The Rise and Fall of Hormone Replacement Therapy

From the lecture series: The Skeptic's Guide to Health, Medicine, and the Media

By Roy Benaroch, M.D., Emory University

Hormone replacement therapy (HRT) burst onto the market as a miracle cure for all the unpleasant symptoms associated with menopause: depression, anxiety, and night sweats. Discover how HRT monopolized the pharmaceutical industry before it abruptly crashed in popularity.

Book with words hormone replacement therapy on a table
(Image: designer491/Shutterstock)

HRT: The Holy Grail for Menopausal Women?

In the last 20 years of the 20th century, from about 1980 until 2002, many women in the United States were treated with what’s known as “hormone replacement therapy” (HRT).

About 40 percent of all U.S. women were prescribed these medications during and after menopause. That’s why the top-selling medication in the United States during most of that time was Premarin, a combination of estrogens that replaced falling hormone levels in menopausal women.

This is a transcript from the video series The Skeptic’s Guide to Health, Medicine, and the Media. Watch it now, on Wondrium.

This medication effectively treated the short-term symptoms women were experiencing: physical things like hot flashes and night sweats, but also symptoms like trouble finding words, or so-called “brain fog,” anxiety, and depression symptoms.

The idea was that by replacing the hormones that fall during menopause would stop the symptoms. It was also thought that hormone replacement would help prevent some of the long-term issues that typically became part of women’s lives after menopause, including osteoporosis, stroke, and heart attacks.

Getting women onto HRT became the standard of care; the popular media was full of stories about how women felt better and stayed healthier on these medications.

Learn more about hormone replacement therapy

The Abrupt End of HRT’s Reign

What happened next is similar to what happened to Icarus when he flew too close to the sun. A huge study published in 2002 grabbed the media’s attention, and the headlines quickly changed to trumpet the “new” knowledge that hormone replacement therapy could cause cancer and other health problems.

Women stopped taking their medications and Premarin prescriptions dropped dramatically. Ironically, the new study’s conclusions weren’t completely unexpected, but they were widely misinterpreted in the media. The tides changed overnight.

In retrospect, it’s clear that HRT had been oversold, to begin with. There hadn’t ever been solid evidence for its long-term benefits.

But the dramatic fall of Premarin wasn’t entirely justified, either. Many women could have continued to benefit safely from treatment for some genuinely troublesome symptoms.

But the era of routine HRT had abruptly come to an end.

Did HRT Deserve the Bad Press?

What happened to Premarin is a fascinating story, from how it became entrenched as standard therapy to the role the media played in how the general public began to perceive menopause.

How did Premarin, which had been a rarely used medication, become a pharmaceutical sales powerhouse?

The scientific literature on HRT had been nearly devoid of good studies supporting its widespread use. Why wasn’t that reported in the media, and why didn’t doctors know this?

Learn more about how to better understand and evaluate the media description of prescription drugs

The History of Menopause

Medically, menopause marks the end of the functional life of a woman’s ovaries. The ovaries will no longer release eggs, fertility is no longer possible, and the monthly cycle of menses ends.

From the point of view of symptoms, it’s not the lack of eggs that are the problem—it’s the end of the ovaries’ other function as an endocrine organ. The ovaries, throughout a woman’s life after puberty, release what is called sex hormones, principally estrogens, and progesterone.

The actions of these hormones are complex and affect just about every other organ system in the body. It’s the fall of these hormones that cause the symptoms that accompany menopause.

Historically, menopause was often framed positively, as a time when women were finally allowed to rest. In 1869, in the book The Physical Life of Woman, George Napheys wrote about menopause as a sort of reward:

“The evening of her days approaches, and if she has observed the precepts of wisdom, she may look forward to a long and placid period of rest, blessed with health, honoured and honoured, yes, loved with a purer flame than any which she inspired in the bloom of youth and beauty.”

Mature Woman Experiencing Hot Flush From Menopause
At the onset of menopause, symptoms like hot flashes and sweating can make it very difficult to sleep. (Image: SpeedKingz/Shutterstock)

Long and placid period of rest, maybe, but women put up with very unpleasant symptoms to get there. Hot flashes and sweating can make it very difficult to sleep; additionally, menopause often involves mood swings, depression and anxiety, physical symptoms like head and body aches, sexual dysfunction and painful intercourse, thinning or excessive hair, and fatigue.

