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Integrating Oral Testosterone Therapy into Clinical Practice

Author Grace Dima covers Integrating Oral Testosterone Therapy into Clinical Practice on BackTable Urology

Grace Dima • May 27, 2024 • 125 hits

New oral testosterone formulations like Jatenzo, Tlando, and Kyzatrex use testosterone undecanoate to bypass liver toxicity issues seen with older oral versions. These medications, taken twice daily, maximize testosterone levels during peak energy times and may lower sex hormone-binding globulin (SHBG) levels, increasing free testosterone.

Kyzatrex overcomes insurance barriers typically associated with oral testosterone therapies by being available as a cash product, simplifying access and reducing administrative burdens. Integrating oral testosterone replacement into urology clinics can enhance patient satisfaction and operational efficiency, especially when supported by Advanced Practice Providers (APPs) and in-office medication dispensing.

This article features excerpts from the BackTable Urology Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable Urology Brief

• New oral testosterone medications (Jatenzo, Tlando, and Kyzatrex) use testosterone undecanoate, which is absorbed via the lymphatic system rather than the liver. This reduces liver toxicity, a significant issue with previous formulations like methyl testosterone.

• New oral testosterone medications may lower SHBG levels, thereby increasing the proportion of free testosterone. Free testosterone is more closely associated with symptom relief including higher energy levels.

• Kyzatrex, formulated with a phytosterol excipient, can be taken with any meal rather than requiring a fatty meal, simplifying administration and improving patient compliance. Additionally, Kyzatrex has demonstrated a lower risk of erythrocytosis compared to injectable testosterone therapies, according to Dr. Andrew Sun.

• Integrating APPs into urology clinics specializing in testosterone replacement therapy and men's health services can significantly enhance clinic efficiency. APPs manage routine follow-ups, diagnostic procedures, and ongoing treatment, allowing urologists to focus on surgeries and complex cases.

Integrating Oral Testosterone Therapy into Clinical Practice

Table of Contents

(1) New Oral Formulations for Testosterone Replacement Therapy

(2) Comparing Oral Testosterone Options & Overcoming Insurance Barriers

(3) Enhancing Clinic Efficiency by Integrating Comprehensive Testosterone Replacement Services

New Oral Formulations for Testosterone Replacement Therapy

Previous formulations of oral testosterone, specifically methyl testosterone, had significant liver toxicity issues, leading to a preference for gels and injections in testosterone replacement therapy. Recently, three new oral testosterone medications, Jatenzo, Tlando, and Kyzatrex, have been introduced. These drugs use testosterone undecanoate, which is absorbed via the lymphatic system, bypassing the liver and reducing toxicity. These medications are typically taken twice a day, with the peak levels of testosterone occurring within two to four hours after ingestion. The dosing schedule aims to maximize testosterone levels during the daytime, aligning with when patients most need energy. Furthermore, oral testosterones may lower SHBG levels. Lower SHBG levels increase the proportion of free testosterone, which is more closely associated with symptom relief than total testosterone levels.

[Dr. Andrew Sun]
The newest, and in many ways, most interesting testosterones are now the oral testosterone. In a lot of ways, you think about all the versions that I've mentioned, they all have some drawbacks, right? Whether it's a side effect drawback. We haven't discussed cost or access, which is a huge issue that every patient and every urologist has knocked their head into a wall over prior authorizations and whatnot.

What do we really want? We want something that the patients can take at home. That's easy. That's got a lot of side effects, and that gets good levels, and that is safe, right? I think oral testosterone has a long history. Originally, there was methyl testosterone, which was metabolized through the liver, and had a lot of liver issues. For a long time, we didn't have orals. That's when the gels proliferated, and injections.

Now, we actually have three different orals, Jatenzo, Tlando, and Kyzatrex. They're all the same drug, testosterone undecanoate. There's slight differences between them, which we'll talk about. The interesting thing about these new oral testosterones is that because of the undecanoate ester, they're not metabolized through the liver. They're actually absorbed via the lymphatic system. They don't pass through the liver, and therefore, don't have a lot of the liver toxicity that we used to see.

It's sort of directly absorbed, and the peak usually hits within about two to four hours or so, but it's still excreted faster than say a depo injection, and that's why it's a twice-a-day dose. Most of them are recommended to take in the morning and in the evening. Sometimes I will actually tell the patients to take it in the morning and in the early afternoon to get maximum testosterone levels during the daytime when they're most likely to require or want that energy, because maybe it's not as necessary in the evenings.

