While there is still some level of caution and concern regarding the use of estrogen therapy for menopause, low-dose pills, patches, and creams for menopausal discomfort available today are significantly safer than those prescribed just a few decades ago. As is often the case with medical advancement, the scientific development of these treatments did not proceed in a straight line. In fact, early precursors to modern hormonal replacement therapy more resembled something produced in Frankenstein's lab rather than the sanitized medical environment we envision today.
HRT found its beginnings in the 1800s in Germany with a highly experimental approach. Ovarian tissue taken from cows was directly injected into German women in an attempt to assuage vasomotor symptoms. This method did find some success, particularly in reversing symptoms of sexual dysfunction. By 1890, Merck & Company laid the groundwork for what was to become modern HRT.
By 1933, a product named Emmenin became the first to be mass marketed and produced for the alleviation of menopausal symptoms. Like most first attempts, it was not cost-effective. However, this advancement marked a medical shift toward "replacing" estrogen production lost during menopause. Shortly thereafter, a less expensive alternative to Emmenin known as Premarin was developed. Named after the pregnant mare urine from which the drug was derived, Premarin is still prescribed today. This breakthrough approach also precipitated the discovery of the synthetic estrogen diethylstilbestrol, DES, in 1938 and approved by the FDA in 1941.
Despite this progress, it was not until the cultural revolution of the 1960s that hormone replacement therapy went mainstream. These drugs afforded women an extension of youth and vitality while bringing to the foreground issues of female bodily autonomy. This confluence of cultural forces made HRT very popular until the 1970s, when HRT prescriptions saw a sharp decline after new studies indicated up to a 14x increased risk of endometrial cancers. However, with the inclusion of progestin in estrogen medications to prevent this outcome, hormone replacement therapy again boomed through the 1980s and early 1990s until a landmark 2002 study by the Women's Health Initiative (WHI). An in-depth analysis of 160,000 menopausal women found that HRT significantly increased risk for breast cancer, heart disease, stroke, blood clots, and urinary incontinence. Following the study's publication, estrogen therapy use declined by 45% and estrogen/progestin therapy use declined by 22%, rendering them into a last-resort, short-term treatment as they remain today.
At the same time, the effectiveness of HRT drugs gave a glimpse into what life could be like for menopausal women. The allure of symptom relief gave rise to safer, low-dose HRT medications to elicit the biological benefits without exposing patients to high doses of exogenous hormones.
