HORMONES

BY JIM DUKE

Get your minds out of the good old gutter. Right off the bat, let me remind you that there are more than just sex hormones. As I started writing this hormone newsletter, I was lucky to receive Wright and Gaby's new book, The Patient’s Book of Natural Healing, (reviewed herein), where they discussed various hormones in one introductory chapter. Until recently, when some journal said HRT for hormone replacement therapy, I assumed that they were almost invariably talking about ERT or estrogen replacement therapy. And nine times out of ten they were. I've rarely heard of TRT (testosterone replacement therapy), but then again, men rarely discuss their problems as openly as do women. I certainly have heard many times about preventing the conversion of T to DHT,i.e. testosterone to dihydrotestosterone. But HRT can refer to adrenal, hypothalmic, pituitary, sex, or thyroid hormones.

      That's the problem with acronyms. TRT could as well stand for thyroxin replacement therapy as testosterone replacement therapy.  In their introductory chapter, "Natural Hormone Therapy", Wright and Gaby (1999), remind us that the word hormone derives from Greek, meaning "spurring on" or "setting in" motion.  Hormones are chemical substances produced in the body that regulate the function of various organs and tissues. Drugs, especially silver bullet hormonal drugs, often upset other hormonal ratios, and many drugs have negative side effects on some of our hormones. Age frequently depletes us of DHEA, estrogen and testosterone.

Wright and Gaby, these great holistic MDs, lament that modern endocrinologists (glandular or hormone specialists) reject the notion that minor deficiencies in hormones can cause major problems, and they fail to see the hazards of artificial hormones. "Appropriate use of human hormones in physiologic doses (i.e., doses similar to what the body normally produces) often results in important clinical benefits and causes fewer side effects than synthetic hormone-like drugs." They may offer the animal glands themselves for replacing deficient hormones. I'm not opposed to glandular therapy, but many vegetarians are.

In this newsletter, I present a terse summary of the herbal approach to hormonal difficulties: licorice, cautiously, for the adrenals, lemonbalm for the thyroid, and legumes for their phytoestrogens. These are important herbal alternatives to some chemical solutions. And whether your hormonal deficiency is adrenal, sexual or thyroid, that TARD feeling (tired and rundown) may be a frequent symptom.

ADRENALS

ADRENOPATHY: Let's talk first about the fight or flight hormonal gland, the adrenals, almond-shaped glands, one atop each kidney. Adrenopathy means simply malfunction of the adrenal system. Just the cortex of the adrenal makes over 40 different steroid molecules. The cortex secretes the corticosteroids (mineralcorticoids, glucocorticoids, and 17 ketosteroids {sex hormones}). Aldosterone, cortisol and DHEA are the major adrenal steroids. The main sex hormone secreted by the adrenals is DHEA (dehydroepiandrosterone, sometimes praised as an antiaging hormone). (Murray and Pizzorno, 1991) DHEA is increasingly produced as one reaches puberty, peaking at age 25-30, then slowly beginning to decline. Some scientists refer to it as a biological clock of aging. (Seachrist, 1995) The medulla of the adrenals secretes adrenaline (epinephrine) and noradrenaline (norepinephrine), which are involved in the fight or flight response. Adrenaline is the emergency hormone. Complete adrenal exhaustion is better known as Addison's disease. Addison's disease is characterized by extreme weakness, weight loss, low blood pressure, gastrointestinal distress, and a brownish pigmentation of the skin and mucous membranes. (Leung, 1984) People with adrenal exhaustion may feel "stressed out", tired, and may be prone to allergies. Excessive adrenal activity may result in the opposite; anxiety, depression, elevated blood sugar and cholesterol, and high blood pressure. For a period, naturopathic physicians were recommending Whole Adrenal Therapy, or Adrenal Cortical Extract (ACE). This extract contains small amounts of all the adrenal steroid hormones from the adrenal cortex of   animals. This whole extract is scarcely available for several reasons, one being FDA regulation. The isolated hormones, like cortisol and DHEA, still available, may not be as effective as the whole natural complex. It still may take cortisol, a hard core drug, for Addison's disease or complete adrenal failure, but many of the immunostimulant herbs, especially licorice, can be cautiously used by knowledgeable practitioners in mild adrenal insufficiency.

