Controversies in the diagnosis and management of testosterone deficiency syndrome.

1342 CMAJ, December 8, 2015, 187(18) ©2015 8872147 Canada Inc. or its licensors Testosterone deficiency syndrome is an area fraught with disagreement and controversy. A new Canadian guideline1 from the Canadian Men’s Health Foundation is welcomed in the light of the huge volume of research on this topic over the last five years. Given the ongoing controversy and changes in our understanding of testosterone deficiency, it is not surprising that there are multiple guidelines available from other developers, including recent updates from the European Association of Urology2 and the International Society for Sexual Medicine.3 The guideline from the Canadian Men’s Health Foundation1 provides recommendations specifically for Canadian physicians and is largely consistent with the 2008 International Society for the Study of the Aging Male4 and 2010 Endocrine Society guidelines.5 The current guideline will be a useful resource for Canadian physicians, but although research studies are bringing clarity to some aspects of caring for patients with testosterone deficiency syndrome, there are still many for which there is no consensus. The diagnosis of testosterone deficiency syndrome is not straightforward. With the known limitations of testosterone measurement and lack of a valid symptom score, it is not surprising that primary care physicians lack confidence in diagnosing the syndrome, especially when experts cannot agree on values. True to the Endocrine Society guideline,5 the new Canadian guideline refers to unequivocal testosterone deficiency syndrome and equivocal testosterone deficiency syndrome without clarifying laboratory values.1 Instead, the authors put weight on a combination of factors — clinical history, physical examination and response to therapy — in making the diagnosis, in addition to measuring testosterone. The European Association of Urology and the International Society for Sexual Medicine set parameters that men with a total testosterone level of less than 8 nmol/L will usually benefit from treatment and that a trial of therapy may be indicated for those with levels between 8 and 12 nmol/L in the presence of substantial symptoms.2,3 Although experts could argue about these levels, the levels do, at least, provide a basis for primary care management and remove the mystique that only an eminent endocrinologist can really diagnose “true” testosterone deficiency. Canadian physicians may find these specific levels helpful as a guide in diagnosis. Several guidelines recommend a trial of treatment as a component of the diagnostic process, particularly in patients with borderline testosterone levels. What is at issue is the length of the trial. The Canadian guideline advises a threemonth trial of treatment,1 as also recommended in the Endocrine Society guideline.5 In line with the International Society for Sexual Medicine guideline,3 I suggest that clinicians consider a minimum period of six months when assessing response. In a randomized controlled trial of testosterone undecanoate in men with type 2 diabetes, my colleagues and I showed that improvement continued until six months, and even extended to 12 months in some patients.6 Contributing factors to long response times in testosterone therapy include compliance issues with topical treatment. In addition, for patients receiving testosterone undecanoate treatment, a three-month trial period would include only two long-acting injections, with peak levels not necessarily being reached. Because men are likely to get a trial of testosterone therapy only once, it is vital that we do it properly and expose them to sustained levels of testosterone for an adequate period to achieve maximal benefit. Controversies in the diagnosis and management of testosterone deficiency syndrome