Bioidentical Hormone Replacement Therapy - History

History

Bioidentical hormones were first used for menopausal symptom relief in the 1930s, after Canadian researcher James Collip developed a method to extract an orally-active estrogen from the urine of pregnant women and marketed it as the active agent in a product called Emmenin. It was supplanted on the market when its manufacturer, Ayerst (later Wyeth Pharmaceuticals), began producing the more easily manufactured conjugated equine estrogens in 1941 under the brand name Premarin; by 1992, Premarin was the most widely prescribed drug in the United States.

In the 1970s, research and reports indicating risks from synthetic conjugated estrogens began to appear. Investigation determined that the addition of a progestogen to estrogen treatment reduced the risks. As early as 1980, the British Medical Journal (now BMJ) recommended oral bioidentical progesterone as an option when side effects from synthetic progestogens otherwise mandated discontinuing treatment. Starting in 1980, side effects caused by synthetic progestin use prompted more research into bioidentical progesterone. In May 1998 the FDA approved Prometrium, an oral bioidentical progesterone product produced by Solvay Pharmaceutical.

Physicians John R. Lee and Jonathan Wright were pioneers in the area of BHRT. Lee authored several popular books on BHRT and promoted custom-compounded BHRT, with the goal of achieving what he called a "natural hormone balance". He based this goal on the clinical testing of saliva to establish where "deficiencies" existed, though agencies such as the FDA and the American Congress of Obstetricians and Gynecologists state that blood and saliva testing is unreliable and biologically meaningless. Lee also believed that progesterone acted as a panacea and general health tonic for many health conditions; he based his claims on anecdotal data rather than peer-reviewed research, and there have been no clinical trials demonstrating this to be true. Wright also authored a popular book on BHRT; he promoted a triple-estrogen formula he called "Triest", which combined the three estrogens (of over 25 types) found in human females: estriol, estradiol and estrone. Previous bioidential formulas had used only estradiol. This triple formula was based on a single unpublished study whose conclusions did not take into account how estrogens are processed and excreted in the body—particularly how the liver processes oral estrogens, converting many of them to estrone. No followup was performed by Wright to replicate these observations. Wright may have been the first proponent of BHRT to use the term "bioidentical"—the word he coined to describe unpatentable, plant-derived molecules he believed were identical to human hormones. However, no structural crystallographic evidence has been used to support the idea that these molecules are actually identical to endogenous human hormones. When the Women's Health Initiative's reports on the unappreciated risks of equine estrogens were released, many prescribers of BHRT used Wright's assertions (and his terminology) to proclaim the superiority of bioidentical molecules despite a lack of scientifically supported evidence. Following the publication of a popular book written by actress Suzanne Somers in 2006, the term "bioidentical" gained more prominence in popular consciousness as a "poorly understood new adjective" regarding hormone replacement therapy.