Testosterone Replacement Therapy (TRT)

BY JEFFREY TURNER, MD


Testosterone (T) preparations have been available for more than 70 years.  In 2013, over 2.2 million Americans were prescribed testosterone.  Interestingly enough, about 1 in 4 men prescribed testosterone do not have a baseline testosterone level drawn as primary care physicians may write the prescription without ordering a blood test first.  In a study of 63,000 men from the Truven Health Marketscan Commercial and Medicare Supplemental Insurance database between 2010 and 2012, 71% of men had their testosterone level checked once, 40% twice, and 29% had no measurement at baseline.  Physicians need to do a better job following men on testosterone replacement. Is testosterone replacement therapy really all that good for anything aside from rejuvenation and virility? 

Let’s break this down to risks and benefits below:

Risks of Prostate Cancer

The most universal risk which has been the controversy of much discussion is the association with prostate cancer.  Clinicians remain concerned that Testosterone Replacement Therapy (TRT) can cause or stimulate prostate carcinogenesis and therefore they are reluctant to prescribe it for the aging male who has a higher risk of prostate cancer.  In the 1940s, Huggins and Hodges discovered the association of testosterone with prostate cancer by demonstrating that castration causes the disease to regress. The reality is that TRT may stimulate the growth of existing prostate cancer cells, but it will not cause cancer to form.  As the general male population grows, so does the risk for prostate cancer--patients should be closely evaluated with digital rectal examinations, PSA checks and prostate imaging such as color Doppler ultrasound.

Risk of Prostate Enlargement

Another controversial topic is the assumption that supplemental testosterone leads to a prostate growth, benign prostate hypertrophy, which leads to worse quality of life due to worsening urinary symptoms.  It has long been assumed that high T levels induce prostate overgrowth, but most studies failed to find the correlation between circulating T levels and BPH.  It has been hypothesized that dihydrotestosterone (DHT) could be more responsible for prostate growth than T.  There have been a number of studies evaluating TRT in hypo-gonadal men with BPH.  The results have suggested that there is actually a trend toward an improvement in urinary symptoms.

Risk of High Red Counts—Polycythemia or Erythrocytosis

Erythrocytosis is the increase in red blood cell mass production which can be the result of testosterone replacement therapy.  This is the most frequent adverse effect associated with TRT.  Recent trials have demonstrated that men on TRT have a 4 times higher chance of having high red blood cell counts.  Some reports have implicated excessively high red blood cell levels with an increased risk for heart attack or stroke. We commonly recommend patients remain on a baby aspirin daily and monitor their blood counts. Some patients may benefit by donating a unit of blood if the levels are too high.

Risk of Obstructive Sleep Apnea

Frequently reported in various literature is the association of worsening sleep apnea symptoms for men on testosterone replacement.  There has been only one randomized control trial to date that addresses this association and it showed that obese men with severe sleep apnea may worsen their oxygenation with TRT at relatively high doses.  This study evaluated injection formulations of testosterone. So far transdermal formulations have not been similarly implicated.

Risk of Infertility

Testosterone replacement leads to inhibition of the pituitary gland located at the base of the brain which can potentially suppress the production of sperm.  Hence, cases of TRT-induced male infertility have been reported. This impact appears to be transient and disappears once TRT is stopped.

Improved Sexual Function

A decreased libido and/or potency remains one of the most common reasons that men desire testosterone replacement.  TRT can certainly improve sexual function in those who have erectile dysfunction primarily due to a low level of testosterone.  Patients need to recognize that there are a series of other reasons for being impotent that are unrelated to low levels of testosterone which must also be investigated as well before concluding that TRT will be the optimal corrective measure.

Improved Cardiovascular Effects

The association of TRT with heart attacks has been very controversial. We must not forget that men with low T levels are at higher risk for poor health due to being more frail and susceptible to other medical issues including obesity and diabetes. As a result, they become more prone to adverse cardiovascular outcomes.  Four out of five of the most recent meta-analyses demonstrated neither a protective or harmful effect of TRT on cardiovascular events. In men with heart failure, it has been demonstrated that low T levels are an independent risk factor for worse outcomes.  Studies also demonstrated that men with heart failure who supplemented with testosterone had a better exercise capacity, oxygen levels, and less fatigue.

Improved Metabolic Effects

Large scale data exists to document the association of low T and worsening blood sugar levels along with a higher chance of developing diabetes. TRT can improve body composition and help to reduce fat which can lead to better control of diabetes.

Reversal of Osteoporosis

Lower testosterone levels are associated with a higher risk of bone fractures and worsening bone health.  TRT has been demonstrated to have a positive effect on bone mineral density.

Improvement in Chronic Kidney Disease

Low T is very common (approximately 50%) in men undergoing dialysis for end stage renal disease. Reduced T levels have in men on hemodialysis have been tied to higher rates of all-cause cardiovascular mortality.   Studies suggest that TRT may improve the levels of a hormone called erythropoeitin (EPO). This hormone stimulates improved production of red blood cells which in turn increases levels of red blood cell mass, energy, stamina, and overall well-being.

Conclusion

It is clear to see that testosterone replacement offers a multitude of benefits which span past merely increasing one’s libido or potency.  The bottom line remains that patients on testosterone supplementation must have close follow-up including both clinical and laboratory evaluation to ensure they are gaining benefit and not placing themselves at increased risk from potential adverse effects.  Physicians must clearly discuss the risks and benefits of supplementation along with employing routine monitoring of PSA, testosterone levels, blood counts, digital rectal examination, and color Doppler ultrasound. 