In the 1800s there were treatments available, primarily herbal products including cannabis and opium. By the end of the 19th century, it was known that animal ovary extracts could relieve at least some of the symptoms of menopause. A product called Ovariin made from dried cow ovaries was sold by Merck as a flavored powder.

The Birth of Premarin: Marketing Magic

In the 1920s, estrogen compounds had been isolated, and oral estrogens soon became available. In 1942, Ayerst Laboratories started marketing an oral estrogen product, Premarin, which was to become one of the best-selling medications in the world. Premarin’s story was both a marketing triumph and, some say, a medical tragedy.

Molecular model of Premarin
Molecular model of Premarin (Image: Glenn Kershner/Shutterstock)

Keep in mind that women had been experiencing menopause since the beginning of time, and though the symptoms were bothersome, most women probably never sought treatment. Menopause, unlike most of the things doctors treat, had never been an illness or a disease—it’s a part of the normal life cycle of half of the humans who have ever been born.

Marketing a drug to treat a non-disease had seldom been done before, but Ayerst was the first to achieve widespread success.

Premarin was initially sold at five times the price of competing products, and its first ad campaigns stressed that it was upscale—that is, to use the tired but very effective phrase, “new and improved.”

Initial ads showed glamorous women surrounded by happy families, having fun. These were direct-to-consumer ads, designed to raise awareness of the product and plant a seed among women—the idea that, “Hey, I can be like these women in the ad.”

Ayerst went a step further, and this is where the real magic began. Society and doctors hadn’t seen menopause as a disease or a treatable condition. That had to change. The drug manufacturer developed an educational program for physicians, concentrating on menopausal symptoms and, of course, therapy.

This effort was essentially a very successful prototype of a kind of hidden advertising that’s continued to be hugely successful. Teach the doctors about a “new” condition so they begin to diagnose it in their patients.

This has happened many times in the last decade, including highly successful campaigns to raise awareness of and prescriptions for things like erectile dysfunction (ED) and restless legs syndrome. Now, these are all real conditions—menopause, ED, and restless legs—that all cause real problems and deserve real treatment.

But it was only after the drugs to treat them became available that disease awareness ads started pummeling doctors and the general public. Plus, ads like these don’t necessarily look like advertisements.

Learn more: Selling Disease

Drug companies sponsor what are called educational symposia or conferences to focus on these diseases, and press releases, books, and media appearances drive magazine articles and headlines.

Once awareness of a health condition is pushed through multiple venues, there is a snowball effect. All of a sudden, something no one used to think about is on everyone’s mind, patients and doctors alike.

Consider the phrase, “Necessity is the mother of invention.” That means when you need something, you invent it. Disease marketing is exactly the opposite: The drug company has something invented already and they create the need for it.

We can’t deny that the symptoms of menopause and other “new” health conditions are very real and can be very troublesome.

But the goal of a media company is to sell stories, and the goal of a drug company is to sell drugs. When these interests work together, that leads to a lot of sales and some unintended consequences as well.

Common Questions About Hormone Replacement Therapy

Q: How do I know if I need Hormone Replacement Therapy (HRT)?

Some common signs indicating a need for Hormone Replacement Therapy are daytime fatigue, loss of muscle strength, and inability to sleep for both men and women in their later years. Women tend to also have vaginal dryness and thinning hair while men are often sluggish and have a lack of sexual desire.

Q: How long does it take to feel the effects of Hormone Replacement Therapy?

It typically takes a few weeks to discover the effects of Hormone Replacement Therapy and can take up to three months.

Q: Does Hormone Replacement Therapy make you gain weight?

In general, menopause will contribute to weight gain, but there is no evidence that Hormone Replacement Therapy causes weight gain.

Q: Are there any risks associated with Hormone Replacement Therapy?

Menopausal women who try Hormone Replacement Therapy may be at increased risk for heart attack, stroke, or possible blood clots. There is a risk for breast cancer as well that goes away after stopping.

This article was updated on May 5, 2020

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