In this episode, Dr. Morgentaler and Dr. Brandon talk about the FDA finally reversing its stance on testosterone risks, what that means for heart health, and why it’s a big win for science—and for patients.
Chapters
00:07 – FDA's New Stance on Testosterone
In this episode, Dr. Morgentaler and Dr. Brandon unpack the FDA’s surprising move to ease its warning on testosterone—and why it’s such a big deal.
00:46 – Understanding the Black Box Warning
They explain what a black box warning really means and how it ended up on testosterone products in the first place.
03:22 – Testosterone and Cardiovascular Health
The doctors dive into new research showing testosterone may not just be safe—it could actually help protect the heart.
09:15 – FDA's Role and Influence
They explore how the FDA shapes medical decisions, where it gets things right, and where it might be holding us back.
15:53 – Testosterone Treatments for Women
Finally, they touch on the frustrating lack of approved testosterone options for women—and why it’s time that changed.
Dr. Brandon:
Hello, Dr. Morgan Ter.
Dr. Morgan Ter:
Hello, Dr. Brandon. Great to see you for another episode of The Sex Doctors podcast.
Dr. Brandon:
There’s been some news in the world of testosterone, and I thought it would be good for us to talk about it.
Dr. Morgan Ter:
I’m aware of it. The FDA made some changes, and that is big news as far as I’m concerned.
Dr. Brandon:
It’s not often that the FDA changes what they’ve written to take away a risk-or at least make something seem less risky. They’re usually in the habit of adding risks.
Dr. Morgan Ter:
Before we start, a small disclaimer: The Sex Doctors podcast is not a substitute for medical or psychological advice. The FDA are protectors of the public and take that role very seriously.
Dr. Brandon:
Sometimes too seriously, one might say. In this particular case, several testosterone products on the market have had a black box warning about blood pressure. The FDA extrapolated that to suggest these products could cause more heart attacks, strokes, and death.
Dr. Morgan Ter:
Can you be more specific about which products?
Dr. Brandon:
The black box warning first appeared in 2018 with the injectable testosterone product Xyosted. Then, when three new oral testosterone pills came out between 2019 and 2022, all three had this warning added.
Dr. Morgan Ter:
A black box warning is the most serious risk the FDA can put on a label. It sounds scary.
Dr. Brandon:
Exactly. Every prescription includes a pamphlet listing all the risks, and the black box warning is literally surrounded by a black box at the top to make it stand out. On February 28th, after negotiations between Marius Pharmaceuticals (which makes the oral testosterone Kyzatrex) and the FDA, they argued that the big Traverse trial, which came out in 2023, showed no increased risk of heart attack, stroke, or death with testosterone compared to placebo. So, the alleged risk in the black box-that a slight increase in blood pressure might lead to increased heart attack, stroke, and death-couldn’t be true.
Dr. Morgan Ter:
And the FDA agreed to change its labeling?
Dr. Brandon:
Yes, they did. That’s exciting-not just for everyone who uses testosterone or physicians who prescribe it, but for me personally. I’ve been advocating for the safety of testosterone for decades. Much of my early work was around prostate cancer, but I was also a lead author on the Androgen Society’s position statement that looked at the Traverse trial and all previous literature on cardiovascular risk. We published a position paper last year that reviewed whether testosterone products increase the risk of heart attack, stroke, or death. The evidence is overwhelming that they do not. In fact, some data suggest testosterone may even be beneficial for the heart, and that low testosterone itself may be a risk for various cardiovascular issues.
Dr. Morgan Ter:
Isn’t that something? Can you speak to the idea that testosterone could be protective?
Dr. Brandon:
Sure. There are at least four randomized controlled trials where testosterone was given versus placebo in men-and in one study, also in women-with congestive heart failure. These studies showed benefits compared to placebo. People with heart failure are short of breath and have limited physical activity, but testosterone improved their ability to work and walk.
Dr. Morgan Ter:
We know men with lower testosterone are at higher risk of coronary artery disease, and it’s correlated with the severity of the disease.
Dr. Brandon:
Right. There are also long-term observational studies-one in the VA population and another in diabetics-where people with low testosterone were either treated or untreated. The mortality rate for those who received testosterone was half that of the untreated group. So, the whole testosterone and cardiovascular issue may be upside down compared to how it’s often described.
Dr. Morgan Ter:
Let’s come back to the blood pressure issue.
Dr. Brandon:
The FDA and platforms like Medscape described the black box warning as being about cardiovascular issues. But the original reason was that newer testosterone products were required to do ambulatory blood pressure monitoring. The average increase in systolic blood pressure was only 1.8 mmHg-so if normal is 120/80, it would be 121.8/80. Blood pressure can easily vary by 10–20 points during the day, so this increase is trivial in my opinion. For some people, blood pressure went up; for others, it went down. On average, it was a tiny increase.
Dr. Morgan Ter:
What does the FDA represent to you?
Dr. Brandon:
The ultimate authority on drugs in this country. The FDA was created to protect public health and has been around since the 1930s. After the thalidomide scandal in the 1950s, where a drug caused birth defects, Congress gave the FDA more power to regulate the pharmaceutical industry. The FDA also governs cosmetics and food, but in medicine, we mostly think of it for drugs. It decides what drugs are approved and what goes on their labels.
Dr. Morgan Ter:
Once a drug is approved, physicians can use it off-label for other indications.
Dr. Brandon:
Exactly. For example, Cialis is approved for erectile dysfunction and urinary symptoms, but doctors also use it off-label for endothelial health. Similarly, some erectile dysfunction injections use drugs not specifically approved for that use. Every specialty has off-label prescribing. But many doctors defer to the FDA’s guidance, even though every specialist knows the FDA sometimes gets things wrong. In the testosterone world, the FDA has often been a hurdle rather than a help. For example, since 2015, the FDA says most men with age-related low testosterone should not be treated. That’s nonsense. They also warn against giving testosterone to men with a history or even suspicion of prostate cancer, but the data now show testosterone does not increase prostate cancer risk.
Dr. Morgan Ter:
So, this change is a good thing.
Dr. Brandon:
Yes. Credit to the FDA for updating their guidance in light of new evidence, and to the pharmaceutical company that pushed for it. This will apply to other testosterone products that used to have the black box warning. Experts look at the science, not just the product labels. The FDA has a lower threshold for saying something might be risky than actually requiring double-blind studies. But congratulations to the manufacturers who challenged the FDA with new data. Maybe one day we’ll see changes regarding prostate cancer and age-related testosterone decline, too.
Dr. Morgan Ter:
And we need a testosterone product for women!
Dr. Brandon:
Exactly. There’s only one testosterone product in the world approved for women-a patch in Australia. There have been applications for new drugs for women in the U.S., but all have been rejected by the FDA. Despite their antagonism toward testosterone, the FDA has approved more than 20 testosterone drugs for men, but zero for women. That’s a topic for another day.
Dr. Morgan Ter:
Great. Dr. Brandon, it’s a pleasure talking with you as always. I hope to see you for another podcast.
Dr. Brandon:
You will. I guarantee it. Can’t wait.
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