FEMALE HORMONES

INTRODUCTION

Hormone Replacement Therapy, Health 2000, February 2000
by Richard H. LeConey, M.D.

There are many components to a successful anti-aging program. Some of the more important are proper nutrition, regular aerobic and resistive exercise, and supplementation of the important antioxidants and vitamins. However, the keystone of a modern anti-aging program consists of a comprehensive hormone replacement program, commonly called HRT.

Science has clearly established that one of the main factors in the aging process is the loss of the essential restorative hormones that occurs, as we grow older. Studies of human populations have shown that there is a steady consistent decline in the production of certain hormones such as human growth hormone, DHEA, thyroid hormone, the female hormones, progesterone and estrogen, and the male hormone, testosterone. The steady decline of these hormones has been shown to be closely correlated with the development of the signs of aging. Other studies show further support for the idea that this hormonal decline is a major causative factor in the appearance of the signs of aging. For example, it was shown that hastening the decline in these hormone levels by surgical removal of the glands that produce them dramatically accelerates the development of the signs of aging. It was then also demonstrated that replacing these hormones and maintaining them at levels associated with a younger age significantly slow the development of the signs of aging.

The basic principle then, of hormone replacement therapy is to identify those hormones which are deficient and then supplement them in sufficient quantity as to restore the blood levels of these hormones to levels that were typically found at approximately age 25. Identification of the deficient hormones is done by laboratory analysis of blood specimens. After the patient is established on hormone replacement, repeat lab analysis provides assurance that the dosage given is both adequate and within safe limits.

While hormone replacement therapy for women has been around for years, hormone replacement therapy for men, with testosterone, is a newer concept that is rapidly gaining acceptance. Very soon, it will be just as common for men to take testosterone supplementation as it is for women to take estrogen and progesterone. In men, the drop in testosterone levels causes many signs and symptoms. One of the most common complaints is fatigue and general lack of energy. These men typically complain of being exhausted at the end of the workday, they say they lack the energy to enjoy evening activities with their families or wives. Somewhat similar to this is the loss of ability to enjoy, or derive any benefits from exercise. Many will state that despite increasing time spent exercising they are unable to appreciate any gain, such as increased endurance, muscle mass or weight loss. Significant weight gain especially in the waist, and hips is also common. Loss of sexual drive and desire is frequently the first and foremost complaint. Many describe subtle personality changes. They feel they become more apathetic and generally less optimistic. Some experience actual depression. Other cognitive changes noted include poor memory, and loss of a certain “clarity of mind”. Other associated medical conditions include late onset type diabetes mellitus and hypothyroidism. Treatment consists of administration of testosterone in a transdermal vanishing cream; in sufficient quantity to restore the blood levels to that of a healthy 25 your old. Amazingly, this results in reversal of all symptoms. Some of these symptoms, such as the mental changes, loss of libido, fatigue and exercise intolerance vanish within a few days. Weight loss, and restoration of muscle mass of course take more time; but frequently are reversed within a few months, especially when coupled with exercise. Also regained is a positive physiological response to exercise, with improvements in endurance, aerobic capacity, and strength. Men will state that testosterone restoration renewed their interest in their work, increased their stamina at work, and increased their enjoyment of their after-work hours. Of course, restoration of the sex drive results in great satisfaction and improved self-esteem.

While hormone replacement therapy for women may have been common practice since the ’60s, new concepts of treatment have dramatically improved patients? satisfaction and safety. In the past, hormone replacement therapy for postmenopausal women consisted of plain estradiol or mixed estrogens derived from horse urine (Premarin). Frequently, the side effects of such treatment were worse than the symptoms of menopause itself. This high dose unopposed estrogen regimen caused severe weight gain, fluid retention, breast tenderness and mood swings, causing many women to abandon the treatment. After only a few years, it was found that this method of treatment, lacking using progesterone, resulted in increased incidence of endometrial cancer (cancer of the lining of the uterus). Progesterone wasn’t the only important ingredient missing from early hormone replacement therapy. Estriol, the other form of estrogen secreted by the ovary was completely ignored. Some evidence now suggests that the omission of estriol may be responsible for the increased incidence of breast cancer also found with early HRT.

Finally, early hormone replacement therapy also neglected to include another very important ovarian hormone: testosterone. The ovaries of a healthy young woman produces a significant amount of testosterone, approximately one tenth of the amount made by a man. This small amount of testosterone, however, has important effects in maintaining a woman’s health and mood. It is also largely responsible ae es with progesterone, for maintaining libido. At menopause, progesterone and testosterone levels fall nearly to zero. The psychological and physical effects can be profound. Severe mood swings, depression, loss of muscle tone and exercise tolerance, weight gain and, frequently, complete loss of sexual desire occur. Estrogen alone provides virtually no relief of the symptoms, in fact, with respect to weight gain, it makes them worse.

Now, by including all the major ovarian hormones, estriol, estradiol, progesterone, and testosterone in a single transdermal vanishing cream that is applied once or twice today, a woman can really feel “right” again. She can feel more like she did in her 20’s. The dryness and thinning of the skin can be corrected as well as dry scalp and brittle, thinning hair. Virtually all of these symptoms, the fatigue, mood swings and depression, loss of libido, weight gain and skin changes can be eliminated with his treatment. Furthermore, with proper adjustment of the estrogen/progesterone ratio, it can be done without the bloating, fluid retention, breast tenderness, and weight gain often associated with estradiol alone. And, by including estriol and progesterone, it can be done without the increased risk of cancer associated with earlier forms of HRT. Those women with positive family history of breast cancer and even women with a personal past history of successfully treated localized breast cancer will require a more intensive monitoring program, but are still eligible for treatment.

FEMALE HORMONE MODULATION THERAPY

Concern about the life-threatening side effects of synthetic hormone drugs has caused many women to be deprived of the benefits of safe natural hormone replacement therapy.

Proper hormone modulation can prevent degenerative disease and improve functioning in both the physical and emotional spheres of life, both at menopause and throughout life. For example, many sexual “dysfunctions,” including lack of desire, can be mitigated when hormone levels are naturally restored to a youthful profile. Menopause might also be delayed and be less traumatic if hormone adjustments are made in time. Numerous female health problems are tied to inadequate hormone balances, as we will show.

Forty-five million women are menopausal in the United States today; another 3.5 million women will become menopausal this year. Based on life expectancy trends, women face the prospect of spending the last one-third to one-half of their lives in a state of hormonal imbalance. The quality and quantity of life for these women will be determined by how well they (and their doctors) manage their hormone replacement.

Hormone Deficiencies: Estrogen

Starting around age 45 to 50, women face a perplexing dilemma regarding estrogen, one of the primary sex hormones. The amount of estrogen naturally produced by their bodies dwindles. This estrogen deficiency causes a wide variety of menopausal miseries, including hot flashes, depression, vaginal dryness, anxiety, and forgetfulness. The menopausal decline in estrogen production is a direct cause of premature aging.

Estrogen replacement therapy (ERT) remains controversial. FDA-approved estrogen drugs have been documented to cause cancer. The most conclusive report showed that women taking estrogen and a me cbleic progestin drug had a 32 to 46% increase in their risk of breast cancer (New England Journal of Medicine, June 15, 1995). These estrogen and progestin drugs carry warning labels listing a shocking array of dangerous side effects.

Although estrogen increases the risk of some types of cancer, it also has critical antiaging benefits, including the prevention of osteoporosis and heart disease and the reversal of some aspects of neurological decline. Many doctors don’t believe that estrogen causes cancer, while others think that combining estrogen with a synthetic progestin neutralizes the risk. Some studies show that estrogen does not cause cancer in the short-term, but in women taking estrogen and/or a synthetic progestin for more than 10 years, there appears to be a significantly elevated risk of breast, ovarian, and uterine cancers.

The report that women had a 32 to 46% increase in their risk of breast cancer while using estrogen alone, or estrogen and a synthetic progestin, was based upon data from the famous Nurses’ Health Study conducted at Harvard Medical School. This study showed that the carcinogenic risk of estrogen-progestin replacement therapy became most pronounced when it was used for 10 or more years.

