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Alternatives to Testosterone Replacement Therapy
While testosterone replacement therapy (TRT) has become more popular and has been proven to be an effective treatment for male hypogonadism, it raises several safety concerns. In this episode of the Better Edge podcast, Joshua A. Halpern, MD, assistant professor of Urology at Northwestern Medicine, discusses alternative therapies to TRT, including selective estrogen receptor modulators (SERMs), human chorionic gonadotropin (hCG) and aromatase inhibitors. These therapies can be used to promote the endogenous production of testosterone. Dr. Halpern recently presented a plenary on this topic at the 2022 American Urological Association Annual Meeting.
Featured Speaker:
Learn more about Dr. Halpern
Joshua Halpern, MD, MS
Dr. Halpern is an Assistant Professor of Urology at Northwestern University Feinberg School of Medicine. After graduating summa cum laude from the University of Pennsylvania with a degree in History, he completed medical school at Weill Cornell Medical College, where he was also elected into the Alpha Omega Alpha Medical Honors Society.Learn more about Dr. Halpern
Transcription:
Melanie Cole: Welcome to Better Edge, a Northwestern Medicine Podcast for Physicians. I'm Melanie Cole. And joining me to discuss alternatives to testosterone replacement therapy is Dr. Joshua Halpern. He's an assistant professor of urology at Northwestern Medicine. Dr. Halpern welcome back to the show. I'm so glad to have you join us today. This is such an interesting topic. As we get into this, please tell us a little bit about the prevalence of testosterone deficiency in men?
Dr. Joshua Halpern: Yeah. So, first of all, thanks for having me back. And Testosterone deficiency is more common than a lot of men think. Although the precise prevalence is really hard to nail down there have been. A lot of studies that have tried to trace this over time on a population based level, but there's really no specific number that we can get at. That number might be in the single digits in guys, in their twenties and thirties, and probably approaches 20, 30, maybe even 40% as we see men in their later decades, sixties, seventies, and eighties.
Melanie Cole: Dr. Halpern I'd like you to give us a quick overview of the history of the AUA guidelines on male infertility, and then we can get into your recently presented. Alternatives to testosterone replacement therapy at the American Urological Association annual meeting. So first I'd like you to just kind of give us a little history of those guidelines.
Dr. Joshua Halpern: So, last year in 2021, we had the inaugural guidelines from the American Urological Association on mail infertility. This is actually a combined guideline with the American Society for Reproductive Medicine. And these are really robust and comprehensive guidelines, helping us with the evaluation and treatment of men with infertility. And as part of those guidelines, there are some recommendations and guidelines, statements about methods of testosterone administration, or how to avoid certain types of testosterone administration. And what medications are really ideal for treating men who have infertility and low testosterone.
Melanie Cole: Now you presented your alternatives. Why don't you tell us a little bit about some of the takeaways from that presentation and some of those alternative to exogenous testosterone therapies.
Dr. Joshua Halpern: Well, I think the key takeaways from the presentation at the AUA, were that for men who have low testosterone, testosterone replacement therapy is really not the only option for treatment. And in fact, for some men, It is distinctly not an appropriate option. And for those patients, we have alternatives. Specifically, for example, we mentioned men with infertility. We know that exogenous testosterone is actually bad for fertility because it can suppress the HPG access and it can suppress spermatogenesis.
So for men with low testosterone and infertility alternatives, to exogenous testosterone are really preferred. There may be some other specific circumstances for men who have low testosterone, but are not trying to achieve pregnancy where these alternatives may be appropriate as well.
Melanie Cole: What's the difference then between the first line management of testosterone replacement therapy, as you're talking about these exogenous testosterone therapies. What's the difference between looking to these alternatives and looking for the first line management of the past, however many years?
Dr. Joshua Halpern: Well, I, I don't know that I would make the distinction between first line management per se and these alternative therapies. I think it probably is very situation dependent. So we know. Exogenous testosterone, which is how we tend to think about testosterone replacement therapy is essentially the process of giving testosterone back to the body through an injection, through a gel or through some other mode of administration that gives testosterone directly to the bloodstream. However, what it does is it shuts down the body's own production of testosterone.
