On Second Thought: Menopausal Hormone Therapy Isn't as Scary as You Think

This transcript has been edited for clarity. 

Hormone replacement therapy (HRT): It was a thing, then it stopped being a thing, and now it's a thing again. So, in the grand tradition of mansplaining, this is On Second Thought.

I think we can all agree that 2025 has been a sh*t year. For the historians watching this video hundreds of years in the future, this is when everything started to go wrong. I'm very sorry. By contrast, the 1990s were great. We saw the elimination of measles from North America, the end of the Cold War, the birth of the internet, and the rise of the Backstreet Boys. Life was pretty sweet. 

The only real wrinkle is that women were routinely prescribed hormones, and that turned out to be kind of a bad idea. What we need to remember is that medical professionals in the 1990s really believed that replacing estrogen in postmenopausal women was a good idea. The reasoning went something like this: When women lose estrogen, they experience menopause. Menopause brings hot flashes, heart disease, osteoporosis, several cancers, dementia, arthritis, weight gain, vaginal dryness, painful intercourse — a lot of bad stuff. So, if we give back estrogen, the disease will go away.

The logic of it was pretty obvious, and it made a lot of sense to a lot of people. True, it was based on observational studies and not on randomized controlled data. But don't get all high and mighty on me; if you were there, you would have done the same thing.

But we must remember something important: Some women were taking hormones to treat the symptoms of menopause (eg, hot flashes, night sweats, vasomotor symptoms), but a lot of women were prescribed hormones for long-term disease prevention. They were healthy, presumably asymptomatic women who were taking hormones to prevent conditions like heart attack and stroke.

Now, fast-forward a few years to the 2000s. We dodged a bullet on Y2K, but a lot of other bad stuff started happening. For our purposes, we're going to focus on 2002 and the publication of the Women's Health Initiative (WHI) study.

The WHI study blew up the practice of prescribing hormones to women. The study was published and the findings indicated that hormones don't reduce cardiovascular disease risk like everybody thought they would. In fact, the report found that hormone use increased the risk for heart disease, stroke, breast cancer, and blood clots. Hormone use was also not associated with reduced mortality. Hormone therapy contributed to the very conditions people were trying to prevent. 

As you can imagine, everybody kind of lost their minds and HRT fell off a cliff. It was an extreme reaction and, in retrospect, a bit of an overcorrection. Everybody rushed to get their patients off HRT because it wasn't preventing heart disease, as expected — but they forgot that it was still very good at treating symptoms of menopause. They kind of threw the baby out with the bathwater and it became bad for everyone.

Now, some 20-odd years later, people can look back and point out some of the problems with the WHI study. One of the main criticisms of the WHI is that the women were about a decade too old. The women in the study had an average age of 63 years, whereas menopause occurs at an average age of 51 years.

Although this is a common criticism, you have to remember what the WHI study was trying to prove or disprove. The point of WHI was to test whether HRT could prevent cardiovascular disease, so they wanted an older, higher-risk population to improve the power of the study. It was a choice (and an understandable one), but it does mean that the study is not reflective of the majority of women who are experiencing menopause. 

Further, the increased risk for heart attacks, strokes, blood clots, and breast cancer was mainly seen in the group of women who received estrogen plus progesterone. The women who received just estrogen didn't really have an increased risk; it was very minimal. However, you must give progesterone to women with an intact uterus, as unopposed estrogen increases the risk for uterine cancer. So, in the WHI study, only the women who had a hysterectomy received just estrogen; you can't really do much about that. 

But the real problem with WHI — you guessed it — is mathematical. Let's dig in.

For illustrative purposes, I'm using the numbers from the estrogen-plus-progesterone group in the original 2002 publication. The numbers are going to be a little bit different if you look at the later follow-up studies, but the points are basically the same. The authors reported hazard ratios of 1 .29 for heart disease, 1.26 for breast cancer, 1.41 for stroke, 2.13 for pulmonary embolism, and 1.22 for total cardiovascular disease. So many people looked at this and said, "Ah, hazard ratio is greater than 1, confidence interval doesn't cross zero, P value of less than .05 — hormones are bad. Moving on." But if we look at the absolute scale, it's a bit more nuanced.

In terms of absolute risk, hormone use was associated with seven extra heart attacks, eight extra strokes, eight extra breast cancers, and 18 extra blood clots. Sure, there were six fewer colorectal cancers and five fewer hip fractures, but we have colonoscopies and bisphosphonates for those. So, overall, it was a negative. 

But that's seven heart attacks, eight strokes, eight breast cancers, and 18 blood clots per 10,000 women per year. The individual risk per woman per year was very small. It's not zero, obviously, and it's not useful for cardiovascular prevention — that's pretty clear. But if you're using hormones to treat menopausal symptoms (like the vasomotor symptoms of hot flashes and night sweats), I think you can say it's fairly safe unless you have a high baseline risk.

I wouldn't give it to someone with a strong family history of breast cancer or thrombophilia or a recent heart attack or stroke. But for a low-risk or average-risk woman, hormone use doesn't lack risk, but it's low enough that it's probably worth it to achieve symptomatic relief of what can be very debilitating symptoms. And the symptoms of menopause can be very debilitating; most women don't end up seeking medical attention and end up suffering in silence.

The rise and fall and rise again of menopausal hormone therapy illustrates a funny paradox. The risks to a population can be significant. If you start giving a lot of women hormones unnecessarily, you're going to cause a lot of extra heart attacks and strokes and blood clots. But the risk to an individual woman is pretty low. Would I prescribe hormones to a woman who has menopausal symptoms? Yes. I actually get this consult all the time. If the patient has no contraindications, high-risk features, or family history, then yeah — I would have no problem starting the therapy to treat the symptoms.

But you probably shouldn't receive lifelong treatment (like we used to recommend). Continue hormone use for as long as menopause symptoms persist. That can be 5 years, or 10 years for many women. For some, it can be up to 20 years. But the point is, you're treating symptoms, not preventing disease. Use it for as long as you need to. If you want to try nonhormonal alternatives (eg, low-dose SSRIs, elinzanetant, fezolinetant), then give that a try. 

Menopausal hormone therapy is exactly what it says it is: It's therapy. It treats the symptoms of menopause, but it's not for prevention. Use it if you need it. Stop it when you don't. Overall, the risks are low for more low-risk women. 

It took almost 30 years to sort this out, but I think we got there. For Medscape, I'm Christopher Labos.