[OA] "Cherchez La Femme": Modulation of Estrogen Receptor Function With Selective Modulators: Clinical Implications in the Field of Urology
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. http://www.sciencedirect.com/science/article/pii/S2050052117300215
Comparative structures of natural and synthetic estrogen and selective estrogen receptor modulators.
Panel A shows naturally occurring estrogens.
Panel B shows the synthetic estrogen diethylstilbestrol.
Panel C shows selective estrogen receptor modulators.
Panel D shows cis- and trans-stereoisomers of clomiphene citrate (enclomiphene and zuclomiphene).
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. http://www.sciencedirect.com/science/article/pii/S2050052117300215
Comparative structures of natural and synthetic estrogen and selective estrogen receptor modulators.
Panel A shows naturally occurring estrogens.
Panel B shows the synthetic estrogen diethylstilbestrol.
Panel C shows selective estrogen receptor modulators.
Panel D shows cis- and trans-stereoisomers of clomiphene citrate (enclomiphene and zuclomiphene).
