Testosterone is certainly about sex, strength, and virility, but it is also associated in complex ways with other aspects of men’s health. Learn more about this, and when testosterone should be assessed and replaced if needed.
Martin M. Miner, M.D., Clinical Associate Professor of Family Medicine and Urology, the Warren Alpert Medical School of Brown University, Co-Director of the Men’s Health Center, The Miriam Hospital, Providence Rhode Island.
During This Episode We Discuss:
- Myths and facts about testosterone.
- Sexual signs and symptoms of low testosterone.
- Who should be on testosterone replacement therapy and who shouldn’t be on it?
- How to determine if your testosterone is low.
- Types of Testosterone Replacement Therapy (TRT) and appropriate monitoring.
“Men have to have both low levels and clinical signs and symptoms of low testosterone to be considered to have testosterone deficiency.”
“Testosterone replacement is complicated. It’s important to find that provider who has the knowledge about appropriate replacement.”
Martin Miner, M.D.
The American Urological Association Guidelines on Testosterone Deficiency
Dr. Richard Pelman (00:06):
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Dr. Richard Pelman (01:06):
Hi, this is Dr. Richard Pelman, your host of the Original Guide to Men’s Health brought to you by the Washington State Urology Society. Our podcast today is all about testosterone*. Have you been hearing about testosterone deficiency**? Are you wondering if you are one of these men? Is testosterone the key to the fountain of youth or better sexual health? Find out the science behind testosterone and testosterone deficiency as we speak with Dr. Martin Miner. Testosterone. Who needs it? Who doesn’t? Find out on this episode of The Original Guide to Men’s Health.
**Testosterone deficiency: https://www.urmc.rochester.edu/urology/adult-patients/andropause-hypogonadism.aspx
Dr. Richard Pelman (01:52):
Many men are interested in testosterone. It seems that now with direct to consumer advertising, we are seeing an awareness about testosterone deficiency that is driving a testosterone market up substantially. There are now guidelines from the American Urological Association on testosterone replacement therapy. These can be found at auanet.org. I have a member of the committee, Dr. Martin Miner, who will be able to give us a little background into why the guidelines were important to establish, and some basics on the guideline and testosterone replacement therapy and testosterone in general. Dr. Miner.
Dr. Martin Miner (02:34):
Thank you, Rich. Testosterone is that hormone which is key to a man’s sense of virility, a man’s sense of youthfulness. And we often think about testosterone in light of the men who have abused anabolic steroids or testosterone, those muscle builders, and look at their bodies and think, “Do we really want to have bodies like that?” Or do we want to be in a position to use a hormone that has been abused in the past? And it’s so controversial. This issue of testosterone repletion for a condition of testosterone deficiency and the guide and the AUA, we did call this testosterone deficiency just like you would talk about another hormone deficiency like thyroid deficiency. The reason that we called it this is because there are many medical conditions that give rise to low testosterone levels. And these men experience symptoms associated with testosterone deficiency. Now these symptoms are rather nonspecific and many people think of them as marked fatigue and diminished energy.
Dr. Martin Miner (04:05):
And clearly it can be marked fatigue and diminished energy. But in this field, what we consider to be classic signs and symptoms of testosterone deficiency are the sexual beginning, the sexual signs and symptoms. And those include a significantly reduced libido or sexual desire, some erectile dysfunction*, and what we call the loss of spontaneous erections. Spontaneous erections are morning erections that men have when they awaken and they feel hard. So these symptoms, the sexual symptoms, plus perhaps some diminished mood, and more fatigue and what I find men describing as a loss of anything satisfactory in life. They’re almost in what they call a brain fog. These are classic signs and symptoms of testosterone deficiency. And when men have those clinical signs and symptoms of testosterone deficiency and low levels, which in the United States is considered to be below 300 nanograms per deciliter, those men are considered as candidates for testosterone therapy. So before we even talk about the advantages or risks of testosterone therapy, I just wanted to clarify that men have to have both low levels and clinical signs and symptoms to be considered to have testosterone deficiency.
*Erectile dysfunction: https://www.mayoclinic.org/diseases-conditions/erectile-dysfunction/symptoms-causes/syc-20355776
Dr. Richard Pelman (05:49):
I like to review with patients, however, that many of the signs and symptoms are multifactorial. So for instance, if I have a patient who has high blood pressure that hasn’t been treated, elevated cholesterol that’s not well-treated diabetes, they’re going to expect that there’s issues as far as erections. And it may not be testosterone based at all. It’s as we call the basic issue as a cardiometabolic* disease that the small blood vessels, small vascular spaces are not responding to blood flow nor are they able to generate the blood flow because of the underlying systemic diseases. So it isn’t necessarily testosterone. So you have to sort that out.
