Canadian Urological Association clinical practice guideline on testosterone deficiency in men: Evidence-based Q&A

Abstract

In 2013, a comprehensive Canada-wide needs assessment revealed that over 25% of Canadian physicians were uncomfortable with the diagnosis and treatment of TD and identified significant knowledge gaps related to patient management. 4 To address the knowledge gaps, the Canadian Clinical Practice Guideline on the Diagnosis and Management of Testosterone Deficiency Syndrome in Adult Males was published in the CMAJ. 5 As part of its mandate, the guideline was offered as a "living document," to be updated periodically in a perpetual effort to incorporate advances in scientific and clinical discovery. The current CUA guideline was approached in this spirit and serves as an educational tool that builds on existing knowledge and offers a contemporary update to the literature. MethodsThe current guideline is structured as a series of Questions & Answers (Q&A) relating to the diagnosis and management of TD. By way of this structure, the guideline offers a practical, evidence-based overview and recommendations related to the diagnosis, treatment, monitoring, risks and benefits of TD and testosterone therapy. It was designed to be a straightforward and user-friendly guide for specialists (urologists, endocrinologists, psychiatrists, geriatricians), general practitioners and the patients they treat. The guideline offers Canadian-specific content with respect to knowledge and attitudes related to TD, laboratory diagnostic testing, Health Canada approved treatment formulations and funding considerations.The authorship group represents a panel of Canadian and international experts in the fields of men's health and TD. Representation is inter-provincial and multi-disciplinary covering the fields of urology, internal medicine/endocrinology and clinical biochemistry.Relevant publications on TD and testosterone therapy were sought using a combination of Medline, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed searches. The search strategy involved a series of key words including: testosterone deficiency, hypogonadism, low testosterone, androgen deficiency, andropause and testosterone replacement therapy. Filters included English language, human studies and an index date up to December 1, 2020. Recently published guidelines from the Canadian Men's Health Foundation, American Urological Association, The Endocrine Society and the European Association of Urology were included as supportive, summative content. [5][6][7][8][9] Whenever possible, guideline statements and recommendations have been assigned levels of evidence (LE) based on the GRADE Working Group framework (LE: high, moderate, low, very low quality of evidence). 10 In brief, randomized controlled trials were initially rated as highquality and observational studies as low-quality evidence. Additionally, the strength or importance of the recommendations was also graded as either "strong" or "weak" based on the quantity, quality, and consistency of the evidence available.Following a systematic search, panel members were asked to review the identif...

Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy

“…16 Multiple national guidelines use elevation in hematocrit as a trigger to stop or change TT in men. TT cessation triggers include 55% from Canadian guidelines, 9 54% from endocrine society guidelines and European urology guidelines, 5,26 and between 50%–54% from American urological guidelines. 10 While the rationale for these cutoffs is not cited in these guidelines, they appear to come from the Framingham heart study, which found an increase in adverse cardiovascular outcomes with a hematocrit of 49% or higher.…”

“…The upper limit of safe hematocrit varies between 48% to 55% and is based off population data of individuals who were not taking TT. 5,8–10 To date, no studies have tested whether the presence of polycythemia during TT leads to adverse events as a primary outcome.…”

Testicular cancer survivorship: Long-term toxicity and management

“…For TCS started on testosterone replacement therapy, followup should be done to assess biochemical and clinical response. 95,97 • Exogenous testosterone administration is contraindicated in TCS seeking future fertility due to the negative impacts testosterone replacement therapy can have on sperm production. 96,98 • In men with symptoms of TD who wish to preserve future fertility, a referral to fertility specialist should be made for consideration of fertility-preserving therapies, such as selective estrogen receptor modulators, aromatase inhibitors, and human chorionic gonadotropin hormone.…”

Are SERMs safe and effective for the treatment of hypogonadism in men?

“…Current American Urological Association and Canadian Urological Association Guidelines note that while greater study on nontraditional testosterone therapies is needed, both organizations support use of SERMs, especially in hypogonadal men who are interested in fertility preservation, as increases in endogenous serum testosterone production do not impact fertility potential, unlike exogenous hormonal replacement. 6,7 Additionally, men with low or low-normal serum LH levels may also be good candidates for the use of SERMs for management of testosterone deficiency.…”