Clinical Urologic Endocrinology: Principles for Men’s Health

Clinical Urologic Endocrinology: Principles for Men’s Health provides an organized, accessible reference on men’s endocrinological health.

Over 30 million men in the US alone suffer from erectile dysfunction and over 13 million men in the US suffer from hypogonadism (low testosterone). One out of seven couples also suffer from subfertility of which 50-60% have male factor involvement. More and more men are coming forward to seek treatment for such issues, which in the past were considered taboo and there is a strong need for a book which provides guidance for practitioners who support men in their reproductive and sexual concerns. This book covers in depth the key issues in male reproductive health in one easy-to-use resource.

Clinical Urologic Endocrinology: Principles for Men’s Health is a valuable reference for urologists, endocrinologists, internal medicine physicians, family medicine physicians, sex therapists, and allied health professionals providing care for men in the areas of sexual health, fertility, and men’s endocrinological health.

• Language: English
• Publisher: Springer
• Release date: Oct 19, 2012
• ISBN: 9781447144052

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Parviz K. Kavoussi, Raymond A. Costabile and Andrea Salonia (eds.)Clinical Urologic Endocrinology2013Principles for Men’s Health10.1007/978-1-4471-4405-2© Springer-Verlag London 2013

Editors

Parviz K. Kavoussi, Raymond A. Costabile and Andrea Salonia

Clinical Urologic EndocrinologyPrinciples for Men’s Health

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Editors

Parviz K. Kavoussi

Department of Urology, Austin Fertility & Reproductive Medicine, Austin, Texas, USA

Raymond A. Costabile

University of Virginia School of Medicine University Of Virginia Hospital, Charlottesville, Virginia, USA

Andrea Salonia

Department of Urology, University Vita-Salute San Raffaele, Milan, Italy

ISBN 978-1-4471-4404-5e-ISBN 978-1-4471-4405-2

Springer London Heidelberg New York Dordrecht

Library of Congress Control Number: 2012950461

© Springer-Verlag London 2013

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Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

This book is dedicated to my father,

Dr. Keikhosrow M. Kavoussi, who has been

my role model in medicine and life

Foreword

I am delighted to contribute to this wonderful volume, Clinical Urologic Endocrinology : Principles for Men ’ s Health , edited by Drs. Parviz Kavoussi, Raymond Costabile, and Andrea Salonia. The world of urology has moved forward rapidly over the last 20 years, and one of the more important developments within Urology is the new focus on men’s health. There is an opportunity and perhaps even an obligation for the urologist to become involved in this area, since many of the medical issues that are predominantly or uniquely male-specific fall within the realm of urology, such as male infertility, sexual dysfunction, and prostate disorders. A critical component of men’s health is the endocrinologic axis, particularly the role of testosterone and its pathologic counterpart, testosterone deficiency, in male health and illness. This textbook is therefore timely, as it provides an up-to-date picture of several key aspects of testosterone for men, with chapters written by leaders in the field.

Urology has a storied relationship with endocrinology. Charles Huggins was awarded the Nobel Prize for his research into the endocrinologic basis of some cancers, beginning with prostate cancer. In 1941 Huggins and his co-author Clarence Hodges reported that that prostate cancer regressed with castration or administration of estrogens, establishing the concept that the prostate was androgen-dependent. That work followed directly from experiments in dogs, one of the few species other than humans that develop benign prostatic hyperplasia (BPH), showing that castration caused prostatic involution. That research in turn was based on case reports from the beginning of the twentieth century reporting that castration cured urinary retention in some men with large prostates. Urologists today routinely prescribe 5-alpha reductase inhibitors to reduce intra-prostatic dihydrotestosterone instead of performing castration to achieve the same symptomatic benefit in men with BPH, thereby practicing urologic endocrinology.