Increased breast cancer risk is not the only danger of using estrogen drugs. A report published in the American Journal of Epidemiology (May 1995) showed that long-term estrogen replacement therapy increased the risk of fatal ovarian cancer. This 7-year study included 240,073 pre-and post-menopausal women. After adjusting for other risk factors, women who used estrogen for 6 to 8 years had a 40% higher risk of deadly ovarian tumors, while women who used estrogen drugs for 11 or more years had a startling 70% higher risk of dying from cancer of the ovaries. The increased carcinogenic risk from estrogen is a serious concern. Cancers of the breast, uterus, and ovaries account for 41% of cancer incidence in U.S. women. Breast cancer is running at epidemic levels, striking 1 in 9 women, up from 1 in 30 women in 1960. Conventional estrogen replacement therapy and estrogen-based oral contraceptives have been used extensively since 1960. Clearly, an alternative is needed to provide the anti-aging and health-enhancing benefits of estrogen, while protecting against its cancer-causing effects.

Synthetic Estrogen Drugs –┬áDangerous

HUMAN ESTROGEN is made up of:

* Estriol 80% of circulating estrogens
* Estrone 10 – 20% of circulating estrogens
* Estradiol 10 – 20% of circulating estrogens

PREMARIN is made up of:

* Estrone 75 – 80%
* Equilin 6 – 15%
* Estradiol + Others 5 – 19%

Equilin is a form of estrogen that is found only in horses. The human body metabolizes Equilin into metabolites that cause excessive growth of the endometrium of the uterus. Plus, as you can see, Premarin is totally out of balance with what the normal ovaries produce and can be a potential source of cancer.

The most popular estrogen drug in the United States is Premarin, which contains estrogens derived from the urine of pregnant mares. Besides the fact that the process of collecting mares’ urine is an inhumane and cruel procedure, the form of estrogen it produces is the most dangerous kind. In humans, estrogen has three different forms, one of which, estriol, is safe and effective. Premarin contains no estriol. Instead it is a “conjugated” estrogen, never intended for human bodies. Other popular estrogen drugs are sold under the names Estrace and Estraderm. Provera is the name of a popular synthetic progestin often given with Premarin to help prevent estrogen-induced uterine cancer. Unfortunately it does not prevent estrogen-induced breast or ovarian cancer.

Estrogen and progestin drugs have well-documented side effects that cause many women to avoid using them. In addition to increased cancer risks, some of the other risks of estrogen/progestin drugs include

* Weight gain.
* Abnormal blood clot formation (thrombosis).
* Increased risk of gallstones, fibroid tumors, and headaches.
* Premenstrual-type symptoms (irritability, fluid retention).

Despite these unpleasant and sometimes lethal side effects, many women use estrogen drugs because of their ability to reduce the unwanted effects of menopause and for their anti-aging properties. Estrogens are steroid hormones that promote youthful cell division in target organs of the body. The anti-aging benefits of estrogen replacement therapy include

* Enhanced skin smoothness, firmness, and elasticity.
* Enhanced moistness of skin and mucous membranes.
* Enhanced muscle tone.
* Reduced genital atrophy and enhanced sex drive in women.
* Reduced menopausal miseries such as hot flashes and anxiety.
* Reduced risk of heart disease and osteoporosis.
* Reduced risk of colon cancer.
* Improved memory and neurological function.
* Protection against Alzheimer’s disease.
* Enhanced immune function.
* A greater feeling of well-being.

Estrogen’s benefits make it desirable for most menopausal women to maintain youthful levels of this hormone. The question is, can the anti-aging benefits of estrogen be obtained without increasing the risk of cancer and arterial blood clots? There are preferable alternatives to these synthetic hormones. Estrogen supplements may be produced from plant sources. These safe and effective estrogens are known as “phytoestrogens,” and they have been studied in great detail. A review of the published literature reveals some interesting findings about plant-derived estrogens. Phytoestrogens from soy have been documented to reduce hot flashes and protect against age-related diseases such as osteoporosis, heart disease, and cancer. There are additional plant-derived extracts that have been shown effective in alleviating menopausal symptoms such as depression, anxiety, insomnia, and vaginal atrophy, and we need to look at them as well.

Black Cohosh – A Safe Phytoestrogen

An important and widely studied plant component used to treat menopause is a standardized extract from the black cohosh plant, also known as Cimicufuga racemosa. This black cohosh extract is approved by the German Ministry of Heal synor the treatment of menopausal symptoms related to estrogen deficiency. Standardized black cohosh has been trademarked under the name Remifemin for sale as a drug in countries throughout the world. More than 1.7 million women in Europe and Australia have used this natural herbal extract to treat menopausal symptoms. Clinical studies show that Remifemin alleviates not only hot flashes, but also depression, anxiety, vaginal atrophy, and a host of other menopausal-related disorders.

A fascinating study involved 60 women who were given either standardized black cohosh extract, Valium, or Premarin (synthetic estrogen) for menopausal symptoms. The women in the black cohosh group were relieved of depression and anxiety more effectively than the women in the Valium or Premarin group. This study was published in a German language medical journal (Med. Welt, 1984, 36: 871-74).

Premarin has been among the best selling drugs on the U.S. market for decades, yet produces terrible side effects. European women, on the other hand, have been using a safe natural herbal extract that’s been shown to work better in alleviating depression and anxiety than these two widely prescribed FDA-approved drugs.

Another study on black cohosh extract involved women under age 40 who produced very little natural estrogen or progesterone because their ovaries had been removed (by hysterectomy). One group received estriol (a weak, but safe form of estrogen); the second group received Premarin; the third took Premarin and a progestin drug; the fourth was given black cohosh extract; and the fifth group received a placebo. This 24-week study rated women according to symptoms that included hot flashes, irritability, heart palpitations, etc. The results of the study showed that women experienced a 30% improvement in all groups receiving different forms of estrogen-progestin and black cohosh extract. There was no improvement in the placebo group. At the conclusion of the study, the majority of women receiving the estrogen drugs or black cohosh extract were symptom-free. But, most importantly, the women receiving the black cohosh extract reported fewer side effects. This study showed that phytotherapy with standardized black cohosh worked as well as estrogen drugs, but produced fewer uncomfortable and dangerous side effects. This research was published in a German journal (Zent bl. Gynakol., 1988, 110:611-18).

The most impressive study on the benefits of this phytoestrogen was carried out by 131 physicians on 629 menopausal women. This study showed that black cohosh extract produced clear improvement in over 80% of patients within 6 to 8 weeks. Both physical and psychological symptoms improved.

Most patients in the above clinical study reported noticeable benefits within 4 weeks. After 6 to 8 weeks, complete resolution of symptoms was reported in a high number of patients (Gynecology, 1982, 1: 14-16).

A placebo-controlled study published in a German journal (Planta Med., 1991, 57) investigated the hormonal mechanisms by which black cohosh alleviates menopausal symptoms. The doctors conducting the study pointed out that hot flashes correspond closely with a surge of luteinizing hormone released from the pituitary gland in response to estrogen deficiency. Black cohosh was shown to suppress increased luteinizing hormone secretion in menopausal women and this effect was specifically linked to a reduction in the incidence of hot flashes.

Black cohosh extract has shown estrogenic effects within the body in several studies, but it does not elevate estrogen levels in the blood. Black cohosh extract appears to bind to estrogen receptors in order to mimic the hormonal effects of the weak estrogen, estriol. Estriol has been shown to protect against the types of cancers that more potent forms of estrogen (estradiol and estrone) appear to cause. Black cohosh extdiol has been referred torms being proestriol-like” because of the rejuvenating effect it exerts on the vaginal, rather than the uterine, lining.

Because of the impressive safety record of standardized black cohosh extract, it is has become a popular natural alternative to FDA-approved estrogen drugs. SEE: EQUIFEM

More Estrogenic Plants

There are other, important plant-derived hormone modulators that are used by alternative physicians to treat menopausal symptoms. It is important to understand that estrogens are continually being modified as they circulate in the body. They are converted from one form to another and are outfitted with numerous other compounds that cause their biological activity to vary considerably. While it may appear that the combination of soy phytoestrogens and standardized black cohosh may provide complete estrogen replacement, there are other hormonal factors to adjust for if the metabolism of youth is to be maintained (or restored).

An extract from the licorice root called glycyrrhetic acid (GA) stimulates the natural conversion of testosterone to estrogen in the body. Glycyrrhetic acid is an antioxidant that is often used to protect the liver and suppress viral activity in hepatitis patients. Offshore cancer clinics prescribe high doses of GA in injectable form to patients because of studies showing that it modulates immune function and suppresses cancer cell replication. It is interesting to note that while FDA-approved estrogen drugs can cause abnormal blood clotting, the GA contained in licorice root inhibits the clotting factor thrombin, thus reducing the risk of a heart attack or stroke. Licorice root extracts have many disease-fighting applications, but for menopausal women, the most important factor is that glycyrrhetic acid extracted from licorice is a safe source of natural estrogen. Numerous studies indicate that GA is an effective estrogen replacement therapy in humans. The Chinese have successfully used licorice extracts for more than 3000 years to treat menopausal disorders.