ADRENAL ANECDOTE: A woman came to me pleading for a miracle, hinting that prednisone, given to her boyfriend as part of the treatment for serious ailments, had shut down his adrenals. I immediately thought of licorice because that is supposed to stimulate the adrenals. Chinese think of licorice as the great harmonizer or master medicine in their mixtures. But her boyfriend was having trouble keeping his blood pressure down and licorice is prone to raise blood pressure. Prednisone may tend to slow or shut down the adrenal gland, where the body usually manufactures its own steroids. Too much steroid may make the adrenal lazy or invalid. Without problems of hypertension or low potassium, licorice would be the first botanical alternative I'd recommend to stimulate a tired adrenal. Perhaps that's why Mowrey (1986) recommends licorice for hypoglycemia, to increase the effectiveness of the adrenal glucocorticoids circulating in the liver, even mimicking the activity of these hormones. Glycyrrhizin, the active ingredient in licorice, has an affinity for the glandular receptors and "inhibits the anti-granulomatous action of cortisone... The anti-inflammatory effect (making licorice useful to some arthritics) is therefore probably due to a release of corticoids from the adrenals." (Mowrey, 1986, parentheses mine) Atrophy of the adrenal cortex may follow prolonged stress, cortisone administration, and just plain aging. (Murray and Pizzorno, 1991) Licorice extract stimulates the adrenal glands, making it useful in fatigue due to adrenal exhaustion.  Licorice and its extracts are safe for normal use in moderate amounts. However, long term use or ingestion of excessive amounts can produce headache, lethargy, sodium and water retention, excessive loss of potassium, and high blood pressure.

If you don't like your info coming from herbalists and naturopaths, listen to Professor Norman G. Bisset, Chelsea Department of Pharmacy, Kings College, London. Glycyrrhizin and its aglycone lie behind the mineral corticoid effects of licorice. There are connections between them and the adrenocortical hormones, since, among other things, these effects are only observed when there is still at least a little functional adrenal cortex. With rat liver preparations, both compounds strongly affect delta-4-5-beta-reductase, which is important in the human liver in regulating cortisol and aldosterone metabolism. This may retard the metabolic excretion of corticosteroids and extend the half-life of cortisol and aldosterone. In Russia, licorice preparations are used collaterally in long-term cortisone treatment, enabling the steroid dose, and hence the side effects, to be reduced.

Mergentime (1993), in an article on better sex, gives long shrift to men, short shrift to women, listing only dong quai as a female aphrodisiac. But there are nutritional implications for women's sexual vitality as well. Vitamin A "supports adrenal function" and "Healthy adrenal glands are important for sexual function in both sexes." That latter quote suggests to me that licorice, the super adrenal stimulator might be useful in frigidity due to adrenal or endocrine insufficiency. Normal sexual function requires a healthy endocrine system. Sexual arousal begins in the hypothalamus of the brain, which chemically       signals the pituitary gland to release gland-stimulating hormones. The pituitary, "master gland of the endocrine system", governs the activity of the thyroid and hormone releasing sex glands. Vitamin B-1 (thiamine) is important to adrenal and thyroid function. Vitamin B-2 (riboflavin) "aids in reproductive function." Vitamin B-3 (niacin) is essential to the pituitary. Niacin flushes are aid to be sexually stimulating. Folic acid is "helpful to ovarian function." Pantothenic acid "supports adrenal function, provides pituitary support," and is "said to improve sexual stamina." Vitamin B-6 is involved in making "neurotransmitters including epinephrine which is thought to be involved in orgasm.” Vitamin B-12 "supports adrenal function." Vitamin C "supports adrenal function." Vitamin E "supports adrenal function." Essential fatty acids, "Vitamin F", are "needed by the thyroid, adrenal and prostate glands." Of amino acids, Mergen-time says lysine is " said to enhance fertility", arginine is "essential to the function of the pituitary", phenylalanine " said to stimulate interest", tyrosine " said to improve sex drive", and histidine " said to improve libido in both sexes" (italics mine). The italics are to emphasize that the sex properties are said to be, by this I suspect Mergentime means that one of his sources said it or reported someone else saying it, and that there is no "hard" proof, in humans at least.

ADRENOPATHIC BOTTOM LINE: Even if my impersonal physician were positive that I was suffering a partial adrenal inadequacy, I'd be reluctant to take his prescription. I'd at least ask him if he didn't think I might experience fewer side effects if I went with my herbal alternative, a high potassium diet with          frequent Pantothenic Salads, and a nibble of my homegrown ginseng and licorice roots (watching my blood pressure), chased with a ginseng tea, sweetened with licorice and molasses. Maybe I'd even resort to that high priced Chinese combo, ginseng and royal jelly, for the pantothenic acid in the royal jelly. Or if poor, I'd stick with oatmeal and molasses, a combination my father almost forced on me sixty years ago in red-clay Alabama. One thing that strikes me in rereading my adrenopathy literature; the important herbs for stimulating the adrenals are also important immunostimulants: astragalus, echinacea, eleuthero, ginseng, and licorice, the ruling herb in so many Chinese formula. 

THYROID

HYPERTHYROIDISM: Hyperthyroidism might be defined as having more than normal thyroid test values of circulating thyroid hormones T3 (5-12 mg/dl) and T4 (5-12 mg/dl). (Graedon's, 1991) Dorland's Medical Dictionary (1974) defines Graves' disease, named after an Irish Physician, Robert James Graves (1796-1853), as “a disorder of the thyroid of unknown etiology, occurring most often in women, and characterized by exophthalmos (big word for "pop eyes"), enlarged pulsating thyroid gland, marked acceleration of the pulse rate, a tendency to profuse sweats, nervous symptoms (including fine muscular tremors, restlessness and irritability), psychic disturbances, emaciation and increased metabolic rate." According to L. K. Altman, MD (New York Times, May 21, 1991) hyperthyroid people can show shortened attention spans, make snap decisions, behave frenetically, and tire more easily than others.

