The concerning methodology in the study byFinkle etal. is
the authors’ use of men taking PDE5-Is as a purported benign
control group. PDE5-Is were originally developed as a
treatment for cardiovascular diseases such as angina
and are currently approved by the US Food and Drug
Administration as treatments for pulmonary hypertension.
They also have known cardiovascular benefits
findings from a recent randomized placebo-controlled trial
that showed PDE5-I use in heart failure patients was
associated with improvements in left ventricular ejection
fraction, diastolic function, exercise tolerance, and overall
clinical condition
. The potential cardiovascular benefits of
PDE5-Is may have contributed to the differences in MI rates
found in the study, and this limitation was not discussed in
the publication. Neither Vigen et al. nor Finkle et al. evaluated
serum testosterone levels after beginning TST. Consequently,
it is difficult to ascertain whether these men were compliant
with the medication or even responded to therapy.
Multiple previous studies have found that low testos-
terone is associated with an increased risk of cardiovascular
and that TST is associated with a reduction in
mortality in hypogonadal men
. The increased rate of MIs
in the TST cohort of the Finkle et al. study may have been the
result of preexisting cardiovascular risk factors present
within the low testosterone group that were not present in
the PDE5-I group. As mentioned previously, it is also
possible that PDE5-I use in the so-called control group
provided some cardiovascular-protective effect.
The question now becomes how these results affect
clinical practice. There is clearly a need for large prospective
placebo-controlled randomized trials such as the Women’s
Health Initiative to determine definitively the cardiovascu-
lar risks of TST. However, until this occurs, physicians
should consider adding to their patient counseling a
discussion about putative cardiovascular risks associated
with TST including the limitations of the current studies.
The recent publications described represent an opportunity
for well-informed physicians to have thorough discussions
with their patients about the risks and benefits of TST and, if
prescribed, to enter into an agreement with the patient to
enable appropriate oversight during treatment.
Conflicts of interest:
Larry I. Lipshultz participates in clinical trials and is
a consultant and speaker for both Auxilium and Endo. The other authors
have nothing to disclose.
Vigen R, O’Donnell CI, Baron AE, et al. Association of testosterone
therapy with mortality, myocardial infarction, and stroke in men
with low testosterone levels. JAMA 2013;310:1829–36.
Basaria S, Coviello AD, Travison TG, et al. Adverse events associated
with testosterone administration. N Engl J Med 2010;363:109–22.
Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with
sildena±l improves left ventricular diastolic function, cardiac ge-
ometry, and clinical status in patients with stable systolic heart
failure: results of a 1-year, prospective, randomized, placebo-
controlled study. Circ Heart Fail 2011;4:8–17.
Ioakeimidis N, Kostis JB. Pharmacologic therapy for erectile dys-
function and its interaction with the cardiovascular system. J
Cardiovasc Pharmacol Ther 2014;19:53–64.
Oskui PM, French WJ, Herring MJ, Mayeda GS, Burstein S, Kloner RA.
Testosterone and the cardiovascular system: a comprehensive
review of the clinical literature. J Am Heart Assoc 2013;2:e000272.
Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM.
Testosterone treatment and mortality in men with low testosterone
levels. J Clin Endocrinol Metab 2012;97:2050–8.
James M. Dupree, Ranjith Ramasamy, Jason R. Kovac,
Gavin Langille, Larry I. Lipshultz
Department of Urology, Baylor College of Medicine, Houston, TX, USA
*Corresponding author. 6624 Fannin Street, #1700, Houston, TX 77030,
E-mail address:
(L.I. Lipshultz).
Re: Global Effects of Smoking, of Quitting, and of Taxing
Jha P, Peto R.
N Engl J Med. 2014;370:60–8
Experts’ summary:
In this outstanding review, Jha et al.
summarize the
reasons and effects of smoking on global health, highlighting
the benefits of smoking cessation and discussing reasons
affecting tobacco consumption. Still approximately 50% and
10% of young men and women, respectively, take up smoking
with relatively few ever stopping. This has led to a steady
increase in the annual tobacco-attributable death toll. Inter-
estingly, smoking patterns have changed over the last century.
Initially, smoking rates increased substantially in many high-
income countries, followed by increasing rates in the middle-
and low-income countries. In addition increasing rates of daily
cigarette consumption were observed during the last century
with comparable changes according to the income classes.
The authors found that in middle age patients, mortality rates
among cigarette smokers were 2–3 fold increased compared
to never smokers. Throughout adulthood this likely leads to a
reduction in life span by an average of about 10 years, which
mainly impairs the life expectancy of those killed by smoking
in the middle age, as those otherwise might have had a life
expectancy of decades. In contrast, smoking cessation
increases life expectancy. Tobacco taxes and consumption
are clearly inversely related especially in low-income and less
educated groups. Moreover, banning advertisement may fur-
ther help decrease overall consumption. Although most for-
mer smokers quit unaided, physician support or multimedia
based counseling can increase the likelihood of successful
quitting. The authors estimated that decreasing smoking
prevalence could prevent several tens of millions of tobacco-
attributable deaths during the next few decades.
Experts’ comments:
Tobacco use is a major preventable cause of premature death
and disease worldwide. Smoking is the best-established
EUROPEAN UROLOGY 66 (2014) 173–178