Dong Quai extract is the supreme female tonic in traditional Chinese medicine. It has been used successfully to alleviate PMS (premenstrual syndrome) and menopausal symptoms by helping to normalize estrogen levels. Dong Quai extract has shown to have a muscle relaxant effect, and has been used as an analgesic and anti-inflammatory agent. Scientists believe that one unique mechanism of action of Don Quai is to promote natural progesterone synthesis. Progesterone, which will be discussed in more detail below, is another hormone whose production declines at menopause. Progesterone is more important than estrogen for preventing and treating osteoporosis because progesterone is directly involved in the production of bone-forming cells called osteoblasts. Many menopausal women use a topical natural progesterone cream to provide for direct absorption of progesterone into the bloodstream.

Another hormone imbalance that women encounter as they grow older is excessive prolactin secretion from the pituitary gland. Prolactin interferes with the beneficial effect of estrogen and may promote the development of estrogen-induced cancers. Prolactin secretion may be suppressed by a natural extract called vitex agnus castus. In a study in a German medical journal (Arzneim. Forsch./Drug Res., (1993, 43 [II]: 7), vitex agnus castus extract was shown to suppress excessive prolactin secretion and promote natural progesterone synthesis over a 3-month period. As with the other plant hormone-modulating extracts, no side effects were observed.

WARNING: Prolactin is so dangerous in patients with hormone-dependent cancers that the Life Extension Foundation advocates prolactin suppression drug therapy for breast and prostate cancer patients.

A Natural Estrogen Replacement Approach

When choosing a natural estrogen replacement program, make sure the ingredients are standardized to meet pharmaceutical potency. An investigation conducted in 1998 of natural estrogen products sold in health food stores showed that many companies were not using the standardized plant extracts that had been used in the published studies to treat menopausal symptoms. Phone calls to these companies confirmed that many extracts were “one-to-one” ratios, which means that relatively little of the active ingredient was present. It should be pointed out that this investigation also found that respected brand-name supplement companies were using pharmaceutical-grade standardized extracts in their products to treat menopausal symptoms.

An ideal multi-ingredient phytoestrogen supplement should contain concentrated pharmaceutical extracts. If the active ingredients are not standardized, one cannot expect to obtain consistent biological activity.

The Epidemic Deficiency of Progesterone

Throughout mature life, women will experience a gradual loss of another critical hormone, progesterone. This decline becomes significant as women get closer to menopause. Symptoms of a progesterone deficit include premenstrual discomfort, night sweats, and hot flashes, along with a loss of the sense of well-being (depressed feelings). During and after menopause, natural progesterone synthesis often grinds to a halt, setting the stage for a host of menopausal miseries and degenerative diseases.

Scientific studies indicate that progesterone may have potential in the hormonal prevention of breast cancer. At a recent scientific conference, persuasive evidence was presented showing that the correct use of natural progesterone could result in a significant reduction in the risk of breast cancer. Progesterone has many beneficial properties, such as the activation of natural killer cells, but one factor of special relevance is that progesterone diminishes the production of a cancer-causing form of estrogen called 4-hydroxy-estrone, while increasing the production of cancer-preventing estriol. In other words, estrogen may be made safe through the concomitant use of progesterone, particularly when taken in natural forms.

In addition to making people feel better, progesterone may help to prevent the mental decline that occurs with aging. Progesterone has been shown to increase neuronal energy production and to protect brain cells.

Progesterone and Estrogen Prevent Osteoporosis

Interestingly, the combined effects of these two critical hormones lead to the prevention of bone loss at all ages, though progesterone deficiencies appear to be a more significant factor as women age.

There are two types of bone regulating cells. The osteoclasts function to dissolve older bone and leave tiny unfilled spaces behind. The osteoblasts then move into these spaces and produce new bone. This process of dissolving older bone mass by osteoclasts and new bone formation by osteoblasts is the mechanism for the repair and continuing strength of bone.

Like all living cells, osteoblasts and osteoclasts require proper hormonal function. Osteoblasts depend primarily on progesterone and testosterone, while osteoclasts need estrogen-like hormones. In the absence of these hormones, osteoblasts and osteoclasts cease to function properly and rapid deterioration of the bone occurs. Osteoporosis can occur when osteoclasts dissolve more bone than what the osteoblasts are able to replace.

Estrogen regulates the activity of osteoclasts, which results in a slowing of dissolving older bone. Progesterone, on the other hand, promotes the production of osteoblasts, which are required to effect new bone formation. Natural progesterone has been shown to stimulate the new bone formation required to prevent and reverse osteoporosis.

Osteoporosis can be caused by mineral and vitamin deficiencies, corticosteroid drugs, poor eating habits, lack of exercise, too much cortisol, and too little testosterone (two other important hormones). The major influence on age-associated bone deterioration, however, would appear to be a severe deficiency of ovarian-secreted progesterone.

An Anti-Aging Hormone

Three years ago, the FDA approved a clinical study entitled, “Use of Natural Progesterone Cream in the Prevention of Osteoporosis: A Randomized Double-Blind Placebo Controlled Trial.” A double-blind study is one in which the researchers are unaware of whi>roup is given the substance being studied or placebo. This ongoing study is being conducted by Dr. Helene Leonetti, M.D., of the Bethlehem Obstetrics Clinic in Bethlehem, PA. The women being studied are in the immediate postmenopausal phase (1 to 5 years after menopause), which is when bone loss is most rapid. After the first year, the positive effects of progesterone became so apparent, that the doctors overseeing the study were “unblinded.” In other words, it became apparent to the doctors which women were receiving progesterone compared to the placebo. The women in the progesterone group experienced the disappearance of lumps and bumps in their breasts, were less depressed, and had fewer hot flashes and better bone densities (though the time interval was too short for this to be significant). An important point brought out was that no women using progesterone cream experienced loss of bone density, while the placebo group showed slight bone loss. The study is about to complete its second year and it will continue for 1 more year. The expectation is that the women on the progesterone will have significantly greater bone density tests compared to the placebo.

New research indicates that progesterone may help prevent mental decline in the elderly. Dr. John Lee, one of the world’s foremost experts on progesterone therapy, has found studies showing that the brain cells concentrate progesterone 20 times higher than blood serum levels. Recovery after brain trauma is better if progesterone levels are higher. Dr. Lee also has pointed out that progesterone has been shown to increase brain cell energy production while suppressing hyper-excitotoxicity. “Excitotoxicity” occurs when too much (or too little) of neurotransmitters such as glutamate are released from brain cells. This type of toxicity is now considered a cause of brain aging and degenerative neurological disease.

Does Hormone Replacement cause cancer in women?

The longest running controversy in women’s health perhaps even in medicine is the issue of estrogen replacement and cancer of the breast and endometrium. As mentioned earlier the issue of endometrial cancer has been pretty widely accepted as resolved with the addition of progesterone. The issue of breast cancer and estradiol is not so clear. Estrogens clearly do promote the rapid growth of cancers that exist but do not clearly cause the cancer in the first place. However, the addition of estriol seems to eliminate the stimulatory effect of estradiol on breast tissue that tends to lead to development of cancer. Still, the risk is limited primarily to women have had breast cancer or a mother with breast cancer. These women may still be treated as long as active cancer is ruled out with mammography and blood screening tests, the benefits are worth the effort. Some doctors, in the past, have refused these women the benefits of hormone replacement out of hand, resulting in significant loss of personal health and quality of life. I believe this is a terrible mistake.

This is similar to the testosterone and prostate cancer issue in men. Again, no study proves that prostate cancer is caused by testosterone, but some prostate cancers are promoted by testosterone. Interestingly the worst of the prostate cancers occur in men with a longstanding low level of testosterone. All men are screened with PSA tests before starting testosterone, any questionable result is studied with prostate ultrasound studies. Routine PSA exams are required for men as are mammograms and breast exams for women. These screening exams should be part of any wellness and longevity program anyway, and should include coloscreen for colon cancer and PAP sue=”s at the intervals appropriate for the patients age. There are a number of other more sensitive studies available for those with higher risk due to genetics or exposure.