It also shuts down the body's production of other hormones that are important for sperm production, things like Lutinizing hormone follicle, stimulating hormone that are made in the pituitary gland and stimulate the testicles to make both sperm and testosterone. These alternative therapies tend to have different mechanisms of action. So some of these medications, for example, ch morphine citrate, or selective estrogen receptor modulators, these are actually going to stimulate the pituitary to make more of the hormones, FSH and LH.
That in turn will increase endogenous testosterone production. You've got other types of therapies such as aromatase inhibitors that block the transformation of testosterone, or rather that block the conversion of testosterone to estradiol, which also may lead to increased exogenous testosterone production. And so these are just other pathways, other mechanisms beyond giving testosterone itself, that can be very beneficial in the right patient.
Melanie Cole: So expand on that, the right patient. What does that mean? Speak a little bit about the indications for use and some of the factors that physicians should consider before recommending these therapies?
Dr. Joshua Halpern: Well, each one of these therapies has a unique indication and a unique side effect profile. And I think as we mention men who are trying to achieve pregnancy are probably one of the main target categories for these medications. Men who are trying to achieve a pregnancy should not be on exogenous testosterone. And so all of these different options are available to them, whether it be [inaudible] and aromatase inhibitor or one option we didn't mention are gonadotropins, such as HCG and FSH.
Now we use a patient's particular circumstances, whether that be their patient history their physical exam, as well as specifically their hormone profile to help determine what might be an optimal treatment for them. The other element that is really important here are a patient's symptoms. So for example, a patient who has low testosterone, who is not having symptoms of low testosterone, or is merely having symptoms of, for example, Low energy and low sex drive. Who's coming to see me for fertility, I might place that patient on a medication like clomitra or a selective estrogen receptor modulator.
However, if that patient has specific symptoms of having high estrogen levels, for example, if they're having breast tenderness, then I might wanna put them on a medication that's going to reduce their estrodiol levels and increase their testosterone levels. And that would be for example, an aromatase inhibitor. And yet there are other patients, for example, some who have inherent genetic abnormalities leading to their low testosterone and infertility, something like common syndrome, for example.
Which is a condition of hypogonad atropic hypogonadism, they necessarily will not respond to some of these other medications. And we need to give them that third option, the gonadotropin option, which is to inject them directly with HCG and FSH. So we really need to individualize this to a patient's history, their symptoms and their hormone profile.
Melanie Cole: So interesting. What an exciting time to be in your field, helping men with this issue. So how are you incorporating these therapies into your practice and when you're counseling, your patients, you're speaking to other providers here, what would you like them to know about counseling patients, about those side effects for these alternative therapies?
Dr. Joshua Halpern: Well, I think first of all, we really use these therapies on a regular basis. So it's important to know that these are not therapeutic options out of left field. These are well described in the infertility guide. Infertility doctors have been using them for decades very, very safely and with great efficacy. But I do think that it's important that we counsel our patients. And when we're thinking of other providers who might be prescribing these medications, is to know that these medications are all being used predominantly in an off-label fashion. So for example, Comotrine citrate is FDA approved for female fertility, but is used off label and men who have infertility and low testosterone.
And likewise, a lot of these medications are approved for other reasons, oftentimes for a female indication and we're using them off label. So patients need to be made aware of this and providers should be made aware of this. But having said that they tend to be very well tolerated medications. Each one of these medications does have some mild side effects, but for the most part, they are tolerated quite well. We very rarely have men who are running into issues when we treat them with a serum, with an aromatase inhibitor or with gonadotropins.
Melanie Cole: As we wrap up Dr. Halpern. I'd like you to reiterate the key things, primary care providers that you would like them to know about when they're considering testosterone replacement therapy, and some of the alternatives that are out there now.
Dr. Joshua Halpern: Well, I think one of the most important takeaways is that exogenous testosterone is really not good for men who are attempting to conceive or interested in future fertility. So in men who are presenting for fertility concerns, we really need to shy away from exogenous testosterone and think about. Trying one of these alternative therapies. And it's important to know that these alternative therapies are tried and true. There's a wealth of data to support their use. And generally they're very well tolerated.
