Does Hormone Replacement Therapy Cause Cancer?

From a lecture series presented by The Great Courses

Does hormone replacement therapy (HRT) cause cancer? HRT was wildly popular in the second half of the 20th century. The therapy promised to treat menopausal symptoms and prevent osteoporosis and cardiovascular disease. But all this changed in 2002 when The Guardian declared, “HRT study cancelled over cancer and stroke fears.”

Book about Hormone Replacement Therapy and syringes

Were Cancer Concerns Well-Founded?

Here’s the irony: Physicians and the popular media both misunderstood the conclusions of this landmark study. It was designed to look at the risks and benefits of using HRT to prevent long-term health issues.

Most of the almost 30,000 women enrolled in the Women’s Health Initiative (WHI) study were already well over 60 years of age, at least a decade past menopause. And subsequent analyses of the huge data sets from the WHI study have shown that the health risks associated with HRT are only really seen in older women.

This is a transcript from the video seriesThe Skeptic’s Guide to Health, Medicine, and the Media. Watch it now, on The Great Courses Plus.

So-called “post-hoc” analyses occurred in published papers in later years following the original WHI study. The analyses scoured large data sets in an attempt to find new insights by asking different questions.

For instance, one post-hoc analysis of the WHI data showed that among women who started hormones within 10 years of menopause, there was no increased cardiovascular risk.

A separate Danish study published in 2012 that only looked at women taking hormones right around menopause showed a significant reduction in both cardiovascular disease and breast cancer. And, for women less than 60 years old, hormone replacement therapy reduced overall mortality by 30 percent.

The bottom line, which is reflected in current guidelines, is that most women in their 40s and 50s struggling with menopausal symptoms should use HRT therapy. These medicines can safely relieve symptoms, improve the quality of life, and even reduce short-term mortality; however, it doesn’t mean women should keep using it forever.

Looking back at the HRT story in hindsight, there are some big lessons. HRT was never as great as our enthusiasm led us to believe when the popular thinking was that all women ought to use it. By the same token, it was never as bad as it seemed to be when the headlines shouted that it was killing women.

Learn more about Hormone Replacement Therapy

The Male Version of Menopause Drugs

There’s another ironic side to this story concerning men. Though men don’t experience something akin to menopause, when, in women, the ovaries completely stop producing hormones over just a few years, men do experience a gradual drop in their sex hormone, testosterone, over decades as they age.

Sure enough, a huge industry has developed in response to treating men for what has become known as “low T.” Testosterone therapy is being pushed to treat a variety of ailments, including fatigue, sexual dysfunction, and declining muscle mass.

The purported benefits of testosterone for men reads like a Christmas gift list: build lean muscles; cut fat; improve your mood; recharge your energy and libido; and turn you back into a youthful, sexual dynamo.

Marketing materials from drug companies, and numerous articles in men’s magazines, have encouraged men to “talk with their doctors” about low T based on vague symptoms and promises of feeling more youthful.

One low-T marketing tool involved a questionnaire that started with “Do you have these symptoms?” and ended with “If you said yes, talk to your doctor.” This was called the Androgen Deficiency in the Aging Male, or ADAM test.

It was originally developed by Dr. John Morley of St. Louis University. He told The New York Times that he wrote it on toilet paper in the bathroom in about 20 minutes.

That quiz was reproduced dozens, maybe hundreds of times, and helped drive U.S. sales of testosterone replacement products to over $2 billion a year.

The boom in testosterone wasn’t limited to the United States—one study showed a remarkable jump in testosterone sales in 37 of 41 countries reporting data from 2000 to 2011.

Genuine low testosterone is referred to in the medical literature as “hypogonadism,” and it is a valid indication for testosterone therapy. Men with genuinely low testosterone levels do experience genuine symptoms that can be serious and at times debilitating, including especially low energy.

Just how many men have genuinely low testosterone is a matter of some debate—there are reasonable questions about just what cutoffs should be used. But many men who’ve been prescribed testosterone haven’t even had their testosterone levels measured, and aren’t being monitored to see if replacement normalizes blood levels or consistently improves symptoms.

Does Testosterone Therapy Live Up to the Hype?

So what do the studies show about routine testosterone use in otherwise-healthy men? A 2016 systematic review of the literature summarized that testosterone supplementation overall did not show consistent benefits for sexual function, mood, or behavior—it doesn’t really work, at least for some of the most important reasons men give for taking it.

Additionally, testosterone supplementation can increase the risk of cardiovascular events like heart attacks. Within 90 days of beginning testosterone, the risk of a heart attack doubles, and that risk is even higher among men with previous heart trouble.

chemical structure of testosterone molecule drawn on chalkboard background with man in front of it

But, and this is an important point, research also shows that men with genuinely low testosterone levels are themselves at a higher risk of heart attacks. So what it seems to come down to are some essential questions: Are we prescribing testosterone for the right patients, for the right reasons?

Men with genuinely low testosterone can benefit from supplementation, and for them, the benefits may well exceed the risks. But the concern is that all of the hype about testosterone has driven prescriptions and sales to too many men, and especially too many men who probably won’t have much benefit.

In 2014, the FDA clamped down on testosterone advertising, declaring that product labels need to explicitly say that testosterone is only to be used for men with objectively low testosterone levels, and that testosterone therapy may raise the risk of cardiovascular problems.

Manufacturers said they would voluntarily curtail their advertising, and you don’t see quite so many mentions of low T in men’s magazines anymore. Sales of testosterone products, predictably, have begun to drop.

Learn more about marketing tactics regarding testosterone

Hormone Replacement Therapy: A Balanced Perspective

But as with hormone replacement for menopausal women, we need to be careful that we don’t push the pendulum too far. The bottom line with hormone replacement for men and women is that it’s not a magic elixir that everyone should take, but neither are these therapies automatically bad.

These nuanced decisions need to be made based on the best medical evidence, considering each patient’s own medical history and individual needs.

Unfortunately, you just don’t get those kinds of “maybe” declarations from the media headlines. Advertising and the popular media tend to oversimplify, presenting things in black and white, when in truth, scientific knowledge is often filled with gaps or grey areas.

Sometimes, we’re too eager to accept advertising claims for the next superpill, especially one that will return our bodies to their youth.

We need to spend less time looking at the headlines and more time looking at what the actual studies say. That means asking the right questions and digging into details.

Only then can we cut through the hype and arrive at an informed decision.

From the lecture series The Skeptic’s Guide to Health, Medicine, and the Media, taught by Professor Roy Benaroch, M.D.

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