When Jatenzo first came out, that was the first one to market, the biggest issue was just access. The insurance companies placed this as a third-line thing, so you had to fail the gels, and fail the injections, and then maybe you could get Jatenzo. With every other medical problem in the world, first-line therapy is usually a pill, right? The second-line therapy is usually an injection, and then the third-line is some surgery. It didn't make a lot of real-world sense to place the pill as a third-line option. It was just very difficult to get. The data was good. There's interesting data as well on SHBG. Going to a little tangent here, so all of our guidelines and most of what we treat is based on total testosterone numbers, right? The guideline number says 300. Now, real-world, does a guy with a testosterone of 302 probably, could benefit from some treatment? Yes. 300, but that's a total testosterone, and that does not take into account the extreme variability in patients' SHBG, sex hormone-binding globulin levels, or their androgen receptors, which we don't really have an assay for.

The more bioavailable version of testosterone, the one that's more correlated with symptoms, even though it's not what our guidelines are written on, is the free testosterone. In general, the more SHBG you have, the more binding globulin binds to the testosterone. That testosterone is not available, and therefore, the free testosterone goes down. We don't really have a great way of necessarily reducing SHBG, so mostly we just say, "Okay, give him more testosterone, get that total number up, and therefore the free will also rise, and we'll hope to get the effect."

What was really interesting about some of the oral testosterone undecanoate data is that it seems to actually lower the SHBG levels, therefore, proportionally increasing the free testosterone levels more than injections, or gels and whatnot. Given that the actual symptomatic benefit of testosterone seems to be coming from the increase in free testosterone, that's actually really revolutionary and attractive, and you can actually lower their SHBG levels and increase their free testosterone.

Listen to the Full Podcast

Testosterone: Navigating Options & Implementation in Clinical Practice with Dr. Andrew Sun on the BackTable Urology Podcast)
Ep 125 Testosterone: Navigating Options & Implementation in Clinical Practice with Dr. Andrew Sun
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Comparing Oral Testosterone Options & Overcoming Insurance Barriers

Insurance coverage for testosterone replacement therapy presents significant challenges, often leading to frustrations for both doctors and patients. According to Dr. Andrew Sun, medications like Jatenzo and Tlando frequently face prior authorization hurdles, causing delays and denials. The administrative burden of prior authorizations is substantial. Medical staff often spend significant time completing paperwork and dealing with denials, which detracts from their ability to focus on patient care.

To address these issues, Kyzatrex has been introduced as a cash product, bypassing the need for insurance approval. This model allows patients to access the medication directly, without the delays associated with insurance claims. By eliminating the insurance middleman, Kyzatrex becomes more accessible and reduces the administrative burden on healthcare providers.

In addition to increased accessibility through the cash product model, Kyzatrex has demonstrated a lower risk of side effects, particularly erythrocytosis, a common concern with injectable testosterone therapies. Although routine hematocrit labs are still ordered for patients on Kyzatrex, the decreased risk of erythrocytosis significantly reduces the mental burden for both physicians and patients. Furthermore, Kyzatrex stands out from other oral testosterone supplements in its ease of use; while it must be taken with a meal, it does not require an especially fatty meal for optimal absorption, thanks to its formulation with a phytosterol excipient.

[Dr. Jose Silva]
Let's talk about what you're doing right now, or have you started doing more of the oral testosterone in your practice?

[Dr. Andrew Sun]
A lot more. I will admit, it was just Jatenzo and Tlando. I, like probably most urologists, maybe tried to write for it once or twice, and it got stuck in a prior authorization somewhere, and then we gave up, right?

[Dr. Jose Silva]
What changed? In terms of Kyzatrex, so what's the difference?

[Dr. Andrew Sun]
Kyzatrex, the difference is the distribution model, because it's not available through CVS, Walgreens, conventional insurance. It's purely a cash product, right? It's just a cash payment. It's the only way you can get it. Now, as a physician, obviously, there are avenues in terms of your practice, in-office dispensing, pharmacy, specialty pharmacy, these kinds of things. For the patients, it's basically, you just take the insurance out of it, because the issue with oral testosterone in its Jatenzo and Tlando formulation was never the drug, it's the access, right?

If you can remove that barrier, and just offer it as a cash product, then it's much more accessible to patients. The truth is that for good or bad, insurance and testosterone just really don't go together. So much of the testosterone now is being done in the community, and it's mostly done through cash pay. Honestly, even testosterone cypionate, the most of the way that I prescribe it is I tell them to use a GoodRx coupon because it's probably cheaper than their insurance anyway, and I don't have the staff or the patients, honestly, to fill out prior authorizations for that forever, especially when it's $10 a month cash pay, right?

