Endocrine_Aspects_of_Sexual_Dysfunction_in_Men

69Endocrine Aspects of Sexual Dysfunction in Men

Alvaro Morales, MD,* Jacques Buvat, MD,†Louis J. Gooren, MD,‡Andre T. Guay, MD,§Jean-Marc Kaufman, MD,¶Hui Meng Tan, MD,#and Luiz O. Torres, MD***Department of Urology, Queen’s Univerisity, Kingston, ON, Canada; †Centre ETPARP, Lille, France, ‡Department ofEndocrinology, Vrije University, Amsterdam, The Netherlands; §Center for Sexual Function/Endocrinology, Lahey ClinicNorthshore, Peabody, MA, USA; ¶Department of Endocrinolgy and Rheumatology, University Hospital Ghent, Ghent,Belgium; #University of Malaya, Selangor, Malaysia; **Funcionarios Belo Horizonte, Minas Gerais, BrazilSummary of Committee. For the complete report please refer to Sexual Medicine: Sexual Dysfunctions in Men andWomen, edited by T.F. Lue, R. Basson, R. Rosen, F. Giuliano, S. Khoury, F. Montorsi, Health Publications, Paris 2004.

ABSTRACTIntroduction.Endocrine disorders of sex steroid hormones may adversely affect men’s sexual function.Aim.To provide expert opinions/recommendations concerning state-of-the-art knowledge for thepathophysiology, diagnosis and treatment of endocrinologic sexual medicine disorders.Methods.An International Consultation in collaboration with the major urology and sexual med-icine associations assembled over 200 multidisciplinary experts from 60 countries into 17 commit-tees. Committee members established specific objectives and scopes for various male and femalesexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respec-tive sexual medicine topic represent the opinion of experts from five continents developed in a sci-entific and debate process. Concerning the Endocrine committee, there were eight experts fromseven countries.Main Outcome Measure.Expert opinions/recommendations are based on grading of evidence-based medical literature, extensive internal committee discussion over 2 years, public presentationand deliberation.Results.Hypogonadism is a clinical and biochemical syndrome characterized by a deficiency inserum androgen levels which may decrease sexual interest, quality of erections and quality of life.Biochemical investigations include testosterone and either bioavailable or calculated free testos-terone; prolactin should be considered when hypogonadism has been documented. If clinically indi-cated, androgen therapy should maintain testosterone within the physiological range avoidingsupraphysiologic values. Digital rectal examination and determination of serum prostate specificantigen values are mandatory prior to therapy and regularly thereafter. Androgen therapy is usuallylong-term requiring regular follow-up, frequent monitoring of blood levels and beneficial andadverse therapeutic responses.Conclusions.Safe and effective treatments for endocrinologic sexual medicine disorders examinedby prospective, placebo-controlled, multi-institutional clinical trials are needed.

Key Words.Hormone Therapy; Endocrine Sexual Dysfunction; Hypogonadism; Androgens;Andropause; Testosterone; Dehydroepiandrosterone; Sex Hormone Binding Globulin; Prolactin

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IntroductionInterest in hormone replacement therapy (HRT)in women has been extrapolated to androgenreplacement therapy in men. This paper discussesthe endocrine aspects of men’s sexual dysfunctionincluding the pathophysiology, diagnostic processand treatment modalities as well as their efficacy.The aim of this paper is to provide guidelines forthe endocrine aspects of men’s sexual dysfunction,focusing on the relationships between hormonalalterations and sexual function. The conceptsdetailed are limited to those aspects pertaining toendocrine alterations related to interference withthe normal sexual response in the adult man.

Aging, Hypogonadism and Sexual Function: New ConceptsThe alteration in androgen production in agingmen has been scientifically recognized for over 70years [1]. Interest has developed recently regard-ing the importance of this condition known asmale climateric, andropause, more appropriately,androgen decline in the aging male (ADAM) orlate onset hypogonadism. The term andropause,although biologically wrong, conveys the conceptof emotional and physical changes that, althoughrelated to aging in general, are also associated withsignificant hormonal alterations.Although hypotestosteronemia is the mostwidely recognized and investigated hormonalalteration associated with the aging process, theproduction of several other hormones is also pro-foundly affected by age and may have implicationsin sexual function. The recommendation of theInternational Society for the Study of the AgingMale (ISSAM) should indicate that other hor-mones besides testosterone (T) can contribute tosexual dysfunction as well as other manifestationslargely attributed to hypogonadism.While vascular problems associated with agingmay be the most prominent cause of erectile dys-function (ED) [2,3] other reasons may also play aprominent causal role. High locations of thecentral nervous system have a direct genital con-nection to the corpus cavernosa of the penis andare of fundamental importance in the control ofsexual behavior and function. Aging is associatedwith a progressive decline in the production ofseveral hormones including testosterone, dehy-droepiandrosterone, thyroxine, melatonin andgrowth hormone [4]. Hypogonadism is associatedwith a decrease in sexual interest and deteriorationin the quality of erectile function, both of whichcan be improved with androgen supplementationtherapy. The therapeutic response has beenexplained as the result of the central and periph-eral activity of androgens.Basic animal research provides the informationintegrating the concepts of decreased sexual func-tion and hormonal alterations in the aging male.In a series of investigations in rodents, Wang andher co-workers [5] have shown that hypothalamic-pituitary functional alterations may not be themajor cause of male gonadal dysfunction. Theyfound evidence of a significant increase in apopto-sis in both the hypothalamus and the gonads, adual alteration that may explain the developmentof hypogonadism in aging. The areas of the forebrain closely linked to the decrease ingonadotropin-releasing hormone (GnRH) due tothis apoptotic process are the same or intimatelyrelated to the areas controlling the penile erectionprocess and the synthesis and release of oxytocin(Figure 1). Similarly, peptides normally character-ized by their ability to release growth hormone(GH) were found capable of inducing penile erections when injected into the paraventricularnucleus (PVN) of experimental animals. GH pro-duction also declines in relation to advancing age.These integrated views remain speculative but areworth additional research.

Epidemiological AspectsGlobal prevalence of hypogonadism in maturemen can be predicted from population projections.In North America several cross-sectional and lon-gitudinal studies [6–8] have confirmed the declinein androgen production associated with age (Table1). It has been estimated that in the United Statesthere are 5 million hypogonadal men but onlyabout 5% receive treatment (Figure 2) [9]. Thedecline in serum testosterone (T) in the agingmale population is, however, a universal phenom-enon. A comprehensive review on studies aimed atthe prevalence of ED has been recently published[10].

Physiological Aspects of Hormones Involved InSexual FunctionAndrogensThe hypothalamic-pituitary gonadal system is aclosed loop feedback control mechanism directedat maintaining normal reproductive function [11].The gonadal hormones have inhibitory effects onthe secretion of LH and FSH. Although testos-70Morales et al.

Journal of Sexual MedicineVol. 1, No. 1, 2004