cortisol levels. Because of the known negative effects of elevated cortisol levels, this additional beneficial effect of progesterone replacement may offer numerous, wide-ranging health benefits.

One more concern about synthetic hormone replacement therapy is its potential effects on blood lipids, and how this may influence the risk of heart disease. One of the big risk factors for coronary artery disease is the level of cholesterol esters in the blood, especially due to elevated cortisol levels. Progesterone has been shown to block cholesterol ester production, though estrogen had no effect.11 Many synthetic progestins have been shown to have a negative influence on blood lipids, while natural progesterone appears to not negatively influence blood lipids.12 13 Additionally, research has shown that natural progesterone can help prevent the abnormal proliferation of vascular smooth muscle cells of the arteries in numerous experimental models that simulate the development of coronary artery disease.14, 15

Progesterone and the breast

For most women, the biggest concern about traditional hormone replacement therapy has been its possible effect on the breast, or more specifically, its effect on breast cancer. Surprisingly, it wasn’t until recently that scientists finally began to publish the results of large studies on the effects of hormone replacement therapy on breast cancer incidence. To make matters worse, these studies showed either no significant effect16 or a significant 26% increase of invasive breast cancer.17 These results have only added to the confusion about the safety of synthetic hormone replacement in regards to breast cancer. These studies used synthetic hormone replacement containing estrogen/progestin combinations.

In contrast to some synthetic progestins,18 natural progesterone has actually shown the ability to inhibit the growth of abnormal breast tissue.19 20 This was shown both in the presence and absence of estrogens, which is a known promoter of tissue growth. Furthermore, in a study examining the effect of topical hormones, including estrogen and progesterone, on the breast tissue of women undergoing breast surgery, it was found that progesterone could reduce tissue proliferation.21 Additionally, progesterone was shown to block the growth promoting effect of estrogen. In fact, another study comparing women with low endogenous progesterone levels to women that had normal endogenous progesterone levels found a 5-fold increase in premenopausal breast cancer risk among those women with low progesterone levels.22

In addition to these clinical findings, experimental evidence also suggests that natural progesterone not only doesn’t stimulate breast cell growth, but also may actually inhibit breast cancer cells. This was shown in a study on the effects of natural progesterone on the growth of breast cancer cells in vitro.23 The researchers found that exposing these cancer cells to progesterone resulted in an increase in apoptosis and cancer cell death. Other provocative research has shown that natural progesterone can have potentially beneficial effects on breast cell proliferation by opposing and blocking the undesirable stimulating effect of estrogen.24 As noted earlier, this protective effect against abnormal breast tissue growth is not seen with most synthetic progestins.19

Progesterone and menopause

For most women, the most unpleasant short term effect of menopause is vasomotor flushing. This is commonly called “hot flashes.” The effect of natural progesterone on this unpleasant effect of menopause has been studied clinically. In one study, patients receiving topical progesterone cream daily for a month had a significant improvement in menopausal symptoms.25 Another study showed that topical progesterone resulted in a significant lessening of the number and intensity of hot flashes in 83% of the subjects.26 These results are somewhat surprising, since most doctors believe that hot flashes are due solely to the lack of estrogen that accompanies menopause. Additional research has compared a synthetic progestin to natural progesterone, and it was found that natural progesterone was much better tolerated and also improved menstrual problems.27

Progesterone and the nervous system

Among the most intriguing aspects of research into the effects of progesterone on the body are its beneficial effects on the brain and nervous system. Again, like in the previous research, the often opposite effects of synthetic progestins and natural progesterone have resulted in some confusion. The large Women’s Health Initiative Memory Study using estrogen and synthetic progestin found a doubling of dementia risk in women over the age of 65.28 Additionally, studies looking at the effect of estrogen alone on cognitive function have not shown any significant benefit.29, 30 This is in spite of research showing that progesterone has unique neuroprotective properties, 31 including protecting neurons from various toxic insults.32 Again, this is likely the result of the very different effects of natural progesterone and synthetic progestins. In fact, one study looking at the effects of natural progesterone versus a synthetic progestin showed a beneficial effect on cognitive function only with natural progesterone.33

Natural progesterone has also shown beneficial effects on the nervous system after brain injuries. The use of progesterone to prevent long term damage from traumatic brain injury has been explored both experimentally in animals 34, 35, 36 and clinically in humans,37 with impressive positive results. The recently published human study showed that progesterone administration to patients with traumatic brain injury could reduce the 30-day death rate by more than 50%, without significant side effects. Additionally, patients with brain injuries were more likely to have good outcomes after recovery when given progesterone.

Unfortunately, natural progesterone is not routinely used as a treatment for brain injuries. Research into the benefits of progesterone on other neurological disorders is progressing even more slowly. We can only hope that the potential benefits of natural progesterone on the brain and nervous system will be further developed into treatments that will someday benefit us all.

