The History of Menopausal Hormone Therapy

The Beginnings of the Menopasual Hormone Therapy Market

1934: First estrogen product called Emmenin, made by Ayerst, for estrogen “replacement” approved by the FDA. Made from human placentae and expensive to manufacture.

1941: Ayerst develops a new, cheaper version made from the urine of pregnant horse mares, called Premarin® = PREgnant MARe urINe. (Clever, huh?)

1943: Wyeth and Ayerst merge.

1966: Feminine Forever, a book by Dr. Robert Wilson, (later found to be a paid consultant to Wyeth) was published and became a best seller. It’s three (3) main messages were: 1.) menopause is caused by estrogen deficiency and can be avoided by estrogen replacement; 2.) estrogen would keep women looking and feeling young and 3.) estrogen would prevent many diseases associated with aging.

Some quotes from Feminine Forever that we can’t resist including: “If a woman refused HRT, the consequences would be unthinkable”. “All post-menopausal women are castrates.” [With estrogen replacement, a woman’s] “breasts and genital organs will not shrivel. She will be much more pleasant to live with and will not become dull and unattractive.” Scathing reviews by the medical community and women followed. For those that want to read more from the book. Caution: Reading more of it may cause an increase in blood pressure.

1975: Premarin prescriptions reach 28 million

Setback #1 Increase in Cancers (Endometrial & Breast)

1975: Two studies (1,2) published in the New England Journal of Medicine confirmed what doctors were seeing, that increases in endometrial cancer (remember estrogen causes growth) were caused by estrogen replacement.

1989: 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.

Solution: Progestins Invented to Protect the Uterus 

1978: New studies showed that when progesterone is added to estrogen, it protects the uterus (remember: progesterone matures cells and tempers estrogen’s growth). Progestins, a synthetic and more potent form of progesterone, (but not progesterone USP) were developed and prescribed with estrogen.

1992: Premarin prescriptions climb back to 31.7 million and become the most frequently prescribed drug in the US. Importantly, Premarin is used for menopause symptom management AND prevention of chronic disease.

1992: Women’s Health Initiative begins to study the preventive effects of estrogen therapy (HRT/HT) might have on chronic diseases of aging females: cardiovascular disease, osteoporosis, and breast cancer.

1997: Premarin sales exceed $1 billion.

2000: Premarin prescriptions reach 46 million –  the most frequently prescribed drug on the market.

2001: Premarin sales are $1.3 billion

Setback #2: WHI Shows Premarin Increases Breast Cancer and Heart Disease

2002: The Women’s Health Initiative (WHI) – which originally set out to demonstrate the preventive benefits of hormone therapy on certain chronic diseases – is stopped early because an INCREASE in these diseases is seen in preliminary results. For the specifics of this study, click here.

A huge pendulum swing then follows. Women across the nation abruptly stop their hormone therapy. Doctors stopped prescribing hormone therapy. Women struggle with symptoms and are left with few options.

Several additional studies are conducted and WHI data is re-examined to reveal major study flaws – most notably that a high % of study subjects had been menopausal for many years.

At this time, we also see an increase in the use and popularity of compounded bioidentical hormone therapy as women and their providers seek an alternative solution for symptom management. Compounded hormone therapy is a controversial topic on which many do not see eye to eye.

Follow on Studies Released – Pendulum Starts Swinging Back

2012: Following additional studies, the pendulum begins to swing back and many providers become comfortable with prescribing hormone therapy to women who are recently menopausal with symptoms with a recommendation for short-term use. North American Menopause Society (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. [Note – keep in mind that it was progestins used NOT progesterone in the WHI trial].

2015: A NAMS-conducted survey of 3,700 US women aged 40 to 84 years found that about a third of those who use hormone therapy (HT) at menopause are using compounded hormones.

The Recent Past: Pendulum Still Swinging

2017 July: North American Menopause Society (NAMS) issues a new statement reflecting a pendulum swing to a little HT is okay, early in menopause, when symptoms are bad, depending on a woman’s risk factors.

2017 December: 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.

2017 December: 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.”

2018 January: Dr. JoAnn Manson releases a statement in this short video saying she thought that the task force portion was too restrictive. [choose login without a password to view]