Melanie Cole, MS (Host): Testosterone supplementation, a Urologist's Perspective, today on Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me today is Dr. Channa Amarasekera. He's an Assistant Professor of Urology at Northwestern Medicine.

Doctor, thank you so much for being with us today. And recent data suggests that many men are on testosterone therapy, even though there may not be a clinical indication. Can you tell us the most common reasons that men seek this therapy.

Channa Amarasekera, MD: So, what some of the common reasons people look for testosterone therapy are because of non-specific symptoms like fatigue, loss of libido, difficulty concentrating, difficulty losing weight, erectile dysfunction. So, these symptoms can often trigger people to seek care for testosterone replacement. And it's very common for testosterone deficiency to cause these symptoms, but the trouble is there are a lot of different medical conditions that can lead to very similar symptoms. So, they're pretty non-specific. The trouble here is trying to figure out who's going to benefit from testosterone replacement and who's not.

Melanie Cole, MS: Well, it's certainly been the subject of much debate and research. Can you share insights into the potential benefits and/or risks with this type of therapy?

Channa Amarasekera, MD: Yeah. So for the man who has those symptoms we discussed, who also has a testosterone level that's low, and that will be considered less than 300 on a morning draw on two separate occasions, then that patient might actually benefit significantly from testosterone replacement. So, they'll have improvement in mood, in concentration, losing weight, building muscle, just general overall feelings of well-being. But if they have a testosterone that's elevated, and they still have these symptoms, it's unlikely that they'll benefit from it.

In terms of some of the risks involved with testosterone replacement, for a long time, there was a great deal of mixed data on what testosterone replacement entailed in terms of risks. But more recently, there's been the TRAVERSE study, which has answered a lot of these questions. That's the largest, randomized clinical controlled trial. And what they found is there's a higher risk of non-fatal arrhythmias, atrial fibrillation, a slightly higher risk of acute kidney injury, and a small signal in terms of pulmonary embolism. But it did not lead to any change in risk of major adverse cardiovascular events. Whereas there are studies looking at low testosterone where people are at risk for major adverse cardiovascular events if they have low T.

Melanie Cole, MS: Such an interesting topic. And doctor, speak about diagnostic criteria and patient selection. Tell us a little bit about your workup before you would recommend this to a patient.

Channa Amarasekera, MD: Yeah. I think it's important to let patients know that from the time you're 40 until forever, really, your testosterone will decline 1 to 2% a year. So, testosterone levels naturally change over time. That said, the delta or the change in testosterone can be fairly dramatic for some patients. And if their testosterone levels are less than 300 nanograms per milliliter on two separate occasions, then that's a reason to consider replacement.

There are some other tests that are recommended with checking a testosterone. So, tests like LH. And if LH is low or low normal, then you would also get a prolactin. In practice though, you know, you generally just order all these tests at once just because patients don't really want to come back for more testing. So, you order a testosterone, a prolactin, LH, FSH, estradiol as part of the initial test typically.

Melanie Cole, MS: What about contraindications? Are there patients for whom this is really not a great option?

Channa Amarasekera, MD: So, there are some absolute contraindications, if someone's in the middle of prostate cancer treatment and they haven't been treated yet. If they have breast cancer, if they have uncontrolled heart failure, if they have a hematocrit that's elevated that has not been addressed. And if they're actively trying to conceive, so fertility is a concern, then giving them testosterone might not be a great idea; also breast cancer, if it hasn't been treated.

Melanie Cole, MS: Doctor, how do you select the type of testosterone given to eligible patients? And speak a little bit about counseling them and the shared decision-making as you're recommending this.

Channa Amarasekera, MD: Yeah. So, the type of testosterone replacement will depend on patient preferences and, you know, what is important to them, but also on insurance coverage and what is covered for the patients. But there are two major branch points, and one is, is this patient interested in fertility preservation? That's important to ask every patient. If they are, then testosterone replacement with exogenous testosterone is not a very good idea, just because it can suppress spermatogenesis and make them infertile.

In those cases, there are three potential options. One is a selective estrogen receptor modifier, things like clomiphene or you can try an aromatase inhibitor like an estrozole or inject with hCG, which can be quite expensive. If fertility is not really an issue, then, you know, any kind of testosterone replacement is okay. And these can come in injections that are either weekly or every other week. They can be gels, patches, nasal sprays, oral pills. It all depends on what's covered by insurance, typically, and what the patients tolerate in terms of cost.

And I'd like to go into some of the pluses and minuses of each option or the more common options, and just a few things to think about when prescribing these. For the patient who has some concerns around fertility, or if they're worried about testicular volume loss, then you would go with the first class of medications I mentioned, which are SERMs or hCG or anastrozole.

With SERMs, they're usually effective for patients with an LH that isn't quite that elevated. Because as you might imagine, if you already have an elevated LH and your brain is telling your testicles to make testosterone, giving something that blocks that signal and produces more LH isn't really going to help your testicles make more. So, SERMs aren't all that helpful if your LH is elevated.

For HCG, the injections are expensive and they are typically injected three times a week, so that could be a barrier for some patients. For aromatase inhibitors, they're really good for patients with symptoms of gynecomastia, and other symptoms of elevated estradiol. So, it can be used in those patients who are also concerned about fertility or testicle volume loss.

For the other testosterone replacement methods, you know, things like injections, with injections, they're on the cheaper side because you can get them through GoodRx or just, you know, prescribe it. And it costs $50 to 100 a month or less. Things to pay attention to are, with injections, you can have a big peak in the value of testosterone right after the injection in the first couple of days afterwards. And then, it can lead to a trough, so patients can feel really good, and then their symptoms can drop off quite dramatically, and you may need to adjust the timing or like the interval between the injections. And it's also thought that the peak value can contribute to erythrocytosis, which can lead to potentially cardiovascular events or clotting, although, you know, there's some debate about that.

In terms of orals, there are two pretty good options. They can reduce the serum's sex hormone-binding globulin levels, so increasing free T. But they do need to be taken twice daily, typically with food. And they're also expensive. They're not often covered by insurance. Nasal sprays like Natesto need to be administered three times a day, which can be, you know, problematic for patients, but it has a very quick on and off, which in some studies have been shown to preserve fertility, though that's, you know, a few studies looking at that.

So, there are many different things to consider in terms of replacement and there are drawbacks and benefits to each one and picking the right replacement method for each patient is critical.

Melanie Cole, MS: Before we wrap up, what advice do you have for physicians who are navigating the challenges associated with prescribing testosterone therapy to their patients?

Channa Amarasekera, MD: Yeah, I think it's underutilized just because there's a lot of fear in terms of major cardiovascular events, and that hasn't really turned out to be true based on the most recent studies, and there are a lot of men who are undertreated who have symptoms consistent with low T, who would probably benefit from testosterone replacement.

So if patients have certain symptoms like unexplained anemia or poorly controlled A1c that suddenly goes out of whack, out of range, it's reasonable to test for testosterone. If it's low, perhaps consider replacing it to see if it helps symptomatically and also with lab values.

Melanie Cole, MS: What a great topic, doctor. Thank you so much for joining us today. And to refer your patient or for more information, please visit breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. Thanks so much for joining us today.