Dr. Martin Miner (06:33):
Absolutely, and that’s where it’s done by a provider who’s knowledgeable about this. And, you know, it’s important to find a provider who has that knowledge and not perhaps to go to one of these testosterone clinics where every man is told that he has low levels and every man is then placed on testosterone. It’s confusing. And it’s very complicated and it’s much more complicated than just testosterone levels. As you said, low sexual desire can be multifaceted and is related to how much, how you feel about work. What kind of stress you have about money, finances. How you feel about your partner. How do you feel about your family? It’s so complicated. So you need to be able to tease out those concerns before you even make a diagnosis of testosterone deficiency. What you also said is very important because testosterone deficiency does not usually occur on an isolated island.
Dr. Martin Miner (07:43):
It doesn’t occur alone. It’s related to what we call comorbid* disease states. And what I mean by that are as men age, they tend to collect medical problems that they didn’t have in their twenties or thirties. Those medical problems include the fact that their bellies are increasing in size, and they develop what’s known as belly fat or visceral adiposity, or specific obesity around their guts. And that’s also consistent with developing elevated blood sugar levels or glucose** levels, elevated triglyceride levels, low good cholesterol levels or HDL levels, and elevated blood pressure. And that’s what we call metabolic syndrome****. So these men, as they age, and they’re not necessarily taking care of themselves. They’re not exercising. They’re not eating right. They’re not sleeping well. They gain weight. They develop problems with their lipids, their blood lipids, or cholesterol and triglycerides. They develop problems with their blood pressure and they may develop pre-diabetes or actual Type 2 Diabetes.
**Blood glucose: https://my.clevelandclinic.org/health/diagnostics/12363-blood-glucose-test
***Serum triglyceride: https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/triglycerides/art-20048186#:~:text=Normal%20%E2%80%94%20Less%20than%20150%20milligrams,5.7%20mmol%2FL%20or%20above)
****Metabolic syndrome: https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916#:~:text=Metabolic%20syndrome%20is%20a%20cluster,abnormal%20cholesterol%20or%20triglyceride%20levels.
Dr. Martin Miner (09:01):
The classic man that I see is in his mid forties or early fifties, and is obese and is not exercising; has difficulty with sleep in that he awakened several times; his wife is saying, or partners, saying that he’s snoring and awakening because he has sleep apnea. And he has all of these metabolic problems, including pre-diabetes or diabetes, and elevated lipids. And he may or may not be on medications for these. That man is a classic man whose testosterone levels are diminishing. And that man may have clinical signs and symptoms of testosterone deficiency, and may need testosterone repletion until he gets his life back together. And testosterone may support him, but it doesn’t do a lot in the absence of exercise and diet, which we can talk about in a minute.
Dr. Richard Pelman (10:05):
So you need to investigate the other underlying illnesses.
Dr. Martin Miner (10:09):
Dr. Richard Pelman (10:11):
And treat them.
Dr. Martin Miner (10:13):
Dr. Richard Pelman (10:13):
And then if modifications occur with improvement in cholesterol and lipids and blood sugar, blood pressure, exercise, and weight loss, the man eventually may not need replacement therapy.
Dr. Martin Miner (10:25):
Absolutely. So I don’t look at testosterone treatment as testosterone treatment for life. There is testosterone treatment for life in certain medical populations. Those men who have testicles removed because of testicular cancer. Those men who have treatment for malignancies and may have radiation to their testes or damage their testes. So their testes are not making testosterone anymore. Those men have a condition of what we call primary testicular failure. Or those men who have a genetic abnormality where their testes aren’t making it and they have Klinefelter’s*, or they have pituitary** damage. Those men have primary testicular failure, and there’s no controversy that those men need testosterone. It’s the men who are aging, who have these medical conditions that we were talking about, who many clinicians believe that if they just implemented lifestyle changes they would not need testosterone repletion. The trouble is these men feel very poorly, both emotionally and physically. And it’s very difficult to get them to engage actively and what they need to do to improve their overall lifestyle. And it may take a couple years. So I use testosterone perhaps as a tool to help them bridge to improved health.
