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.