EURURO Vol. 72 No. 6

1009 1030

endothelial dysfunction, which are not necessarily due to
androgen deficiency In addition, TD induced by
metabolic diseases is usually mild. It is conceivable that in
trials including hypogonadal patients, those with diabetes-
or obesity-associated TD have higher baseline T levels
possibly leading to a lower effect of TTh. Although the
presence of metabolic derangements could diminish the
efficacy of TTh on ED, the positive effect of TTh on body
composition and insulin sensitivity might counter-
balance the lower efficacy. In addition, the positive effect of
TTh on both ED (present study) and body composition
increase as a function of trial duration, suggesting the
possibility of a positive interaction between decrease in fat
mass and/or increase in lean mass and ED response to TTh.
Interestingly, age at enrollment did not affect TTh
responsiveness in terms of EF, suggesting that TTh could
be offered to all hypogonadal patients, even to the older
ones, after a careful evaluation of its safety.
The positive effect of TTh on libido is also in line with
previous findings . Similar results were obtained for
other aspects of sexual function including intercourse and
overall satisfaction.
Finally, we here confirm the results of a previous meta-
analysis by our group , showing that TTh is able to
improve orgasmic function as detected by IIEF specific
subdomains. Both experimental and clinical studies have
documented that T is profoundly involved in the regulation
of the male ejaculatory reflex In line with our finding, a
recent, large, placebo-controlled trial performed on more
than 700 patients documented that a 2% transdermal T
solution was able to improve orgasmic and ejaculatory
function, although the associated bother did not improve
.
Several limitations should be recognized. The present
meta-analysis was not registered on PROSPERO and
individual levels of T at endpoint were not available. Hence,
no possible comparisons between patients who normalized
or were unable to normalize T levels at endpoint were
possible. Similarly, no possible comparisons between
patients with or without diabetes at enrolment were
possible. Meta-analyses are based on the synthetic reports
of the average results obtained in each study, without
access to patient-level data. For this reason, some of the
original information of each study is lost in meta-analyses.
However, the possibility of combining a large number of
investigations allows for a much greater statistical power,
limiting the problem of casual results because of small
sample size. It is also possible that some of the results
noticed here are caused by the effects of unadjusted
confounders. Hence, great caution is required in the
interpretation of results, which should be confirmed in
large-scale observational studies.
5. Conclusions
In conclusion, the present results confirm that TTh provides
several important sexual benefits, and by extension,
strongly indicates that sexual dysfunctions are a hallmark
of TD. Although it has been proposed by the Food and Drugs
Administration that hypogonadism should only be treated
in men with a limited list of underlying conditions, which
has been called ‘‘classic hypogonadism’’ nearly all
studies included in this meta-analysis were comprised of
populations of men without classic hypogonadism. For
example, in the T trial 63% of the participants were
obese. The positive results reported here thus indicate that
symptomatic testosterone-deficient men benefit from TTh
regardless of the underlying etiology. Conversely, the use of
TTh as a supplementation for a lifestyle change must be
avoided and discouraged. These results provide scientific
evidence that directly contradicts the recommendation to
limit the use of TTh only to men with classic hypogonadism
. Although the positive effects of TTh on hypogonadal
men with ED were more apparent in lean subjects, it is
possible that the positive effect of TTh on body composition
can eventually result in an improvement of ED even
in hypogonadal obese patients, after longer-term therapy.
Author contributions: Mario Maggi had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Corona, Maggi.
Acquisition of data: Corona, Rastrelli.
Analysis and interpretation of data: Corona, Rastrelli, Morgentaler, Sforza,
Maggi.
Drafting of the manuscript: Corona, Rastrelli.
Critical revision of the manuscript for important intellectual content:
Corona, Rastrelli, Morgentaler, Sforza, Mannucci, Maggi.
Statistical analysis: Corona, Rastrelli, Mannucci.
Obtaining funding: None.
Administrative, technical, or material support: Corona.
Supervision: Maggi, Morgentaler.
Other: None.
Financial disclosures: Mario Maggi certifies that all conflicts of interest,
including specific financial interests and relationships and affiliations
relevant to the subject matter or materials discussed in the manuscript
(eg, employment/affiliation, grants or funding, consultancies, honorar-
ia, stock ownership or options, expert testimony, royalties, or patents
filed, received, or pending), are the following: Corona has received
consultancy fees from Bayer, Besins, Otsuka, Eli-Lilly, and Menarini;
Maggi has received consultancies from Besins, Bayer, Prostrakan, GSK,
Eli-Lilly, and Menarini; Morgentaler has received consultancies from
Besins, Endo Pharmaceuticals, AbbVie In, Bayer, BioTE, and Aytu
BioScience, Inc.
Funding/Support and role of the sponsor: None.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
.
References
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