An excerpt from my new book Undoctored.
This one little tale about hormonal health of human females, pregnant horses, and drug patents paints a microcosm of the bigger healthcare picture. It is an example of how when money becomes the primary goal, health may not be served.
For years, physicians prescribed estrogen hormone replacement for women experiencing menopause, believing that drugs like Premarin, manufactured by harvesting estrogens from the urine of pregnant horses, prevented osteoporosis, improved cholesterol values, and reduced cardiovascular risk, since preliminary epidemiological studies, not real clinical studies of proper design, had suggested such benefits. Despite the lack of evidence, Wyeth-Ayerst (now part of Pfizer) spent many millions of dollars advertising Premarin and promoted its use to doctors, causing it to be the number-one most widely prescribed drug for years.
After several decades of being accepted as a routine prescription, regarded as no worse than aspirin for a headache, the whole thing fell apart in 2002 with the publication of higher-quality (randomized, controlled) studies, such as the 16,000-participant Women’s Health Initiative, demonstrating that horse estrogens increased risk for heart attack, stroke, blood clots, breast cancer, and endometrial cancer.7 Though still available, Premarin has fallen from its perch as the most widely prescribed medication.
There’s more to this story: Premarin is nonhuman, a mixture of various estrogens sourced from the urine of pregnant mares (horses), very different from their human counterparts. (No surprise: Pick a species—frog, chipmunk, horse—and female estrogens and other hormones are going to differ from that of humans. Menstrual cycles, periods of fertility, and birthing methods all vary among frogs, chipmunks, horses, and other species, so it should come as no shock that their hormones also differ.) While human females produce estrogens such as estradiol, estrone, and estriol, horses express equalin, equalinin, estradiene, and a number of other estrogens not found in any human. These horse estrogens differ in structure and effect from human estrogens. The effects of these nonhuman estrogens, when administered to humans, were not fully understood during Premarin’s heyday and remain incompletely understood even today.
Why administer such a hodgepodge of nonhuman, cross-species hormones with uncertain effects in the first place? And why chance the uncertainties of nonhuman estrogens when human estrogens—hormones identical to human estradiol, estrone, and estriol—are available?
Were there studies demonstrating that horse urine–sourced estrogens were superior to human estrogens?
There are no studies demonstrating superiority of horse estrogens over human estrogens. The reasons for resorting to this nonhuman source was simple: patent protection. Patents play a huge role in the pharmaceutical industry. If hundreds of millions of dollars are spent by a drug company to develop a potential drug, the company needs to make sure its intellectual property is protected and a competitor can’t just copy it and wipe out any hope of exclusivity. One of the unique estrogens in Premarin, delta 8,9-dehydroestrone sulfate—not naturally found in any human female—is patent-protected and played a big role in protecting this drug franchise. Delta 8,9-dehydroestrone sulfate was absent from generic versions manufactured by several competitors, and Wyeth argued that it was essential to the mix. The lack of delta 8,9-dehydroestrone sulfate was declared by the FDA to be grounds for nonapproval of generic “equivalents” for many years. Horse urine and the estrogens it contains were also plentiful (think about the phrase “pee like a racehorse”), making it cheaper to extract large quantities from horse urine than from comparatively pee-challenged pregnant female humans. Even today, with wide availability of human estrogens at low cost, the majority of doctors have no idea that there are alternatives to horse urine estrogens.
Nobody fights for entities that are not patentable. Natural human estrogens are available but nonpatentable, since they have been part of the informational public domain for many years. Therefore, no drug company wants to touch them unless some manipulation, such as a novel method of administration or a biochemical modification, is exploitable. While millions of women were exposed to the uncertainties of nonhuman hormones, human hormones were available but rarely prescribed. In addition to the disservice committed to all those women, all the money spent on research—over 3,000 studies in total—to validate the use of nonhuman hormones (but not directed toward better understanding the use of human hormones) created an informational void that persists even today. At the very least, the use of human hormones avoids all the uncertainties of administering nonhuman estrogens like equalinin and delta 8,9- dehydroestrone sulfate.
Trying to ride this wild bucking bronco of nonhuman horse estrogens highlights the misguided motivations of health care that lead to pursuit of patent protection and maximizing profit, even when safer, more logical, cheaper solutions are available.