Drugs Compromising Male Sexual Health

703 Pages·2008·3.76 MB·English

by  Walter Krause

Walter Krause
Drugs Compromising Male Sexual Health
Walter Krause
Drugs Compromising
Male Sexual Health
123
Walter Krause, Em. Prof. Dr. med.
Universitätsklinikum Gießen und Marburg
Klinik für Dermatologie und Allergologie
35033 Marburg
Germany
Library of Congress Control Number: 2007935896
ISBN 978-3-540-69859-3 Springer Berlin Heidelberg New York
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Foreword 
Foreword
Testosterone is my favourite hormone, a focus of my research. In the public mind it is
the body’s most potent chemical, making the difference between a 90-pound weakling
and a he-man, between a milquetoast and a lothario. Steroid analogues, stacked by
muscle builders, are supposed to cause out-of-control “’roid rages”. Some people be-
lieve an injection of testosterone propelled Floyd Landis from also-ran to his “miracu-
lous Stage 17” of the Tour de France.
The hormone has become part of the language of popular culture. The New York Times
carried the following passages in the previous 2 weeks:
“I always thought downtown had a high testosterone level”, referring to the high male-
to-female ratio of residents in lower Manhattan (14 April 2007).
“It is the kind of gathering that, at its most primal, has testosterone flowing more freely
than the on-the-house spirits”, referring to a news conference prior to a boxing match
(20 April 2007).
“[T]hese are testosterone-fueled domains, largely defined by bulging muscles and ex-
ploding guns”, in a review of an action movie (20 April 2007).
“[T]his film is about [auto racing] surfaces, for young men with testosterone to burn”,
from a review of another action movie (14 April 2007).
For decades, testosterone has been proposed as a pharmaceutical fountain of youth,
presumably capable of rebuilding aging muscle, restoring strength and vigor, bolster-
ing masculine assertiveness, and resuscitating libido and penetrating power. For nearly
as long, testosterone has been suspected of adverse side effects, particularly on the
prostate. Recent reassessment of hormone replacement therapy for postmenopausal
women may have muted calls for male hormone replacement. Still, that popular image
of testosterone is “tempting stuff” to men in decline.
Homer tells us that Achilles was given a choice of dying young as a famous hero, or
living a long and happy, but otherwise ordinary, life. It was a difficult decision. Achilles
vacillated, but after the death of Petroclus he opted for swift glory. Today, for an aging
male, the Achillean choice might be framed as 10 years of vigorous life (on testoster-
one replacement), or 20 years of continuing dilapidation. This seems to me an easier
choice: I would opt for 10 strong years.
Medically sophisticated readers know that the options are not so clear-cut. As Wal-
ter Krause points out, supplementing testosterone (beyond a low threshold level) does
not measurably improve a man’s sexual functioning, which wanes with age anyway.
I would add that exogenous testosterone does improve muscle mass, but its other
claimed benefits are not reliably sustained in the research literature. The popular im-
pression of its Herculean effects on male psyches and athletic prowess, promoted by
our mass media, is almost certainly as mythical as Hercules. On the other hand, gener-
ally deleterious effects on the prostate are not confirmed either.
I Foreword
There is really no Achillean choice between one decade of vigor and two of se-
nescence. Medicine offers lesser trade-offs: some alleviation of ills at the cost of some
side effects. Professor Krause shows us when the side effects do, or do not, include
compromising “that most male of activities”. For example, specific serotonin reuptake
inhibitors (SSRIs), while relieving depression, promote erectile and orgasmic dysfunc-
tion. Sometimes side effects can be turned to advantage. The SSRIs are useful in treat-
ing premature ejaculation.
Occasionally the trade-off is too good to pass up. Phosphodiesterase inhibitors,
most famously Viagra, restore potency with adverse effects that are generally mild
and self-limiting. Initial fears of increased risk of heart attack, provoking all those jokes
about dying happy, are not sustained. Professor Krause’s database shows no general
cardiac side effects in most studies, and no increase in myocardial infarction (excepting
men taking nitrate medications).
In overview, the first part of this book is short and will be read with profit by anyone
inclined to open the volume in the first place. It contains concise, up-to-date descrip-
tions of testicular function, erection and ejaculation.
The second, bulky part of this book − the database of drugs − is not a page turner,
but readers will be rewarded by digesting selected portions. In exhaustively catalogu-
ing and summarizing the literature on adverse drug effects on male sexual health, and
evaluating the quality of each study, Professor Krause gives the best demonstration
I have seen of inconsistency among research reports − some deserving trust, others
not. This may not be big news to experienced researchers, but I suspect it will surprise
many clinicians. (I wish science and health journalists would spend some time in the
database, because it might help them realize that novel findings reported in the press
and on television are often irreproducible.)
Readers must turn elsewhere for discussions of bias and fraud in medical research.
Here, even stipulating the honesty and objectivity of researchers, one can only wonder
how some of their work made it into print. In any sensible overview of the research
