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Testosterone and Prostate Cancer: Testing & Treatment Modalities

Author Olivia Reid covers Testosterone and Prostate Cancer: Testing & Treatment Modalities on BackTable Urology

Olivia Reid • Dec 21, 2023 • 48 hits

Urologist Jose Silva and endocrinologist Rodrigo Valderrábano explore the complexities of testosterone and prostate cancer care treatment, sharing critical clinical insights and diagnostic techniques. Dr. Valderrábano advocates for a comprehensive approach that considers the limitations of conventional assays in measuring testosterone levels. It is vital to evaluate not solely total testosterone but also free testosterone and sex hormone-binding globulin levels, alongside LH and FSH, to differentiate primary from secondary hypogonadism. Historical factors like childhood mumps or testicular trauma have been known to contribute to future hypogonadism.

Doctors Silva and Valderrábano also delve into the practical considerations of various treatment modalities for testosterone replacement, including injections, gels, patches, pellets, and newer formulations; each of which come with their own challenges in accessibility and insurance coverage.

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

• Testosterone plays a vital role in male physiology, impacting development, sexual function, energy, and muscular strength.

• There are many challenges in accurately measuring testosterone levels due to assay variability and diurnal fluctuations. Thus, clinical guidelines include considerations of total and free testosterone levels alongside symptomatic presentations.

• In testing for hypogonadism, the use of liquid chromatography-mass spectrometry to measure total and free testosterone has shown more accurate results than the previously used conventional arrays.

• Historical events such as childhood mumps or testicular trauma can contribute to future hypogonadism in males.

• Testosterone gels allow for steady delivery and reduced pituitary suppression compared to injections, which may pose peak-and-valley effects throughout the day.

• Considerations and hesitations with newer formulations for testosterone treatment, like testosterone undecanoate pills and intranasal formulations, have arisen due to limited accessibility and insurance coverage, despite reported benefits in clinical trials.

Testosterone and Prostate Cancer: Testing & Treatment Modalities

Table of Contents

(1) Testosterone and Prostate Cancer Treatment

(2) Differentiating Hypogonadism with Comprehensive Hormone Testing

(3) Comparing Testosterone Replacement Therapies

Testosterone and Prostate Cancer Treatment

Dr. Rodrigo Valderrábano details the intricate relationship between testosterone and prostate cancer treatment, explaining the pivotal role testosterone plays in male physiology. Testosterone, primarily secreted from the testicles and regulated by the pituitary gland, impacts not just male physical traits but also sustains sexual function, energy levels, and muscular strength in adulthood. It has been found that there is a significant connection between testosterone, estrogen, and bone health, meaning that testosterone's conversion into estrogen contributes significantly to maintaining bone density in men.

Dr. Valderrábano emphasizes the need for a nuanced approach to diagnosing low testosterone based on symptoms, cautioning against relying solely on lab values due to their variability throughout the day. Furthermore, the complexities of determining hypogonadism in patients involves considering the interplay of comorbidities, necessitating the correlation of low testosterone levels with symptomatic presentations. Such comorbidities could include conditions like obesity and sleep apnea, which could potentially be managed through lifestyle interventions like weight loss before taking a more aggressive approach for the elevated estrogen levels through aromatase inhibitors or clomiphene treatments.

[Dr. Jose Silva]
You mentioned bone health. We as urologists, we treat prostate cancer and we start patients on Lupron or other anti-hormonal treatment. We mention the consequences, but not going into details or follow-up in terms of what's going on with the patient's body. Let's talk about what testosterone means in the body and why we need it.

[Dr. Rodrigo Valderrábano]
Sure. Testosterone is the male-type hormone. It is secreted in men mostly from the testicles. It's controlled by the pituitary gland, so we have hormones that go from the brain and tell the testicles what to do and then testosterone and estrogen get sensed in the brain. That's how we maintain our balance. Testosterone has a huge role in development obviously of a male phenotype, so male characteristics, but in adulthood, it is very important to maintain sexual function. It's important to maintain energy and vitality and also proper muscular strength and muscular mass.