And so beyond infertility patients, there may be other men, as I mentioned, depending on their symptom profile and their hormone profile, who might benefit from these alternatives. And it's something that we should really consider to be in our armamentarium. When we're thinking about treating the patient with low Testosterone.
Melanie Cole: Thank you so much, Dr. Halpern what an informative podcast. This was. You're such a great guest. Thank you again for joining us and to refer your patient or for more information, please visit our website at breakthroughsforphysiciansd.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.
Melanie Cole: Welcome to Better Edge, a Northwestern Medicine Podcast for Physicians. I'm Melanie Cole. And joining me to discuss alternatives to testosterone replacement therapy is Dr. Joshua Halpern. He's an assistant professor of urology at Northwestern Medicine. Dr. Halpern welcome back to the show. I'm so glad to have you join us today. This is such an interesting topic. As we get into this, please tell us a little bit about the prevalence of testosterone deficiency in men?
Dr. Joshua Halpern: Yeah. So, first of all, thanks for having me back. And Testosterone deficiency is more common than a lot of men think. Although the precise prevalence is really hard to nail down there have been. A lot of studies that have tried to trace this over time on a population based level, but there's really no specific number that we can get at. That number might be in the single digits in guys, in their twenties and thirties, and probably approaches 20, 30, maybe even 40% as we see men in their later decades, sixties, seventies, and eighties.
Melanie Cole: Dr. Halpern I'd like you to give us a quick overview of the history of the AUA guidelines on male infertility, and then we can get into your recently presented. Alternatives to testosterone replacement therapy at the American Urological Association annual meeting. So first I'd like you to just kind of give us a little history of those guidelines.
Dr. Joshua Halpern: So, last year in 2021, we had the inaugural guidelines from the American Urological Association on mail infertility. This is actually a combined guideline with the American Society for Reproductive Medicine. And these are really robust and comprehensive guidelines, helping us with the evaluation and treatment of men with infertility. And as part of those guidelines, there are some recommendations and guidelines, statements about methods of testosterone administration, or how to avoid certain types of testosterone administration. And what medications are really ideal for treating men who have infertility and low testosterone.
Melanie Cole: Now you presented your alternatives. Why don't you tell us a little bit about some of the takeaways from that presentation and some of those alternative to exogenous testosterone therapies.
Dr. Joshua Halpern: Well, I think the key takeaways from the presentation at the AUA, were that for men who have low testosterone, testosterone replacement therapy is really not the only option for treatment. And in fact, for some men, It is distinctly not an appropriate option. And for those patients, we have alternatives. Specifically, for example, we mentioned men with infertility. We know that exogenous testosterone is actually bad for fertility because it can suppress the HPG access and it can suppress spermatogenesis.
So for men with low testosterone and infertility alternatives, to exogenous testosterone are really preferred. There may be some other specific circumstances for men who have low testosterone, but are not trying to achieve pregnancy where these alternatives may be appropriate as well.
Melanie Cole: What's the difference then between the first line management of testosterone replacement therapy, as you're talking about these exogenous testosterone therapies. What's the difference between looking to these alternatives and looking for the first line management of the past, however many years?
Dr. Joshua Halpern: Well, I, I don't know that I would make the distinction between first line management per se and these alternative therapies. I think it probably is very situation dependent. So we know. Exogenous testosterone, which is how we tend to think about testosterone replacement therapy is essentially the process of giving testosterone back to the body through an injection, through a gel or through some other mode of administration that gives testosterone directly to the bloodstream. However, what it does is it shuts down the body's own production of testosterone.
It also shuts down the body's production of other hormones that are important for sperm production, things like Lutinizing hormone follicle, stimulating hormone that are made in the pituitary gland and stimulate the testicles to make both sperm and testosterone. These alternative therapies tend to have different mechanisms of action. So some of these medications, for example, ch morphine citrate, or selective estrogen receptor modulators, these are actually going to stimulate the pituitary to make more of the hormones, FSH and LH.