Thyrotropic is defined in Dorland's 25th as having an influence on the thyroid gland. They also define thyrotropic as "pertaining to or marked by thyrotropism" which they define as affinity for the thyroid. That's sort of like the word immunomodulator. Things that boost and things that suppress the immune    system are immunomodulatory and things that boost and things that suppress the thyroid are thyrotropic. The level of thyroid hormone production depends on levels of thyroid-stimulating hormone (TSH) released by the pituitary, by iodine availability, and by the health  of the thyroid. TSH levels are further regulated by the hypothalamus and other regulatory mechanisms, so that homeostatically, TSH increases as thyroid hormones decrease and TSH decreases when thyroid hormones increase. (Dharmananda, 1993)

HYPOTHYROIDISM: Just below the Adam's apple resides your thyroid gland which secrets two hormones: about 90% thyroxine T4 and about 10% triiodothyronine, with traces of poorly understood diodotyrosine (DIT) and monoiodotyrosine (MIT).

Thyroid disease affects about 2.5% of Americans, especially older females. Women are 8 times more likely to suffer hypothyroidism, 4 times more likely for hyperthyroidism, and 2 times as likely    to suffer thyroid tumors, than men.  Hypothyroidism might be defined as having less than normal thyroid test values of circulating thyroid hormones T3 (5-12 mg/dl) and T4 (5-12 mg/dl), or more simply a deficiency of thyroid hormones. Regulating metabolism in every cell of the body, such hormones can affect almost every body function. Severity in adults may be an almost benign subclinical hypothyroidism to severe life-threatening myxoedema.  Murray and Pizzorno list as symptoms: low basal body temperature, sensitivity to cold, decreased libido, depression, difficulty losing weight, dry skin, headaches, fatigue or lethargy, dysmenorrhea, slow Achilles reflex, and recurrent infections. Goiter is more a symptom than a disease, too loosely defined as a swelling in the neck. I think it more proper to define goiter as a swelling of the thyroid gland, as is defined in Martindale (1993). Goiter can be associated with both hyper- and hypo-thyroidism. (Too much thyroid hormone as in Grave's disease can cause goiter. Too little can lead to hypothyroid goiters, and may be due to too little hormone or too little iodine (as in endemic goiter). Euthyroid goiters also occur.

Most of the naturopaths I have consulted about hypothyroidism are skeptical of the herbal approaches, i,e., rosmarinic- and lithospermic-acid-containing herbs and even the iodine, instead suggesting glandular extracts (which some vegetarians find repulsive ethically). Synthetic thyroid preparations lack the DIT and MIT found in the glandular preparations. Some patients do better on just synthetic T3, more on just T4, but the whole extract with all four may be best for most, if the herbs don't work for you. 

Wright and Gaby (1999) don't even mention my favorite herb for hypothyroidism, seaweed. Science generally discounts much of the folkloric stuff about the amphoteric effects of seaweed as (a) not confirmed in traditional cultures, and (b) no more than a useful source of iodine.

Some studies suggest that bugle weed, lemon balm and several other herbs well endowed with rosmarinic acid may be amphithyroid, increasing hypoactive and depressing hyperactive thyroids. Bugle, gromwell, lemon balm, selfheal and verbena might be indicated for hypothyroidism as well as hyperthyroidism. Finally and equally controversially, the crucifers, when salted with iodized salt, or alternated meal-to-meal with kelps, might seem to be helpful in both hyper- and hypo- and euthyroid conditions. 

I feel that crucifers in general, when iodine balance is good, might not be goiterogenic, they induce goiter only when iodine is deficient. We might be better off alternating seaweeds (iodine rich) with crucifers (isothiocyanate rich). Seems to be another one of those hormonal balancing acts. Given ample food and nutrients, the homeostatic body is better able to maintain thryoid levels than when given some super silver bullet.

THYROID NUTRITION: Thyroid hormones are made from tyrosine and iodine. A mixture of mustard greens and seaweed could provide the best natural sources of both. A tea of walnut(and I'll predict butternut) hulls or leaves can reportedly double thyroxine levels. Naturopaths (MAP 1991) note that vitamins A and E and zinc are involved in the manufacture of thyroid hormone. Ascorbic acid, niacin, pyridoxine and riboflavin are also necessary for normal manufacture. Hence they recommend 300 ug iodine, 250 mg tyrosine, 25,IU vitamin A, 30 mg zinc picolinate, 400 IU vitamin E, 15 mg riboflavin, 25-50 mg niacin, 25-50 mg pyridoxine and 1000 mg ascorbic acid. My old redneck mustard greens tyranically top the tyrosine charts at 1.9% on a zero moisture basis. Balch and Balch recommend higher doses of tyrosine, 500 mg twice daily on an empty stomach, rendering my mustard greens approach difficult. It would take a bit more than 50 g dry mustard greens to provide 1,000 mg tyrosine, but that means closer to half a kilo of fresh mustard greens.

