Women's Health Update: Wild Yam, Natural Progesterone, Unraveling the Confusion

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The use of the term "natural" progesterone is what really seduced us down the path of misunderstanding. Along with misleading labels on cereal boxes, soda drinks, and sweetened foods the term "natural" has once again created great confusion in the minds of the consumer. This time though, the confusion pervades the alternative medicine camp from within. Practitioners, natural products vendors, patients, over-the-counter consumers, educators, have all contributed to this momentum of delusion, both knowingly at times, and unknowingly.

History of Progesterone

The history of progesterone has its roots in the chemical history of the Pill. The isolation of progesterone first occurred in 1933 by Corner and Allen with the help of the research laboratory at Eastman Kodak Company. They used high-vacuum distillation of the oils extracted from corpora lutea to isolate the hormone in a crystalline form, which they named "Progestin."( 1) In 1934, German researchers converted the dihydroxy compound pregnandiol to progesterone and succeeded in synthesizing progesterone from stigmasterol.( 2) At that time, the early production of progesterone required one ton of cholesterol, obtained from the brains and spinal cords of cattle and the grease from sheep's wool, to obtain 20 pounds of starting material from which commercial quantities of progesterone could be produced. Progesterone, when available, was quoted at $1,000 per gram.

The door to the development of the Pill was opened by Russell E. Marker who first determined the configuration of the sarsapogenin side chain with some sarsaparilla obtained from Mexico. Meanwhile, the Japanese had isolated a product called diosgenin from Dioscorea Tokoro, which Marker felt was even more suitable for hormone production than sarsapogenin. Marker utilized a unique chemical process whereby he was able to remove the side chain and derive progesterone from diosgenin. This changed progesterone from an expensive rarity to the cheapest of all steroid hormones. A subsequent discovery modified the progesterone molecule to make it orally effective. Marker went on a search for plants that stored diosgenin, which then led him to Mexico. The story warrants a Hollywood movie - full of intrigue, deception, scandal, corporate envy and trickery, bribery, even violent harassment and murder.

Marker's first Mexican source of diosgenin was Dioscorea macrostachya or cabeza de negro. He switched to Dioscorea barbasco which was more difficult to collect but yielded a much higher amount of diosgenin, about 5 times the concentration. He ended up deciding on cabeza de negro because it was considerably easier to collect in the wild.

After many disappointments in setting up financial backing and securing stable business manufacturing companies, Marker established his own Botanica-Mex SA because of continued harassment of the workers at Botanica-Mex, production of progesterone and dehydroepiandrosterone (DHEA) was discontinued in March of 1946. The equipment and the unprocessed roots were sold to Gedeon Richter SA, which started production under the name Hormo-Synth SA, later changed to Diosynth SA, and eventually sold to Organon of Holland, which is using it at the present time under the name of Quimica Esteroides SA.

In 1951, a process using microbes enabled Upjohn to produce and patent cortisone from saponins. As a result, the USDA financed a survey of over 6,000 plants. The most productive genera were Dioscorea, Yucca, Trillium, Smilax and Agave.

In 1952, Frank Colton, a chemist at Searle independently synthesized a closely related 19-nor compound, norethynodrel, which was in fact the first orally active progestational agent to receive a US patent issued in 1955.

Another significant historical event in the history of progesterone was the research and writings of Dr. Katherine Dalton. Her work on PMS and treatment with natural progesterone created a new wave of interest in progesterone as well as a milestone in women's health care in recognizing premenstrual syndrome as an identifiable and treatable clinical condition. Her research and clinical findings, although disputed by many, set the stage for the modern day use of natural progesterone in alternative medicine venues. Modern names such as Dr. John Lee and Jerilynn Prior, MD continue to stretch the conventional thinking on the role of progesterone as a bonetrophic hormone.

On January 24, 1996, Columbia Laboratories, Inc. announced an investment by Wyeth-Ayerst Laboratories of $1.5 million in addition to the previous $9.5 million investment. This was in response to the French regulatory authorities' announcement of natural progesterone's approval for use in in vitro fertilization procedures. Crinone, a sustained release, vaginally-delivered, natural progesterone product will be marketed by Wyeth-Ayerst, which has worldwide marketing rights to the product through a licensing and supply agreement with Columbia Laboratories. Other clinical indications have been approved for use in the UK and Finland; including the prevention of hyperplasia and endometrial cancer, for use in vitro fertilization procedures, to help reduce the symptoms of Premenstrual Syndrome (PMS), for menstrual irregularities, dysmenorrhea, dysfunctional uterine bleeding, and for infertility due to inadequate progesterone production. Crinone will have a bioadhesive delivery system whi ch enables the natural progesterone to achieve a "first uterine pass effect." Progesterone is preferentially delivered to the uterus and high systemic concentrations are avoided.