That in turn will increase endogenous testosterone production. You've got other types of therapies such as aromatase inhibitors that block the transformation of testosterone, or rather that block the conversion of testosterone to estradiol, which also may lead to increased exogenous testosterone production. And so these are just other pathways, other mechanisms beyond giving testosterone itself, that can be very beneficial in the right patient.
Melanie Cole: So expand on that, the right patient. What does that mean? Speak a little bit about the indications for use and some of the factors that physicians should consider before recommending these therapies?
Dr. Joshua Halpern: Well, each one of these therapies has a unique indication and a unique side effect profile. And I think as we mention men who are trying to achieve pregnancy are probably one of the main target categories for these medications. Men who are trying to achieve a pregnancy should not be on exogenous testosterone. And so all of these different options are available to them, whether it be [inaudible] and aromatase inhibitor or one option we didn't mention are gonadotropins, such as HCG and FSH.
Now we use a patient's particular circumstances, whether that be their patient history their physical exam, as well as specifically their hormone profile to help determine what might be an optimal treatment for them. The other element that is really important here are a patient's symptoms. So for example, a patient who has low testosterone, who is not having symptoms of low testosterone, or is merely having symptoms of, for example, Low energy and low sex drive. Who's coming to see me for fertility, I might place that patient on a medication like clomitra or a selective estrogen receptor modulator.
However, if that patient has specific symptoms of having high estrogen levels, for example, if they're having breast tenderness, then I might wanna put them on a medication that's going to reduce their estrodiol levels and increase their testosterone levels. And that would be for example, an aromatase inhibitor. And yet there are other patients, for example, some who have inherent genetic abnormalities leading to their low testosterone and infertility, something like common syndrome, for example.
Which is a condition of hypogonad atropic hypogonadism, they necessarily will not respond to some of these other medications. And we need to give them that third option, the gonadotropin option, which is to inject them directly with HCG and FSH. So we really need to individualize this to a patient's history, their symptoms and their hormone profile.
Melanie Cole: So interesting. What an exciting time to be in your field, helping men with this issue. So how are you incorporating these therapies into your practice and when you're counseling, your patients, you're speaking to other providers here, what would you like them to know about counseling patients, about those side effects for these alternative therapies?
Dr. Joshua Halpern: Well, I think first of all, we really use these therapies on a regular basis. So it's important to know that these are not therapeutic options out of left field. These are well described in the infertility guide. Infertility doctors have been using them for decades very, very safely and with great efficacy. But I do think that it's important that we counsel our patients. And when we're thinking of other providers who might be prescribing these medications, is to know that these medications are all being used predominantly in an off-label fashion. So for example, Comotrine citrate is FDA approved for female fertility, but is used off label and men who have infertility and low testosterone.
And likewise, a lot of these medications are approved for other reasons, oftentimes for a female indication and we're using them off label. So patients need to be made aware of this and providers should be made aware of this. But having said that they tend to be very well tolerated medications. Each one of these medications does have some mild side effects, but for the most part, they are tolerated quite well. We very rarely have men who are running into issues when we treat them with a serum, with an aromatase inhibitor or with gonadotropins.
Melanie Cole: As we wrap up Dr. Halpern. I'd like you to reiterate the key things, primary care providers that you would like them to know about when they're considering testosterone replacement therapy, and some of the alternatives that are out there now.
Dr. Joshua Halpern: Well, I think one of the most important takeaways is that exogenous testosterone is really not good for men who are attempting to conceive or interested in future fertility. So in men who are presenting for fertility concerns, we really need to shy away from exogenous testosterone and think about. Trying one of these alternative therapies. And it's important to know that these alternative therapies are tried and true. There's a wealth of data to support their use. And generally they're very well tolerated.
And so beyond infertility patients, there may be other men, as I mentioned, depending on their symptom profile and their hormone profile, who might benefit from these alternatives. And it's something that we should really consider to be in our armamentarium. When we're thinking about treating the patient with low Testosterone.
Melanie Cole: Thank you so much, Dr. Halpern what an informative podcast. This was. You're such a great guest. Thank you again for joining us and to refer your patient or for more information, please visit our website at breakthroughsforphysiciansd.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.