Menopausal hormone therapy (MHT) has proven an effective treatment for the amelioration of symptoms of menopause. The idea that a substance was the missing factor in a woman’s body after menopause dates to the 1800’s when cow ovarian tissue was injected into German women in a successful attempt to reverse the sexual symptoms of menopause. The early 1900’s saw the rise of commercialized menopause “treatments” that ranged in substance, and even theoretical, efficacy. The role of estrogen was first accurately described in Guinea pigs in 1917 by Dr. Papanicolaou. (The inventor of the Pap smear scam)
The late 1800s and beginning of the 1900s saw the beginning of the Second Industrial Revolution, where advancements in manufacturing and globalization were rapidly changing. Two studies in Germany published in March and April 1886, women who were either ovariectomized or experiencing menopausal symptoms with injected ovarian tissue. F. Mainzer and R. Mond prescribed oral therapy of 5-20 g/day of bovine ovarian tissue. The patients experienced a dramatic reduction in sexual dysfunction. After switching to non-ovarian tissue, the treatment was ineffective. A third publication from Austria, in May 1896, showed that 0.2-0.8 g/day of dried ovarian tissue from reproductive age cows, resulted in symptomatic improvement in four of seven patients, six of whom were ovariectomized and one with physiological menopause. These studies were quickly followed by another by Mainzer, in June 1896, demonstrating that 1.0-7.5 g/day of dried bovine or porcine ovarian tissue was successful for reducing the symptoms of sexual dysfunction.[4]
Report: 9 out of 10 Drug Companies Spend More on Marketing than Research
Dr. Charles Edward Brown-Séquard, known as the “Father of Endocrinology,” experimented on himself with an extract of guinea pig and dog testicles in 1889. This injection resulted in his claim that he had “rejuvenated himself,” and suggested that these extracts may have the same effect on women. Ultimately, this was the seed for commercialization of sex hormone therapy. In the 1890s, Merck & Company produced Ovariin in both powder and pill form, a treatment for menopause made from powdered cow ovaries that successfully treated symptoms of menopause.[5]
The Dark Side of hormone prescription
Although during the Great Depression in the United States, the first MHT product, Emmenin, was commercially produced and sold in 1933 in the United States by James Collip at Ayerst. See picture 1. This was the first form of bio-identical hormone therapy and was derived from the urine of pregnant women. However, Emmenin was expensive to produce and was replaced in 1941 by Premarin, which was made from conjugated equine estrogens.[11] The name Premarin derives from the pregnant mare urine from which these estrogens were derived.[12] Premarin was marketed to orally “replace” a woman’s estrogen. Later, other routes of administration included an estrogen patch, produced by Searle in 1928, as well as oral ethinyl estradiol, produced by Schering in 1937.[13, 14] The synthetic estrogen, diethylstilbestrol (DES) was discovered in 1938, and was granted FDA approval in 1941. It was suggested that DES might stimulate bone growth.[14]
In 1993, the first large randomized control trial (RCT) for menopausal hormone therapy began. The Heart and Estrogen/Progestin Replacement Study (HERS) examined the effects of estrogen-progestogen therapy on postmenopausal women with CHD. No significant differences in the progression of CHD were observed in women taking conjugated equine estrogen (CEE) (0.625mg) and medroxyprogesterone acetate (MPG) (2.5mg), and the placebo group. However, after the first year of the study the incidence of cardiac events in women in the treatment group was higher than that in women on placebo. This was, however, found to be negligible over the next three years, when the two groups were compared. Overall, no benefit was found in women with CHD taking hormone therapy. A second large RCT, HERS II, followed the participants for another 2.7 years, in which no significant benefits for CHD risk were identified. As a result, HT was recommended against for secondary prevention of CHD.[1] Despite this conclusion, in 1996, the United States Preventive Services Task Force (USPSTF) advised that all postmenopausal women consider using preventative hormone therapy.[28]
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The relationship between the effect of estrogen therapy and breast cancer led to the Gap Hypothesis, which posited that there is very little or no increased risk for breast cancer if hormone therapy was started at least five years after menopause occurred. This was investigated and supported by the data from the prospective, observational Million Women study in Britain. [35] However, the authors found a significant increase in risk of breast cancer in women who had begun therapy less than five years before menopause, regardless of type or length of therapy, or weight of women. In a study by Coombs et al., the risk of breast cancer in women using hormone therapy increased from a baseline 6.1% to 6.3% with use of estrogen therapy and 6.7% with use of estrogen-progestogen use, although the risk returned to baseline rapidly when therapy was stopped. Length of time on therapy was also important, as breast cancer risk increased 2.75% if hormone therapy had been used for more than five years and 1.85% if used two to five years.[30]
Was mother-of-two Jane's sudden heart attack at just 50 despite being fit and healthy a sign that HRT isn't right for all women?
Conclusion
The history of our understanding of menopause and estrogen supplementation is an interesting story that highlights many pitfalls of new therapies and evolving understanding of mechanisms of disease. From exciting claims that estrogen could be “the fountain of youth”, help with osteoporosis and reduce heart disease in women, to concerns of thromboembolic disease, breast and endometrial cancer, it has been a highly debated topic in the last 50 years. While new research is emerging every day, oral estrogen use in post-menopausal women is currently limited to the short term treatment of vasomotor flushing, and topical estrogen for vaginal atrophy. Overall, the risks and benefits of female hormone therapy should be considered by clinicians and patients, and treatment decisions made on an individual basis.
