Drugs Compromising Male Sexual Health

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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.
 VI 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 VII

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

 iDXA and VFA (vertebral fracture assessment) 

1 Male Sexual Health

Male sexual health was defined by the 1994 International
Conference on Population and Development in Cairo and
the 1995 Fourth World Conference on Women held in Bei-
jing. The conferences expanded the right to family planning
to include the right to better sexual and reproductive health.
On the basis of the World Health Organization’s definition of
health, the Cairo Programme defines reproductive health as:
a state of complete physical, mental and social well-being
and … not merely the absence of disease or infirmity, in all mat-
ters relating to the reproductive system and to its functions and
processes. Reproductive health therefore implies that people are
able to have a satisfying and safe sex life and that they have the
capability to reproduce and the freedom to decide if, when and
how often to do so. Implicit in this last condition are the right
of men and women to be informed and to have access to safe,
effective, affordable and acceptable methods of family plan-
ning of their choice, as well as other methods of their choice
for regulation of fertility which are not against the law, and the
right of access to appropriate health-care services that will en-
able women to go safely through pregnancy and childbirth and
provide couples with the best chance of having a healthy infant
(paragraph 72).
(Published by the United Nations Department of Public
Information − DPI/1877 − February 1997)
Reproductive rights are further elucidated by the UNFPA
(source: UNFPA website):
Attaining the goals of sustainable, equitable development
requires that individuals are able to exercise control over their
sexual and reproductive lives. This includes the rights to:
• Reproductive health as a component of overall health,
throughout the life cycle, for both men and women
• Reproductive decision-making, including voluntary choice
in marriage, family formation and determination of the
number, timing and spacing of one’s children and the right
to have access to the information and means needed to exer-
cise voluntary choice
• Equality and equity for men and women, to enable individu-
als to make free and informed choices in all spheres of life,
free from discrimination based on gender
• Sexual and reproductive security, including freedom from
sexual violence and coercion, and the right to privacy.

In this sense, the term “male sexual health” comprises satisfy-

ing sexual function including the social aspects of partner-
ship and gender identification, the psychological conditions
of libido and arousal, as well as the physiological reactions of
  1 Male Sexual Health

1 erection and ejaculation, but also the undisturbed function

of androgen production and sperm maturation by the testes
leading to the ability to induce a pregnancy in the female
partner.
 1.1 Structure and Physiology of the Testis 

1.1 Structure and Physiology

of the Testis
1.1.1 Introduction

The testis is a paired organ located in the scrotum. It con-

sists of two different functional compartments: (a) the semi-
niferous tubules; and (b) the interstitial tissue. The tubules
contain the spermatogenetic tissue, the volume of which
amounts to up to 90% of the testicular volume. The intersti-
tial tissue contains the blood and lymph vessels, the nerves,
the connective tissue and the immune cells, and the Leydig
cells, in which the testosterone biosynthesis takes place.
The tubuli seminiferi are surrounded by a wall containing
myofibroblasts. There contractions, which support the trans-
port of the spermatozoa, are probably moderated by oxy-
tocin. In the lumen of the tubules, there are two cell types,
the Sertoli cells and the germ cells. The process of germ cell
development in the male from the primordial germ cells,
through spermatogonia, spermatocytes and spermatids to
the mature haploid spermatozoa is called spermatogenesis
The Sertoli cells have different functions: (a) forming of
the blood−testis barrier, which guarantees the intratubular
milieu; (b) “feeding” of the germ cells and facilitating their
differentiation in the spermatogenesis; (c) phagocytosis
of the residues of the sperm cytoplasm as well as of apop-
totic germ cells; and (d) secretion of steroid hormones and
inhibin. Sertoli cells yield an exclusive structure: the ecto-
plasmic specialization (Toyama et al. 2003), which comprises
the plasma membrane, a subsurface cistern formed by the
endoplasmic reticulum and a layer of microfilaments that
consists of actin between the two structures. One type of the
ectoplasmic specialization is localized in the adjoining parts
of the Sertoli cells (Sertoli−Sertoli junction); another type is
present in that region of the Sertoli cells which faces the ac-
rosomal region of the differentiating spermatids. It is similar
to the hemidesmosomes of the basal cells of the epidermis
(Sertoli−spermatid junction; Fig. 1.1.1).
Within the ectoplasmic specialization there are several
proteins, in part specific to the two types of junctions: ZO-1;
ZO-2; ZO-e; occludin, which binds to ZO-1; the claudin fam-
ily; and symplektin. Some of these proteins are found also
in other junctional regions of epithelial cells. Fimbrin, vincu-
lin and espin are found as actin-binding or actin-bundling
proteins. Disturbance of one of the types of ectoplasmic
specialization by different toxins leads to defects in the sper-
  1 Male Sexual Health