literature, it is essential to consider the quality of each report, as Professor Krause has
done. It will be a long time before this volume is replaced by a better source on drugs
that affect male sexual function.
Allan Mazur
Professor of Public Affairs
The Maxwell School
Syracuse University
Syracuse, NY
Preface II
Preface
Adverse effects of drugs on sexual functions are often neglected in practical medicine,
because they are usually mild or moderate and rarely prompt hospital admissions, de-
nominated as severe ADEs. In addition, standard textbooks of pharmacology and those
which discuss drug side effects consider these topics only marginally, and well-known
sexual side effects are not mentioned. There are, of course, a number of review articles
on the possible adverse effects of drugs on sexual dysfunction, in particular on erectile
dysfunction. But delineations of the exact figures of the incidence of sexual adverse
effects in a concrete drug are often lacking in these papers. Reviews also frequently do
not describe the database of the reported adverse effects, thus leaving the quality of
evidence uncertain.
This book summarizes quotations from the literature which describe particular ef-
fects of drugs on male sexual functions. A special concern of the composition is the in-
formation on the quality rating of the reports quoted, and to reflect the overall quality
of evidence that supports a specific adverse effect of a pharmacological or therapeutic
subgroup of drugs. The quality rating is expressed in analogy to the grading system for
clinical studies of the Scottish Intercollegiate Guidelines Network (SIGN). The system-
atic of drugs follows the ATC/DDD system published by the WHO.
The book is intended to encourage physicians who use any of the drugs mentioned
for treatment in their patients to ask their patients about adverse effects, and to give
attention to possible observations in their patients. A collection of these observations
will enhance our knowledge of the compromising of male sexual health by drugs.
Marburg, October 2007
Walter Krause
Contents IX
Contents
1 Male Sexual Health .................................... 1
1.1 Structure and Physiology of the Testis ................... 3
1.1.1 Introduction ............................................ 3
1.1.2 The Spermatozoa ....................................... 6
1.1.3 Sperm Motility .......................................... 8
1.1.4 Capacitation and Acrosome Reaction ................... 10
1.1.5 Fertilization of the Oocyte .............................. 11
1.1.6 Testing Substances that Compromise Spermatogenesis
and Fertility (adapted from Creasy 1997) ................ 12
1.1.7 Testosterone Production and Testosterone Effects ...... 14
1.2 Physiology of Erection .................................. 23
1.2.1 Introduction ............................................ 23
1.2.2 Role of Androgens in Erection .......................... 28
1.2.3 Priapism ................................................ 29
1.3 Physiology of Ejaculation ............................... 31
2 Drugs Which Compromise Male Sexual Health ........ 35
2.1 Adverse Drug Effects .................................... 37
2.2 Male Sexual Health and Drugs .......................... 41
2.3 Drugs Which Compromise Testicular Function .......... 45
2.4 Drugs Which Compromise Erectile Function ............ 385
2.5 Drugs Which Compromise Ejaculation .................. 637
2.6 Database of Drugs ...................................... 681
Subject Index .................................................. 697
Acronyms and Abbreviations Used in the Text XI
Acronyms and Abbreviations
Used in the Text
Acronym/abbreviation Definition
19NT-HPP 19-nortestosterone hexyloxyphenylpropionate
5-ASA 5-amino salicylic acid
5-PDE 5-phosphodiesterase
ABVD Bleomycin, dacarbazine, doxorubicin, vinblastine
ADEs Adverse drug effects, adverse drug events
BSFI Brief Male Sexual Function Inventory
CASA Computer-assisted semen analysis
CI Confidence interval
ClVPP Lomustine, prednisone, procarbazine, vinblastine
COPP Cyclophosphamide, prednisone, procarbacine, Vincristine
CPA Cyproterone acetate
CVB Cisplatin, vindesine, bleomycin
DHEA Dehydroepiandrosterone
DSG Desogestrel
e.d. Erectile dysfunction
FISH Fluorescence in-situ hybridization
FSH Follicle-stimulation hormone
GnRH Gonadotropin-releasing hormone
Gy Gray
hCG Human chorionic gonadotropin
HDL High-density lipoprotein
hMG Human menopausal gonadotropin
ICSI Intracytoplasmatic sperm injection
ICSI-TESE Intracytoplasmatic sperm injection after testicular Sperm
extraction
XII Acronyms and Abbreviations Used in the Text
IELT Intravaginal ejaculation latency time
IHH Idiopathic hypogonadotropic hypogonadism
IIEF International index of erectile function
IPSS International prostate symptom score
IU International unit
IVF In-vitro fertilization
LH Luteinizing hormone
LNG Levonorgestrel
LUTS Lower urinary tract symptoms
MOPP Mechlorethamine, vincristine, procarbazine, Prednisone
MPA Medroxprogesterone acetate
MVPP Mustine, vinblastine, procarbazine, prednisolone
n.g. Not given
NETE Norethisterone enanthate
NIH National Institutes of Health (Bethesda, Maryland)
NOVP Mitoxantrone, prednisone, vinblastine, vincristine
NPT Nocturnal penile tumescence
OR Odds ratio
PADIC Cisplatin, dacarbazine, doxorubicin
POMB-ACE Bleomycin, cisplatin, cyclophosphamide, Dactinomycin,
etoposide, methotrexate, vincristine
PTSD Post-traumatic stress disorder
RCT Randomized control trial
RR Relative risk
SHBG Sexual hormone binding globulin
T Testosterone
TESE Testicular sperm extraction
VBP±A Vinblastine, bleomycin, cisplatin, adrimycin, Zona pellucida