[Dr. Jose Silva]
That's very important, you mentioned the staff. The burden that the staff gets is just filling papers, getting denials, it just takes away from what they're intended to do, and they're bringing patients to the office, and getting that patient in, and working that patient, and doing stuff that will help you really not help the insurance.

[Dr. Andrew Sun]
Absolutely. I thought this would be a bigger issue, but the patients understand it too, because they've all also dealt with it. I'm waiting for the prescription, the pharmacy says it's not approved. Then, it's been a year and now, wait, I have to come off the testosterone, and then do two more low normal morning labs just to be able to prove that I still have low T, even though there's no biological reason why I should have changed at all. It's definitely a big burden.

Because Kyzatrex is available as a cash product, I have started to prescribe it a lot more, and I prescribe it as a first line drug, because I think that is where orals sort of in general belong, right? Most people, when offered an option for most issues, their first thought is, "Can I take a pill for that?" We didn't have a pill or an inaccessible pill, so we had to tell them, "You have a gel or an injection." Now, the first line option in my mind should be a pill, because it's easy. The safety profile is also outstanding. I'll talk about that for a second.

We talked about injections, polycythemia, erythrocytosis, these kinds of issues. The oral testosterone undecanoate data, for example, in the Kyzatrex clinical trial, the percentage of erythrocytosis was zero, literally zero, which is a huge burden alleviated from my mind, and the patient's mind. Honestly, from their schedule, because we definitely have these guys, right? They're donating every three months, and we're constantly keeping an eye on the hematocrit and stuff. To not have to do that, it's a huge time saving for everybody, and it takes a sort of mental burden off of all of us, right?

[Dr. Jose Silva]
Do you still order the lab just in case?

[Dr. Andrew Sun]:
Oh, yes, I still order the labs. My general protocol is if I'm changing something, I'm going to check it in three months. If I haven't changed anything, and you've been pretty static, it'll be six months, basically for everybody. I still order the labs. I'm still always checking their testosterone, their free, their estradiol, their hematocrit, their PSA. The monitoring is the same, but I just haven't seen that hematocrit issue that we normally get so often.

The one thing is, I was talking about how to take it. Oral testosterone does have to be taken with a meal. The original testosterone, like Jatenzo, has to be taken with a fatty meal. One of the other unique things about Kyzatrex is that it's formulated with a phytosterol excipient that basically helps its absorption in the lymphatic system. You still need to take it with a meal, but it does not have to be a particularly fatty meal. You just have to take it with any meal, because this phytosterol excipient helps the absorption through the lymphatic system. It makes it a little bit easier for people.

[Dr. Jose Silva]
I guess based on that patient of yours that you had that took the Natesto as a booster, you can do the Natesto first, then after workout, eat something, and get the Kyzatrex. Maybe.

[Dr. Andrew Sun]
Maybe a little Clomid, a little Natesto, a little Kyzatrex. I didn't tell him to do that, of course. Actually, that brings up a good point, which is that, one of the most interesting things, like I said about Natesto, is that it's quick on, quick off. The oral testosterones seem to have that same effect, right? That's why you have to take it twice a day. I've also been tracking, there's no data for this, so just, this is my own personal data, but in looking at those patients, when I check their FSH and LH levels after being on therapy, they definitely go down, but they do not seem to go to zero either, which, of course, piques all sorts of interest in terms of, is this also, testis sparing, you could say?

Is it preserving fertility? I think these are interesting questions that hopefully we'll get some answers to. That is part of my idea of better testosterone. You would love to be able to get a testosterone that gets the same symptomatic benefits as testosterone replacement, which Clomid sometimes does not, but without the complete endogenous suppression and the side effects that the patient can also take at home. I think it's very revolutionary.

[Dr. Jose Silva]
Andrew, for that patient that goes to your office expecting that the insurance covers everything, how do you talk to that patient and tell them, "Hey, we can waste our time dealing with insurance or we can do this." How is that talk?

[Dr. Andrew Sun]:
Yes, that's how I say it. I tell them, look, testosterone and insurance do not mix. Your insurance company is going to make us jump through 20 hoops. If there's one thing that urologists and patients can always agree on, it's our mutual disdain for insurance companies. I tell them, "You got to do these two morning labs, probably you have to fail two things. Even still, you might have to continuously redo this authorization every year."
Most patients understand that. I think people are understanding that some of this stuff is just in the realm of cash pay. It's not that expensive. I also tell patients, if you want generic injections, old mainstay, you drop the medication, you do the needle, you do it yourself. You're looking at maybe $30, $40 a month, right? That is not bad. A dollar a day for your testosterone. If you want a fancy version of testosterone, whether that's a Xyosted, whether that's a Natesto, whether that's an oral, or whether that's cash pay pellets, you're looking at about $150 to $175 a month, which seems like a lot more than the injections, but it's a Starbucks a day, but it's giving you a lot more energy and health benefits than that Starbucks every day is.