Progesterone May Prevent Breast Cancer

A large base of evidence suggests that progesterone is protective against, as well as a potential treatment for, breast cancer (Cowan, 1981; Hagen, 1998.) A study by Chang (1995) showed transdermal estradiol increased cell proliferation rate by 230%, while transdermal progesterone decreased the cell proliferation rate by over 400%. A combination estradiol – progesterone cream maintained the normal proliferation rate. This is direct evidence that estradiol (a potent estrogen) stimulates hyperproliferation of breast tissue cells and progesterone prevents hyperproliferation.

A second study by noted researcher Bent Formby, Ph.D. (1998) was published with insightful results. To determine the biologic mechanism of why progesterone inhibits the proliferation of breast cancer cells, a variety of cancer cell lines with different receptors and different expression of genes were exposed to progesterone. Exposure to progesterone induced a maximal 90% inhibition of cell proliferation in T47-D breast cancer cells and no measurable response in MDA-231 progesterone-receptor negative breast cancer cells. Further research along the same lines should be able to specify exactly when progesterone therapy would be most effective.

Previous retrospective studies have shown that women undergoing breast cancer operations during the luteal phase of the menstrual cycle (the span between ovulation and the start of menstruation), when progesterone is higher, have much longer survival times. Angiogenesis (new blood supply) is essential for tumor growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. Dr. P. E. Mohr in the British Journal of Cancer (1996) reported that women with a progesterone level of 4 mg/mL or more at the time of their breast cancer surgery had a significantly better survival rate at 18 years than those with a lower serum level of progesterone. In those women with good progesterone levels at the time of their surgery, it was revealed that approximately 65% were surviving 18 years later, whereas only 35% of the women with low progesterone levels survived.

A study done by Cowan et al. in 1981, published in the American Journal of Epidemiology, showed that the incidence of breast cancer was 5.4 times greater in women with low progesterone than in women who had good progesterone levels. Some final evidence confirming progesterone-protective effects on breast tissue comes from a study by J. M. Foidart in Fertility and Sterility (April, 1998.) Either a placebo gel, an estrogen gel, a progesterone gel, or a combination estrogen/progesterone gel was applied to women’s breasts for 14 days prior to breast surgery. After surgery, the breast tissue was analyzed and it was found that estradiol increased breast cell proliferation and that progesterone greatly decreased proliferation.

As Dr. Lee explains, “The goal of progesterone supplementation is to restore normal physiologic levels of bioavailable progesterone.” That is why testing saliva or blood progesterone levels is important, especially for premenopausal women who are using progesterone cream to alleviate premenstrual syndrome (PMS) symptoms. In women whose doctors are prescribing excess amounts of supplemental estrogen, the administration of progesterone may enable the dose of estrogen to bes ofuced, since progesterone restores sensitivity to estrogen receptors on cell membranes. Saliva tests are available to ascertain progesterone and other hormone levels in the body.

Potential Dangers of FDA-Approved Synthetic Progesterone Drugs

The issue of synthetic versus natural hormones is as important with progesterone as it is with estrogen. Just as the pharmaceutical industry created their dangerous estrogen drug Premarin, they produced a pseudo-progesterone named Provera. As with Premarin, the warning label on Provera is full of dangers alluding to the possibility of birth defects, breast cancer, blood clots, fluid retention, acne, rashes, weight gain, and depression. Such drugs as Provera are classified as “progestins,” not as progesterones. The side effects of Premarin and Provera may be the main reason women stop taking their replacement hormones, and are definitely the reason that HRT has such a questionable and spotty reputation.

An alternative to artificial progestins is the option of using natural progesterone products. Products like the Life Extension Foundation’s Pro-Fem use progesterone derived from soybeans. Not only are such soy-based or wild yam-based natural progesterones far safer than synthetic drugs, they are as easily utilized as the real progesterone manufactured within the human body. The preferable forms of natural progesterone are creams that are rubbed in to appropriate areas. This route of administration bypasses the liver and allows hormone delivery toof m place where it is needed the most. For example, progesterone cream applied to the breasts slows cell proliferation and eases breast pain. As to safety, according to Northrup (1994), “There is virtually no danger of overdose.” (Note that a woman cannot simply eat wild yams or wild yam products. The human body does not have the means of converting plants into progesterone molecules. Processing is a requirement, though processed phytohormones are still “natural.”)

In addition to the established and dangerous progestins such as Provera the FDA has just approved a drug called Prometrium, which is an oral pill containing 200 mg of natural progesterone to be taken daily. This is overkill because your liver will go into overdrive trying to excrete this acute, overabundant supply of progesterone. Most of this oral progesterone drug that is not detoxified by the liver will be unavailable for cellular use. Progesterone cream is better utilized and much more economical. Dr. Foidart, in another study in May 1998 on transdermal replacement hormone therapy, states that avoidance of the “first passage effect” (through liver) is prevented by the transdermal application of hormones and probably explains the superiority of this route of hormone administration. Natural progesterone should not be confused with the synthetic FDA-approved progestins that cause many side effects. Synthetic progestins do not provide the broad spectrum of benefits that have been documented for natural progesterone.

Hormone Deficiencies: DHEA

DHEA (dehydroepiandrosterone) is a precursor of estrogen and testosterone, so taking DHEA might raise the levels of these hormones. DHEA is a good starting place for hormone modulation in the aging female.

While there have been contradictions in the research on DHEA, it appears to be a true rejuvenative hormone to at least a moderate degree, improving mood, neurological functions, immune system functioning, bone growth, energy, and feelings of well-being. In a review of research, the journal Endocrine News (1996) reported that DHEA, given until the patient’s blood levels matched those found in their teenage years, resulted in “remarkable improvement of physical and psychological well-being in both genders. This finding in addition to the absence of side effects provides great promise for the replacement strategy.” It should be noted that because DHEA may raise estrogen levels, it is recommended that it be taken with melatonin to provide a safeguard against breast cell proliferation. (Melatonin is a pineal hormone with multiple benefits and no significant side effects. Most importantly, it appears to protect against breast cancer.)

Though women usually have less DHEA than do men, both sexes lose it at about the same rate, suggesting that it is an age-related decline, not just a result of menopause. Peak levels are typically reached when women are in their third decade of life, following which they begin to lose approximately 2% per year (Wright and Morganthaler, 1997). As with all hormones, blood levels are only one criterion to establish in supplementation. The ultimate goal is individual functioning.

Hormone Imbalances Affect All Ages

While the need to supplement hormones becomes critical at menopause, many health problems are caused by hormonal imbalances. There is no need to wait until menopause to improve your physical and emotional state by spending some time modulating the levels of these substances with safe and natural supplements.

Hormonal dysfunctions are found to be the cause of many menstrual complaints, the most prominent being premenstrual syndrome, commonly called PMS. For many years, women had their PMS complaints diminished, ignored, or attributed to psychosomatic causes. In truth, the complex hormonal interactions required to produce a “normal” menstrual cycle are easily disturbed by a variety of biochemical, environmental, and psychological sources. There are dozens of uncomfortable and painful symptoms of PMS, and their appearance may occur from a few days before menstruation begins, to several weeks before bleeding starts. Women with PMS tend to have relatively high levels of estrogen coupled with relatively low levels of progesterone. This estrogen-progesterone balance is critical to most of the hggesh problems discussed in this protocol. Other factors associated with PMS are diet, obesity, vitamin and mineral deficiencies, and an imbalance in hormone-like compounds called eicosanoids (which may be corrected with dietary and supplement alterations, to be discussed later).

Menstrual cramps are not the same as PMS. It is common to have PMS and painless periods, while women without PMS may have severe cramping during their periods. Cramps are caused by uterine contractions, and have been treated with birth control pills (hormones) to eliminate the ovulation-related hormonal changes that lead to cramping. Since excess prostaglandin production causes contractions of the smooth muscles, another treatment is to use medications such as ibuprofen that inhibit prostaglandins. Prostaglandins are chemicals that regulate involuntary muscles: blood vessels, uterus, and intestines. They are one form of eicosanoids, mentioned as causative agents in PMS.

Irregular Menstruation

When a woman regularly misses her period or commonly bleeds (spots) between periods, she has a condition called “dysfunctional uterine bleeding,” which frequently is associated with an estrogen-progesterone imbalance, though thyroid or pituitary problems are other possible causes. Conventional medical treatment utilizes standard birth control pills to regulate periods. It should be noted that modern contraceptive pills are far safer than they once were, plus they offer a quick and easy solution to the problem. Unfortunately, they don’t act precisely or individually in the manner of true hormone modulation.