Why do I need a progesterone supplement?

If you’re approaching menopause, you may have begun to experience a variety of symptoms like hot flashes, sleeplessness, more intense PMS, irregular periods, or heavy bleeding. All these symptoms are due to a decline in progesterone. Eventually, with the onset of menopause, although estrogen continues to be stored and steadily secreted by fat cells, progesterone generation comes to a halt—which means you may have additional or different symptoms.

Lucky for us, researchers like Dr. John Lee have discovered that most women in our society suffer from a hormonal imbalance called estrogen dominance. That means estrogen is unopposed or unbalanced by the diminished level of progesterone. In fact, Dr. Lee says, “I would propose that a new syndrome be recognized: that of estrogen dominance.” (What Your Doctor My Not Tell You About Menopause. NY, Warner Books, 1996)38, 39, 40

In addition to the unpleasantries that most women in our culture experience during this period of their lives, estrogen unopposed by progesterone also decreases sex drive, increases the likelihood of fibrocystic breasts, uterine fibroids, uterine (endometrial) cancer, and breast cancer. That’s why it’s so important to replenish your progesterone levels with a natural progesterone supplement.

Progesterone and the skeletal System

If you’re a woman who is over 35 years old, your bone mass has already peaked. If you’re between 45 and 50 years old, your bone mass is already decreasing. And if you’ve already reached menopause, you may lose 5 to 10 percent of your total bone mass during the first five years after menopause begins.

The health of our bones is the result of the interplay of many different hormones, including progesterone, estrogen, testosterone, vitamin D, and other hormones and growth factors. Although long term studies utilizing estrogen and synthetic progestin have shown negative effects on cardiovascular health, they have also shown positive results on bone health and post menopausal fracture rates.41

The effect of using natural progesterone alone on bone health has unfortunately and surprisingly not been extensively studied. This is mainly because natural progesterone is relatively inexpensive, and has not been the focus of pharmaceutical company research. However, it has been scientifically established that natural progesterone plays a major role in bone health through its beneficial effects on osteoblasts, the cells responsible for actually building bone.42 Additionally, a high level of natural progesterone has been shown to prevent bone loss in women caused by low estrogen levels.43

For the past 20 years, Dr. John Lee has been successfully using natural progesterone supplements for reversing excessive bone loss and preventing new fractures in women with osteoporosis. Interestingly, Dr. Lee says that natural progesterone builds bone with or without estrogen therapy. In cases of severe osteoporosis, Dr. Lee found that natural progesterone could increase bone density within six months. Many of the women in his study added natural progesterone to their estrogen therapy, but others dropped the estrogen and utilized only natural progesterone. Both groups gained bone mass while on natural progesterone.44

Natural versus synthetic hormones

The hormones your body normally produces—estrone, estradiol, estriol, progesterone, and testosterone—are all natural hormones. The drugs usually prescribed by doctors are synthetic analogs (slightly altered versions) of the natural hormone. They have been altered to allow patent protection, not to make them work better.

Natural hormones used in hormone replacement used to come from human beings. According to Joseph Needham (Science and Civilization in China, Volume 5, part 5, Cambridge University Press, 1983), Taoist physicians made and used preparations of human urine solids containing sex steroids from at least the 11th century onward, and possibly as long as 2,000 years ago.45

The next best thing

Today natural hormones used for hormone replacement originate from the wild yam (Diascorea species), which is rich in precursor molecules (the source of another substance). Biochemists are able to easily convert these precursor molecules into other molecules that are identical in every way to natural hormones.

How can a hormone that got its start in a vegetable and was converted in a test tube be considered “natural” in a human female? The word ‘natural’ actually refers to the structure of the hormone molecule, not its source. For natural progesterone, chemists extract the hormone called cholesterol in the lab, and then convert that hormonal raw material into progesterone—natural progesterone identical to what your body produces.

What have “yams” got to do with it?

The Mexican wild yam has a long history of medicinal and food use. It is rich in diosgenin, a precursor of progesterone, DHEA, testosterone, and the three human estrogens—estriol, estrone, and estradiol. The plant has been used traditionally for thousands of years to nourish the female reproductive system and reduce the symptoms of PMS and menopause. In 1943, wild yam attracted the attention of mainstream medicine when scientists extracted the female hormone progesterone from this plant. In fact, until 1970, this plant was the sole source of progesterone used in birth control pills.

Beware of the “yam scam”

But please be aware that you can’t get progesterone from eating yams! The yams we eat are not even true yams and have little to no plant steroid activity. And the human body cannot make progesterone from wild yam. You can get the benefits of natural progesterone by using natural progesterone made from the Mexican wild yam – Dioscorea species.