*Klinefelter’s Syndrome: https://www.nhs.uk/conditions/klinefelters-syndrome/
Dr. Richard Pelman (11:59):
The man who is approached to improve lifestyle, learn what sort of diet is best for him in his particular situation, learn what sort of exercises give him the most benefit, what medications seem to control the issues that he has may need testosterone for what, a year or two?
Dr. Martin Miner (12:22):
It’s all to be individualized. And some men may need it for longer. But what’s most important is that it’s appropriately diagnosed, evaluated, and that the cause of it is determined. And that it’s…Then if treatment is implemented that this man is being monitored, meaning that he has ongoing levels and to ensure that they’re in a therapeutic or physiologic range and not too high. And that this man has no complications of the testosterone therapy. And if that’s the case, and this is what you talked, you spoke about the AUA guidelines. Well the AUA guidelines are a collection of 31 statements that are supported by a massive text that was peer reviewed and shows various levels of evidence. And what we tried to use were the highest grades of level of evidence to support these 31 statements. They all are focused on the diagnosis, and the treatment and monitoring of testosterone therapy. And it’s the first guideline by the American Urological Association to develop and synthesize these statements for providers.
Dr. Richard Pelman (13:53):
So in general, if you were a man who was initiating testosterone therapy, say he was your patient, or the guidelines would say monitoring should be done every…?
Dr. Martin Miner (14:03):
Six months to a year once on therapy. And therapy includes…There are gels. There are injections. There are pellets. There are intranasal preparations now. So there are various forms. There is not an oral form, at least in the U S that’s been approved by the FDA. But there are multiple forms of therapy. So it can be personalized to that man without fear of transfer to hit any member of his family, which is a consideration that we must think about, and done in a safe fashion so that we can evaluate on an ongoing basis that man’s response to therapy.
Dr. Richard Pelman (14:49):
Now, I have seen some men who have been to clinics where they automatically are started on a medication to prevent the over conversion of their testosterone to an estrogen, estradiol*. We all realize that testosterone is a benefit to muscles, but we tend not to realize that some testosterone is converted by subcutaneous tissue enzymes or an enzyme, aromatase, to an estradiol that goes into our bones. and that men need the estradiol to keep their bones healthy. But if you get extra testosterone, you may get too much. Now, do you automatically start people on an inhibitor** or do you just monitor levels?
**Aromatase and Aromatase Inhibitors: https://www.breastcancer.org/treatment/hormonal/aromatase_inhibitors
Dr. Martin Miner (15:31):
Well, what you bring up is a very good point because this is when you’re monitoring therapy. You’re asking that man about different side effects. It’s not recommended that you routinely draw a serum estradiol. Estradiol in men is needed for strong bones. It’s needed actually for sexual function and what we don’t want to lower estradiol, which is often done in the weightlifting arena. Those men take these aromatase inhibitors to effectively lower their serum estradiol, but it’s not done with a physiologic basis. If a man is taking testosterone, any complaints of some breast tenderness, or breast fullness, or nipple discharge, then clearly we have to measure serum estradiol levels. If his mood becomes emotionally labile or he becomes very tearful, we might measure estradiol levels. But lowering estradiol levels without clinical symptoms is not routinely recommended nor done.
Dr. Richard Pelman (16:48):
Okay. And in the same vein of seeing some men who are automatically placed on another product, HCG*, to prevent testicular shrinkage**. This would occur because the body is seeing exogenous testosterone. The pituitary receptors no longer need to feed back to the testes to produce testosterone. And so as I tell patients, the boys get pink slips, they stop producing and in some men there is testicular atrophy. The HCG would prevent that. Is that a routine?
*HCG (Human Chorionic Gonadotropin): https://www.mayoclinic.org/healthy-lifestyle/weight-loss/expert-answers/hcg-diet/faq-20058164#:~:text=HCG%20is%20human%20chorionic%20gonadotropin,to%20work%20for%20weight%20loss.
Dr. Martin Miner (17:21):
Well, what the guidelines direct is that fertility is a vital concern for men. And men at any age have to be assessed for fertility concerns if they want to preserve fertility. And that means they have to have testicles that can produce both sperm and testosterone. When you give exogenous or testosterone outside of the body, whether it’s injections or gels, however, you do suppress testosterone production but you also suppress sperm production. In a man of childbearing age, and that’s up for debate, you may give that man human chorionic gonadotropin or HCG to preserve his fertility status. And that’s just while you’re supplementing testosterone. You may use it to, or you may give that men another agent that off-label like clomiphene citrate, which is called a SERM, a selective estrogen receptor modulator*, just because you don’t want to give testosterone and you don’t want to stop that hypothalamic-pituitary-gonadal axis.