Excessive menstrual bleeding, named “menorrhagia,” always is uncomfortable and often is an incredibly inconvenient problem, interfering with the natural patterns of life. In its most severe forms, menorrhagia can lead to anemia, requiring nutritional supplements just for that deficit alone. The most common form of benign breast pain comes from the hormonal changes of the menstrual cycle. Breast tissue is affected by cyclic change, just like the uterus. Fluid buildup occurs premenstrually, but has no way of being discharged in the way the uterus releases its menstrual flow. Breast fluid must be reabsorbed, and sensitivity and pain may result. In other cases, breast pain seems unrelated to menstrual patterns and the causes aren’t always clear, but alterations in hormones such as estrogen, progesterone, and prolactin (a hormone whose function is to stimulate lactation) have been implicated. Of the most concern is that breast tissue is extremely sensitive to estrogen. High estrogen levels lead to tissue growth, cyst formation, and pain (as well as cancer, to be discussed later). Because progesterone balances estrogen by “down-regulating” the estrogen receptor cells in the breast, it blocks estrogen’s “grow” signals. The result is to decrease the proliferation of cell tissues, protecting them from the dangerous, negative effects of even modest amounts of estrogen.

Too Many Sex Hormones Cause Excessive Tissue Growth

Benign fibroid uterine tumors are the number one reason for hysterectomies in the United States (Hutchins, 1990). Their cause is unknown and they often prove asymptomatic, depending on their size and location. However, some may lead to excessive bleeding, pelvic pressure, and frequent urination. Fibroids causing health problems such as anemia must be treated, often with different levels of surgery. In some cases, fibroids may be managed with the help of progesterone. Typically, fibroids shrink after menopause because of the reduction in endogenous (self-produced) estrogen that occurs. As we have mentioned, estrogen is a growth-stimulating hormone.

Polycystic ovaries is a condition directly caused by a hormone imbalance due to an excess of androgens (the “male” hormone), where normal egg development is prevented. When eggs are underdeveloped, numerous small cysts are formed. Standard medical treatment includes prescription birth control pills, anti-androgenic medications, or synthetic progestin to prevent the uterine lining from suffering from excessive hormonal stimulation. Alternatively, natural progesterone may reduce symptoms without the side effects of progestins.

Another tissue-growth health concern is endometrial hyperplasia, an excess of glandular tissue in the uterine lining. This condition is most common in women with irregular periods, irregular egg production, and irregular sloughing of the lining of the uterus. Usually it is not dangerous and often simply goes away. Physicians monitor hyperplasia to make sure that abnormal cells are not present and that the condition does not become chronic. Traditional treatment involves giving a synthetic progesterone such as Provera to cause the uterine lining to slough off, removing the excess tissues. If this fails, a D and C (dilation and curettage) may be performed. Again, the safe alternative of natural progesterone will decrease estrogen receptor cells, often clearing up the problem.

Endometriosis is a condition involving the migration of endometrial tissue to other areas of the body, typically within the pelvis (but occasionally even further away from its point of origin). It may lead to pelvic pain, menstrual dysfunction, bowel pain, or infertility. Endometriosis is hormone-dependent, involving high levels of estrogen. Its actual causes are only theoretical at this time, though its pain is extremely factual. Again, conventional treatment is hormonal, using birth control pills, synthetic progesterone, or drugs such as Lupron, which make a woman temporarily menopausal. The goal is to reduce the level of estrogen in the system, leading to a drop in “grow” signals to the endometrial tissues. Many physicians now prefer the use of natural progesterone, either in over-the-counter creams or, in some cases, a more concentrated cream from a compounding pharmacist (one who individually makes compounds by prescription) or natural progesterone capsules. SEE BELOW

Possibly the most controversial area involving the use of exogenous (produced outside the body) hormones is the effect such treatment has on breast tissue. The concerns regard birth control pills as well as standard menopausal hormone replacement therapy and range from enlarged, tender breasts to deadly breast cancer. Breast tissue may be the most estrogen-sensitive area of the body. Combine this with eicosanoid imbalances and possible links to the growth hormones used in the dairy industry, and there are multiple reasons why breast cancer rates rise with age and are the leading cause of death in women in the menopausal years (National Center for Health Statistics, 1987).

Again, primary focus is on the relative balance of estrogen and progesterone. While the breasts are saturated with estrogen receptor cells, the presence of sufficient progesterone “down-regulates” such receptors, protecting against the powerful “grow” signals of estrogen. In addition, a compound called I3C (indole-3-carbinol) affects estrogen metabolism in ways that reduce the risk of breast cancer (Telang et al., 1997). The Life Extension Foundation offers a safe IC3 product in pill form.

The shortsighted and sometimes anti-female model of traditional medicine is best represented by the “therapeutic” technique of prophylactic breast and ovary removal. Women born with a gene labeled “BRCA 1” have a significantly increased risk of breast cancer because the gene causes an excessive ovarian production of estrogen (Stratton et al., 1997). As we have learned, estrogen is a stimulator of breast cancer cells. The response of many physicians is to surgically remove the offending tissue. While that may be a last-ditch necessity in some cases, it seems both appropriate and less damaging to attempt first to lower estrogen’s dangerous effects through other means, including IC3 and progesterone supplements.

The cause of ovarian cancer is far less evident than the causes of breast cancer, but hormonal levels do appear to have a role. For example, Helizisouer et al. (1995) discovered a strong connection between ovarian cancer and the “male” hormone androgen. Another hormonal connection involves birth control pills. Women taking these medications have a lower risk of getting ovarian cancer, possibly because of the decrease in ovarian stimulation. Conversely, fertility drugs increase ovarian activity and are linked to higher rates of ovarian cancer.

The most important fact about uterine cancer is straightforward and the same as in other malignancies of the reproductive system: estrogen encourages the growth of uterine tissue.

Lack of Libido Is Not Just in Your Head

Most of the discussion of loss of sexual desire has centered on the problems of menopause. Yet this problem is far more common in women of all ages than is recognized, largely because of the societal pressure on women to be sexual and from their individual needs to please their partners. Many of the situations thus have psychological roots and are beyond the intent of this protocol. However, hormones play a significant and often undiscovered role.

Research with menopausal women has been the origin of much of our knowledge in this area. Davis (1998) points out that while using androgens with postmenopausal women successfully increases their sexual desire, the bigger picture is that androgen levels fall significantly throughout the reproductive years and probably affect desire from an early age. In addition, research by Braunstein, reported as a Reuters Health news release, indicated that testosterone delivered through a transdermal patch increased women’s perception of orgasmic pleasure. Some androgens in particular (DHEA and DHEA-sulfate) decline steadily from early adulthood (Longcope, 1998). Other androgens show more decline closer to menopause. Treatment with androgens is safe and effective for these dysfunctions when given at low levels and paired with progesterone (Slayden, 1998). Many women lose their sexual desires after giving birth. Many of these sexual problems are directly tied to general postpartum depression. The goal is to modulate the estrogen-progesterone balance to reach earlier, healthier levels, reducing as many negative postpartum outcomes as possible, including loss of libido. Also available as treatments are antidepressant medications, the most successful of which are the SSRIs (specific serotonin reuptake inhibitors) such as Prozac, Zoloft, and Paxil.

Alzheimer’s and Hormone Deficits

Alzheimer’s, like osteoporosis, is looked at as a condition of old age. However, some forms of dementia do occur at younger ages (for instance, by definition, pre-senile dementia). The dementing process of Alzheimer’s is associated with a variety of socioeconomic factors as well. There is some evidence that estrogen may protect against Alzheimer’s because those women with the highest estrogen levels have the lowest rate of occurrence of the disease. (Northrup, 1998). In addition, the biochemical actions of estrogen, as well as those of two other hormones, DHEA and pregnenolone, increase connections among brain cells, and enhance memory (Flood et al., 1992). **Wright and Morganthaler (1997), in their book Natural Hormone Replacement, specifically call for hormone replacement as a means of preventing senility and Alzheimer’s disease. These researchers also emphasize the significant differences between synthetic and natural hormones, both in safety and effectiveness.
Hormone Modulation

The process of achieving proper female hormonal balance is not a one-step procedure. This protocol will describe a series of events that will optimize the benefits available to all women who empower themselves in their personal health care. It is possible to take shortcuts in regulating hormones, and many positive outcomes may be achieved even without careful modulation. However, it is recommended that these concerns be addressed as much as possible.

