Plant-Derived Estrogens—Safer Than Premarin?

A drug company is trying to cash in on the public's desire to buy herbs or other products from plant sources and to avoid medications. Nothing wrong with that--if the product really is a plant. The newest estrogen product, Cenestin, is billed by its manufacturer, Duramed Pharmaceuticals, Inc., as the "only conjugated estrogens product with a mixture of nine estrogens synthesized from 100% soy and yam sources."

In the ad campaign, a fortyish woman sits on a large block of ice under the headline, "Made from plants! Isn't that cool?" Lest you miss the point, a large green leaf appears on one side of the ice block. Cenestin is competing with numerous other estrogen drugs, chief among them is Wyeth-Ayerst's Premarin, which is derived from the urine of pregnant horses. Understandably, Duramed is distancing itself from Wyeth-Ayerst's product, describing Cenestin as from "plant sources not from animal waste."

Are plant-derived synthetic conjugated estrogens any safer than Premarin? "Chemically, it makes no difference whether you synthesize a molecule, such as estradiol [the most potent naturally occurring estrogen in mammals], in the laboratory or whether you obtain it from natural sources, such as a pregnant mare's urine or plants. A chemical is the same chemical irrespective of what its sources are," answered Samuel Epstein, MD, School of Public Health, University of Illinois at Chicago and author of The Politics of Cancer--Revisited. "The problem now is that the natural product market, which has its share of scams like other markets, has an element in it that is trying to persuade women that estradiol or progesterone from plant sources is safe unlike estradiol or progesterone synthesized in the laboratory, which is unsafe. And that really is just total nonsense."

Duramed made a commendable attempt several years ago to offer women a low-cost, generic alternative to Premarin, which is also a mixture of conjugated estrogens. Premarin has dominated the estrogen market for decades because it is the drug used by women in most of the studies that have suggested (see below, Estrogen and Heart Disease) low rates of heart disease and osteoporosis. Unfortunately, Duramed lost out to Wyeth-Ayerst's well-financed campaign to convince the Food & Drug Administration (FDA) and women's groups that the generic drug should not be approved because it lacked a type of estrogen found only in horse urine.

When Duramed failed to get FDA approval as a generic equivalent to Premarin, the company had to submit its product to the type of testing required of any new drug. Thus far, Cenestin has received approval only for the short-term treatment of hot flashes and night sweats that many women experience with menopause. For the Duramed-sponsored clinical trial, 120 menopausal women were randomly assigned to take either Cenestin or a placebo (dummy pill) for 12 weeks. According to Duramed, there was an 81% reduction in hot flashes in women taking Cenestin, compared to 58% for women taking the placebo. These results have not yet been published.

Unfortunately, Cenestin is not less expensive than Premarin. Most women in the trial needed two 0.625-mg tablets daily to control symptoms, which is twice the usual dosage of other estrogens. According to The Medical Letter (7/30/99), the cost of a month's supply of each estrogen product is the same--about $l4.60. The rate of adverse effects is expected to be the same as Premarin and other estrogen regimens, according to The Medical Letter, which identified headache, breast tenderness, edema, nausea and other gastrointestinal symptoms as the most common.

Cenestin's role in preventing bone loss has yet to be proven. A Duramed spokesman told HealthFacts that the company plans to conduct the required two-year clinical trial to win FDA approval of Cenestin as a means of preventing osteoporosis. Other estrogen preparations approved for this purpose are Premarin, Estratab, Menest, Estrace, Ogen, Ortho-Est, Climara, and Estraderm.

While these drugs can stop bone loss, no long-term, randomized clinical trials have evaluated estrogen's ability to reduce the rate of fracture. Furthermore, estrogen loss is merely one of many risk factors associated with hip fracture in old age. The majority of falls among the elderly do not result in fracture, but the 5% that do are associated with risk factors, such as impaired vision, poor muscle strength, and inappropriate prescription drugs (e.g., tranquilizers, barbiturates). Taking estrogen for osteoporosis prevention means prolonged, possibly lifelong, usage. Plant-derived synthetic estrogens may be perceived as the safer course than Premarin, but there is little information about long-term effects.

For Further Consideration:

Some women may want to avoid Premarin for ethical reasons. The maltreatment of pregnant mares used in the production of this drug is described by People for the Ethical Treatment of Animals. For information, contact them at 501 Front St., Norfolk, VA 23510, (757) 622-PETA, or visit the Web site (www.peta-online.org). According to PETA, Premarin is the only estrogen drug on the market made with animal-derived estrogen.