HORMONE REPLACEMENT THERAPY

Holly Atkinson, MD (in an unpublished letter to the editor, 1997) puts it interestingly.  The phytoestrogens and estrogens are like slightly different master keys to the same lock--the estrogen receptor. Inserted in the receptor, the phytoestrogen prevents the estrogen from stimulating certain tissues to proliferate (e.g. breast and uterine lining). They also seem to trick the hypothalamus and pituitary gland (which help regulate female hormones) into thinking the body has enough estrogen. "Isoflavones are much more potent than lignans when it comes to interacting with estrogen receptors. But lignan-containing foods, particularly whole grains such as wheat, rye and flax seeds, are also high in fiber. Fiber helps increase the elimination of estrogen by the bowel and reduces intestinal reabsorption of estrogen." These two mechanisms lower circulating natural estrogen in the body, thereby perhaps, over time, reducing the risk of breast, ovarian and uterine cancers. In one study, young rats consuming isoflavones from birth to puberty were remarkably resistant to breast cancer when exposed to a known carcinogen later in life. Dr. Kenneth Setchell is quoted as having said: "It may be that a lifetime of eating soy products is the secret to the lower cancer rates in Asian women." We should mention green tea, kudzu, marine algae, garlic, mung bean and its sprouts, perilla and wasabi, are other plant foods frequently consumed in the orient that might also contribute to that epidemiology. [1]37

Atkinson emphasizes in bold letters "If you're interested in adding phytoestrogens to your diet to try to ease menopausal symptoms or to hedge your bets against heart disease, slowly increase your consumption of soy products. Your goal should be to work up to 24 to 45  milligrams of isoflavones a day - the amount consumed by the average Japanese woman.  (3.5 oz tofu contains 33.7 mg isoflavone BUT also contains 9 g fat. A half ounce Psoralea (15 g) would contain 35 mg isoflavonoids with only 1.5 g fat).

Women who ate the most fiber (from cereals, vegetables and fruits) had a 29 to 46 percent lower risk of endometrial    cancer than women who ate low fiber diets. The same was true for women whose diets were high in soy and legumes (bold emphasis mine; soy is a legume, just about ten times higher in fat than most other normally eaten legumes). Other phytoestrogen rich foods, such as whole grains, vegetables, fruits and seaweeds, also appear to protect against endometrial cancer. Though soy may have 10 to 20% more fiber AND slightly more phytoestrogenic genistein and daidzein than some Phaseolus beans in my database, soy also may have 10 times more fat. True confession: though our black and brown beans are much lower in fat, our peanuts are even higher in fat than soybeans.

My conclusion. If you enjoy black beans or pinto beans more than soybeans, you'll get more isoflavones and less fat eating 3/4 cup of those beans as opposed to half a cup of soybeans. If you're like me, you'll enjoy those Phaseolus beans even more.

At age 70, with prostate cancer a real hazard, I'll go with a cup of black beans, for their genistein, 3 brazilnuts for their 200 ug selenium, pepitos pumpkin seed) for their amino acids, and tomato ketchup for its lycopene. I believe that will improve my odds against prostate cancer and a woman's odds against hormone dependent cancers as well.

HRT: Only 15 percent of American women use conventional hormone replacement therapy. The other 85 percent are looking for natural options, as are many of the 15 percent. (Rob McCaleb, HerbalGram  41:10 1997)

Pizzorno (1998) presents a concise overview of the female hormonal cycle. As in the male, hormone secretions in females are controlled by the pituitary. Unlike the male, the mature female hormones cycle each month until about age 50. The cycle is (1) the follicular phase when the pituitary releases follicle stimulating hormone (FSH) which stimulates the ovarian follicles to increase in number and size, one ripening into an egg, (2) the luteal phase begins when a burst of luteinizing hormone (LH) cause the release of the ripe egg as the other follicles begin to degenerate, and estrogen production declines. Cells surrounding the egg mature into the corpus luteum. The corpeus luteum, stimulated by LH, secretes more progesterone. If fertilization fails to occur, the corpus luteum will degenerate in about a week, and (3) the menstrual phase, during which the lining of the uterus degenerates and is excreted. If fertilization is achieved, the pituitary secretes prolactin, which signals the breasts to prepare for milk production. 