You cannot get a significant amount of hormones from using creams based directly on wild yam or even by eating Mexican wild yam. Your body doesn’t have the chemical cofactors required to convert them into useful hormones. This has to be done in a laboratory. This hasn’t stopped entrepreneurs, though, from marketing yam creams as sources of various steroid hormones. Make sure the product you use is not just unprocessed Mexican yam, but instead a scientifically produced product using the highest pharmaceutical-grade USP progesterone.

Frequently asked questions:

Why hasn’t my doctor told me about natural hormones?

Your doctor probably doesn’t know about natural hormones simply because their use isn’t taught in medical school or promoted by pharmaceutical companies. Because natural hormones cannot be patented for the same reasons you can’t patent natural air, water or vitamins, there’s little or no incentive for the pharmaceutical industry to spend the $200 million or more necessary to run all the clinical trials and do all the paperwork to get even one of these hormones approved by the Food and Drug Administration (FDA).

With no multinational drug industry to pay the enormous costs, the large definitive studies that might demonstrate efficacy better than competing drugs will never be done. Almost all doctors see only the studies for the benefits and risks of Premarin®, Provera® and other patentable “hormones”; studies which the pharmaceutical industry has conducted itself or underwritten.

What’s the difference between natural progesterone and synthetic progesterone?

According to Christianne Northrup, M.D., obstetrician-gynecologist, internationally recognized authority on women’s health and healing, and bestselling author of Women’s Bodies, Women’s Wisdom (Bantam Books, New York, 1994), and The Wisdom of Menopause (Bantam Books, New York, 2001), there are no side effects with natural progesterone at the usual doses. Natural progesterone is a precursor molecule that can be converted in the body to other important, necessary hormones.

Synthetic progestins, on the other hand, as found in Provera®, have many known side effects including bloating, headache, and weight gain. “Unfortunately, many women are told their synthetic progestin is the same as progesterone. But synthetic progestins can actually increase PMS symptoms because taking a synthetic progestin decreases the body’s natural progesterone levels,” says Dr. Northrup. Also, there is evidence that when synthetic progesterone is used, it appears to increase the risk of breast cancer.

And there’s a huge difference economically. Man-made hormones not found in nature are far more profitable for the pharmaceutical companies than natural hormones because, unlike natural substances, they can be patented.

Where should I apply the cream or spray?

Progesterone is most easily absorbed where the skin is relatively thin and soft, such as the face, neck, upper chest, breasts, inner arms, backs of the knees, palms of the hands and tops of the feet. Just be sure to alternate sites so that the progesterone is absorbed into the fat layer under the skin. If you apply it to the same spot all the time, the fat will become saturated in that area and you won’t get optimal absorption.

When should I use natural progesterone?

Progesterone should be used for 14 days before the expected day of your period, stopping the day or so before it begins. For example: Start between days 12 to 15 and end on day 26 of the menstrual cycle. For postmenopausal women and post-hysterectomy, use for two weeks of the month, and then discontinue for two weeks. Repeat to mimic your pre-menopausal cycle. Since natural progesterone doesn’t produce side effects, flexibility in dosing carries no risk.

What is the recommended dosage of natural progesterone?

The goal is to use enough to eliminate any symptoms of progesterone deficiency. This should fall in the range of 10 mg to 50 mg per day.
Dr. Northrup says that, “Each woman’s need varies, so you may have to experiment to find a dose that works for you. Many women are able to decrease their dosages over time once their symptoms have been completely relieved. It is more effective, however, to start out with dosages that are on the high end of usual dosages and stay with these for several months.”

What if I’ve had cancer?

If you’ve had cancer, and hormone replacement is clearly indicated, some natural healthcare practitioners prefer to recommend natural progesterone only, because it’s clearly anti-carcinogenic.

Although the risk of breast cancer from estrogen replacement therapy remains controversial, the increased risk of endometrial cancer is largely eliminated when a natural progesterone is taken along with the estrogen.

A study conducted in Taiwan focused on forty premenopausal women who had undergone a breast lumpectomy. Ten to 13 days before surgery, the women were randomly assigned to apply a topical gel containing either estradiol, progesterone, estradiol plus progesterone, or a placebo each day. When the researchers examined postsurgical breast tissue from around the lump, they found increased proliferation of breast epithelial cells in the samples from the women who had used the estradiol-only gel compared with the placebo. By contrast, cell proliferation was significantly reduced in the tissue samples from the women who had used either the estradiol/progesterone gel or the progesterone-only gel.46 The study concluded that progesterone does not increase the proliferation of normal epithelial breast tissue, indicating that it doesn’t increase the proliferation of cancerous tissue either.

Natural progesterone has improved the quality of life for millions of women, and it may very well help you too. The proven benefits of natural progesterone far out weigh the negative effects of traditional hormone replacement therapy, and I urge you to consider natural progresterone to address your “time of life” changes.

Caution: Do not use during pregnancy or during menstruation if you typically have a heavy menstrual flow.

References:

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