The history of menopause hormone therapy is a pendulum that’s been swinging since the 1930s
We’ve divided the history of menopause hormone therapy into 4 eras.
The icons are clickable where there is specific research instrumental in the history of menopausal hormone therapy.
Era 1 (1934-1975) — The Beginnings of the Menopausal Hormone Therapy Market
1934 — 1st oral estrogen product made from human placentae
Emmenin, made by Ayerst, for estrogen "replacement" approved by the FDA. Made from human placentae and expensive to manufacture.
1966 — Feminine Forever is published
Written by Dr. Robert Wilson, GYN (later found to be a paid consultant the company making Premarin) Feminine Forever is a best seller. 3 key messages: 1- estrogen deficiency can be avoided with estrogen replacement; 2 - estrogen keeps women looking and feeling young; 3-estrogen prevents diseases associated with aging. Excerpts below. Click the icon for responses.
1975 — Premarin® the 5th most prescribed drug in the US
Premarin® prescriptions reach 28 million
Excerpts from Feminine Forever
“If a woman refused HRT, the consequences would be unthinkable”.
“All post-menopausal women are castrates.”
[With estrogen replacement] “breasts and genital organs will not shrivel. She will be much more pleasant to live with and will not become dull and unattractive.”
Era 2 (1975-2002) — Setback: increase in cancers (endometrial & breast) then recovery: Progestins added to protect endometrium (uterus) but not breast
1978 — progestins added protect the uterus
New studies showed that when a progestin was given with an estrogen, it protected the uterus from cancerous overgrowth. Progestins, used for contraception, began to be prescribed with estrogen products to protect against endometrial cancer. Progestins are a progesterone-like product but not the same as progesterone made by our bodies. Click on the icon to learn more about the differences.
1989 — a link between estrogen therapy and breast cancer
A study published by the New England Journal of Medicine, suggests a link between estrogen therapy and breast cancer. Interestingly, the very last line of this abstract raises the question of whether the progestins involved could play a role. Prescriptions come to a halt.
1991 — The Women’s Health Initiative (WHI) begins
Sponsored by the National Institutes of Health (NIH), the WHI (4 trials) is one of the largest U.S. prevention studies ever conducted, enrolling over 161,000 diverse postmenopausal women to determine strategies for preventing heart disease, breast and colorectal cancer, and osteoporosis.
1992 — Premarin® the #1 prescribed drug in the US.
Premarin® prescriptions reach 31.7 million.
1997 — The Collaborative Group on Hormonal Factors in Breast Cancer
The Collaborative Group on Hormonal Factors in Breast Cancer pooled individual data from 51 epidemiological studies (52,705 women with breast cancer, 108,411 without) covering roughly 90% of the world's evidence on MHT and breast cancer risk. Findings: 1. breast cancer risk rose with duration of MHT use, 2. the excess risk faded after stopping, 3. risk disappeared 5 years after stopping.
Era 3 (2002-2011) — A 2nd setback: The Women’s Health Initiative Trial Results Show an Increase in Breast Cancer and Heart Disease
2002 — 2008 Sales of Premarin®, Prempro®and Prempro® low dose plummet
Prempro®is an oral prescription hormone replacement medication that combines conjugated estrogens and medroxyprogesterone (MPA). Premarin® and MPA were the 2 drugs used in the WHI trial. This graph in the New York Times archive shows how sales dropped after the WHI findings.
2012 — providers become comfortable prescribing menopausal hormone therapy “used for the shortest amount of time”
Following additional studies, the pendulum begins to swing back and many providers become comfortable with prescribing menopausal hormone therapy to women who are recently menopausal with symptoms with a recommendation for short-term use. The Menopause Society (formerly NAMS) issues a statement saying for symptom management and for high-risk osteoporosis, estrogen therapy can be started at menopause and used for the shortest amount of time. The statement is not in favor of combined estrogen and progesterone therapy for longer than 3-5 years as that showed an increase in breast cancer.
2015 — 33% of hormone products used are compounded
A survey conducted by The Menopause Society finds that of 3,700 US women aged 40 to 84 years, about a third of those who use menopausal hormone therapy (MHT) are using compounded products.
Era 4 (2017-present)— The Pendulum is Still Swinging
2017 December — update on breast cancer risk with MHT
The New England Journal of Medicine publishes an article about contemporary hormonal contraception and the risk of breast cancer finding that "the risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer duration of use; however, absolute increases in risk were small."
2017 December — USTSF estrogen therapy not reccomended
US Preventive Services Task Force releases a Recommendation Statement on Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women. In it, they don't recommend estrogen therapy for the prevention of chronic conditions.
2020 July – NASEM committee report on clinical utility of compounded hormone therapy issued
The committee concluded there is insufficient evidence to support the clinical utility of cBHT. Based on their
examination of the evidence, to address public health concerns, the committee recommends restricted use of
cBHT, assessments of their difficulty to compound, and additional education, oversight, and research.
examination of the evidence, to address public health concerns, the committee recommends restricted use of
cBHT, assessments of their difficulty to compound, and additional education, oversight, and research.
2022 — The Menopause Society issues new guidelines: younger than 60, within 10 years of menopause
"For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome VMS and prevention of bone loss."
2025 October — “The Swinging Pendulum of Menopausal Hormone Therapy” in JAMA
Rebecca Thurston, PhD and prolific midlife women's health researcher publishes a piece in JAMA titled The Swinging Pendulum of Menopausal Hormone Therapy, It begins, "Few medications have captured the imagination—and provoked such ire—as menopausal hormone therapy (MHT)."