Fig. 1.1.1 There are two types of ectoplasmic specialization in the Sertoli cells (Sc): (a) one between Sertoli
cells and spermatids (Sd; arrowheads), placed near the tubular lumen (Lu), and those between two Sertoli
cells (Se 1, Se 2; arrows) and the spermatogonia (Sg), localized at the basal lamina (BL); and (b) the ectoplas-
mic specialization between adjoining Sertoli cells, which is composed of tight junctions (bottom, arrow-
heads). Asterisks represent the subsurface cistern of the endoplasmic reticulum. (From Toyama et al. 2003)
1.1 Structure and Physiology of the Testis 

matogenesis. Compounds acting in this way are oestrogens.

Also genetic alterations may influence the proteins of ecto-
plasmic specialization. In this sense, Sertoli cells are the most
relevant cells of the testis in terms of protection of spermato-
genesis, but also in terms of vulnerability.
Another type of cell-to-cell interaction among Sertoli
cells, and between Sertoli cells and germ cells, is mediated
by gap junctions, which link the neighbouring cells to each
other. As channels, they allow direct transportation of mol-
ecules with a molecular mass of up to approximately 1 kDa,
a process by which the cells exchange signals of metabolism
and cell differentiation. The constituents of the gap junc-
tions are connexins, a protein family of at least 20 members
in mammals. In the rat testis, transcripts for 11 connexins
have been identified. Connexin 43 and connexin 31 are of
particular importance. In the seminiferous tubules, gap junc-
tions containing connexin 43 form an intercellular network,
which possibly coordinates the metabolic influences of Ser-
toli cells on germ cell differentiation. The state of gap junc-
tions between the testicular cells is controlled by endocrine
and paracrine messengers, such as gonadotropins, steroid
hormones and thyroid hormones. Environmental toxins and
endocrine disruptors may impair the gap junctions (Pointis
and Segretain 2005).
The other cell types of the tubules are classified as germ
cells. The germinal stem cells lie in the niche on the basal
lamina of seminiferous tubules. Culturing these cells in vitro
is now possible, but the goal of a spermatogenesis in vitro
is still far away (Ogawa et al. 2005). The cells differentiate
through four mitoses and the meiosis to the haploid sper-
matozoa. During these processes, the germ cells are embed-
ded in the Sertoli cells and migrate from the basement of
the tubules to the adluminal compartment. Spermatogonia
type A pale are the stem cells, which remain in the tubules
for further generations. Spermatogonia type A dark are the
first type of differentiating cells. They divide mitotically to
spermatogonia type B; they divide again to form the primary
spermatocytes. These spermatocytes undergo the first mei-
otic division in a long-standing process of chromosome ar-
rangement as zygotene, leptotene and pachytene spermato-
cytes, leading to secondary spermatocytes which contain
half of the chromosomes but a diploid amount of DNA. The
secondary spermatocytes divide mitotically into the haploid
spermatides, which differentiate during spermiogenesis to
the mature spermatozoa. The spermatids are interconnected
by intercellular bridges, which dissolve with maturation. Dur-
ing spermiogenesis (a) the nucleus is condensed to about
10% of the original volume, mainly by replacing the differ-
ent histones by four types of protamines, (b) the acrosome
evolves from the Golgi apparatus, forming the acrosomal
  1 Male Sexual Health

