The terms menopausal hormone therapy, estrogen therapy, hormone replacement therapy, and bioidentical hormones can be perplexing to one’s understanding. However, they aimed for the same outcome, which is managing symptoms associated with menopause and other hormonal disorders. From the 19th century until today, these terms have brought deep questioning around us and are still debated in the scientific and medical world through ongoing research. This article is about the history of hormone therapy (HT). It highlights valuable information on the root of HT, its evolution, and its present use.
How did Hormone Therapy (HT) emerge?
Hormone therapy (HT) has been around since the late 19th century. It started following two studies led in Germany that were published in March and April 1886, during which women who experienced menopausal symptoms were given bovine ovarian tissue. As a result, those women underwent a sudden drop in sexual dysfunction. In May 1896, A third study from Austria showed that dried ovarian tissue from reproductive-age cows improved the physiological menopausal symptoms in four out of seven women participants. Shortly in June 1896, another study reported that the use of dried bovine successfully reduced the symptoms of sexual dysfunction. During the same time, the Father of Endocrinology, Dr. Charles Edward Brown-Séquard, injected an extract of guinea pig and dog testicles in a self-experiment in 1889 and claimed that he had rejuvenated himself through the injection. Dr. Brown-Séquard advised that these extracts might be also beneficial to women. Following these studies came the production of Ovariin, a menopausal symptoms treatment that is made from powdered cow ovaries by Merck & Company in the 1890s.
How did Hormone Therapy (HT) transform during the 20th century?
Estrogen and the role of the hypothalamic-pituitary-adrenal (HPA) axis in guinea pigs were first described by Stockard and Papanicolaou in 1917. Following his interest in the human reproductive system, George Papanicolaou was able to differentiate between normal and malignant cervical cells from cultured swabs. As a result, came the Papanicolaou test in 1943 which tests for the detection of cervical cancer. Other entities such as Long and Evans described the estrous cycle in rats and published their discovery on the tissue changes during the menstrual cycle in 1922. Allen and Doisy studied some actions of estrogen in animal models. This latest finding formed the seed for additional research in hormones and helped identify estrogen’s presence in multiple determinants such as mammalian tissues, excreta, and plants.
Emmenin was the first form of bio-identical hormone therapy produced in 1933 in the United States by Dr. James Collip at Ayerst with the collaboration of the Canadian pharmaceutical company, McKenna & Harrison, Ltd. It was made of the urine of pregnant women. Emmenin was discontinued during the great depression. Then in 1938, Diethylstilbestrol (DES) a synthetic form of female estrogen was invented. It granted FDA’s approval 3 years later. DES was suggested as a solution for improving bone density following an Albright et al study that concluded low ovarian hormone can cause loss of bone. DES was used by a lot of women until it was banned in 1975 after several complaints from users on the risks associated with it. women had complained of cervical cancer, a rare vaginal tumor in girls exposed to the medication in utero, and other health complications during the time of use of the medication.
In 1942, the year following the approval of DES, Premarin (also called estrogen therapy) made its apparition. Premarin is a synthetic estrogen derived from the estrogen of pregnant mare urine. It was approved by the FDA and made available that same year for use. It was advertised as a replacement for a woman’s estrogen. It was widely used by women. Estrogen therapy gained popularity following several publications and books that suggested its use. The famous book of Dr. Robert Wilson, Feminine Forever amplified the use of estrogen therapy for menopausal symptoms reduction. By 1975, estrogen was the fifth most prescribed drug in the United States.
When did controversy arise and change the extensive use of HT?
In the 1970s, studies started to show a correlation between the use of estrogen replacement therapy and the risk of endometrial or uterine cancer. Following a report of a dramatic increased risk of endometrial cancer, the FDA called for a warning on all estrogen products that specified the risk for blood clots and cancer. Consequently, estrogen therapy use abruptly decreased. During that time, estrogen was given alone without progesterone. To correct this problem, doctors introduced progestin (a synthetic form of progesterone) to be taken intermittently with estrogen. However, instead of creating a great hormonal balance, women experienced bleeding like they used to in their menstrual cycle.
How did Hormone Replacement Therapy (HRT) gain traction?
Additional studies led in the 1980’s, gave a positive boost to Hormone Replacement Therapy (HRT) by suggesting that women who used HRT were at lower risk of developing coronary artery disease (CAD), heart attack, and osteoporosis (loss of bone strength and density. HRT gained popularity with the introduction of Prempo (a combination of estrogen and progestin pill) in 1996. Prempo is also known as conjugated equine estrogen. It gained its approval from the FDA and was quickly used by millions of women. Despite the propaganda on the great effects of HRT, some studies and additional data from the Breast Cancer Detection Demonstration project published in the Journal of the American Medical Association enumerated that HRT increased the risk of breast, liver, and colon cancer in users.
How did the Women’s Health Initiative (WHI) emerge?
Following all the turmoil on HRT and its consequences. The National Institute of Health (NIH) decided to lead a massive study that gave birth to the Women’s Health Initiative (WHI) in 1993. This study was led by cardiologists to determine the effects of HRT as the first prevention for CAD; and was set up to measure the rates of CAD, breast cancer, strokes, a second heart attack, deep vein thrombosis (clot in the veins), fractures due to osteoporosis, and colon cancer. It included more than twenty-six thousand women, aged fifty to seventy-nine who were divided into two main groups. A group of postmenopausal women who had never undergone a hysterectomy was randomized to receive Prempo or a placebo. A second group of women who had experienced a hysterectomy were randomized with Premarin or a placebo. However, after five years of follow up, the results of the study demonstrated an increase in breast cancer, stroke, pulmonary embolism, myocardial infarction risk, and a low incidence of fracture related to osteoporosis in women on Prempo. For the participants who received Premarin, data showed a slight increase in the number of strokes but no increased risk of CAD was found.
What does the WHI result imply to us?
The result of the study caused a significant decrease in the use of HT. Patients and providers voiced their concerns about the safety of these medications and the position of the FDA in their approval. Entities such as the American College of Obstetricians and Gynecologists (ACOG) and the North American Menopause Society known today as the Menopause Society concluded that HT should be used for the shortest time possible to relieve menopausal symptoms.
Despite all the critiques on the WHI study, the latter serves as a guidebook to help direct our decision when considering the use of HT. Today HT is more personalized to the benefit of the users while balancing potential risks. The FDA recently removed the “black box” safety warnings on HT products for menopause. These warnings once claimed hormone therapy could raise the risk of cancer, stroke, and dementia. But new evidence shows those fears were largely overstated. Bioidentical hormones are on the rise and available on the market. Continuous studies are being conducted to minimize the risks, maximize the benefits, and refine treatment protocol.
The history of HT evidenced the powerful nature of medical science. From the late 19th century experiments until today, HT has notably evolved. Researchers continue to explore the subject to provide safe and effective treatment to those needing help balancing their hormones and managing their menopausal symptoms.
References
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