Last week, the Pentagon posted a video on X announcing they will be mandating testosterone screening for troops in the military aged 30 and above. If they test low, they will be offered voluntary testosterone replacement therapy.
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At the same time, FDA has announced it will be loosening safety warnings on the labels for testosterone replacement therapy. The primary evidence base to guide that decision is cited as the 2023 TRAVERSE trial.
However, screening experts, endocrine specialists, and even the first author of the TRAVERSE study said that this trial was not designed to study the effectiveness of long-term TRT use. It was designed to look primarily at cardiovascular risk.
The big issue isn’t TRT use itself, it is the overinterpretation of evidence to broaden the use of TRT therapy in people who may not need it.
“The risks of over testing, over treatment, over diagnosis—cannot be overstated,” said Claire Marie Porter, a reporter with The Cancer Letter.
Should one screen an asymptomatic population for a condition that no major medical society recommends screening for? That’s where many experts draw the line.
In this episode of The Cancer Letter Podcast, Claire and Jacquelyn Cobb, associate editor of The Cancer Letter, discuss the implications of overuse of TRT, in oncology and otherwise.
“Anxiety is not the only consequence of overscreening,” Jacquelyn said. “There are actually potential health outcomes that could come from over screening. And I think that’s sort of the missing link, that there could be harm introduced that was not necessary.”
Some of those harms could include fertility decrease, prostate changes, hormone suppression, and more.
“If you are on testosterone replacement therapy for long periods of time, your pituitary glands will stop making it,” Claire said. “Increased PSA testing will likely happen—the Endocrine Society recommends it—which means more biopsies, more false positives, more anxiety, and just decades of treatment beginning in your thirties.”
TRT has an accepted role for men with diagnosed hypogonadism, but population-wide testing is a very different policy, experts say.
“Many sources were like, this is basically an uncharted, natural, human experiment,” Claire said.
This episode is sponsored by the American Society of Clinical Oncology. Learn more at asco.org/ascoaction.
Stories mentioned in this podcast include:
- Cancer hospitals brace for impact, as CMS moves to slash 340B payments by 33%
- Hegseth orders testosterone testing for troops as FDA moves to loosen TRT prostate cancer warnings
- The Susan Wojcicki Foundation pushes for rethinking of strategies for early lung cancer detection
- Gary Morrow, a pioneer in supportive oncology, dies of prostate cancer complications at 82
This episode was transcribed using transcription services. It has been reviewed by our editorial staff, but the transcript may be imperfect.
The following is a transcript of this week’s In the Headlines, a weekly series on The Cancer Letter Podcast:
Jacquelyn Cobb: This week on The Cancer Letter Podcast.
Claire: Everyone knows that you don’t give testosterone to men with active prostate cancer, but what about those who have not yet been screened? The screening age for an asymptomatic or average health man is 50. And so, these men in the military, population-wide screening for them, but they’ve never had any type of PSA testing. And there are silent prostate cancers, which I didn’t really know about until this story. Researchers are saying and endocrinologists are saying that the very trial that FDA is basing their primary evidence on is being kind of over-interpreted. And I think a recurring kind of refrain or motif throughout this story that was given to me unprompted via my reporting was “the absence of evidence does not equal evidence of absence.” So, “the absence of evidence does not equal safety and effectiveness,” which is essentially what FDA [is doing] according to this press release. This is all speculative because it’s just the announcements, but that seems to be what’s happening.
Paul Goldberg: You’re listening to The Cancer Letter Podcast. The Cancer Letter is a weekly independent magazine covering oncology since 1973. I’m your host, Paul Goldberg, editor and publisher of The Cancer Letter.
Jacquelyn Cobb: And I’m your host, Jacquelyn Cobb, associate editor of The Cancer Letter. We’ll be bringing you the latest stories, groundbreaking research, and critical conversations shaping oncology.
Paul Goldberg: So let’s get going.
Jacquelyn Cobb: Hi, Claire. How are you?
Claire: Hi. I’m fine. How are you?
Jacquelyn Cobb: I am good. I have my huge chair here behind me, but I’m-
Claire: Yeah, you do.
Jacquelyn Cobb: … a little off-kilter. I don’t know. I’d never realized I don’t sit straight until I saw it.
Claire: [inaudible 00:02:04] like a whole La-Z-Boy desk chair?
Jacquelyn Cobb: Oh my god.
Claire: Oh, yeah. Look at that thing.
Jacquelyn Cobb: It’s ginormous. It’s so big.
Claire: Oh my gosh. Like a loveseat on a swivel.
Jacquelyn Cobb: Literally. And Paul was not a fan as you could expect being very [inaudible 00:02:16]
Claire: He loves his chairs.
