INTRODUCTION: Selective estrogen receptor modulators (SERMs) have been used 
off-label in men for more than 50 years. SERMs exert their action on the 
estrogen receptor agonistically or antagonistically. A fundamental knowledge of 
the complex molecular action and physiology of SERMs is important in 
understanding their use and future directions of study in men.
AIM: To review the basic science and mechanism of the action of estrogens, the 
estrogen receptor, and SERMs, and the existing clinical publications on the use 
of SERMs in men for infertility and hypogonadism with their strengths and 
weaknesses and to identify the need for future studies.
METHODS: After a review of publications on the basic science of estrogen 
receptors, a chronologic review of published evidence-based studies on the use 
of SERMs in men for infertility and hypogonadism was undertaken.
MAIN OUTCOME MEASURES: Clinical publications were assessed for type of study, 
inclusion criteria, outcome measurements, and results. Strengths and weaknesses 
of the publications were assessed and discussed.
RESULTS: Few prospective rigorously controlled trials have been undertaken on 
the use of SERMs in men. Most existing trials are largely retrospective 
anecdotal studies with inconsistent inclusion and end-point measurements. The 
SERMs are complex and at times can produce paradoxical results. Their action 
likely depends on the genetics of the individual, his tissue-specific 
composition of estrogen receptors, the molecular structure and pharmacodynamics 
of the SERMs, and their metabolism.
CONCLUSION: Rigorously controlled trials of the use of SERMs in men are needed 
to better identify their clinical benefit and long-term safety in infertile and 
hypogonadal men. Recent placebo-controlled pharmaceutical industry SERM trials 
have demonstrated short-term safety and efficacy in men with secondary 
hypogonadism and eventually might provide an alternative to exogenous 
testosterone replacement therapy in men with secondary hypogonadism. Helo S, 
Wynia B, McCullough A. "Cherchez La Femme": Modulation of Estrogen Receptor 
Function With Selective Modulators: Clinical Implications in the Field of 
Urology. Sex Med Rev 2017;5:365-386.