FDA head explains decision to drop ‘black box’ warnings from menopause hormone treatment

Geoff Bennett:

Today, the FDA announced it would begin asking drug companies to remove so-called black box warnings for hormones prescribed to treat symptoms of menopause.

Amna Nawaz:

The FDA says the warning has dissuaded generations of women from taking advantage of the medication that could help them.

Ali Rogin digs into the details.

Ali Rogin:

That's right.

Companies added this warning in the early 2000s following a claim from researchers in a large women's health study that the drugs carried an increased risk of breast cancer. Many experts say that risk does not exist for many menopause hormone therapy candidates.

To help explain today's announcement, I'm joined by FDA Commissioner Dr. Marty Makary.

Commissioner Makary, welcome back to the "News Hour."

Dr. Marty Makary, FDA Commissioner:

Good to be with you. Thank you, Ali.

Ali Rogin:

Why is the FDA making these label changes?

Dr. Marty Makary:

Well, the fear machine that started 23 years ago with this tragic, misinterpreted study and the results has resulted in a distorted perception of risk.

And about 50 million women since that time have been denied, never offered or convinced out of hormone replacement therapy, including all of its short-term and long-term benefits. And some of those benefits are profound, including reducing the risk of cardiovascular disease and heart attacks. That's the number one cause of death in women.

And no study subsequently has ever found, no clinical trial has ever shown that the risk of breast cancer mortality is increased with hormone replacement therapy. So women deserve all the facts, and women's health issues have historically not gotten the attention they deserve.

In this administration, we are working hard to make sure issues of women's health get the attention they deserve.

Ali Rogin:

Now, in terms of the perception of risk, I want to break it down. There's two types of estrogen, broadly speaking. There's local, which can be a cream. It's applied directly to an area. And then there's systemic, which takes the form of a pill or a patch and works its way through the bloodstream.

This announcement today is going to apply to label changes for both. Some experts say that that is too broad of a move, because the risk-benefit ratio for systemic estrogen is a little bit more nuanced than that for local, and that actually these two types of estrogen should be classed completely differently. How do you respond to that?

Dr. Marty Makary:

Well, that's right.

Tragically, the black box warning was placed on all estrogen products, be it local or systemic. Now, for the systemic estrogen products, there is an important nuance that will be in the package insert, and that is, if you start it more than 10 years after the onset of menopause, that risk-benefit ratio inverts, and most doctors do not prescribe it after age 60 or after 10 years after the onset of menopause.

And that's an important distinction, because maintaining a continuous level of intrinsic estrogen or exogenous estrogen through these hormone replacement products is probably critical to maintaining a high level of nitric oxide that keeps the blood vessel wall soft and healthy.

And that may be why we see such a dramatic drop in heart attack rates long term, in one study in circulation from two years ago, a 48 percent decline in heart attacks that were fatal and a 30 percent decline in all-cause mortality, also a significant reduction in the rate of bone fractures later in life and a reduced rate of cognitive decline.

Those are the long-term benefits on top of alleviating the short-term symptoms of menopause, the hot flashes, night sweats, mood swings, and weight gain.

Ali Rogin:

Right. And there's broad agreement that all types of estrogen do affect the side effects of menopause, but some experts will point out that the preventive elements of it are less well-established. There are certainly studies that point to it being indicated. There are some that point against it.

So what do you say to folks who say that why not just put the applications where there is the clearest evidence? Why not highlight those and not the other ones?

Dr. Marty Makary:

Well, there's an old guard in the medical establishment. They got hormone replacement wrong. They created the fear machine.

Remember, we got as a medical field opioids are not addictive wrong for 15 years. We got saturated fat causes heart disease wrong for 50 years. We got kids should avoid peanut butter until they're 3 years of age wrong for 13-plus years.

And so the groupthink really got this so tragically wrong. This is maybe one of the greatest mistakes in modern medicine. The data are overwhelming. The systemic meta analyses are in. They have been published. Who are treated by OB-GYN doctors who are more comfortable understanding and prescribing hormones in women, they have been really at the forefront of the correct understanding of the literature.

But there's an old guard dogma that lingers. And if you talk to primary care doctors today, some of them will still say, I don't ever prescribe it because of that breast cancer risk, even though no clinical trial has ever found an increase in breast cancer mortality.

Ali Rogin:

The FDA is moving to remove these warning labels from hormone replacement therapy, citing the needless fear that it instilled in women.

But the FDA is also calling for a label change to acetaminophen, also known as Tylenol, citing an association between use and pregnancy and autism in children, although no causal relationship has been established. Does the FDA have a consistent standard here in the application of these warning labels? And how do you respond to people who might see those two examples as contradictory?

Dr. Marty Makary:

So, first of all, no comparison whatsoever.

We, in the pregnancy section of the package insert, include all the information that's known about a medication and pregnancy. And so there are different studies about acetaminophen and pregnancy. The dean of the Harvard School of Public Health has stated very clearly he believes there's a causal relationship with neurodevelopmental disorders like autism.

There was a study out of Mount Sinai and Harvard that did show an association. So all of that information is going to be there. There will be references to studies that support and studies that don't support that association in the label.

But hormone replacement therapy for postmenopausal women is at a totally different level. There has been a black box warning, which scares women out of taking it, even after they get the prescription. And if you look at the long-term profound health benefits for women, there may be no other medication in the modern era, except perhaps antibiotics or vaccines, that may improve the health outcomes of women on a population level more than hormone replacement therapy in postmenopausal women.

Ali Rogin:

I want to just say that you have cited Harvard. You have done it on several occasions, saying that the Harvard dean cited a causal relationship. He has not said that. I reached out to Harvard to confirm that.

What he said was — quote — "This biological evidence lends support to the possibility of a causal relationship between prenatal acetaminophen exposure and neurodevelopmental disorders."

Dr. Marty Makary:

He said that later.

In 2018, he said — quote, unquote — "There's a causal relationship."

Ali Rogin:

I asked Harvard, and they said this is the most accurate reflection of the science. This was two months ago.

However, what is the basis on which the FDA is making these decisions? It seems like you're making one decision based on ending fearmongering, and you're making another that increases the risk that women might perceive and go to their doctors and call and be worried about it.

Dr. Marty Makary:

Well, over 20 studies have shown an association. And the dean of the Harvard School of Public Health — and this is important to get this correct — has stated that there is a causal relationship.

Ali Rogin:

He has not.

Dr. Marty Makary:

Now, you can call the communications office at Harvard, and they'll tell you some party line. But we'll send you the reference, and it is a very clear statement in 2018.

Ali Rogin:

Please do.

Dr. Marty Makary:

I can read it to you now if you give me 30 seconds to pull it up. But he has said there's a causal relationship.

Once it was said recently, then he ran for the hills and was hiding behind a fig leaf and had no public statement, except the generic statement that you're reading.

So, look, I don't know whether or not there's an association, but he clearly is on record saying there is. And he was one of the authors of the Mount Sinai Harvard study that said there is a relationship, an association between prenatal acetaminophen and neurodevelopmental disorders.

Ali Rogin:

Well, the hormone replacement therapy announcement was changed because of the warnings of one doctor with the Women's Health Initiative. And now you're citing one man in making the acetaminophen reference.

FDA Commissioner Dr. Marty Makary, thank you so much for joining us.

Dr. Marty Makary:

Thank you.