Jacquelyn Cobb: Yes, yes. The chair connoisseur that he is. I think he said something about it looking like a certain… Yes. I’ll leave Paul’s sassiness to himself. He can share if he feels or has the desire to.
Claire: All right.
Jacquelyn Cobb: But yeah, I’ll take us through last week’s headline. I’m really, really excited to talk to you, Claire, about your story. So I’ll try to hold that in for a little bit, but I don’t know, it might slip out a little. So our cover story last week was Sara wrote this monster story about 340B, which is something that we have been sort of apprehensive of covering since I’ve been working at The Cancer Letter. It’s just such a beast. It’s so complicated. And Sara really took it on and really broke it down.
There was a new CMS, a set of actions from CMS that changed the reimbursement structure and the reporting requirements of the 340B program, and it just caused this uproar and sort of this rehashing of this conversation because the main argument is that some groups feel that there is “rampant waste, fraud, and abuse” in the 340B system. But obviously, it’s intended to help safety in our hospitals, be able to have sort of that discounted price structure so that they have a little bit of wiggle room with money to support uninsured and people who need a little bit more support. So a really cool story. I still don’t feel like at all an expert even after reading the story because there are just so many different perspectives. But if you want almost like a textbook or just a document to go back and refer to, the cover story last week is really, really good for that.
The second story, which is what we’re talking about today, why we have Claire on the podcast, she wrote a story. I’m just going to read the headline for now because the temptation to go into it is too much. The headline was Hegseth, Jesus, orders testosterone testing for troops as FDA moves to loosen TRT prostate cancer warnings. So we will get into that. But we had two really powerful guest editorials/submitted articles. One was a guest editorial by Christine Berg, who’s a clinical advisor, I believe, apologies if the title is a little bit off, but for the Susan Wojcicki Foundation. Another apology, I’ve never heard that pronounced out loud, the limitations of being a print journalist, so if I’m mispronouncing that, please forgive me.
But it was a really incredible story where this foundation has its really interesting, unique sort of origin story of being related to Google and YouTube CEOs and lending out their garage to these people, just really cool lore in the tech space, but they’re entering into the world of early lung cancer detection and screening. And it was a really, really interesting conversation after the introduction of the foundation. After the article introduced the foundation, Dr. Berg really went into detail about how low-dose CT as a lung cancer screening has been approved or recommended by USPSTF for very high-risk groups, which in that case is people with a history of heavy smoking. But unfortunately, as smoking rates really go down and there are these different demographics with different risk factors that are now popping up that have higher lung cancer rates or might be at high risk for lung cancer, those people are really getting missed by this current screening paradigm. So it was really, really fascinating.
Christine Berg worked on the National Lung Cancer Screening Trial and the other big one, the prostate, lung, ovarian cancer, I think PLCO, the two really huge NCI-driven screening trials. So it was a really, really cool story. Just as a little screening nerd, I think I was really excited about that one. And then, last thing, I know this is really dragging on. I don’t know why I have so much to say about these stories for last week, but we had this incredible, incredible obituary for Gary Morrow. And he was sort of a pioneer in supportive oncology. He was really responsible for the development of anti-emetics, my medical knowledge, but basically, anti-nausea meds and other supportive medications so that people could actually complete their course of cancer treatment. In that case, it’s chemotherapy, things like that, so that they could actually complete it and therefore have, hopefully, the efficacy maximized.
And that story was just so beautifully written. It was written by a science writer at Wilmot Cancer Institute where Gary Morrow was employed. And you could just really tell that he had a really big impact on the entire community there. It’s just infused in the writing and the photos and every interaction I had with people from Wilmot for this story. And the last thing I’ll say is just the photos are really, really moving and really precious. So yeah, so long, long, long walkthrough, but yeah, it was a really good issue last week, and I clearly had a lot to say.
Is your head spinning from the pace of health policy news? Are you struggling to figure out what it all means for the cancer community? Find the resources you need on ASCO in Action, the online information hub from the American Society of Clinical Oncology and the Association for Clinical Oncology. ASCO in Action has news and analysis on issues like federal research funding, prior authorization, and reimbursement, and visitors can find ways to get involved in advocacy efforts. Visit ASCO in Action at asco.org/ascoaction, all one word, today.
But Claire, obviously, I was light on the backstory of your story. Do you want to maybe give us the elevator pitch or as long as you want clearly for your story?
