Elsevier

Mayo Clinic Proceedings

Volume 90, Issue 8, August 2015, Pages 1104-1115
Mayo Clinic Proceedings

Review
Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for Male Hypogonadism: A Systematic Analysis

https://doi.org/10.1016/j.mayocp.2015.06.002Get rights and content

Abstract

“Testosterone Therapy in Men With Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline” (Guidelines), published in 2010, serves as an important guide for the treatment of hypogonadal men. Using the Guidelines as a basis, we searched for the most recent level 1 evidence that continues to support the recommendations or provide an impetus to modify all or some of them. We performed a systematic analysis with a PubMed query from January 1, 2010, through March 2, 2015, using the following key words: testosterone/deficiency, testosterone/therapeutic use, cardiovascular, morbidity, mortality, screening, sexual function, lower urinary tract symptoms, obstructive sleep apnea, prostate cancer, fertility, bone mineral density, osteoporosis, quality of life, cognitive, erectile dysfunction, and adverse effects. We identified 17 trials representing level 1 evidence that specifically addressed recommendations made in the Guidelines. Trials examining outcomes of testosterone replacement therapy in men with severe lower urinary tract symptoms and untreated obstructive sleep apnea were identified, potentially refuting the current dogma against treatment in the setting of these conditions. Hypogonadal men with type 2 diabetes mellitus and metabolic syndrome were examined in several trials, demonstrating the beneficial effects of therapy on sexual function and insulin sensitivity. Several trials served as reinforcing evidence for the beneficial effects of testosterone therapy on osteoporosis, muscle strength, and symptoms of frailty. As in the Guidelines, inconsistent effects on quality of life, well-being, and erectile function were also noted in publications. Despite controversies surrounding cardiovascular morbidity and treatment in the setting of prostate cancer, no studies examining these issues as primary end points were identified. The low number of eligible studies since 2010 is a limitation of this analysis.

Section snippets

Methods

We queried PubMed for articles published from January 1, 2010, through March 2, 2015, using the following search terms: (Testosterone/therapeutic use[MeSH terms] OR testosterone/deficiency [MeSH terms]) AND (cardiovascular OR morbidity OR mortality OR screening OR sexual function OR lower urinary tract symptoms OR obstructive sleep apnea OR prostate cancer OR fertility OR bone mineral density OR osteoporosis OR quality of life OR cognitive OR erectile dysfunction OR adverse effects). The date

Results

Of an original cohort of 462 abstracts, 26 articles (representing 17 trials) were selected for inclusion (Figure). The potential for bias was assessed and incorporated into the reported findings (Table).8 On the basis of these findings, we present a critical reassessment of several of the 2010 Guidelines as reflected by recent level 1a evidence trials and outlined herein.

Discussion

The 2010 Guidelines serve as a comprehensive and important tool for the evaluation and treatment of male hypogonadism. However, since their publication, several high-quality, level 1 studies examining contraindications, adverse events, and benefits of TRT have been published. These recent studies have examined specific populations underrepresented in the Guidelines, notably those with frailty and MetS.

There remain significant gaps in the literature, highlighted in the preceding systematic

Conclusion

A systematic analysis of level 1 evidence trials examining the safety and efficacy of TRT published since 2010 largely reinforces the Endocrine Society Guidelines. New trials indicate that severe LUTS and untreated OSA may not be absolute contraindications to TRT. Beneficial effects of TRT in men with MetS or frailty may be useful additions to future guideline recommendations. There is a lack of high-quality prospective trials examining the effects of TRT on CV morbidity.

Acknowledgment

AbbVie provided financial support for editorial assistance by Stephen Gutkin, Rete Biomedical Communications Corp (Wyckoff, NJ). The authors were not compensated for their roles in developing the manuscript. AbbVie did not conduct any review of the manuscript. The content and opinions expressed in the manuscript are solely those of the authors.

This systematic literature review was supported by AbbVie (North Chicago, IL).

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    Potential Competing Interests: Dr Seftel is on the editorial board of the Journal of Urology; Dr Niederberger is a member of the American Urological Association Journal of Urology Urological Survey Editorial Committee, is the American Society of Reproductive Medicine co-editor-in-chief of Fertility and Sterility, is the founder and chief technology officer of NexHand, and has received research grant support from Ferring and IBSA.

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