[Dr. Jose Silva]
The relationship between bone and testosterone, what is it?

[Dr. Rodrigo Valderrábano]
That's an interesting and maybe a more loaded question than you thought. Testosterone interacts with bone in many different ways. Testosterone gets converted into estrogen and estrogen maintains bone. That's why women after menopause will lose bone mass. Actually, many people thought that estrogen was for women and testosterone was for men. Actually, it's also estrogen for men that controls bone density, but all of the majority of estrogen in men is derived from testosterone. Anything that affects testosterone will, in effect, then move on to estrogen and then to bone.

In the setting of prostate cancer, it's incredible to me that we don't pay attention to this as much as we should. When women get treated with anti-hormonal agents for breast cancer, it's a huge deal. It's really come more into the forefront of therapy, especially now that our treatments are getting better and now we worry about long-term effects of our medications. Definitely, testosterone is indirectly the main driver of bone health in men. Obviously, if you have low testosterone and you have low muscle mass and strength, that also will by virtue of decreased loading on bone and decreased torsion and tension on bone, you will also start losing bone over time.

[Dr. Jose Silva]
You mentioned low testosterone. You as an endocrinologist, what are the parameters to say that the patient has low testosterone? Based on symptoms or a combination of both? Because I know it's always changing. Or people have their own information, their own opinion on what exactly is low testosterone.

[Dr. Rodrigo Valderrábano]
Yes, this is exactly why I had to give that disclaimer because you can get into trouble with all these. I think it's important to recognize a couple of things. Number one, the radioactive immunoassays, the regular tests that are used for testosterone are pretty bad in terms of that they're not very precise. That's one thing. If you got a blood test done on separate assays, if you've got five blood tests and got them done at the same time but on different assays, you might get different numbers.

Another thing that's really important, testosterone naturally goes down during the day. We did a study when I was at Stanford in Palo Alto where we looked at people that had gotten their testosterone level at the VA and outside. The take-home message is even just an hour later, testosterone could be lowered by like 100 points, so it could make a real difference. We try to use good tests. We try to standardize it, do it early in the morning, 8:00 to 10:00 in the morning. Then, don't just think about the number. There's a lot of other things that can affect testosterone like sex hormone-binding globulin. Exercise and stress can move it around and then it bounces back naturally. We really want more than one test to determine whether testosterone is really low. Current guidelines agree that around 300 or maybe under 275 total testosterone is considered low. In terms of free testosterone, which we look at as well, if you directly measure free testosterone, you can use those numbers too, but I like to think about the number 75 micrograms. That's because in our group when we looked at young men who didn't have diseases, everyone was 75 or up for free testosterone.

When you see low testosterone, you start thinking about it, and then you have to have symptoms. That's really the thing. You need to have especially sexual symptoms, so you asked, are people having morning or nighttime erections. You ask about libido, sexual desire. The caveat is that there are many things that go into sexual desire: state of mind, whether you've slept or not. All of these things are also important. You really need the low number and you need symptoms to really determine whether someone's hypogonadal.

It gets dicey because people that have obstructive sleep apnea or people that are obese can have lower numbers for their testosterone, but it doesn't mean that they are hypogonadal. It's just that their comorbidities are bringing testosterone down. There ideally, you would have someone lose weight and testosterone would bounce back up, whereas for someone that has an organic disease due to pituitary problems or testicular problems, you really do need to think about giving testosterone.

[Dr. Jose Silva]
Then that patient that you just mentioned, sometimes I see that they have elevated estrogen. Is it something that you should start those patients on aromatase inhibitors to boost their testosterone or it depends just on the symptoms?