Another version of that product called Utrogestan, is produced by the French pharmaceutical house Besins-Iscovesco. It is widely used for Hormone Replacement Therapy (HRT) in Mexico and Europe. Schering-Plough Corporation licensed micronized progesterone from LaSalle Laboratories, an affiliate of the French company, and supplied it in 200mg capsules for the PEPI trial. Schering plans to market that drug as Prometrium in the US, but doctors won't be able to prescribe it for HRT until it is approved by the FDA for treating secondary amenorrhea as many of the progestins were originally.

Currently, micronized progesterone can be purchased as a raw material; because it's considered a natural substance, it doesn't require FDA approval. Compounding pharmacies offer progesterone pills, tablets, gels, creams, and suppositories by prescription.

Sources for the raw materials include either Dioscorea barbasco or soybeans. The diosgenin, which I will discuss shortly, can be found in significant amounts, in either plant source.

Dioscorea villosa (Wild Yam)

The 600 plus species of Dioscorea are found mostly in the tropics and subtropics throughout the world. Over 50 yam species contain bitter, and often toxic saponins which lend them as inedible. Some of the yams are fit for eating. In Sturtevant's Edible Plants of the World, over 25 edible species are listed, although many other known edible species exist in the Pacific Islands. The wild yam eaten in America isn't really even a yam. It is a type of sweet potato, Ipomoea batatas. It is interesting to note that the yams that we eat contain high amounts of beta carotene. Beta carotene is needed by the corpus luteum in its post-ovulatory production of progesterone.

In traditional herbal medicine in the US, wild yam usually refers to Dioscorea villosa, found in woods from New England and Minnesota, south to Virginia and Texas. The rhizome of Dioscorea villosa was a favorite herb among Eclectic physicians in the mid to late 19th century. It was known as wild yam and colic root. About the year 1850, botanic druggists noticed the admixture by root-diggers of the rhizone and for a considerable time rejected it as an adulteration. The diggers insisted, however, that both "roots" were obtained from vines almost identical in appearance and finally purchasers were compelled to accept them, more especially as the true rhizomes became very scarce. Since then, the two rhizomes were sold indiscriminately.( 3)

The therapeutic value of this plant appears to reside in an acrid resin. The so-called dioscorein is not a definite principle of the rhizome, but is simply a dried solid extract. A substance closely resembling saponin is in large amounts in the rhizome. Wild yam also contains an abundance of starch.( 4)

Traditional therapeutic uses of wild yam include abdominal colic, spasmodic hiccough, painful vomiting, gastritis, irritable bowel symptoms, dysmenorrhea, indigestion, chronic hepatic congestion, flatulence, urinary tract spasms, and rheumatism.

Natural Progesterone vs. Wild Yam

Progesterone is termed "natural" progesterone, regardless of its source. "Natural" progesterone has the same molecular structure as the progesterone molecule found in animals, including humans. This is distinct from progestins not found in nature. Many people mistakenly believe that many plants contain hormones. Only a few animal hormones have been discovered in plants. Estrone, one of six identified types of estrogen, occurs in a few plants, palm-kernel oil, moghat roots and date palm pollen, for example. The amount of hormones in these plants is minimal.

Wild yams do not contain progesterone. Some yams do contain a sapogenin called diosgenin. Dioscorea barbasco (Mexican wild yam) contains considerably more diosgenin than Dioscorea villosa. Diosgenin is extracted from the Mexican wild yam in the laboratory. The diosgenin is then converted to pregnenalone and then progesterone, utilizing various reagents and enzymes. This all occurs in the laboratory. The human body cannot convert diosgenin to progesterone. This is why I prefer to use the term Quasi-natural to make a distinction between what is found in nature as is and what occurs in the laboratory. Medicine occurs on a continuum, from the most natural substance like a plant in the wild to a synthetic substance created in the laboratory. Many medicines are derived or created from somewhere in between the two. I would promote four categories of medicines: 1) Natural, such as pure plants; 2) Quasi-natural medicines, such as those synthesized from plant or animal material; 3) Friend ly pharmaceuticals, such as those associated with minimal side effects and toxicity; 4) Un-friendly pharmaceuticals, such as those associated with significant side effects, toxicity, and expense.

Many wild yam products on the market are being marketed as natural progesterone but in fact contain no progesterone. Other products come with false information such as "wild yam has a very high concentration of a substance called diosgenin which converts in the body to natural progesterone." Other companies promote the misleading concept of "natural progesterone from wild yam."

According to a document researched and produced by Aeron Life Cycles Laboratories (1933 Davis St., Ste. 310, San Leandro CA 94577) 11 of the 27 commercial products they researched had more than 400mg of natural progesterone per 1 oz. of cream; 5 of the 27 products had between 2 and 15mg of progesterone per 1 oz. of cream and 11 more products had less than 2mg or no progesterone per 1 oz. of cream.

