Review
Luteinizing Hormone–Releasing Hormone Agonists: A Quick Reference for Prevalence Rates of Potential Adverse Effects

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Abstract

Men with prostate cancer (PCa) frequently undergo androgen deprivation therapy (ADT), typically in the form of a depot injection of luteinizing hormone-releasing hormone agonists (LHRHa). LHRHa are associated with many adverse effects (eg, hot flashes, sexual dysfunction, loss of muscle mass, osteopenia, metabolic syndrome), which drastically impact patient quality of life. This literature review, which includes a comprehensive table documenting prevalence rates, provides a quick reference for health care professionals involved in the care of men undergoing ADT with LHRHa. Primary sources were acquired from PubMed using the search terms “androgen deprivation therapy” and each potentially adverse effect (eg, “androgen deprivation therapy and hot flashes”). Commonly cited review articles were also examined for citations of original studies containing prevalence rates. More than 270 articles were reviewed. In contrast to many existing reviews, rates are cited exclusively from original sources. The prevalence rates, obtained from original sources, suggest that more than half of documented adverse effects are experienced by as many as 40% or more of patients. A critique of the literature is also provided. Although there is a vast literature of both original and review articles on specific adverse effects of LHRHa, the quality of research on prevalence rates for some adverse effects is subpar. Many review articles contain inaccuracies and do not cite original sources. The table of prevalence rates will serve as a quick reference for health care providers when counseling patients and will aid in the development of evidence-based patient education materials.

Introduction

An estimated 600,000 patients in North America at any one time are receiving androgen deprivation therapy (ADT)1 to treat prostate cancer (PCa). As a result of improved PCa detection with prostate-specific antigen (PSA) testing, patients are being diagnosed with PCa and treated with ADT at younger ages than in past decades.2 Approximately 50% of patients with high-risk (PSA level > 20.0 ng/mL) PCa and up to 75% of patients receiving external beam radiation therapy will commence ADT.2, 3 Although ADT is an effective way to manage PCa and allows many men to live their lives free of PCa symptoms, it is associated with significant adverse effects that reduce their quality of life (QOL).4, 5 Average survival time for patients treated with ADT after a primary treatment has failed has reached 7 years (median, 84 months).6 Therefore, patients must cope with the adverse effects of treatment for a considerable amount of time. Despite current attempts to inform patients about managing adverse effects, patients continue to report being inadequately prepared to handle the adverse effects of ADT.7, 8, 9

Patients want to know the prevalence rates of adverse treatment effects so that they can anticipate the probability of experiencing them. The purpose of this literature review is to provide a clinical resource from which to draw information about prevalence rates of adverse effects of LHRHa used to treat PCa. Although some information exists on websites like www.drugs.com, these list adverse effects and prevalence rates that differ substantially from those reported in the urologic literature. It has also been noted that the drug information provided from pharmacies on LHRHa is often inconsistent and largely incomplete10 and that even reputable online sources of ADT information lack reliability and accuracy.11

Section snippets

Methods of ADT

The drugs most commonly used for ADT administration are depot injections of luteinizing hormone or gonadotropin-releasing hormone agonists or analogues (LHRHa or GnRHa, hereafter referred to as LHRHa) and more recently LHRH antagonists, which result in chemical castration. Most patients receive these injections every 3, 4, or 6 months.

A less common alternative to chemical castration is bilateral orchiectomy, which also eliminates approximately 90% to 95% of the body's testosterone, but in

Material and Methods

Primary sources were sought through PubMed using the search terms “androgen deprivation therapy” and each potentially adverse effect (eg, “gynecomastia,” “metabolic syndrome”). Articles documenting other methods of androgen deprivation to the exclusion of LHRHa (eg, diethylstilbestrol/estradiol, oral NSAA, or orchiectomy alone) were not included in the review. Articles were restricted to the English language. Review articles were also examined for citations of original studies that included

Results

Table 1 presents the prevalence rates of LHRHa-related adverse effects.

Discussion

LHRHa are associated with adverse effects that have numerous psychosocial and medical implications. Declines in physical, sexual, emotional, and cognitive functioning prove difficult to adapt to for patients and partners. Patients with PCa report a desire to be adequately informed about the beneficial and adverse effects of treatment before beginning treatment, to have a health care professional talk to them about treatment complications, and to be given information about how to manage adverse

Conclusion

There is a vast literature describing the life-altering effects of LHRHa and the extensive physiological and psychosocial complications that can arise from this treatment. However, many review articles contain inaccuracies and do not cite original sources. To make informed decisions about treatment, patients need to know the prevalence rates of these adverse effects. This article references only original sources regarding prevalence rates and provides a comprehensive, easy to reference table

Acknowledgments

The authors sincerely thank the following people for providing feedback on the manuscript and/or prevalence rates table before submission: Dr Richard Wassersug, Dr Paul Abel, Dr Paul Schellhammer, Dr Celestia Higano, Dr Larry Goldenberg, and Michelle Chang, BSc Pharm.

This work was supported in part by the following awards: Canadian Male Sexual Health Council, Social Sciences and Humanities Research Council of Canada, Alberta Innovates—Health Solutions, and the University of Calgary Program for

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