Claire: Yeah, I’d love to. And I also wanted to just shout-out to Katie for putting this story on our radar. I’m glad I got to report it. And I feel like last time we did the podcast or maybe I feel like when you and I are on the podcast, we’re always kind of talking about this really niche cultural manospheric thing, which is kind of fun. I don’t know. We’re here with our bangs…
Jacquelyn Cobb: It is funny. Wasn’t it the dietary guidelines, I feel like?
Claire: We were talking about protein.
Jacquelyn Cobb: Yes.
Claire: Yes. Yes, protein. And now, we’re talking about looksmaxxing essentially. I’m just kidding.
Jacquelyn Cobb: Oh my god.
Claire: The Pentagon via a video posted on X called The High-T Department of War, posted by Secretary Pete Hegseth, emphasis on the war, has announced that they will be mandating screening for low testosterone testing for men in the military, 30 and older, starting with their annual. I guess they have these annual periodic screenings, and that will be a mandated part of that. And if they test low for T, they will have the option of taking testosterone replacement therapy. Men under age 30 can voluntarily also choose to get the screening for testosterone. And then, at the same time, the FDA has announced that it will be loosening safety warnings on the labels for TRT. They have said that they’re making these changes after reviewing current evidence, and the primary evidence that they mentioned in their press release is this trial called the TRAVERSE trial, which occurred in 2023 and resulted in the removal of a black box safety warning on TRT.
But the juicy part here is that every screening expert and endocrinologist that I spoke with for this story, including the first author of that TRAVERSE trial, said that this trial was never designed to study the effectiveness of long-term testosterone replacement therapy use. It was designed to look at cardiovascular risk. And the study was asking, “Is testosterone reasonably safe over about two years?” It didn’t ask, “Should healthy asymptomatic younger men be screened?” It didn’t ask, “Should millions of more men receive TRT or does TRT improve long-term health? What happens after 20 to 30 years? And then, relevant to us, what about underlying prostate cancers?”
Everyone knows that you don’t give testosterone to men with active prostate cancer, but what about those who have not yet been screened? The screening age for an asymptomatic or average health man is 50. And so, these men in the military, population-wide screening for them, but they’ve never had any type of PSA testing. And there are silent prostate cancers, which I didn’t really know about until this story. Researchers are saying and endocrinologists are saying that the very trial that FDA is basing their primary evidence on is being kind of over-interpreted. And I think a recurring kind of refrain or motif throughout this story that was given to me unprompted via my reporting was “the absence of evidence does not equal evidence of absence.” So, “the absence of evidence does not equal safety and effectiveness,” which is essentially what FDA [is doing] according to this press release. This is all speculative because it’s just the announcements, but that seems to be what’s happening.
So that’s the thrust. It’s a lot of different kinds of stories meeting and converging, and it was hard to write, I will say. It was like I had to sit with it for a long time, just also educate myself on TRT and so many parallels between the TRT story and the HRT story and the Women’s Health Initiative stuff, which I’ve done reporting on. So anyways, it was super interesting and very fun.
Jacquelyn Cobb: Yeah, I think that was just to give you my perspective as an editor or as a reporter on a different side of the issue last week, it was just really interesting to me because I feel like, and this is wrong, just please nobody take this out of context, but my incorrect impression before reading your story was just outdated information that TRT is bad for prostate cancer. And that is, again, kind of true. Like you said, you don’t want to give it to active prostate cancer, but it was an unformed, unresearched idea in my head that I hadn’t had any reason to look into at that point. Just that it’s a bad combo, they’re related, just don’t do it, and so for me, to read your story, you have to talk about the cardiovascular risks and all of these sort of non-cancer topics because that really is a huge part of the meat of the actual story and the news of what’s happening.
But obviously, for our readers, we also have to look into this prostate cancer concern, and it’s weird because there’s really not that much evidence, which is the whole thing that you just said. It’s a weird kind of spot for us to be in. And just as a small kudos to you, just cardiovascular disease and just trying to learn about the screening and the measures of efficacy and all these things, I would be terrified to even try to tackle that after knowing how complicated it is in oncology. And so, I feel like the marriage of those two things, it just adds to the complexity of the story. But yeah, I think the prostate cancer thing was a little odd for me because I still don’t know that I feel, and maybe it’s just that we don’t know and that’s what you’re saying, but I don’t feel confident about the relationship between TRT and prostate cancer completely.