Dr. Richard Pelman (18:50):
So in man who comes in who’s still interested in fertility is not yet complete as far as his family, his hypogonadal. First choice would generally be to use clomiphene citrate* and stay away from testosterone because the clomiphene can intrinsically raise testosterone through the pituitary gonadal axis without impairing sperm production.
*Clomiphene citrate: https://www.ncbi.nlm.nih.gov/books/NBK559292/
Dr. Martin Miner (19:16):
Exactly. That’s what I tend to do first. And I tend to do that, and I don’t have an arbitrary age, but I tend to do that in all men under the age of 40 and try to preserve their, both their fertility and their own production of testosterone. I don’t take stopping their own testosterone in a light fashion. I take it very seriously. I don’t, Usually it can be restarted, but there are situations or cases where it’s very difficult to restart.
Dr. Richard Pelman (19:50):
So in that case, you’re talking about a man who is receiving exogenous testosterone replacement therapy who’s then intrinsic testosterone ceases to be produced. Now that’s not what the clomiphene citrate, that’s actually with testosterone. And then going back to the HCG, what if a man just cosmetically wanted to preserve testes volume? Is that an indication for HCG?
Dr. Martin Miner (20:14):
I have done that for men who are very focused on their testicular size. And there are men who are very focused on their testicular size because it’s a vital issue to them. Often HCG can be expensive. It’s not covered by insurers, often it’s compounded. And if those men are willing to pay the cost of the medication, then I will give it to them. Again, it’s part of their monitoring.
Dr. Richard Pelman (20:45):
That’s an injection?
Dr. Martin Miner (20:46):
Yes. It’s two to three times a week. It’s injected what we call subcutaneously* into the belly. So it gets a little bit, there’s a bit of effort that goes into this. We teach men how, if they’re giving themselves injections, we teach them how to do it at home, which they do into their thighs, or they can inject subcutaneously into their belly fat. But, and that’s usually at least once a week. And then your, if you add HCG or adding another compound that they may have to inject three times a week, you try to make it as simple as possible because compliance or the ability to follow the protocol of testosterone therapy can become very complicated.
*Subcutaneous injection: https://medlineplus.gov/ency/patientinstructions/000430.htm
Dr. Richard Pelman (21:35):
So let’s go back to our patient who comes in, who we realize has the symptoms and signs of testosterone deficiency along with other conditions, has a laboratory value of a low testosterone. According to the guidelines, we repeat that.
Dr. Martin Miner (21:53):
We repeat that on a different day. If both of those levels are low, and that man has clinical signs and symptoms of testosterone deficiency, he can be given a six month, a three to six month trial of testosterone repletion. If he’s not improved after three to six months, it’s unlikely that his clinical signs and symptoms, which you already pointed out can be quite vague and related to multiple other life issues, it’s not likely that those clinical signs and symptoms are related to testosterone deficiency. And therefore we would consider discontinuing the testosterone therapy. That’s very important and that’s one of the guiding statements of the guideline. In addition, there have been two issues that I should point out that were discussed in thorough by the guidelines. The first are cardiovascular issues or worries that taking testosterone therapy,and restoring testosterone therapy and physiologic dosages can somehow cause an increased risk of heart attacks* and strokes.
*Testosterone and Heart Attacks: https://www.mayoclinic.org/healthy-lifestyle/mens-health/expert-answers/testosterone-therapy-side-effects/faq-20090015
Dr. Martin Miner (23:07):
There were four publications between 2010 and 2014, which were published, which raised this issue and received a lot of publicity in the media. These studies, despite the fact that one of them was published in the Journal of the American Medical Association, were deemed by most doctors to be highly flawed in their structure and analysis. So, while it’s possible that testosterone may cause an increased risk of heart attacks and strokes, it’s unlikely. And it’s not likely that that risk is going to be clinically significant. But it is important to tell patients that the safety study of testosterone therapy has not yet been completed. And it’s just beginning and it’s going to require six years. And hopefully we will have analysis and data to suggest that testosterone repletion, at least in physiologic levels, is safe. But it does need to be monitored. The second issue is whether or not testosterone therapy causes prostate cancer*.
