EURURO Vol. 72 No. 6

Letter to the Editor

Re: Giovanni Corona, Giulia Rastrelli,

Abraham Morgentaler, Alessandra Sforza,

Edoardo Mannucci, Mario Maggi. Meta-analysis

of Results of Testosterone Therapy on

Sexual Function Based on International Index

of Erectile Function Scores. Eur Urol 2017;72:

1000–11

The meta-analysis by Corona et al

[1]

has comprehensively

analyzed the impact of testosterone therapy (TTh) in men

with sexual dysfunction, relying on the International Index

of Erectile Function (IIEF) questionnaire as an effective

outcome indicator. After thoroughly analyzing data from

2298 men, the authors concluded that TTh is associated

with sexual function improvement (particularly erectile

function) in hypogonadal men. Although testosterone (T)

deficiency is known to possibly have a detrimental impact

on sexual function

[2] ,

the authors should be complimented

for applying a rigorous statistical analysis capable of better

clarifying this complex relationship, which is still the source

of an infinite critical disagreement today. Respectfully,

some aspects deserve further discussion.

First, the original sin of T trials is to evaluate question-

naire-based improvement of erectile function (EF) on a

continuous scale ignoring the clinical meaning of this

improvement. Every study included presents a generic

estimate of EF improvement in men with wide-ranging

levels of erectile dysfunction (ED) severity (some of them

actually potent according to the Cappelleri’s criteria)

[3]

and

comorbid conditions other than low T levels. The authors

tried to overcome this inherent fault by interpreting the

pooled mean improvement of EF according to the minimal

clinically important differences

[3] ,

thus concluding that

the observed IIEF improvement is clinically significant only

in men with mild ED. However, the authors report that the

improvement in overall EF component was unaffected by

mean basal IIEF at meta-regression analysis. Since basal

mean IIEF values varied consistently among the included

studies, we argue that a stratification approach could

have been more appropriate in order to avoid this apparent

contradiction (ie, reporting subgroup estimates according

to the baseline ED severity rather than relying on

meta-regression analysis). Generally speaking, these con-

clusions should be regarded as hypothesis generating rather

than hypothesis testing

[4] .

Second, as a partial consequence, T clinical effect on EF

cannot be fully unraveled if both relatively healthy and

comorbid men are indistinctly included in TTh trials. Since a

low IIEF-EF score was associated with a lower general

health status

[5]

, hypogonadal men with severe ED are

likely not to benefit only from TTh due to the coexistence of

a comorbid pathogenetic process (eg, vasculogenic ED). Is

this enough to conclude that TTh is not properly improving

EF in men with severe ED? No, as long as ED pathogenesis

will not be adequately assessed among men enrolled in TTh

trials.

Overall, we consider the current meta-analysis of robust

and valuable support for the everyday clinical counselling in

men with low T levels and sexual dysfunction, though the

real impact of TTh in terms of EF improvement still remains

to be revealed.

Conflicts of interest:

The authors have nothing to disclose.

References

[1] Corona G, Rastrelli G, Morgentaler A, Sforza A, Mannucci E, Maggi

M. Meta-analysis of results of testosterone therapy on sexual

function based on International Index of Erectile Function Scores.

Eur Urol 2017;72:1000–11.

http://dx.doi.org/10.1016/j.eururo. 2017.03.032 .

[2] Mirone V, Debruyne F, Dohle G, et al. European Association of

Urology position statement on the role of the urologist in the

management of male hypogonadism and testosterone therapy.

Eur Urol 2017;72:164–7.

http://dx.doi.org/10.1016/j.eururo. 2017.02.022 .

[3] Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important

differences in the erectile function domain of the International

Index of Erectile Function scale. Eur Urol 2011;60:1010–6.

http://dx.doi.org/10.1016/j.eururo.2011.07.053

[4]

Thompson SG, Higgins JPT. How should meta-regression analyses be undertaken and interpreted? Stat Med 2002;1573:1559–73.

[5] Capogrosso P, Ventimiglia E, Boeri L, et al. Sexual functioning

mirrors overall men’s health status, even irrespective of cardiovas-

cular risk factors. Andrology 2017;5:63–9.

http://dx.doi.org/10. 1111/andr.12299

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DOI of original article:

http://dx.doi.org/10.1016/j.eururo.2017.03.032

http://dx.doi.org/10.1016/j.eururo.2017.05.050

0302-2838/