Claire: Yeah, I don’t think anyone does. Yeah, I was just saying that we have short-term data. Testosterone is safe. It doesn’t cause prostate cancer. But yeah, I guess the question is what about all of these? There are underlying prostate cancers that would never have caused the man any type of symptoms or harm as well, prostate cancers that you can live with. And what does testosterone do to those? We don’t know. Nobody knows. It’s just anyone’s guess. So that’s what I think it is. And then, the list of actual side effects of long-term testosterone use, they’re pretty vast. There’s fertility suppression. One of my sources said that testosterone is a very effective contraceptive. So giving testosterone to men who may or may not need it. I think another important piece of this is that not every testosterone test is the same. Your testosterone levels fluctuate throughout the day, throughout the week. So a low test does not mean that you have hypogonadism. And so, just the risks of the overtesting, overscreening, overdiagnosis cannot be overstated.
Jacquelyn Cobb: Yeah.
Claire: But also, another source pointed out that if you are on testosterone replacement therapy for long periods of time, your pituitary glands will stop making it. They’ll be tricked into complacency essentially, so weaning off of that is really difficult. Increased PSA testing will likely happen—the Endocrine Society recommends it—which means more biopsies, more false positives, more anxiety, and just decades of beginning treatment in your 30s. So many sources were like, “This is basically an uncharted natural human experiment.”
Jacquelyn Cobb: Oh my gosh.
Claire: And that’s not being hyperbolic. Those are real trade-offs. You know?
Jacquelyn Cobb: Yeah. And it is weird. I mean, I know only because this is the podcast do I bring this up and, again, that’s the big hedge here, but it’s like as a consumer of media, take The Cancer Letter out of it, it’s such a thing right now, testosterone, all of these. And I don’t know if it’s technically manosphere. I’m not really clear on what the definitions are and all that, but I’ve seen it in a lot of the podcasts and the Diary of a CEO and Joe Rogan, that sort of genre. And it seems odd to me that… It’s just such an unfortunate thing where testosterone is such… It’s really catching on to this moment where it’s like hypermasculinity, Department of War, having… And I mean, the words that Hegseth was using were like… What was it?
Claire: War fighters-
Jacquelyn Cobb: War fighters, warrior-
Claire: Optimizing war fighters’ performance, and no mention of women in the military, by the way, who also could benefit from testosterone technically. You know?
Jacquelyn Cobb: Well-
Claire: Yeah. So it feels very much like this isn’t just about medicine. This is about culture and-
Jacquelyn Cobb: Yes.
Claire: We’ve been hearing about biohacking and declining testosterone and male vitality. Yeah, it’s a cultural thing. And now, policy is kind of beginning to reflect that.
Jacquelyn Cobb: Yeah. Yeah. And it is really freaky. I mean, I’m not going to say too much because I don’t want to give it away, but I feel like, and not even just me, I feel like you, me, and Sara are all sort of working on big screening stories. It’s cancer screening stories, and it’s really intense, sort of counterintuitive, and weird and sort of utilitarian. It’s a tricky thing. And so, just to see this outside of that, the 30-year-olds, I don’t know. I feel like it’s because of our positioning and where our reporting is right now. I feel like this seems all the more like… Shocking maybe is a little bit too strong of a word, but you know what I mean? Wow. Surprising. Notable.
Claire: Yeah. And I will say, I do feel like the whole… We talk a ton about overscreening and the risks of overscreening and overdiagnosis at The Cancer Letter. But before The Cancer Letter, this is not something that I was really aware of. Even as a health reporter, I was always kind of reporting more from the, I guess, the patient point of view or the specialist point of view and the personal point of view where I’m a hypochondriac, give me all the tests. I would rather know everything and have anxiety than be blindsided. But that’s not how health works. That’s not how policy should be made. I think something I’ve learned over the past few years being here is that medicine has this really long history of finding diseases that people don’t actually have.
When you test lots of asymptomatic healthy people, you will inevitably create false positives. I think one of my sources was like, “Are we diagnosing illnesses or are we creating patients” which is something I think about a lot, and it’s hard to… Yeah, from a personal perspective, I feel like a chronic patient or I want to be a patient. Put me in an MRI. I just want to know. You know?
Jacquelyn Cobb: Yeah. Yes.
Claire: Full body scan. Yeah.
Jacquelyn Cobb: Give me the clean bill of health. I think that’s what it’s… I mean, and I’m really getting on a tangent here, so I’ll cut myself off if I go too far. And I might’ve even told this anecdote on the podcast already, which it’s going to start happening more and more, I think, if I keep doing the podcast long enough. But I just have such a core memory for me in my undergraduate biology degree, where it was a precision medicine class, and the idea was posed to the whole class of if there was a test that could predict with… I think it was in the context of the Huntington’s genetic test, but the question I think was Alzheimer’s at the time. It was like if there was a test that could predict for 100% accuracy that you were either going to get Alzheimer’s or not, take sensitivity and specificity and the actual performance of the test out of it, would you want to know, knowing that we can’t do anything about it?