The major sex hormones are testosterone in the male, and estrogen and progesterone in the female, but all of us, male and female alike, make all of these and need all of these. Estrogen and testosterone affect the development of secondary sex characteristics. They also play a big role in anabolism, promoting body building in such tissues as bone, connective tissue and muscle, among others. Both estrogen and testosterone may play a role in preventing osteoporosis. Older men prescribed testosterone often exhibit improved attitudes, memory, mood, muscle mass and sex drive. Low testosterone correlates with higher incidence of angina, atherosclerosis, depression, high blood pressure, high cholesterol, high triglycerides, osteoporosis, and thromboses. Early  pharmaceutical firms unfortunately went for an unnatural hormone, methyltestosterone, which had angina and liver cancer as a side effect. Whether or not you believe in testosterone for the prostate, you should always have your PSA tested (See the Men's Health issue and the Urogenital issue). Anything leading to hormonal imbalance between these pituitary and ovarian hormones can trigger multiple dysfunctional syndromes during the menstrual cycle or menopause. And that's where the balancing herbs come in.

Some 1 in 4-6 postmenopausal women take ERT to relieve such things as hot flashes and insomnia. ERT seems to facilitate memory and new-task learning, protect against heart disease and osteoporosis, and its effect on Alzheimer's is being studied.  A study reported in Lancet (Aug. 17, 1996) showed that women who had taken estrogen for just 1 year were less likely to develop Alzheimer's. But estrogen may increase risks for endometrial and perhaps breast cancer. Coupling  progesterone with estrogen may minimize endometrial cancer risks.

Of all the physical experiences that happen to women going through menopause, hot flashes may be most bothersome. Sensations of intense heat primarily in  the upper body (arms, chest, neck, head), followed usually by profuse sweating, are experienced to some extent by most menopausal women. Some women experience an occasional flash every few months, others as many as 10-12 flashes in a day. The most commonly prescribed alternative therapies are herbals, e.g., black cohosh, dong quai, licorice and chastetree. Herbal mixtures containing one or more of these are also common.

BLACK COHOSH ANECDOTE: QUESTION: Dear Jim, I have a query about Cimicifuga racemosa as a phytoestrogen. I have heard that Cimicifuga may be contraindicated in cases of too much  estrogen such as in endometriosis or myomas, as it may potentiate the effects of estrogen rather than acting as a competitive inhibitor, (like plants such as Linum usitatissimum [flax], Trifolium pratense [red clover], or Glycine max [soy]). It may interfere with negative feedback of estrogen, thus causing more circulating estrogens, and possibly the same may be said for Chamaelirium lutea and Dioscorea villosa, therefore, these herbs have an excellent role to play where there is low estrogen as in menopause, but   perhaps should be avoided in premenopausal women where there is too much estrogen. I would like to hear your comments on these confusing matters.;

ANSWER: In few cases have I been as confused as with the phytoestrogens and breast-cancer positive proliferation stimulation. Germans reported formononetin in Cimicifuga two decades or so ago and now seem to wish to forget all that,      trying to take it out. I had thought that formononetin, like the other estrogenic isoflavones in clover, biochanin, and daidzein and genistein, worked the same way. But I'm getting mixed signals on that too. Wish I could give you a scholarly and learned answer to the BIG question: Which is safer for menopause

ERT, estrogen replacement therapy, or PERT, phytoestrogen replacement therapy?

My answer for today, if I had to take an estrogen, I'd rather it were a nat-  ural phytoestrogenic SERM (Selective Estrogen Receptor Modulator) than a synthetic SERM.

SERMs - Selective Estrogen Receptor Modulators. With Andy Weil and the Harvard Health Letter all espousing SERMs, its no surprise we are hearing about herbal SERMs. SERM is the abbreviation of a rather new pharmaceutical concept, selective estrogen receptor modulator. According to my non-binding interpretationall phytoestrogens that bind to estrogen receptors (and I think that's a lot if not all of them) will modulate selectively. Raloxifene HCl (EvistaŇ), the second (after Tamoxifen citrate [NolvadexŇ]) in a predicted swarm of SERMs, was recently approved by the FDA for preventing osteoporosis. I'll wager that the estrogenic isoflavones daidzein and genistein, found in several legume supplements, are herbal SERMs. That's why I'll wager that most of our genes have already experienced many herbal SERMs over the course of our evolution.

SERMs are intended to provide the cardiovascular and bone-protective benefits of estrogen, without the concomitant risk of breast and uterine cancers. 

Renewed interest in SERMs renewed my interest in Knight and Eden's (1995) nuggets on phytoestrogens. Genistein is the "most widely studied isoflavone." It inhibits tyrosine kinase, DNA topoisomerases I and II and ribosomal S6 kinase. There we read that "a low dose of genistein was equivalent to Premarin (Wyeth-Ayerst Laboratories) in maintaining bone mass in ovariectomised rats." Phytoestrogens are "attenuated estrogens", with coumestrol 0.002 as potent as estradiol, genistein 0.00084, equol 0.00061, daidzein 0.00013, bio-chanin A (<0.00006) and formononetin (<0.000006). "The estrogen receptor complexes formed by estradiol and  isoflavonoids are functionally equivalent. Confirmation of isoflavone-estrogen receptor interaction was provided with inhibition by tamoxifen of any iso-flavone estrogenic activity compared to controls. The comparative dissociation constant of genistein for the estrogen receptor determined in competitive binding experiments is 100 to 100,000 times higher than that of estradiol and diethylstilbestrol.  The use of unopposed estrogens increases the risk of endometrial carcinoma and a higher risk of endometrial cancer associated with increasing duration of tamoxifen use has also been reported."