Additional important contributions to urological endocrinology include the work of Patrick Walsh, M.D., who is best known today for developing the nerve-sparing radical prostatectomy, which ushered in the modern era of prostate cancer surgery. However in the 1970s Dr. Walsh’s work with endocrine pioneer Jean Wilson led to improved understanding of male genital differentiation. And ­urologists have been involved in the management of hormone-producing adrenal tumors since the early days of modern surgery. A quarter-century ago Frank Hinman, Jr., M.D., established the Endocrine Forum at the annual meeting of the American Urological Association, which has regularly been one of the most popular events at that meeting. Upon retirement Dr. Hinman passed leadership of the Endocrine Forum to Dr. Lipshultz, one of the pioneers in the field of male infertility and a contributing author of this text. I have been honored to serve as Dr. Lipshultz’s co-chair of this event for the last decade. Urology’s relationship to endocrinology is long and deep.

Today, testosterone is recognized as a critical hormone in male development, and no less as a critical agent involved in a man’s adult health, affecting multiple systems – sexual, reproductive, prostate, bone, muscle, fat, and brain. Although testosterone was first synthesized in the 1930s, the fear of prostate cancer severely restricted its use until the last one to two decades. Despite its age, the field of testosterone is still relatively young, in the sense that there is still much to be learned and there are extensive opportunities for exploration.

In 1988 when I began my own urological practice at Beth Israel Deaconess (now Beth Israel Deaconess Medical Center) in Boston as part of the Harvard Medical School faculty, there was almost no urological experience related to testosterone treatment. Its use was limited almost exclusively to men with obvious and severe testosterone deficiency due to: congenital or chromosomal issues, e.g., Klinefelter’s disease; pituitary or hypothalamic abnormalities or corrective treatments (surgery, radiation); and men who were anorchic due to surgery (e.g., for bilateral testicular cancer) or trauma. Even in cases where urologists had removed both testicles, testosterone therapy was almost always referred out to endocrinologists. As specialists in prostate disease, urologists had an additional reason to shy away from testosterone therapy, since it was universally believed that higher testosterone levels increased the risk of developing prostate cancer.

My own interest in testosterone therapy arose from work I had performed in a research laboratory as an undergraduate at Harvard University, investigating the effects of testosterone and other sex steroids on the sexual behavior of the American chameleon, Anolis carolinensis , under the tutelage of David Crews, Ph.D. Although I had received essentially no training in testosterone therapy during medical school or urological residency, my research experience made me curious about the effects of testosterone in men. I was surprised at how many of my patients with sexual dysfunction or infertility had low levels of serum testosterone, and I was pleasantly surprised when I treated several men and they responded well, often with benefits that are well described today but were largely unknown at the time. These included an increased sense of energy and well-being, and improved concentration and motivation. The lack of awareness of the symptoms and health impact of testosterone deficiency coupled with the fear of stimulating occult prostate cancer meant that there were only a handful of urologists and other specialists in the early and mid-1990s who offered testosterone therapy to otherwise healthy men with characteristic or suggestive symptoms.

The field was transformed by advances in clinical research, the introduction of more convenient treatment modalities, and reduced concern regarding prostate cancer. Physicians today recognize that testosterone deficiency is common and can occur in the healthiest of men at nearly any age, although it is clearly increased with age and co-morbidities, such as obesity and diabetes. The symptom complex has been better characterized, and includes reduced desire, erectile dysfunction, ejaculatory dysfunction, decreased energy, fatigue, decreased muscle mass, increased fat, and depressed mood. Testosterone deficiency is also intimately associated with important medical conditions, such as diabetes, metabolic syndrome, osteoporosis, and atherosclerosis. Testosterone therapy has been shown to produce symptomatic improvement in many men, and new evidence suggests that there may also be significant benefits of testosterone therapy for underlying medical conditions, such as impaired glucose metabolism and reduced bone density. Testosterone has also been implicated in what is arguably the most important health measure of all-longevity. Several observational studies now show that men with normal serum concentrations of testosterone have reduced mortality compared with men with low levels. And one retrospective study reported that intervention with testosterone therapy improved survival in testosterone deficient men.

In my opinion, the association of testosterone with so many significant health issues means that a serum testosterone concentration is the single most important indicator of a man’s health status, exceeding in importance other commonly used tests, such as glucose, cholesterol, or PSA.