1 cap of the mature spermatozoa and (c) the flagellum is forti-

fied (Kim et al. 2002). An important factor in the regulation
of spermatid maturation is cAMP-responsive element modu-
lator (CREM). When the mature spermatids leave the testis,
they are designated as spermatozoa.
Gene expression of spermatids ceases after replacement
of histones by protamines. The transcription takes place in
the round spermatides, and a translation of transcripts is pos-
sible in later spermatids, e.g. for production of new proteins
used in maturating spermatids such as protamines. Genes
expressed during spermiogenesis avoid methylation in male
germ cells, even if they are methylated in somatic cells. The
methylation in germ cells is somewhat similar to the gene
methylation in cancer cells (Tanaka and Baba 2005).
Cells of spermatogenesis may undergo apoptosis at all cell
stages; more than half of cells of the different stages of dif-
ferentiation are eliminated by apoptosis. By morphological
criteria, the peak has been observed in type-A spermatogo-
nia, in primary spermatocytes and in maturing spermatids.
Apoptosis is important also for the cessation of the prepu-
beral germ cell wave, which occurs in many mammalian tes-
tes. Apoptotic cells are either shed into the lumen of the tu-
bules or they are phagocytosed by Sertoli cells. Sertoli cells
express the Fas ligand, which helps to eliminate Fas-positive
germ cells, and the phagocytosis of spermatogenic cells,
when they externalize the phosphatidyl serine as a marker of
apoptosis, is performed also by Sertoli cells via a class-B scav-
enger receptor. They also attack Fas-positive immune cells,
thus possibly supporting the maintenance of the testis as an
immune-privileged region. CREM, which is highly expressed
in postmeiotic cells, is also involved in apoptosis (Nakanishi
and Shiratsuchi 2003).
The process of spermatogenesis, including mitoses, meio-
sis, differentiation and apoptosis, is regulated not only by the
gonadotropins FSH, LH and testosterone, but also by local
control signals that regulate cell function (Lamb and Nie-
derberger 1994), among which are epidermal growth factor,
fibroblast-like growth factors, transforming growth factors,
interleukin and insulin-like growth factors I and II. There are
also growth factors unique to the testis secreted by Sertoli
cells; among these are inhibins, activins and the Muellerian-
inhibiting substance. The FSH receptors are found in the Ser-
toli cells and spermatogonia.

1.1.2 The Spermatozoa

The spermatozoa transport the male genome through the
female genital tract in order to procreate the embryo after
1.1 Structure and Physiology of the Testis 

fusion with the oocyte. The spermatozoa are motile cells that
consist of the head, which contains the DNA, the midpiece,
which contains mitochondria, which produce the kinetic en-
ergy, and the tail, which gives the spermatozoa their motility.
The spermatozoa undergo multiple changes of their surface
and their general characteristics on their (mainly passive)
passage through the male genital tract as well as on their
(mainly active) migration through the female genital tract.
The cytoplasm of mature spermatozoa contains practi-
cally none of the cellular machineries necessary for protein
synthesis. The constituent proteins of spermatozoa are
generally synthesized in spermatocytes and/or spermatids
(Toshimori 2003), but they are pivotally altered during
epididymal passage. During the passage, the spermatozoa
gain motility, the ability to bind to the zona pellucida and
fuse with the oocyte membrane by changes in their plasma
membrane. They undergo intense changes in protein com-
position: some proteins of testicular origin are removed or
altered, whereas others are added from epididymal sources.
Some major proteins secreted in the epididymis have been
identified in different species, among them lactoferrin,
clusterin and different enzymes acting in the carbohydrate
metabolism, e.g glycosidases and glycosyltransferases.
Clusterin is most common among the species as a whole;
the other proteins are secreted in species-specific amounts.
Some of the proteins are bound to, or integrated into, the
sperm membrane, e.g. the cysteine-rich secretory protein
(CRISP), which is found in the postacrosomal region of
ejaculated sperm. Also in human spermatozoa, proteins of
epididymal origin were identified in the membrane (HE1-5).
There is a high concentration of enzymes in the epididymal
fluid, which may contribute to the remodelling of the sperm
membrane. Epididymal proteins are also involved in protec-
tion of sperm against oxidative injury (e.g. the gamma-
glutamyl transpeptidase, GGT), in immune protection (e.g.
clusterin protection against complement-induced cell lysis)
and in antimicrobial activity of semen (e.g. hCAP-18). On the
other hand, also proteins dissolved from the spermatozoa
activate the epididymal secretions. A better understanding
of the role of epididymal proteins in sperm maturation will
allow the development of male contraceptives and will also
facilitate the understanding of untoward effects of drugs
(Dacheux et al. 2003).
Some of the proteins are secreted in an apocrine man-
ner by the epididymal epithelium and appear in exosomes,
called epididymosomes (Sullivan et al. 2005). These epi-
didymosomes interact with spermatozoa. Among the pro-
teins are two enzymes involved in the polyol pathway: an
aldose reductase and a sorbitol dehydrogenase, as is the
macrophage migration inhibitory factor (MIF). Also, one of
  1 Male Sexual Health