SERMs have evolved from mere laboratory curiosities into drugs that hold promise for preventing several major disorders in women. If The New York Times, JAMA, and Scientific American herald angiostatin and endostatin, raloxifene and tamoxifen as cancer regulators or preventatives, respectively, how do we get them to look at the safer and cheaper natural regulators and preventives, like one cheap, natural isoflavone, say genistein. In May, 2000, it was announced by the federal government that tamoxifen, the chemopreventive darling of the American Cancer Society and the National Cancer Institute, was in fact a carcinogen. (C&E News. p. 8 May 22, 2000)

HERBAL ESTROGENS

BLACK COHOSH (Cimicifuga racemosa): This joins the ranks of many other major American herbs, better studied in Europe than in the United States. Schulz et al. (1998)suggest that there are three main roles for phytotherapy in gynecology: dysmenorrhea, menopausal complaints, and PMS. In Germany, two herbs stand out, chastetree for PMS and black cohosh for menopausal complaints. Endocrine effects of the cohosh are presumably exerted on the pituitary. Cohosh lipophilic extracts (wherein dwell the hormonally active principles) reduce levels of luteinizing hormone, unlike synthetic estrogens, which affect FSH, LH and prolactin release. Five controlled (but not double-blind) studies using doses equivalent to 40 mg/day crude drug "support the therapeutic efficacy of black cohosh extract in menopausal women... There are no case reports of toxic effects from the herb, and there appears to be no specific toxicity associated with any of its known constituents. Two of the 5 showed mild side effects (dizziness, GI distress, headache, weight gain). Because of insufficient data, use during pregnancy and lactation is not advised. No other contraindications are known. The duration of use should not exceed three months.” (Schulz et al., 1998) Way back when, Weiss said black cohosh (Cimicifuga racemosa) contains estrogenic substances, indicated mainly in menopause, aiding particularly the "vegetative dysregulation and mental symptoms." In 1991, Duker et al., studying the activities of cohosh extracts in ovariectomised rats concluded that LH suppression by the extracts is caused by at least three different compounds, acting synergistically. They also studied 110 menopausal women, giving cohosh root extract (8 mg/day) or placebo. After 8 weeks, luteinizing hormone (LH) levels were significantly reduced, FSH levels were not, implying significant estrogenic activity. (Werbach and Murray, 1994) Duker et al. showed that vaginal cytology was affected similarly by cohosh and pharmaceutical estrogen. Cohosh compounds compete at least in vitro with 17-beta-estradiol for estrogen receptor binding sites. Wright and Gaby (1999) add that although many herbal remedies, e.g., alfalfa, black cohosh, dong quai, ginseng, and licorice are freqently effective, the one backed strongest by clinical evidence is black cohosh. Small wonder that black cohosh sales rose almost 50% in the first 8 months of 1999, in a generally level market. (Blumenthal, 1999)

CHASTETREE (Vitex agnus-castus): Hoffmann (1986) suggests it is a normalizing herb, normalizing the activity of female sex hormones. "It is thus indicated for dysmenorrhea, premenstrual stress and other disorders related to hormone function. It is especially beneficial during menopausal changes." Weiss (1988) heaps equal praise on this non-GRAS herb, joining the ranks of hawthorn, ginkgo, and other non-GRAS well-respected "European" herbs. Of chastetree, Weiss says, without citing a source (he was an MD): "It causes increased luteinizing hormone production and inhibits the release of FSH (follicle stimulating hormone). This leads to a shift in the ratio of estrogens to gestagens, in favor of the gestagens, and hence a corpus luteum effect." Time-Life (1996) suggests that combinations of chastetree, motherwort and wild yam (and other herbs) may help rapid heartbeat that comes with hot flashes. Dr. Joseph Pizzorno, N.D., Director of the John Bastyr School of Naturopathic Medicine, has managed to get many alternative therapies declared insurance-reimbursable in Washington State. He was praised for this accomplishment by former Surgeon General, C. Everett Koop. Since then he has outlined ten of his natural alternative recommendations. "The conditions for the body to heal depend on healthy diet, exercise, and attitudes. Herbs, vitamins and other substances often can stimulate healing, but unless the underlying reasons for the illness are corrected, improvement will be only temporary." Pizzorno recommends for menopausal patients ample amounts of foods that contain phytoestrogens (alfalfa, anise, broccoli, brussel sprouts, cabbage, celery, fennel, nuts, and whole grains are named), and 40 drops of a 1:5 tincture of Vitex. Pizzorno reminds us, "Many women find special nutrients from plants (such as genistein from soybean products) a better choice than synthetic estrogens or the animal estrogen Premarin. One cup of soybeans provides the equivalent effect of one tablet of Premarin. Only three ounces of soy a day yields positive results.”  