This volume addresses many of the primary concerns for the physician or health care provider interested in testosterone deficiency and its treatment, as well as related endocrinopathies. The reader will learn about the physiology and epidemiology of testosterone deficiency, as well as the endocrinologic basis for sexual dysfunction and male infertility. Topics covered in this volume include how to diagnose, treat, and monitor men with testosterone deficiency. A chapter of particular interest to me is the relationship of testosterone and prostate cancer by Mohit Khera, M.D., due to my own involvement in this area over many years. Despite strong evidence to the contrary, there still exists concern among physicians that testosterone therapy is risky for prostate cancer. A recent and controversial issue is whether it may be reasonable to offer testosterone therapy to men with a history of prostate cancer. Readers are recommended to the excellent chapter by Dr. Khera to gain perspective on this and related issues regarding testosterone and prostate cancer.

This is an important volume, addressing a new and exciting area of men’s health. I am confident that the reader will find the material valuable and stimulating.

Abraham Morgentaler

Preface

Since the days of the nineteenth century, we have come a long way in our understanding of the importance of the male hormonal milieu and how the hypothalamic-pituitary-gonadal axis functions, self-regulates, and the best treatments when it is not optimized. In 1889, before the Societe de Biologie in Paris, the neurologist/physiologist Charles-Edouard Brown-Sequard first claimed to have improved his own physical strength and intellectual capacity by self-injecting liquid testiculaire. This was a formulation prepared from animal testicles, primarily canine and guinea pig. Although we have certainly refined our treatments since then and the field has significantly advanced, especially over the last two decades largely due to the work of many of the contributors to this text, there are still unanswered questions and gaps in our knowledge.

We are advancing our understanding for the sake of our patients, and the largest step forward was recognizing the importance of the hormonal axis for men’s health. Low testosterone is the major focus, but this text will also discuss other hormonal interactions in the realm of urologic endocrinology, which spans in its relevance to multiple types of health care providers, in essence any providing care for men.

Drs. Butenandt and Ruzicka won the Nobel Prize in 1939 for isolating testosterone and the clinical impact of this hormone on our patients has carried no lesser importance since that time. With 481,000 new cases of low testosterone in American men between the ages of 40 and 69 each year and an estimation that less than 5 % of hypogonadal men in the United States are being treated, the task falls upon health care providers to educate our patients and the public on the importance of this hormonal deficiency and the benefits of appropriate treatment. This means that providers caring for hypogonadal men must be well versed in the process, the evaluation, the treatment options, and the risks; which is the aim of this text. It is crucial to overcome the current barriers to treatment of men with low testosterone including the current lack of consensus in the definition of low testosterone, the lack of confidence in diagnostic testing, the non-specificity of the generalized and vague signs and symptoms of low testosterone, the perception that low testosterone is a difficult and time consuming health issue for providers to manage, and the powerful fear that treating low testosterone may induce prostate cancer, which continues to be disproved with multiple studies.

As a urologist treating hypogonadal men in clinical practice, I have the privilege of seeing the impact of this cholesterol derived hormone on my patients every day. What was once thought of as purely the male sex hormone is now known to be so much more. With the typical improvements in energy levels, libido, erections, mood, motivation, sleep, cognitive concentration, and body composition, it is evident what a positive impact this hormone can have on a man’s quality of life. There are also the health benefits to consider for our patients. Although the studies are ongoing to help solidify our understanding of the impact of this hormone on lipid profiles, glucose metabolism, bone mineral density, obesity, cardiovascular fitness, and metabolic syndrome; there is accumulating data moving in a positive direction. Clinical judgment is still needed to select the appropriate candidates for treatment and this text will help the health care provider in making such decisions, as well as the most appropriate modality of treatment for each individual man.

Acknowledgements

My acknowledgements go to the contributors of the text, including all authors and my co-editors, whose work has made this text possible. I would also like to acknowledge my cousin, Dr. Louis R. Kavoussi, who has always encouraged me to write and edit to contribute to the field.