[Dr. Rodrigo Valderrábano]
Like I was mentioning before, most of the estrogen in the body comes from testosterone in men. The more fat mass you have, the more aromatase you have, and so you have higher levels of estrogen. There you would want to treat the root cause. You would want to try and get someone to lose weight and that could go away. There are no FDA-approved indications for the use of aromatase inhibitors for men that have high estradiol levels. There are some case reports that it can help, certainly, but you have to be careful about how you do it. You could also affect bone density by giving aromatase inhibitors. That's the big thing in women with breast cancer, that you can lose 10 to 15% of your bone mass in a year. Very, very high levels of bone loss, so because of my focus on bone, I'm less keen on using aromatase inhibitors. We always want to at least try to get the person to lose some weight beforehand. Improving sleep apnea may help with testosterone levels as well. At the very least it's a good idea.

[Dr. Jose Silva]
Because those patients, they always say, "Well, I don't have the energy to lose weight. I need something now." Then, they want the testosterone. I say that in my clinic I see both. I have the patient that just continues doing nothing. He says that testosterone doesn't work, but the other one that really motivates himself and starts losing weight and at some point, like you said, maybe they don't need the testosterone anymore. I think the few cases of patients that once I start testosterone they don't need any more are the ones that lose a lot of weight.

[Dr. Rodrigo Valderrábano]
Yes, that definitely does help. Testosterone is an anabolic hormone, if they don't also increase their physical activity, they're going to actually gain weight with the testosterone but you're right, there's a subset of people that have terrible symptoms and you give them testosterone and they do really well. I've had patients like that as well in my clinic. That's why you have to personalize what you do.

For these people that have obesity and sleep apnea, you could also consider using clomiphene. Clomiphene is a serum, a selective estrogen receptor modulator that is used in fertility. Essentially what it does is it helps increase cycling of our pituitary hormones, on our gonadotropins and some people do really, really well on the clomiphene. It's an off-label use, but there are studies that have taken it out to two to three years and it's very safe. Without the risk factors that we deal with when we treat with testosterone. Honestly, there's less bother in the prescription and it's not a controlled substance and some people do excellent on it.

Listen to the Full Podcast

Testosterone Replacement in Prostate Cancer Survivors with Dr. Rodrigo Valderrabano on the BackTable Urology Podcast)
Ep 98 Testosterone Replacement in Prostate Cancer Survivors with Dr. Rodrigo Valderrabano
00:00 / 01:04

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Differentiating Hypogonadism with Comprehensive Hormone Testing

Dr. Rodrigo Valderrábano elaborates on the diagnostic approach for hypogonadal patients visiting his clinic. There is a need for a comprehensive workup, particularly in assessing testosterone levels. This is due to the limitations of conventional assays, which has given rise to an alternative approach to measure total and free testosterone using liquid chromatography-mass spectroscopy. Sex hormone-binding globulin levels must be considered alongside total testosterone because low total testosterone coupled with normal free testosterone might not signify hypogonadism. Additionally, the evaluation of the luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels is often completed during this workup due to its ability to differentiate between primary and secondary hypogonadism. Dr. Valderrábano shares insights into potential causes of hypogonadism, such as childhood mumps or testicular trauma, explaining how these historical events might lead to future testosterone deficiencies and altered hormonal axes.

[Dr. Jose Silva]
Awesome. No, that's great information. Rodrigo, when a patient goes to your clinic, they have hypogonadal symptoms, what test do you order?

