Platinum Priority – Editorial Referring to the article published on pp. 99–112 of this issue Determining the Role of Testosterone Deficiency in Sexual Function: The Beginning of the End or the End of the Beginning? Alvaro Morales * Department of Urology, Queen’s University, Kingston, Ontario, Canada A timely, well searched, and succinctly presented review on the topic of testosterone (T) and sexual function by Isidori et al. [1] appears in this month’s issue of European Urology. Considering the controversies surrounding all aspects on T deficiency syndrome (TDS), this is not an easy task. TDS is a preferable terminology, since it does not exclude situations like Klinefelter syndrome, which is otherwise competently discussed in the article. The paper focuses on erectile function and the authors succeeded in delivering a judicious appraisal of the pertinent literature in a remarkably comprehensive manner, including the less known basic mechanisms of hormonal dependence of the erectile process. This is a stimulating area, as illustrated by a report showing an increase in endothelial progenitor cells following T therapy that resulted in improvements in endothelial function [2], a fundamental erectile mechanism. Publications such as these are the best response to the chorus of skeptics suggesting that almost everything that one reads about T is not believable [3]. Some areas in the review merit further clarification, starting with diagnostic concerns. Table 1 of the review mentions the use of questionnaires [1], but it does not indicate their major drawback: their lack of specificity. Even those developed to screen explicitly for hypogonadism in men with sexual dysfunction [4] remain undependable. These tools, however, are useful in assessing in an objective and systematized manner the response to T therapy. The laboratory diagnosis also requires elaboration. There is a consensus that measuring total serum T on two separate occasions is sufficient in most instances. There is still a significant population of men with TDS in whom the reference intervals remain borderline. In this situation, the Endocrine Society Guideline and others [5] recommend determination of free or bioavailable T, either measured or calculated. Both unambiguously recommend assessment of gonadotropins, although this does not seem to be the case for all, according to references cited by Isidori et al. [1]. In addition to the well-known circadian and ultradian varia- tions in T levels in the same individual, issues of analytical variability are less well recognized among clinicians and deserve wider appreciation and understanding. The very important aspect of the length of treatment necessary for optimal results (time course of T effects) has been dealt with very well. There is a pervasive belief that the sexual response following T supplementation is achieved within the initial 3 mo. Isidori et al. present cogent evidence that a longer period may be necessary even for sexual manifestations (the most sensitive to T supplementation) to resolve [1]. This is particularly relevant in light of recent evidence indicating that compliance issues are problematic even with transdermal T gels: Only 34.7% of patients are still on medication at 6 mo, while at 12 mo, this figure is a dismal 15.4% [6]. Both patients and their physicians need to be aware of the need for adequate treatment duration. The authors’ algorithm provides a practical overview of hypogonadism. Under the headings of secondary hypogo- nadism and pituitary, determination of iron saturation to rule out hemochromatosis should have been included; it is a relatively common cause of T deficiency and becomes symptomatic in a similar age group (>40 yr). The proposed treatment algorithm is convenient and well thought out, but I take issue with the recommended use of phosphodiesterase type 5 inhibitor (PDE5-I) treat- ment after only two discrepant T measurements. This situation suitably illustrates the shortcomings of biochem- ical assessment of gonadal steroids. If the discrepancies are EUROPEAN UROLOGY 65 (2014) 113–114 available at www.sciencedirect.com journal homepage: www.europeanurology.com DOI of original article: http://dx.doi.org/10.1016/j.eururo.2013.08.048. * 59 Lakeshore Blvd., Kingston, Ontario K7 M 6R4, Canada. Tel. +1 613 389 9275; Fax: +1 623 389 9275. E-mail address: moralesa@queensu.ca. 0302-2838/$ – see back matter # 2013 Published by Elsevier B.V. on behalf of European Association of Urology. http://dx.doi.org/10.1016/j.eururo.2013.09.028