Contents

1 Anatomy and Physiology of Androgen Regulation in Men 1

Jerald Marifke and Jay Sandlow

2 Development of the Male Reproductive System 11

Pravin K. Rao and Arthur L. Burnett

3 Epidemiology and Diagnosis of Hypogonadism 25

Mikkel Fode, Susanne A. Quallich, Yacov Reisman, Jens Sønksen and Dana A. Ohl

4 Testosterone and Sexual Function 41

Wayland Hsiao and John P. Mulhall

5 Treatment of Hypogonadism in Men 59

Akanksha Mehta, Darius A. Paduch and Marc Goldstein

6 Hypogonadism and Prostate Cancer: To Treat or Not to Treat 89

Mohit Khera

7 Testosterone and Male Infertility 103

Tung-Chin Hsieh, Matthew McIntyre and Larry Lipshultz

8 Specific Endocrinopathies and Male Infertility 123

Vincent Harisaran, Eugene Cone and Kathleen Hwang

Index139

Contributors

Arthur L. Burnett

Department of Urology, Johns Hopkins Hospital, Baltimore, MD, USA

Eugene Cone

Department of Urology, Warren Alpert Medical School of Brown University, Providence, RI, USA

Raymond A. Costabile

Department of Urology, University of Virginia School of Medicine, Charlottesville, VA, USA

Mikkel Fode

Department of Urology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

Marc Goldstein

Department of Urology, Center for Male Reproductive Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA

Vincent Harisaran

Department of Urology, Rhode Island Hospital, Providence, RI, USA

Wayland Hsiao

Department of Urology, Emory University, Atlanta, GA, USA

Tung-Chin Hsieh

Department of Urology, Baylor College of Medicine, Houston, TX, USA

Kathleen Hwang

Department of Urology, Warren Alpert Medical School of Brown University, Providence, RI, USA

Parviz K. Kavoussi

Department of Urology, Austin Fertility & Reproductive Medicine, Austin, TX, USA

Mohit Khera

Division of Male Reproductive Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA

Larry Lipshultz

Department of Urology, Baylor College of Medicine, Houston, TX, USA

Jerald Marifke

Division of Endocrinology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

Matthew McIntyre

Department of Urology, Baylor college of Medicine, Houston, TX, USA

Akanksha Mehta

Department of Urology, Weill Cornell Medical College, New York, NY, USA

John P. Mulhall

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Dana A. Ohl

Department of Urology, University of Michigan, Ann Arbor, MI, USA

Darius A. Paduch

Department of Urology, Center for Male Reproductive Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA

Susanne A. Quallich

Department of Urology, University of Michigan, Ann Arbor, MI, USA

Pravin K. Rao

Department of Urology, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Yacov Reisman

Department of Urology, Amstelland Hospital, Amsterdam, The Netherlands

Andrea Salonia

Department of Urology, University Vita-Salute San Raffaele, Milan, Italy

Jay Sandlow

Department of Urology, Medical College of Wisconsin, Milwaukee, WI, USA

Jens Sønksen

Department of Urology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

Parviz K. Kavoussi, Raymond A. Costabile and Andrea Salonia (eds.)Clinical Urologic Endocrinology2013Principles for Men’s Health10.1007/978-1-4471-4405-2_1© Springer-Verlag London 2013

1. Anatomy and Physiology of Androgen Regulation in Men

Jerald Marifke¹   and Jay Sandlow²  

(1)

Division of Endocrinology, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA

(2)

Department of Urology, Medical College of Wisconsin, 9200 W. Wisconsin Ave, Milwaukee, WI 53226, USA

Jerald Marifke (Corresponding author)

Email: [e-mail]

Jay Sandlow

Email: [e-mail]

Abstract

The purpose of this chapter is to provide the reader with an understanding of the hypothalamic-pituitary axis relative to the production of androgens and sperm in the testes. The physiologic action of the androgens will be reviewed as well. A detailed discussion of gonadotropin-releasing hormone (GnRH) and its effect on the anterior pituitary regarding production and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with the end result in production of testosterone and spermatozoa will be outlined. The conversion and actions of androgens will be discussed. The two main pathways leading to the initiation of androgen action will be presented, as is a