DONG QUAI (Angelica sinensis): Dr. Andy Weil (1998) states categorically (wish I could do that) that "dong quai is nontoxic and DOES NOT have estrogenic activity". He frequently prescribes the "female ginseng" dong quai for      difficult or irregular menstruation, endometriosis, hot flashes (with chastetree and damiana), other menopausal symptoms, PMS, and weakness following childbirth. He suggests two dong quai root capsules twice a day or one dropper-full of tincture in warm water twice a day, allowing 6 to 8 weeks for progress. He reports good results with his special combo for hot flashes, which includes two capsules or one dropper tincture of each: chastetree, damiana, and dong quai, once a day at midday, continuing until the hot flashes taper off.

RED CLOVER (Trifolium pratense): A Medscape search specifying 1998 references on June 11 showed 335 entries for soybean, 305 for genistein, and 13 for clover. Is soy 100 times better than clover as a phytoestrogen? Is genistein 100 times better than red clover's mix of biochanin, daidzein, formononetin and genistein? I think not. But who knows? At least the antiangiogenic genistein is more readily available, and perhaps 1,000 times cheaper than the all but unavailable "miracle cure" angiostatin. Herbalists use red clover in cancer support formulas, and have for 30 years or so. Dr. John Christopher and Dr. Shook both had red clover compounds for cancer, unofficially, of course.

An ad on the reverse of p. 26 in Whole Foods, March 1998, introduced a new clover product from Australia.  It rather deflated me because the product advertised was riding on claims I had been making (public domain) for five years. They claim that the typical American diet is seriously lacking in natural plant estrogens, while Asian and Mediterranean diets, based on beans, mung beans, soy and other legumes, are better endowed with phytoestrogens. "Women on these diets maintain their own familiar sense of physical, mental and emotional well-being."

Data from Buchbauer, Jirovetz and Nikiforov (1996) gives new emphasis to the value of red clover flowers in folk  cancer cures and preventive approaches.  Counting only four, biochanin-A, daid-zein, formononetin, and genistein, the red clover flowers have over 0.1% estrogenic isoflavones. Though low in genistein (16 ppms), there's close to 460 ppms daidzein, 390 ppms formononetin, and 340 ppms biochanin. These have been linked, at least epidemiologically, with improved odds against breast and prostate cancers, and there are strong studies suggesting why they are helpful in this regard. But a Buchbauer et al. new paper adds limonene, a major anticancer answer, to this anticancer potpourri, along with quantitative data on several other minor actors, like benzaldehyde, coumarin and maltol. 

But now, more than a decade since it was published, science is discovering some mechanisms. What better place for news than a newsletter, like Science News (May 12, 1990). Science News reporter Kathy Fackelmann reports that Dr. Stephen Barnes and his colleagues discovered a compound in soybean that resembles the anticancer drug tamoxifen. They suggest that a tamoxifen look-alike "may block cancer at an early stage, presumably when the estrogen receptors still Function." Attributing results to genistein, a weakly estrogenic compound found in red clover as well as   soybean and other legumes, Barnes speculated that genistein may discourage tumor growth by blocking off estrogen receptors. “Its value as a cancer-preventive might depend on lifelong use”, the researchers suggested. Breast cancer may be initiated when there is genetic damage to normal breast cells at age 15-25. The immune system copes with most of the damaged cells, but a few damaged cells might survive. "By blocking a wayward cell's growth at this preclinical stage, genistein might give the immune system a better shot at destroying the cells."  It is rewarding to read such speculation in Science News. Ten years ago the Quack Busters suggested that anyone talking about regulating the immune system was a quack. Now as the last decade of the millenium is drawing to a close, we find scientists talking about isoflavones like genistein regulating the immune system and perhaps preventing the spread of breast cancer.

Until there are controlled clinical trials on humans, using orally administered clover teas, we will not have tested the long established folklore. Until there are long-term epidemiological studies on humans ingesting standardized extracts of red clover, we won't know that red clover can or cannot prevent cancer. The price tag for proving a new drug safe and efficacious has risen again. According to the Chemical Marketing Reporter (1990), it cost $231 million back then to prove a new drug safe and efficacious. Recently the figure has risen to $500 million. What drug company would want to invest $500 million in proving that red clover flowers could cure or prevent cancer?

I'll continue to enjoy my red clover bouillon, but it is against the law for me or anyone else to prescribe clover for the prevention or cure of breast or prostate cancer. Red clover has not been proven safe and efficacious. Nor, however, has it been proved dangerous and/or inefficacious. There's little economic incentive to prove clover safe and efficacious. Genetically targeted for colon cancer, I occasionally indulge my flights into folk fantasy, and graze on clover flowers, sans honey bee, or make a clover tea.