Both natural and synthetic hormones come with synthetic instructions: the dosages specified on the labels are for the “average” woman, one who doesn’t exist. While these dosages may achieve much of the symptom relief these products advertise, it would be unusual to realize optimal hormone modulation for all the hormones discussed using only the amounts listed. While this protocol will offer dosages to be taken, these should be considered as starting points, not as final goals. The individualization that offers the greatest amount of long-term health improvement is based on testing and feedback.

People do not regulate the temperature in their homes by simply setting the air conditioning thermostat on a “recommended” number and leaving it there indefinitely. They check the actual temperature, assess their own comfort levels, and make adjustments for time of day and season of the year. If we are this careful with air conditioning, why would we be reluctant to adjust such a critical matter as hormone level? Adjustment only can be achieved by self-evaluation and testing before and after hormone-affecting supplements are taken. Despite labels recommending “one capsule a day,” only personal symptom change and blood level differences can determine what actually works well. Most of this testing takes place at the initiation of supplements, though periodic re-evaluation is a necessity. Testing before any supplements are taken is called “baseline” measurement, and may be invaluable in the future. When new medical problems arise, knowing these earlier baseline standards allows for more accurate diagnosis and treatment. Testing may be performed in several ways.

Blood Testing

This measurement technique has the advantage of widespread established technology and standards, plus the capability of being done by mail. (The Life Extension Foundation offers such a service.) It is critical to remember that different labs have different standards. For example, Laboratory A has methods of testing that lead it to declare that a given hormone for a 30-year-old, non-pregnant of n has a “normal range” of 4 to 7. Laboratory B may use different specimen collection methods or measurement techniques, and declares the “normal range” of scores to be between 3.2 and 6.4. One lab’s standards should not be used to evaluate testing by another source. In addition, it is impossible to give a representative sample of all the possible optimal or even average scores because these figures change based on age, pregnancy status, menopausal status, the particular day within each woman’s menstrual cycle, and time of day. For example, cortisol norms may have substantial differences based on whether the sample was taken in the morning or the afternoon. In the end, each woman must compare her current scores with the average scores for a desired age from the same lab’s norms.

So the main hormones produced by a females ovaries are:

**ESTROGENS
*Estrone
*Estriol
*Estradiol

**PROGESTERONE
**TESTOSTERONE

These are the 5 basic hormones that should be checked in every female’s blood if you are experiencing problems.

Additionally, the following hormones may need to be checked: LH (Lutenizing Hormone), FSH (Follicle Stimulating Hormone), Prolactin and perhaps several others if needed.

Saliva Testing?

This measurement technique does not have the standards that blood testing enjoys, but it is available by mail order and offers a degree of convenience. Standards are important when attempting to emulate the results of published studies. Some argue that saliva testing is more accurate than blood testing; others disagree.

Urine Testing

The use of the 24-hour urine test may be the most accurate form of measurement because hormones are secreted in “bursts” rather than steadily throughout the day (Wright and Morganthaler, 1997). By collecting a full day’s worth of urine, a woman gets a more complete picture of her actual levels. The shortcoming of this test is the difficulty involved in its collection: every drop of urine must be gathered during the 24-hour period.

When evaluating the effectiveness of either a new supplement or a change in dosage of an ongoing supplement, it is recommended that testing intervals of 45 days be used. Because some hormones gradually convert into other hormones (known as a “cascade”), waiting 45 days ensures accuracy.

Making Choices That Are Right for You

While a positive doctor-patient interaction always is beneficial, such cooperation is even more important for women dealing with hormonal issues. Some women insist on having female health care providers, fearing that their PMS or menopausal complaints may be dismissed too easily or treated too routinely. Their fears are sometimes warranted. But the key to choosing and keeping a physician is finding someone (male or female) who listens and includes you in the health feedback loop. Symptom improvement may be accomplished with minimal effort, but achieving true hormone modulation requires time and patience.

The selection of hormone modulation goals is a complex decision based on personal philosophy, resources, time, and fortitude. Philosophically, a woman must strike a personal balance between acceptable methods and acceptable outcomes. Choices involve types of hormones used, their sources, the costs, side effects, desired results and both short- and long-term benefits and risks. In addition, there is a choice to be made in terms of outcome priorities: is symptom reduction sufficient by itself or are optimal blood levels also required? Is it more important to use only plant hormone sources or to change blood hormone levels back to those of a younger age? These are the types of decisions to be made by each woman.

This protocol now offers generalized recommendation concerning the modulation of hormones. The choices presented will include, whenever possible, the most natural forms of supplements available.

ESTROGEN REPLACEMENT — ESTRIOL THERAPY

Some women experience such severe menopausal symptoms that natural, safe forms of estrogen supplements do not provide sufficient relief If this occurs, and a woman is afraid of the cancer risks and side effects of long-term therapy with estrogen drugs approved by the FDA, there is a third option. Estriol is used extensively in Europe for estrogen replacement therapy in menopausal and postmenopausal women, but to date has rarely been used for that purpose in the United States. Estriol can, however, be obtained in the U.S. from compounding pharmacies with a doctor’s prescription. Pure estriol powder is mixed into a special transdermal cream where it can then be applied to the skin several times daily.

Evidence suggests that estriol offers many of the benefits of more traditional estrogen-replacement therapies, but without the harsh side effects or longer term dangers often encountered by other substances and trademarked products.

The primary forms of estrogen include three substances: estrone, estradiol and estriol. Estrone sulphate is the form of estrogen found in Premarin, while estradiol is the form of estrogen found in the products Estrace and Estraderm.

Estrone and estradiol, known as “conjugated estrogens,” significantly increase the risk of breast and ovarian cancer when taken for more than 10 years. According to the Merck Manual, conjugated estrogens are substances that even have been listed as known carcinogens, yet they are the unquestioned choices of too many physicians.

Estriol, on the other hand, is a weak estrogen that provides the anti-aging benefits of estrogen replacement therapy, apparently without the risk of cancer. Consider this evidence of its benignity: during pregnancy, huge amounts of estriol are secreted by the placenta to protect the fetus. Urinary assay of estriol is used to assess the fetus’ viability.

Since estriol is a weak estrogen, larger amounts must be used for estrogen replacement therapy. Estriol is used in doses of 2 to 8 mg a day. A dose of 2 to 4 mg of estriol is equivalent to, and as effective as, 0.6 to 1.25 mg of conjugated estrogens such as Premarin. One of the most common side effects of standard estrogen therapy is endometrial hyperplasia, or hyperproliferation of the cells of the uterine lining, a condition that often turns into uterine cancer. This condition, which sometimes occurs at younger ages, will be described in more detail later. However, most investigators have found that the use of the alternative estriol therapy, even at the high dose of 8 mg a day, does not cause endometrial hyperplasia.

In one study by scientists at the Medical College of Georgia in Augusta, 52 women with severe menopausal symptoms were given estriol succinate continuously for 6 months in doses of 2 to 8 mg a day. Significant improvements in symptoms were noted within 1 month of the start of the study, and they persisted as long as estriol therapy was continued. The degree of symptom improvement was directly related to the dose. Symptom relief was moderate at 2 mg a day, but marked at 8 mg a day.

Estriol therapy also reversed vaginal atrophy and improved the quality of cervical mucus. No breakthrough bleeding occurred in any of the subjects and biopsies of the inner mucous membrane of the uterus failed to show endometrial hyperplasia in any case, regardless of the dose of estriol used. The scientists concluded, “Estriol therapy may be employed in dosages up to 8 mg/day continuously, especially in those patients in whom other estrogens induce undesired side effects such as nausea, breakthrough bleeding, or endometrial hyperplasia, and the recurrence of hot flashes during cyclic therapy of more potent estrogens…. Being a weak estrogen, it does not induce endometrial proliferation or breakthrough bleeding of any consequence, while modifying menopausal symptoms.”

C. Lauritzen at the University of Ulm in Germany conducted a large, long-term study of estriol therapy for the symptoms of menopause. The investigators concluded, “Estriol therapy was successful in 92% of all cases. In 71%, hot flashes and sweating were completely eliminated, in 21% they were ameliorated, becoming weaker and occurring more seldom…. Depressive moods were abolished in 24% of the cases, and in 33% they were ameliorated, so that an overall improvement occurred in 57%.” The study also found that forgetfulness; loss of concentration, irritability, and heart palpitations was remarkably improved towards normal. Also, the number of patients suffering from migraine headaches decreased from 33 to 12, and atrophying of the vulva was completely eliminated in 44 of 61 cases, and showed improvement in 12 cases.