And obviously, that’s, I think, a little bit different because Alzheimer’s is, in this hypothetical situation, it’s like a far future thing. You could prepare for it. You could live your life differently. There are all these sort of things that go into it. But the main logic, and I felt really strongly at that point in my life in college. I was like, “I want to know.” You know what I mean? Like what you said, I was like, “I want to know. I don’t want to…” This is a silly example, but I don’t want to go be an investment banker and spend my entire life doing something really hard when I’m… You know what I mean? It would change my calculus of how I want to live my life, and I felt like that was important. And that was most of the conversation at that point.
There were some other interesting ethical questions about 16-year-olds and blah. You know what I mean? All of these other things. But now, you’re saying at The Cancer Letter, I think that and this is very specifically within the context of cancer screening, but I think it does extend a little bit further into just screening in general, but I’m just not as confident, but the idea that the knowing or not knowing is not the only consequence. The anxiety is not the only consequence. There are actually potential health outcomes that could come from overscreening. And I think that’s sort of the missing link of there could be harm introduced that was not necessary. And that’s the thing that I learned that changed or shifted, maybe not changed, because I definitely still have that. I definitely still have that desire to know. I think that that’s a little human. For whoever has that drive, that instinct, I feel like that’s really hard to just eradicate. You know?
Claire: Sure, sure. It’s also kind of a luxury. I mean, I’m saying these things from a point of, I would say, health privilege, access to medical care and good insurance, and I also don’t have any chronic health problems as far as I know or scary family histories. So just to be like, “Oh, just tell me all the stuff,” I mean, I think Dr. Brawley, not to bring him into every single conversation, but we’ve talked a lot about this, about how there are limited resources. So someone like me who doesn’t need to be getting all of these, I’m not saying that I’m doing this, but my brain would love to get all the tests, test me every morning for cancer to make sure nothing changed since yesterday. But it becomes a health equity issue pretty quickly.
And the mammography conversation that we’ve been having over the past couple of years and prophylactic and mastectomies, those are real things that have happened to real people, and unnecessary ones, I’m saying. And then, unnecessary biopsies would be a side effect of this situation in this population. Yeah. So I mean, there are real harms. I might not be subject to them or feel like I’m subject to them. But yeah, good thing I’m not the one who’s making health policy decisions. I’m just talking about it.
Jacquelyn Cobb: That’s why there are very, very educated, smart people doing that. But well, in this case, just going back to the story, I mean, I’m not going to say anything about the education or intelligence, but it is a little bit of a speedy and not… As you said, your sources said that there seems to be a dearth of evidence supporting this policy change, which I think we just walked through why we feel the way we feel about this story, which is great. I mean, I feel like we could talk about this for hours, so to say is there anything else is a little misleading, but is there anything you want to talk about before we wrap up?
Claire: No. Yeah. I mean, I think we covered all the big things. I will say it was fun to report this story because I feel like people were ready to talk about it. It’s something that… My one source, I think I ended the story with, Brad Anawalt, said the less evidence that we have, the more fervor there tends to be on both sides. The more drama and the more… And then, that goes both ways. If there’s a big outroar and a lot of people have a lot of opinions about a thing, it often points to the fact that no one really has an answer. And that’s the whole point here is that no one’s arguing that men with low testosterone diagnosed with hypogonadism should not be receiving testosterone. That is a game changer for many men. That’s not the conversation. Yeah, we’re talking about otherwise healthy men. And so, yeah, I think it’s just the Endocrine Society is calling for a men’s health initiative, a randomized controlled gold standard trial that can look at these things and give us some definitive answers, but it just doesn’t exist.
Jacquelyn Cobb: Yeah. I just want to read that quote because it’s so good-
Claire: Yeah, do it.
Jacquelyn Cobb: … and I feel like it’s a nice way to wrap up. “TRT is one of those areas where there’s lots of fervor, there are lots of opinions, and in the usual manner, the more heated the debate is, it’s usually because there’s not enough evidence to point one way or another.” And that’s really good, and it definitely has a string through a lot of the stories that we’re working on. So it’s really, really wonderful. Well, thank you, Claire. It’s always such a pleasure to have you. And listeners, I will see you next week.
Thank you for joining us on The Cancer Letter Podcast, where we explore the stories shaping the future of oncology. For more in-depth reporting and analysis, visit us at cancerletter.com. With over 200 site license subscriptions, you may already have access through your workplace. If you found this episode valuable, don’t forget to subscribe, rate, and share. Together, we’ll keep the conversation going.
Paul Goldberg: Until next time, stay informed, stay engaged, and thank you for listening.