I was a little bit surprised at how little resistance there was to that. I think we all get it, and sometimes I just level with the patients. I tell them I don't have enough staff or time in the day. I would need to hire three people to sit in a room just filling out this paperwork, and you'll have to wait two extra months just to try and get this medication. It's just not worth our time. We want you to get on treatment, and we want you to get the symptomatic benefits, and we want to know that that's going to happen. They're like, "Yes, sure, let's do it." Actually, it works out pretty well.

Enhancing Clinic Efficiency by Integrating Comprehensive Testosterone Replacement Services

Integrating testosterone replacement into urology clinics can not only enhance patient satisfaction and access but also boost the clinic’s profitability when executed effectively. Establishing men’s health centers that focus on testosterone replacement therapies, erectile dysfunction, and post-prostatectomy rehabilitation streamlines operations and improves efficiency through centralized care and standardized protocols.

APPs play a crucial role in these clinics by managing routine follow-ups, diagnostic procedures, and ongoing treatment. This delegation allows urologists to concentrate on surgeries and complex cases, improving overall efficiency and patient care. By incorporating APPs into the practice, clinics can offer comprehensive care while alleviating the administrative burden on urologists.

Clinics can further streamline the testosterone replacement process by offering in-office dispensing, providing immediate access to medications like Kyzatrex and enhancing patient convenience and adherence to treatment. This "one-stop-shop" approach eliminates the need for patients to visit external pharmacies. Additionally, large group practices can partner with specialty pharmacies or establish their own in-house pharmacies to manage medication distribution effectively, simplifying logistics and reducing delays. Partnering with specialty pharmacies also allows for the direct shipment of medications to patients, which is particularly beneficial in states where in-office dispensing is not permitted.

[Dr. Jose Silva]
Excellent. I think we have covered a lot of stuff regarding testosterone. In terms of how can you make it profitable as a urologist? Because sometimes, I'm sure your partners were happy when they started sending the testosterone patient to you. Because sometimes those testosterone patients, it takes a while to talk to them, and we as surgeons, we're trying to get people in the OR. How does a urologist make money out of this?

[Dr. Andrew Sun]
There's definitely a lot of pieces to that, and I think having a sort of dedicated men's health center is definitely advantageous because we deal with it all the time so that our partners don't have to deal with it. Because we deal with it so much, our efficiency and our sort of talk track, most of what I'd I'd just explained about all the different testosterones, I basically have it written down.

When the patients are coming in, they just sort of get this primer. It's like, "Here are all the options. Here's the pluses and minuses." It's a much quicker conversation that way. A few things, right? The dedicated center is really nice to be able to centralize that. I cannot overstate enough the importance of having APPs in the men's health space in general, but especially testosterone.

Most of this long-term follow-up is a great thing to have APPs help out with. I have two. They don't really work for me. I work for them because I just talk to the patients and hopefully do surgery, right? They're really doing all that. In fact, my APPs do my duplex ultrasounds, my xiaflex, my trimix, my testosterone management. It really helps alleviate the burden so that I can concentrate on surgery. APPs are huge.

Then it's about, how do you actually make it a meaningful part of your practice from a financial standpoint? In that realm, we want, I think, to take a little bit of a lesson from the hormone clinics, right? A lot of these places have definitely figured out a business model. I'm not saying that it's necessarily the right business model, but many versions of testosterone can be utilized in that fashion.

For example, Kyzatrex, like we talked about, oral testosterone, since it's not available through CVS, you can get the product to a patient either through in-office dispensing, and UroGPO, Specialty Networks has contracts and agreements with some of these companies, and you can purchase the medication and do in-office dispensing, you can utilize a pharmacy if you have the many large group practices, like our practice, we have our own pharmacy that helps us work with these kinds of medications, oncolytics, a lot of things.

or you can use Specialty Pharmacy. In that sense, at least you are sort of unburdening yourself from a lot of the paperwork, which in and of itself is actually significant revenue-saving, right?



You can also dispense testosterone yourself, if you have the means to do that. I think the other thing to make people aware of is that, yes, if you just take testosterone for what it is, it definitely, for many urologists, it seems like a burden, but if you can unburden yourself from many of those insurance hassles, that's 90% of it. The realization that the low T patient almost always has other relevant urologic diagnoses to treat, right?