“Remarkably,” the scientists added, “the quality of the skin improved according to the subjective impression of patients and physicians in a high percentage of cases…. In no case, did a deterioration of symptoms occur.”

As described above, one of the major benefits of estrogen therapy is prevention of the bone loss associated with menopause. Postmenopausal women taking the correct estrogen experience 50% fewer bone fractures than women of comparable age who have not taken estrogen.

Although no studies have yet been conducted in the U.S. to determine whether estriol therapy can prevent osteoporosis, a prospective double-blind study was conducted in 136 postmenopausal women at the Chinese Great Wall Hospital in Beijing, China using nylestriol (CEE), a long-acting estriol derivative. The doctors found that the placebo group had significantly greater loss of bone mass and higher low-density lipoprotein levels when compared with the treated group. They concluded, “CEE is an effective estrogen for preventing bone loss and lipid disorders in postmenopausal women, just as is the more popular conjugated estrogen (Premarin), but is more convenient. Long-term CEE medication, its effects on the endometrium and the regimen of progestin combination await further study.”

There also is direct evidence from animal studies, and indirect evidence from human studies, that estriol can prevent breast cancer. Much of this work has been done by Dr. H. M. Lemon and associates of the Department of Internal Medicine at the University of Nebraska Medical Center in Omaha. In one study, they induced mammary tumors by radiation in female rats. In the control group, 75% developed tumors.

However, among those animals receiving estriol, just 48% developed tumors. In another study by the Lemon team, estriol was shown to have “the most significant anti-mammary carcinogenic activity of 22 tested compounds [because]… estriol is less likely to induce proliferative changes in the target organs of cancer-prone women than estrone or estradiol.”

Because of these anticancer effects of estriol in animals, Lemon looked at the question of whether estriol is related in any way to breast cancer in humans. He found that women with breast cancer have low levels of estriol relative to other forms ofactirogen. The evidence about estriol as a safe alternative estrogen therapy can be summed up well by the Medical College of Georgia scientists, who concluded, “Estriol deserves a place in our therapeutic resources.”

TRI-EST (Tri-Estrogen — Estriol, Estradiol, and Estrone)

This is a form of estrogen replacement that has been getting a lot of attention lately, although it’s still not widely prescribed. There is no major pharmaceutical company putting out Tri-Est, but you can get it with a doctor’s prescription from a compounding pharmacy made into capsules or a transdermal cream.

Tri-estrogen is, not so surprisingly, a combination of the three major estrogens your body makes — estrone, estradiol, and estriol. Usually it is produced in as 10% estrone; 10% estradiol, and 80% estriol, but this ratio can be adjusted depending upon your specific needs.

The theory behind tri-estrogen is a simple one: By taking it, you get the benefits from three different estrogens, and they are in a ratio similar to that which your body produces. The bulk of tri-est is estriol, which is the weakest form of estrogen produced on our bodies — and, as mentioned before, not only is it the least likely to cause breast cancer, some studies have shown that it actually helps prevent it. So by taking all three estrogens — very small doses of the stronger ones and a higher one of the weakest one, you can eliminate menopausal symptoms, fight osteoporosis and heart disease and help prevent the increased risk of breast cancer.

It’s a great theory, and one that bears watching. The only problem: As with other newer forms of estrogen, there haven’t been any long-term studies done on this.

* Standard dosage: 1.25 mgs twice a day to treat mild to moderate symptoms ; 2.5 mgs twice a day for moderate to severe estrogen deficiency; also available in 5 mg dosage

* Pros: Natural; appears to have fewer health risks than other estrogens, while preventing osteoporosis and heart disease and eliminating symptoms.

* Cons: May be too weak for some women, particularly those who have just had surgical menopause; no long-term studies have yet been conducted on this form of estrogen replacement.

TRI-EST OR BI-EST (Tri-Estrogen or Bi-Estrogen)

The human body produces several forms of estrogen, and the three major estrogens are estradiol, estrone and estriol. Estradiol is the main estrogen produced by the ovaries, and testosterone and estrone may also be converted to estradiol. Estrone is the main estrogen after menopause; androstenedione produced by the adrenal glands is converted to estrone in fat cells. Estriol is the main estrogen in pregnancy.

Tri-Estrogen contains all three estrogens. Bi-Estrogen contains estradiol and estriol. These estrogens are manufactured from certain molecules in soy or wild yam, and they are bio-identical to our own human hormones, that is, they are molecular copies of human hormones. By way of contrast, the estrogen in Premarin is mainly estrone, like our own mammalian estrone, extracted from pregnant mare’s urine, but the product contains many other substances as well, including an equine estrogen not found in our bodies naturally. The birth control pills contain synthetic estrogens and progestins, not bio-identical hormones.

Tri-Estrogen and Bi-Estrogen are not patented products, they are not brand names. They are made up into tablets, capsules or creams by compounding pharmacies. The dosages can be individually prescribed and compounded based upon a woman’s needs. Usually the doctor prescribes individual dosages based upon a woman’s symptoms and hormone levels. Natural progesterone and natural testosterone can be added to the capsules or creams.

Tri-Estrogen contains 80% estriol, 10% estradiol and 10% estrone, but it can be adjusted. Some women need more estradiol for severe hot flashes. That is how Bi-Estrogen came along. Bi-Estrogen has 20% estradiol and 80% estriol. If a woman’s body makes enough estrone, but she experiences more hot flashes and difficulty sleeping than is relieved by Tri-Estrogen, then Bi-Estrogen may work better.

Tri-Estrogen and Bi-Estrogen are considered “weaker” than Premarin or pure estradiol products such as the patch or estradiol capsules. Very often they are better suited to relieve symptoms in women who are premenopausal or perimenopausal, when problems are caused by wildly fluctuating hormone levels rather than low hormone levels as in postmenopause. Tri-Estrogen and Bi-Estrogen will often result in less side effects: less bleeding, less headaches and less breast tenderness than Premarin or pure estradiol products.

In fact, most perimenopausal symptoms are caused by fluctuating hormone levels. When a woman is postmenopausal, her hot flashes and night sweats eventually go away. Then the purpose of hormone replacement is usually to relieve problems of vaginal dryness, difficulties with arousal, depressed mood, lack of libido, and to treat low bone density. More estradiol and testosterone may become necessary.

It has long been known that estriol is the main hormone in pregnancy, and that it has a special affinity for vaginal tissue. It has been effective in preventing frequent urinary tract infections in postmenopausal women. Over-the-counter estriol cream for vaginal atrophy has been available for decades in Europe. But there is not a great deal more known about estriol, how it differs in its effects from estradiol and estrone. A study of 26 non-pregnant women between the ages of 18 and 40 was done in 1999 to investigate levels of estriol relative to estradiol and estrone. There was a wide variation in serum concentrations of estriol from woman to woman, but in all women and on all days of the cycle, the estriol was in at least 3 times to about 9 times greater concentration than the sum of estradiol and estrone. Although the role of estriol in the body has not been discovered, it is likely that it has one, since it is always present in significant concentrations in premenopausal women.

Studies of estriol used for bone density protection are likewise mixed, but since Tri-Estrogen and Bi-Estrogen both contain estradiol, they would have some positive effect on bone density. Recent studies are showing that even very low levels (and very low doses) of estradiol are associated with better bone density than estradiol at 0 pg/ml.

Priming the Hormonal Pump

Before individual sex hormones are supplemented it is suggested that a “priming” procedure be used. This priming is based on the “cascade” effects of DHEA as it gradually converts into all of the other hormones. To protect against the possible over-conversion of estrogen, women should add melatonin as a cancer safeguard. The priming dosages are as follows:

* DHEA, 15 mg once or twice daily.
* Melatonin, 3 mg at bedtime.

This simple hormone priming may bring hormones back to the desired levels and eliminate any symptoms. If this does not occur, specific recommendations are now made for individual hormone adjustment. Remember, wait 45 days before testing to determine the effect of each new supplement or new supplement dose.

Should estriol alone not achieve a woman’s goal, the next step is the utilization of a compound estrogen drug such as Tri-Est, the medication described earlier as having three forms of estrogen in the same proportion found in human females. Typically, women are prescribed 1.25 mg of estriol twice daily for mild menopausal symptoms. Stronger symptoms may require double the dosage. If Tri-Est is not available it is possible to have a cooperative physician order individualized estrogen mixtures from formulary pharmacies. In this way, if the Tri-Est with only 20% of the more dangerous estradiol and estrone fails to alleviate symptoms, a drug may be made with 40 or 60% estradiol. This is still a better choice than the standard medications with 80% estradiol. This graduated protocol is appropriate for any situation requiring supplemental estrogen. A natural product such as Natural Estrogen is recommended for PMS, menopause, and hormonally related health concerns related to estrogen deficit.