Some companies have products saying Wild Yam 3% cream. These products would be in the less than 2mg or no progesterone category. Products stating Wild Yam 7% would be in the 2-15 mg progesterone per 1 oz. Most of the products that contain more than 400 mg of progesterone per 1 oz. of cream are not available over the counter and are prescribed by licensed health care practitioners. This policy is inconsistent, and in my opinion, unfortunate. These higher doses of progesterone are best utilized under the care of a practitioner due to their ability to create breakthrough progesterone bleeding, tender breasts, sleepiness, bloating, as well as the potential for self-treating when a clinical condition needs accurate diagnosis. Some companies that do have these more potent products available for self-treating do have excellent medical support services and experienced staff that serve as resources to consumers.

Clinical Applications of Natural Progesterone

Typically, the most potent products are prescribed at 1/2 tsp. applied topically twice per day. At this dosage, the patient is getting from 60mg to 70mg per day of natural progesterone. Oral micronized natural progesterone is taken usually anywhere from 100mg to 400mg per day depending on the clinical situation. The oral progesterone is the only form of natural progesterone that has been studied in clinical trials to test the effect on blood lipids and on protecting the uterus from estrogen. In the Postmenopausal Estrogen/Progestin Intervention Trial (PEPI) estrogen taken with natural progesterone and estrogen taken alone produced the most favorable increases in HDL levels. The two other estrogen/progestin combinations tested also produced significantly greater increases in HDL-cholesterol levels than a placebo. The PEPI Trial also tested three estrogen/progestin combinations and endometrial hyperplasia. Estrogen taken with oral micronized progesterone showed no endometrial hype rplasia. Nor did estrogen taken with two different doses of medroxyprogesterone acetate. Estrogen taken alone, called unopposed estrogen, caused a high rate of endometrial hyperplasia.( 5)

Topical natural progesterone products have not been well studied although they are commonly used to treat a variety of conditions. These include premenstrual syndrome, anovulatory cycles, dysfunctional uterine bleeding, endometriosis, uterine fibroids, heavy menstrual bleeding, and menopausal symptoms. One small study by Dr. John Lee presents 3% progesterone cream as part of a treatment protocol. He asserts that his study showed a reduction in fracture rate, an increase in bone density, and the safety of using natural progesterone. Dr. Jerilynn Prior proposes that natural progesterone is a bone-building hormone: Progesterone binds to receptors on osteoblasts,( 7) increases the rate of bone formation and remodelling,( 8) and slows bone loss in postmenopausal women.( 9-11) This point of view is controversial yet optimistic in the prevention of osteoporosis.

Wild yam is used in tincture form, topical creams and gels, capsules, teas, tablets, and sublingual. Its therapeutic value was stated earlier but is currently in common use for the treatment of PMS, uterine cramps, abdominal colic, and menstrual irregularity.

The next time you are faced with the selection of a wild yam product or a "natural" progesterone product, carefully read the marketing or educational material for accuracy. Understand if you are using a wild yam product or a progesterone product. Know your clinical goals and therapeutic end point. Know which products get you there safely and effectively. Know who's giving you the straight scoop based on knowledge and not hype. Know who's practicing medicine responsibly based on facts, knowledge, logic, and clinical experience.
References

(1.) Perone N, The Progestins. Pharmacology of the Contraceptive Steroids. Goldzieher, New York 1994.

(2.) Perone N, The Progestins. Pharmacology of the Contraceptive Steroids. Goldzieher, New York 1994.

(3.) Felter-Lloyd. Dioscorea villosa. King's American Dispensatory. Pg. 659. Ed. Eclectic Institute, Portland, Oregon.

(4.) Felter-Lloyd. Dioscorea villosa. King's American Dispensatory. Pg. 660. Ed. Eclectic Institute. Portland, Oregon.

(5.) The Writing Group. Effects of Estrogen or Estrogen/Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women. JAMA. 1995; 273:199-208.

(6.) Lee J. Osteoporosis Reversal, The Role of Progesterone. International Clinical Nutrition Review, July, 1990 Vol. 10 No. 3: 384-391.

(7.) Feldman DL, Dziak R, Koehler R, Stem P: Cytoplasmic glucocorticoid ginding proteins in bone cells. Endocrinology 1975;96:29-36.

(8.) Snow GR, Anderson C: The effect of 17 beta estradiol and progestagen on trabecular bone remodelling in oophorectomized dogs. Calc Tiss Inc. 1986; 39:198-205.

(9.) Abdalla HI, Hart DM, Lindsay R, Leggate I, Hooke A: Prevention of bone mineral loss in postmenopausal women by norethisterone. Obstet Gynecol 1985; 66:789-92.

(10.) Lindsay R, Hart DM, Purdee D, et al: Comparative effective of estrogen and a progestogen on bone loss in postmenopausal women. Clin Sci Mol Med 1978; 54:93-95.

(11.) Dequeker J, DeMuylder E: Longterm Progestogen treatment and bone remodelling in premenopausal women: a longitudinal study. Maturitas 1982; 4:309-13.

Townsend Letter for Doctors & Patients.

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By Tori Hudson

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