ED, BPH, PSA issues, prostate cancer, you're screening all these guys for PSA, and, if you get them into your practice, simultaneously, you're helping these guys out a lot, you're giving them a much better quality of life, you're doing it in a safe and responsible way, checking the labs, and being on top of things medically, but they're also in your practice, and eventually, when you have other things that come up, that's what we as urologists are equipped to do. They may not be getting that from this sort of pure hormone clinic situation.

[Dr. Jose Silva]
Andrew, you mentioned a lot of things, how to be successful. If there's any specific thing that you want to add in terms of how to successfully execute the men's health program?

[Dr. Andrew Sun]
I think it definitely takes somebody with passion, and not every urologist has that passion, and that's okay, because a lot of us do, and if you have that person, and you give them the means to execute on that vision, it can be a huge boon for any urology practice. You're going to take care of more patients, you're going to improve patients' quality of life. We've spent most of our time talking about testosterone, but obviously, in the men's health clinic, we also do a lot of post-prostatectomy rehab, and quality of life, and erectile dysfunction, and sexual dysfunction, and these are issues that patients definitely have.

These are issues that young men care about, and are ways to engage them in healthcare to hopefully better their outcomes in the future. They can be good ancillary streams for any practice. If you develop a champion in that space, and I can't state it enough, APPs are a huge part of it, I think so.

[Dr. Jose Silva]
Andrew, you mentioned that, for example, Kyzatrex is not in CVS, and you cannot get it in a regular pharmacy. How do you get the access? How can you get it?

[Dr. Andrew Sun]
A lot of different ways. For our practice, we have a pharmacy, and so, I basically have it in my pharmacy. It's really convenient, because I can see a patient, I can talk to them, and say, "Okay, here are the options, what version of testosterone do you want to do? You want to start the pill? Great. Walk down the hall, pick it up, go home today, take the pill tomorrow morning." You can't do that with any version of testosterone. That makes our practice so much easier, my life so much easier.

One thing I want to mention for follow-up, I think telemedicine has been really crucial. The initial low-T consult to explain all these options to really do a good job, going through all that, it does take a while. Low-T follow-ups do not take that much time. My first half hour of my clinic is just stacked telemedicine consults, which are mostly the three-month or six-month follow-ups. Once I have them on a stable pathway, then, my PAs, we share that telemedicine group of patients, we're doing testosterone follow-ups, and, that you can do 6, 7, 8, 9, 10 patients when it's just a testosterone follow-up in a pretty quick amount of time.

That's been a huge thing. I definitely think telemedicine should be chunked into a block, right?

[Dr. Jose Silva]
I do it at the end of the day.

[Dr. Andrew Sun]
Yes, at the beginning of the day or at the end of the day, for sure. In terms of access, pharmacy is one option. In-office dispensing is another option. Some states don't allow it, but most states do. Many urology practices already do this with oncolytic drugs and whatnot, the prostate cancer medications. It's a relatively straightforward thing to set up for in-office dispensing.

Then the third option is that there are some specialty pharmacies that, Marius Pharmaceuticals, the company that makes Kyzatrex has partnered with, you can send the prescription to them, and they can basically send it to the patient. A variety of different options, all of which significantly increase the access to care for the patients and decrease my paperwork burden, which is great.

[Dr. Jose Silva]
Exactly. Andrew, anything else you want to add? I think we covered a lot. I think you were very on point, and you explained everything very well. Anything else?

[Dr. Andrew Sun]
No, I think, every urologist, I'm sure, has dealt with testosterone. My goal is to convince everybody out there that men's health stuff, whether it's testosterone, whether it's Peyronie's, it can be actually really rewarding patient-wise, cognitively, scientifically, and practice-wise. You don't really have to see it as a burden. If there's somebody that should be doing this, it should be us, right? Urologists, men's health, we should be the ones that help the patients out with these kinds of options.

There's a lot of options out there. You definitely want to be complete in sort of explaining all of the different ways that these things affect, because there's probably more misinformation about testosterone on the internet than almost anything else, right? A lot of great options. Yes, the world is your oyster when it comes to testosterone.

Podcast Contributors

Dr. Andrew Sun discusses Testosterone: Navigating Options & Implementation in Clinical Practice on the BackTable 125 Podcast

Dr. Andrew Sun

Dr. Andrew Sun is a men's health urologist at Urology Partners of North Texas in Arlington.

Dr. Jose Silva discusses Testosterone: Navigating Options & Implementation in Clinical Practice on the BackTable 125 Podcast

Dr. Jose Silva

Dr. Jose Silva is a board certified urologist practicing in Central Florida.

Cite This Podcast

BackTable, LLC (Producer). (2023, October 6). Ep. 125 – Testosterone: Navigating Options & Implementation in Clinical Practice [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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