Progesterone Supplementation

The steps for progesterone supplementation are the same for both situations in which progesterone is needed to balance estrogen and those specifically calling for progesterone because it is the treatment of choice.

Natural progesterone is more beneficial than synthetic “progestin” drugs that are often prescribed to balance the negative effects of synthetic estrogen drugs. Natural progesterone in the form of transdermal creams is extremely safe. Overdoses have not been reported.

An alternative to artificial progestins is the option of using natural progesterone products. Not only are such soy-based natural progesterones far safer than synthetic drugs, they are as easily utilized as the real progesterone manufactured within the human body. The preferable forms of natural progesterone are creams that are rubbed into different areas of the skin. This route of administration bypasses the liver and allows hormone delivery to the place where it is needed the most.

Dosages should be adjusted/increased as required when attempting to balance estrogen levels. The cream should be massaged into soft tissue areas such as breasts, underarms, and inner thighs on a rotating basis to avoid the over saturation of cells.

DHEA Supplementation

DHEA is a precursor of estrogen and testosterone, so taking DHEA might raise the levels of these other hormones. It has been recommended previously in this protocol that DHEA is a good starting place for hormone modulation because of this ability.

It was recommended that women utilize a starting dose of 15 mg once or twice a day. Since DHEA is a precursor of testosterone as well as estrogen, many women find both hormones will rise to more youthful levels by supplementing DHEA alone. As needed, women may adjust DHEA dosages to 25 mg twice daily. **On a cautionary note, women with reproductive cancer should not take DHEA. In fact any woman with a family history of ovarian cancer, or a high score on an ovarian cancer blood screening test known as CA 125, should avoid all androgen supplements. As always, the best judge of dosage level is a test of blood level. The objective of DHEA supplementation is to achieve the blood levels that are considered normal for a 20-to 30-year-old woman (Yen, 1990). A DHEA blood test will greatly assist in proper dosing.

Hormone Modulation: Supportive Lifestyle and Nutrients

Every hormone discussed in this protocol is influenced by both environmental and nutritional factors. Here are some of the most important of these factors:

* Stress. There are strong correlations between excessive stress and such problems as adrenal insufficiency, lack of menstrual cycle, PMS, vaginitis, urinary incontinence, bone loss, and infertility.
* Smoking. Obviously, the link between cancer and smoking is well documented. Less well known is smoking’s connection to bone loss, cervical dysplasia, miscarriage, and Alzheimer’s disease.
* Exercise. The obvious connection here is to osteoporosis. But lack of regular exercise plays a role in adrenal disease, cardiopulmonary disorders, loss of libido, and menstrual problems.
* Obesity. Some menstrual disorders are found more often in overweight women. In fact, a diet that lowers body fat may lower estrogen levels as well.
* Nutrition. Here are some areas in which dietary supplements play an important role in the development and treatment of hormonally related diseases:
* Vitamin E. Research at Johns Hopkins Medical School demonstrated 600 IUs a day of vitamin E raised both estriol and progesterone levels in a group of women with fibroid breast disease. Both estriol and progesterone help 2,rotect against estrogen’s possible tumor-creating effects.
* Calcium, magnesium, and vitamin D3. Any women with bone loss should supplement her diet with at least 1000 mg of elemental calcium, 600 mg of elemental magnesium, and 400 IUs of vitamin D3 a day. SEE: OSTEO-B PLUS
* Antioxidants. The addition of such antioxidants as vitamin C, vitamin E, CoQ10, grape seed-skin extract (proanthocyanidins) and Lipoic Acid may be of great assistance when treating a number of the disorders in this protocol, including cardiac problems and cancers.
* Fats. Diets high in synthetic hydrogenated fats producing Trans Fatty Acids lead to heart disease, cancers, and an imbalance in the eicosanoid hormones (an important factor in fibroid cysts.) In contrast, diets high in essential fatty acids and the naturally occurring saturated fats help to balance eicosanoids. Other eicosanoid imbalance links include uterine cramps, pelvic pain, and breast pain.
* High-potency B-complex vitamins. Various B vitamins have been examined by researchers. Abraham (1983) found vitamin B6 to be helpful in reducing menstrual cramps. More recently, Mills (1996) showed that supplementing the B-complex group in women with endometriosis produced a significant decrease in symptoms.
* Bioflavonoids. Supplements of this member of the vitamin C complex appear to actually inhibit excessive estrogen synthesis (Kellis and Vickery, 1984).

Summary
The need to modulate the relative levels of the primary female hormones is of critical importance throughout life. Beyond the well-publicized hormone replacement therapy for menopausal symptoms, such disorders as PMS, endometriosis, several types of cancer, sexual dysfunctions, fibroid tumors, osteoporosis, cardiac disease, and Alzheimer’s disease are closely related to hormonal imbalances. Many disorders are linked to either excessive or deficient estrogen levels, particularly as they compare to the amount of progesterone available. Not only should hormones be modulated regularly, but natural sources for hormone supplementation should be used. Synthetic and non-human analogue hormones carry with them unwanted, even deadly side effects. Hormone modulation requires individualization, and works best when carefully monitored through laboratory testing. Both lifestyle and nutritional variables play an important role in hormone modulation.

Estrogen is an anti-aging hormone that provides many beneficial effects throughout the body. The major drawback to conventional estrogen replacement therapy is the increased risk of certain cancers. FDA-approved estrogen drugs have other adverse side effects that preclude many women from effectively using them. Natural plant extracts provide the body with safe and possibly more effective estrogen replacement.

Menopause is not just an estrogen deficiency. Numerous hormone imbalances threaten the health of menopausal women. The published literature has identified several plant extracts that favorably modulate hormone balance in aging women.

The decline in progesterone production is correlated with increased bone loss and increased risk of cancer. Many of the effects associated with normal aging can be attributed to a progesterone deficiency, so progesterone replacement therapy may be another missing link to solving the human aging process. The beneficial effects of natural progesterone have now been shown in women and men. Progesterone protects against many of the detrimental changes of aging, and the only downside is that too much can make a person feel sleepy or even euphoric. Please note that it usually takes 2 to 4 weeks for topically applied progesterone to build up to sufficient levels in the body to cause noticeable effects.

Individual symptomatic improvement and blood analysis of estrogen, progesterone, testosterone, prolactin, luteinizing hormone, and follicular stimulating hormone (FSH) by a physician can help determine how well natural hormone modulation therapy is working.

The proper intake of hormone-modulating plant extracts, phytoestrogens, DHEA, natural progesterone, and other natural hormones may provide significant health benefits to the aging female.

The following nutrients and drugs are suggested to restore hormone balance in aging women or women with symptoms of an imbalance:

1. Natural progesterone cream from Compounding Pharmacy: Apply topically to the skin (follow directions as per your physician).
2. Natural Estrogens: Take as directed by your physician.
3. DHEA: Take one 15-mg capsule, 1 to 2 times a day.
4. EQUI-FEM (multivitamin supplement): Take 1-2 tablets, 3 times a day.
5. Melatonin: Take 2 to 3 mg only at bedtime.
6. Supplement with BIOMEGA-3 and BLACKCURRANT SEED oil to restore fatty acid balance and for the production of the ?good? prostaglandins.
7. Consider Estriol or Tri-Est if menopausal symptoms are not alleviated by nonprescription therapies. Blood testing may also indicate the need for additional estrogen or progesterone.

Blood or saliva testing after 45 days is mandatory to verify you are taking the proper dosages.

For more information. Contact the National Institute on Aging, (800) 222-2225.

Other Resources:
For further information on menopause and hormone replacement therapy contact:

American College of Obstetricians and Gynecologists (ACOG)
409 12th Street, SW
Box 96920
Washington, DC 20090
202-484-8748
Internet website:
http://www.acog.org

North American Menopause Society
Box 94527
Cleveland, OH 44101
216-844-8748
Internet website:
http://www.menopause.org

The International Academy of Compounding Pharmacists (IACP) P.O. Box 1365
Sugar Land, TX 77487
Email: iacpinfo@iacprx.org
Phone: 281-933-8400
800-927-4227
Fax: 281-495-0602
Internet website:
http://www.iacprx.org/