The Quest for the Prodigal Hard-On

BY RALPH BLUM

There is no doubt that all the main prostate cancer treatments—surgery, radiation or hormone therapy—are likely to affect erections. And although many men who are diagnosed with prostate cancer are older, and may therefore already be subject to the ordinary fatigue and malfunction of nature’s ultimate erector set, the degree to which sexual function returns—or fails to return—after treatment is still a matter of major concern for a number of us.

 

There is no set formula or predictable schedule for recovery of sexual function after prostate cancer treatment. If you choose surgery, your chance of recovering potency is partly dependent on the experience and skill of your surgeon. The minuscule nerves that control erections are located dangerously close to the prostate, and damage to or actual removal of those nerves during surgery causes permanent erectile dysfunction. Viagra or Cialis only works if the nerves can be spared. And even with successful nerve-sparing surgery it can take up to 12 months for the restoration of the natural ability to have an erection.

 

The radiation options—seed implants or IMRT—are associated with a significantly better chances for maintaining erectile dysfunction. But the reality is that radiation therapy still can cause erectile dysfunction because of the inflammation or scarring that occurs around the nerves.

 

Hormone therapy, another treatment alternative, causes total dissolution of sex drive, and you don’t even care that it’s gone! Fatigue, joint pain, depression and hot flashes are not exactly a turn-on either. And yet even without a libido, an erection can be achieved through the manipulation of modern pharmacology—that is if you can dredge up enough desire to give it a try for your partner’s sake—but even with a pharmacological assist, personal satisfaction is often seriously diminished.

 

There is, moreover, a “use it or lose it” caveat: many doctors who specialize in erectile dysfunction encourage sexual activity as soon as possible after treatment (or in the case of hormone therapy during treatment) on the grounds that the nerves and muscles that control erections can atrophy if they are not used for a long period of time.

 

If prostate cancer has already affected your ability to achieve erection, there are various options that might help—penile injections, a vacuum pump device, implantable pellets, or penile implants. I will present the pros and cons of these methods for inducing an erection in my next Blog. In the meantime, keep in mind that there are ways you can express your love for your partner and attain sexual gratification that don’t include penetration. Ways that include intimacy and tenderness, lest we forget.

Sexuality and Intimacy after Prostate Cancer Treatment

BY MARK SCHOLZ, MD

My life is turning into an evangelistic crusade to raise awareness about the risks of prostate cancer treatment.  Tens of thousands of men are undergoing unnecessary radical prostate cancer therapy with dire sexual consequences. These inappropriate and often fatefully wrong treatment choices are made because men are often completely unaware of the irreversible effects of the treatment itself.

Thankfully, I am not alone in this battle to inform men about the harm associated with prostate surgery. Another prostate oncologist, Dr. Celestia Higano from the University of Washington, recently published a scientific review on this very topic in the Journal of Clinical Oncology (JCO). For those of you who haven’t heard of the JCO, I consider it to be the most prestigious scientific cancer journal in the world.

Today’s blog will offer quote seven selected sections from Dr. Higano’s important article. To add some gravitas to the eye opening statements you are about to read, please realize that every one of her comments was referenced to a specific scientific report.  In other words, these statements have nothing to do with opinions. They are genuine outcomes from published scientific studies.

So without further ado let’s start with the first quote from the article:

Quote #1: “Unfortunately, many couples believe that even if they have problems with erectile dysfunction (ED) … they will be able to resume their normal sexual practices through the advances of modern technology.4 They are not informed that sexual function will never be the same after any form of therapy and they are often unprepared for the changes in their sexual and intimate relationship.” (Italics mine)

Quote #2: “PDE5 inhibitors (Viagra, Cialis) and other erectile aids are not successful for all patients with ED and, even when effective, half the patients stop using them within one year.11 Why couples stop using ED therapies has not been adequately investigated , but disappointment that sex life is not the same … likely contributes to this outcome.”

Quote #3: “In a Memorial Sloan-Kettering series of 475 men … 20% of men who had radical prostatectomy (RP) had climacturia at one year, and climactauria as associated with both painful orgasm and penile shortening.13” (Climacturia means that orgasm results in the ejaculation of urine instead of semen).

Quote #4: “At the Karolinska Institute, 1,288 patients had either open or robotic-assisted laparoscopic RP, and of the 691 men who were sexually active, 38% reported climacturia at least sometime during sexual activity. Of the men who reported climacturia, 72% had climacturia less than half the time, 17% more than half the time, and 11% all the time.14”

Quote #5: “In a review of 1,459 men who had RP at New York University, climacturia was found to decrease from 44% at 3 months to 22% at 24 months after surgery. Climacturia is a common complication of RP but is often overshadowed by concerns about ED and overt urinary incontinence.14-16”

Quote #6: “In a study of VED (vacuum erectile device) use after RP, the length and circumference of the penis decreased in 63% of patients who did not use a VED after RP compared with only 23% who did.18-20”

Quote #7: “Surgery can also result in Peyronie’s disease (also called, “crooked penis”) in up to 16% of patients.23"

When patient are informed of the dire consequences of surgery they are often mystified as to why urologists, who must be aware of the damage surgery causes, continue vigorously to recommend it. I have heard many patients voice the opinion that urologists are driven by a selfish desire for financial gain.   

The financial motive, however, fails to ring true. As medical procedures go, prostate surgery is poorly reimbursed. Also, when urologists are diagnosed with prostate cancer they themselves often proceed with a radical prostatectomy. So money is not the primary issue. Rather, consider that performing surgery is part of the very fabric of a surgeons’ persona. From a surgeon’s point of view, if you are not operating, you are not a surgeon.

Men considering surgery for prostate cancer need to be aware of its substantial risks. And when getting advice about which treatment to select, patients also need to realize that surgeons usually can’t provide balanced advice. They are too close to the trees to see the forest.