[Dr. Rodrigo Valderrábano]
Again, very important. Generally, I'm the testosterone guy, I'll do a little bit more extensive workup. Generally, when they come to me, they've already had some testosterone level. I generally will look at what they've had done. A lot of the time the testosterone levels get drawn in the afternoon, especially in younger men when they go to clinics after work. I will order a total testosterone and free testosterone measured by mass spectrometry liquid chromatography. That's still not perfect, but it's better than radioactive immunoassay. You can order sex hormone-binding globulin. A lot of older men have lower levels of sex hormone-binding globulin and that will bring your total testosterone down and make it look like you have low total testosterone, but then you get the free testosterone and that's normal. Sex hormone-binding globulin carries testosterone and the total testosterone level is an additive of testosterone that's bound to sex hormone-binding globulin and free testosterone. If you find a low total testosterone, but a low sex hormone-binding globulin and a normal free testosterone, this is a person that may not have hypogonadism. Then to confirm, what you want to do is look at the LH and FSH, the luteinizing hormone and follicular stimulating hormone. People that have secondary hypogonadism that might be normal or it might be slightly low. In people that have testicular problems, that should be high.

One thing that never fails to surprise me are people that have had mumps in childhood. If you go out long enough, there's almost 50% of people that eventually get low testosterone levels after having mumps, mumps orchitis. They don't always remember having testicular swelling in childhood but I think it's- you get a hit and then when you're young and healthy, your testicles are able to overcome the hit and make up for it, then as you get older and you get less vascular supply, things start changing and then eventually, the testicles can't keep up and you make low testosterone. There you would see high LH and FSH and for me, that's a slam dunk because if the end organ isn't working, those are the easiest cases, then you definitely will treat with testosterone.

Sometimes people get hit by trauma to the testicles, which could do it, and then you have high LH and FSH. I had a guy who practiced Krav Maga and I guess he had an overzealous instructor that kicked him in the testicles a couple of times then he actually had hypogonadism.

[Dr. Jose Silva]
Wow. FSH and LH, you would order all the time? It just depends on the patient if they're younger?

[Dr. Rodrigo Valderrábano]
No, I would order it in the full workup. Before deciding on treatment, I would do it for sure. It also gives you a baseline, and then if you end up suppressing FSH and LH later-so if it's normal, and then let's say after a year of testosterone, the person wants to stop or wean off, you can get LH and FSH again. If they're very suppressed, they're zero or they're almost undetectable or very low, then you know that they're very suppressed, you have to take it easy and you may want to consider doing something like weaning off the testosterone, but also giving clomid at the same time to boost that axis back up.

[Dr. Jose Silva]
For follow-up, do you always do FSH, or just if you want to wean them off?

[Dr. Rodrigo Valderrábano]
It's case by case. I wouldn't just do FSH, LH all the time in terms of monitoring, but if I want to know whether I have suppressed them or sometimes when people come and they've been on testosterone for years and I want to see where they're at, then I would definitely get that.

[Dr. Jose Silva]
Patients that want to keep fertility, are you doing growth hormone in those patients or?

[Dr. Rodrigo Valderrábano]
Do you mean HCG?

[Dr. Jose Silva]
HCG, yes.

[Dr. Rodrigo Valderrábano]
Essentially, human chorionic gonadotropin, HCG, is essentially a mimic of LH. You would do that when the pituitary-it's a way to bypass the pituitary gland. Typically, people that have received testosterone, you can get away with using clomiphene and restarting the axis, and then if that doesn't work, you could try LH, HCG, and then if that doesn't work, then it's up to you guys in the urology world to do the testicular biopsies and see if they can retrieve some sperm directly, but those are rough, they're associated with very, very high rates of hypogonadism if they aren't hypogonadal.

Comparing Testosterone Replacement Therapies

There are a variety of testosterone replacement options, however, Dr. Valderrábano prefers testosterone gels due to their steady delivery, which mimics the body's natural testosterone release and minimizes pituitary suppression when compared to testosterone injections. With this, there are practical aspects and cautions regarding gel application, especially in households with small children or female partners, due to the increased risk of accidental exposure. Injections are also a viable option, although, concerns arise with peak-and-valley effects towards the end of the dosing interval, mitigated by more frequent, smaller doses. Other alternatives like patches, though effective, can cause dermatitis and may dislodge, particularly in active individuals. Newer options such as testosterone pellets, testosterone undecanoate pills, and intranasal formulations have been added to the market, yet may pose challenges in accessibility and insurance coverage, according to Dr. Valderrábano.