1 the surface proteins, P25b, which is necessary for the bind-

ing to the surface of the egg, is added to spermatozoa by
epididymosomes. In-vitro studies showed that the transfer
of epididymosomal proteins to specific membrane domains
of spermatozoa is saturable, as well as temperature- and pH-
dependent, and is optimal at pH 6.5. The presence of zinc in
the incubation medium, but not of calcium or magnesium,
significantly increases the efficiency of protein transfer.
Mature sperm cells in the adult male show a great mor-
phological variety, in particular of the head. There is, how-
ever, no association with aberrations of the genetic informa-
tion. In fertile men, no significant association between the
number of morphologically abnormal spermatozoa and
those bearing chromosomal abnormalities as evaluated by
the hamster-oocyte penetration test was found. This asso-
ciation was also lacking in men with known chromosomal
translocations. By fluorescence in-situ hybridization analysis
(FISH), no association of abnormal morphology and abnor-
mal chromosomes in spermatozoa could be shown. Also in
defined morphological abnormalities, such as globozoo-
spermia or multiflagellate sperm, no increased rate of chro-
mosomal abnormalities could be found (Sun et al. 2006).

1.1.3 Sperm Motility

Sperm motility throughout the female genital tract is guar-

anteed by sperm-innate sources. The migration is directed by
physical and chemical entities; among them are substances
which bind to an olfactory receptor (Serrano and Garcia-Su-
arez 2001). Spermatozoa move in a symmetrical, lower-am-
plitude waveform that drives them in a more or less straight
line. In certain conditions, spermatozoa gain “hyperactivated
motility”, which enables them to move progressively also in
a more viscous environment, such as the fallopian tube. This
special form of movement is associated with the ability of
sperm to fertilize the oocyte (Turner 2006).
A prerequisite for successful sperm motility is the flagellar
ultrastructure. In the midpiece of the flagellum there are nine
outer dense fibres right inside the plasma membrane and
the mitochondrial sheath. The axoneme is situated within
this ring, which contains other microtubule doublets with
associated dynein arms, radial spokes and a central pair of
microtubule doublets (Fig. 1.1.2). The axoneme is highly con-
served structure consisting mainly of α and β tubulins. The
motor proteins are the dyneins, which cause a sliding of the
microtubules along one another, and which lead to a bend-
ing of the flagellum. The outer dense fibres store the kinetic
energy and adds it via elastic return to the movement.
 1.1 Structure and Physiology of the Testis 

The energy transfer requires glycolysis; spermatozoa are

able to store glycogen and may even be capable of gluco-
neogenesis. In the mitochondrial sheath, sperm-specific
isoforms of the lactate dehydrogenase and the hexokinase
are present. In some species, the presence of the key glu-
coneogenic enzyme fructose-1,6-bisphosphatase was dem-
onstrated. Biophysically, a diffusion of ATP from mitochon-
dria along the sperm tail as far as to the tip over a length

Fig. 1.1.2 a Representation of the spermatozoon and the ultrastructure of the flagellum. b A section of
the midpiece shows outer dense fibres (ODF) below the mitochondrial sheath (MS) and the plasma mem-
brane (PM). Two ODFs have been replaced by two longitudinal columns (LC), connected by transversal ribs
(TR), In the centre, there are the nine outer microtubule doublets of the axoneme (OMDA) with dynein arms
(DA) and radial spokes (RS) and the central pair of microtubule doublets (CP). c At the end of the principal
piece the structure is similar, but there is no longer a mitochondrial sheath. d In the end piece, no more
ODF are left. (From Turner 2006)