SOYBEAN (Glycine max):I am not yet sure how many beans, if any, would compete with soybeans for genistein or total estrogenic isoflavones or total antiangiogenic and/or estrogenic isoflavones, but I may be dying to know.  Especially if I had melanoma, like two other guys (25% of the male professionals) in my lab did. One's a survivor. One's not. The Graedons mention soybean as one good source of estrogens (in the broad sense). Messina and Barnes (1991) tell us that one cup of soybeans (usually figures to 200 g) provides about 300 mg iso-flavones. Postmenopausal women consuming 200 mg isoflavones demonstrated signs of estrogenic activity, compared to controls. Soy-eaters had more superficial cells which line the vagina, which can offset vaginal drying and irritation so common in postmenopausal women. (Messina and Barnes, 1991, as paraphrased by Werbach and Murray, 1994) A copyrighted (1995) Publication from the Consumer Affairs Department, Giant of Maryland Inc., overstates the case: "Genistein is an isoflavone unique to soy and has a chemical structure similar to the female hormone estrogen. Recent evidence links genistein to reduced risk of breast cancer and reduced symptoms of menopause." 

Let me now predict that soy scientists will cease saying that soy is the unique source of genistein, as some have claimed for the last 5 years. I predict that in the face of new data, soy scientists will change their tune, appropriately, and say that soy is richer than some legumes in total daidzein and genistein. 

Yin and Yang

The pop literature would have you believe that wild yam contains progesterone, and that sarsaparilla, contains testosterone. Not true. But I find it very romantic to find them both wrapped around each other along the Patuxent River. So romantic that I have renamed my phenology valley, (the ginseng producing valley on the back cover of my Herbalbum CD) Yin Yang Yuan, meaning Female-Male Garden. And I have both the yin Dioscorea  and the yang Smilax growing there, sometimes intimately entwined around each other, almost reminiscent of strands of DNA. Both Dioscorea and Smilax contain diosgenin, which chemists can convert into any of the hormones, DHEA, estrogen, progesterone, or testosterone. Both also contain sitosterol which is also very weakly regarded as phytohormonal.

Folklore developed the belief that wild yam is more useful for females (yin), and sarsaparilla is more useful for males (yang). In Moerman's excellent and authoritative book, Medicinal Plants of Native America (1986), only one use is cited for Dioscorea villosa: for the relief of pain during childbirth. The macho "Carrion Flower" (Smilax) is used for afterbirth, backache, body odor, boils, constipation, cramps, dysmenorrhea, gastrosis, hoarseness, nephrosis, pain, and pulmonosis.

DHEA and DHSEA

Steven Dentali, PhD, (1996) is quite adamant about DHEA. "Natural DHEA and... progesterone are not found in wild yam. Furthermore there is no reliable evidence... that our bodies make DHEA, progesterone or any other hormone from plant material, although there is plenty to show it doesn't. Some species of wild yam (Dioscorea) do contain the precursor diosgenin used in industrial hormonal manufacturing. This is a steroidal derivative with a spiroketal side chain which is removed in industrial hormonal manufacture."

Dr. Alan R. Gaby, MD, states that DHEA does appear to be effective for many   different conditions, including auto-immune diseases, depression, fatigue, menopausal symptoms and osteoporosis. And "perhaps most exciting, DHEA seems to reverse manifestations of aging in some patients." (Gaby, 1996) 

Unfairly and skillfully taking a quote out of context, I can accurately quote JAMA (Skolnick, 1996) as saying that DHEA "can help burn fat, build muscle mass, boost libido, strengthen the immune system, prevent heart disease, cancer and non-insulin dependent diabetes, retard memory loss, help in the treatment of Lupus, and prevent or slow the progression of Alzheimer's and Parkinson's diseases." But I clean my slate by quoting from the following paragraph "not one of these benefits has yet been demonstrated in a large randomized placebo-controlled clinical trial. Higher serum levels of the hormone may be associated with increased risk for ovarian and perhaps prostate or other types of cancer."  Arthur Schwartz, Professor of Microbiology at Temple University, who has studied the metabolic effects of DHEA since the 1970s, is quoted by Skolnick (1996)as saying: "There's no evidence that this hormone is found in any food. Patients... are not going to boost their DHEA levels with Mexican yam (Dioscorea mexicana) or wild yam (Dioscorea villosa)." So the wild yam creams boasting of natural DHEA are probably guilty of false advertising. (JAD)

The FDA says this about DHEA "this substance isn't an approved drug for any indication." The FDA in 1985 responded to the first wave of Fountain of Youth fever over DHEA by prohibiting OTC sales. But that ban ended with DSHEA in 1994. "The law shifted the burden onto the FDA to prove that a nutritional supplement is harmful before the agency could regulate its sale. As a result, many powerful and potentially dangerous drugs can now be marketed as nutritional supplements without proof of safety or efficacy." (Skolnick, 1996)

I predict that large doses of any one hormone, out of their natural contexts and ratios will have serious side effects, sooner or later. That's why I prefer food farmacy and herbal approaches to silver bullet hormones.