*Prostate cancer: https://www.mayoclinic.org/diseases-conditions/prostate-cancer/symptoms-causes/syc-20353087
Dr. Martin Miner (24:26):
This has been a concern for the last 15 or 20 years. When a man develops testosterone, when men develop prostate cancer on that test, that prostate cancer has spread or metastasized. That man is often given a medication which blocks the production of testosterone and it’s called androgen ablation therapy*. So that man is often chemically castrated or brought down to very low levels of serum testosterone so that the prostate cancer will not grow. The thought was if you give, if you have the treatment of prostate cancer involves ablation of the production of testosterone or prevention of the production of testosterone, then it must mean that giving testosterone will cause prostate cancer. And that’s a statement that can NOT be made. And there’s much evidence to support the fact that testosterone does not cause prostate cancer. That is also a significant element of the guidelines, but it’s still on the product insert that testosterone can cause prostate and breast cancer in men.
*Androgen Ablation Therapy: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/androgen-ablation
Dr. Richard Pelman (25:52):
So I think it’s an important distinction to make that it doesn’t create prostate cancer if it’s not there. But if a man is harboring prostate cancer and doesn’t know that he has it and goes on testosterone, it potentially could accelerate it.
Dr. Martin Miner (26:07):
Well that’s a belief. And that’s not in the American Urological Association* guidelines. But that’s a belief that’s actually stated in the Endocrine Society** guidelines, which were also published just in the past month.
*American Urological Association: https://www.auanet.org/
**Endocrine Society: https://www.endocrine.org/
Dr. Richard Pelman (26:22):
So if a man was concerned about having prostate cancer, that is part of our screening as to is it okay to put this man on testosterone replacement therapy?
Dr. Martin Miner (26:33):
Exactly. So a man should have his prostate evaluated. He should have a PSA*, although PSA is a controversial test by itself. He should have a PSA. And if that PSA is elevated, the basis for that elevation in PSA needs to be determined prior to his implementation of testosterone therapy.
*PSA (Prostate Specific Antigen): https://www.cancer.gov/types/prostate/psa-fact-sheet
Dr. Richard Pelman (26:56):
And so generally a man with a low and normal stable PSA and a normal digital rectal exam* is assumed not to have prostate cancer, and would be a candidate to safely go on testosterone, at least from the prostate cancer point of view.
*Digital Rectal Exam: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/digital-rectal-examination
Dr. Martin Miner (27:10):
Exactly, exactly. And even if he has a family history of prostate cancer, he would be deemed safe to go on testosterone therapy. But again, what’s very important is that this man be monitored at least every six months to a year with levels, including a PSA and hematocrit* because testosterone can increase. T hematocrit is a measure of the viscosity of the red blood cells and or the viscosity of the blood. The thickness of the blood. And testosterone has a direct effect on the bone marrow* to increase red blood cells viscosity.
**Red Blood Cell (RBC) Production: https://medlineplus.gov/ency/anatomyvideos/000104.htm#:~:text=Red%20blood%20cells%20are%20formed,a%20new%20red%20blood%20cell.
Dr. Richard Pelman (27:47):
I also teach men how to do a self breast examination* once a month just to make certain that they aren’t at risk. It seems it’s a low incidence of breast cancer in men in general, but of the men who did get breast cancer it can be elevated in those on replacements. So they should be aware of that.
*Self breast exam: https://medlineplus.gov/ency/article/001993.htm
Dr. Martin Miner (28:07):
Absolutely. So in conclusion, I just want to say that I believe that testosterone therapy can be safe as long as those in men who are deemed candidates for testosterone therapy are selectively chosen or individualized; a long as the therapy is also individualized or customized for that man; and that as long as that man is being monitored closely, whether that’s done by his primary care provider or urologist or another individual who’s comfortable and experienced with testosterone therapy. That’s important, but it should be done by someone who does treat men with testosterone deficiency on a regular basis.
Dr. Richard Pelman (29:00):
I agree. Well, thank you.
Dr. Martin Miner (29:04):
Dr. Richard Pelman (29:05):
This completes another podcast chapter of the Washington State Urology Society’s Original Guide to Men’s Health. This is Dr. Richard Pelman reminding you to take care of yourself. Washington State Urology Society wishes to thank all contributors who volunteered their time and knowledge. The information presented is the opinion of the speakers. This society also wishes to thank Sean Fox for his invaluable technical assistance, music theme San Juan Bells written and performed by Dr. Dave Whiting. The podcasts are the property of the Washington State Urology Society. Reproduction and use without the expressed consent of the society is strictly prohibited. For more information about men’s health visit wsus.org or visit your physician or care provider.