[Dr. Jose Silva]
Yes, recently, I think there's a shortage of clomiphene, clomid, and it is been a challenge for patients to continue their treatments, but we're using compounding pharmacies and definitely that has helped but the regular pharmacies, for some reason they don't have it at least in the Orlando area. Rodrigo, in terms of treatment options for testosterone, I find myself always giving injections at the end of the day because that's mostly what the insurance covers. What's your preference?

[Dr. Rodrigo Valderrábano]
Yes actually, the injections are totally reasonable, but my preference is actually the gels.

[Dr. Jose Silva]
They're more natural. They do what the body is supposed to do. They boost in the morning, but they don't at night.

[Dr. Rodrigo Valderrábano]
Yes, that's right. I do it because you get less pituitary suppression. If somebody's on injections for a long time, they can have androgen withdrawal when you try to wean them off. With the gels, you get an even level of testosterone. You don't get these peaks and valleys. Most people do well on it.

The thing to consider with the gels is that if you have small kids or if you have a female spouse, it can get dicey if they get the gel on them. It really dries within 15 minutes but there is some trace gel there for several hours after. If you have small kids and they're jumping on you and they get some of it on them, things can get hairy, literally.

The injections are very good too. Generally, my second go-to are usually the injections, but what I find is sometimes at the tail end, so if you're doing for example, 200 milligrams every two weeks at the tail end, some people are running out and then they feel really fatigued at the tail end, but what you can do then is instead of doing 200 every two weeks, you could do 100 every week and that's good. Some other forms, there's patches as well. I've seen that work for some people, but they do cause a lot of dermatitis and the patch falls off and then that's the problem, but that's available.

[Dr. Jose Silva]
Yes. Especially patients that sweat a lot. It falls. Yes. They're going to the gym, yes.

[Dr. Rodrigo Valderrábano]
Definitely in the Orlando area it's a bigger problem than in the Boston area, but those are good. You have the-- I don't know if you implant the pellets? Some people really like those.

[Dr. Jose Silva]
No, I'm not doing that in the clinic. I started doing it, but it was a mess trying to get the insurance to cover it. It took too many resources from the office so I just stopped doing it.

[Dr. Rodrigo Valderrábano]
People like it while it's on, and then they can get some scar tissue. I've never seen someone that really stays on it for years and years. They'll use it for a while and then they'll stop. Then, there's a pill now that's a testosterone undecanoate pill. That one, it's hard to cover because it's newer and more expensive. That also in the clinical trials, it did increase blood pressure a little bit. I sometimes hesitate to use those in people that have high blood pressure.

[Dr. Jose Silva]
There's also, I think it's new: the intranasal one, have you seen that one? They use it four or five times, I think it's three or four times a day. I usually use the intranasal chart. Supposedly in terms of the axis, it doesn't have any major side effects. That's how they sell it because it is short-acting, but I think I tried twice for patients and the insurance didn't cover it.

[Dr. Rodrigo Valderrábano]
Yes, I haven't been able to access that myself either. I'm not as familiar with the data on those, so I can't comment on the effectiveness of it, but I know it is out there.

Podcast Contributors

Dr. Rodrigo Valderrabano discusses Testosterone Replacement in Prostate Cancer Survivors on the BackTable 98 Podcast

Dr. Rodrigo Valderrabano

Dr. Rodrigo Valderrabano is an endocrinologist with Brigham and Women's Hospital in Boston, Massachussetts.

Dr. Jose Silva discusses Testosterone Replacement in Prostate Cancer Survivors on the BackTable 98 Podcast

Dr. Jose Silva

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

Cite This Podcast

BackTable, LLC (Producer). (2023, May 17). Ep. 98 – Testosterone Replacement in Prostate Cancer Survivors [Audio podcast]. Retrieved from

Disclaimer: The Materials available on 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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