FAKULTAS KEDOKTERAN

UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 8- Basic Anatomy and Physiology

Raden Argarini

raden-a@fk.unair.ac.id
Sex Organs

Primary sex organs (Gonads)

• Definition: organs that produce gametes (Male, testes –
testicle)
• Function: produce germ celss/ gamet (gametogenesis/
Spermatogenesis) and sex hormone (androgen secretion)

Secondary sex organs:

• Definition: Organs other than gonad that is essential for
reproduction (duct system, gland and penis)
• Function: storage, survival, and conveyance
Anatomy of Male Reproductive Organ

 Primary sex organs

• Testes
 Reproduction duct
• epididimis
• vas deferens
• Ejaculate duct
• uretra/penis
 Glands
• vesika seminalis
• prostat
• bulbouretra
 Hormone
• androgen
Secondary characteristics

• Develop at puberty
• Distinguish the sexes
• Play role in mate attraction
Sex determination in humans

TDF

https://ib.bioninja.com.au/standard-level/topic-6-human-physiology/66-
hormones-homeostasis-and/sex-development.html
Sex differentiation

• Determined by genetic and hormones

produced by mother and fetus 
• Wk 5-6 Gonad began to develop
• Duktus Wolffian (mesonephric)
Reproductive tract (Vas deferens)
• Duktus Mullerian (paramesonephric) 
oviduct
• Wk 8-9testis is developed and begin
to produce testosterone (and Mullerian
inhibiting hormone)
Sex differentiation

Figure 26-3a: Sexual development in the human embryo

Gen and hormones in sex organs development
Development of external
genitalia

• Phallus: a small shaft of

tissue with a swollen
gland
• Urogenital fold: a pair of
medial tissue folds slightly
posterior to the phallus

From Velkey JM et al. Normal Vulva: Embryology,

Anatomy, and Histology, in: Vulvar Pathology, editted by
Hoang MP, Selim MA. 2015 Springer-Verlag New York
 A. Wk 6-10  the process of

Descent of Testes descent of the testes is begin.

via inguinal canal.
B. The beginning of the formation
of the vaginal process is visible.
It enters with the testis into the
inguinal canal. Shown in blue is
the gubernaculum that becomes
increasingly shorter.
C. Between the 3rd and 7th month
of pregnancy the testes remain
near the inguinal canal in order
to pass through it. The vaginal
A B process lengthens while the
gubernaculum shortens,
thereby drawing the testis, the
deferent duct and its vessels on
both sides downwards.
D. Wk 28  testes enter the
scrotum

1. Gubernaculum testis 4. Testis

2. Penis 5. Peritoneal cavity
C D 3. Inguinal canal 6. Duct deferent
Scrotum
 Pendulous pouch
 The skin contains: sebaceous and sweat gland, sparse hair,
rich sensory innervation, darker pigmentation
 Testes are kept at a temperature about 35° C (2-4 ° C cooler
than body temp)  essential for sperm production
Scrotum thermoregulation
 Scrotum:
• Skin: thin, minimal
subcutaneous fat, scant
hair
• Muscle: Contracted, it
conserves heat; relaxed it
is smooth and elongated,
permitting the circulation of
air that effects cooling
 Evaporative Convective
(Radiation) cooling
 Sweat Glands on scrotum
 Pampiniform Plexus
Testicular heat stress

Durairajanayagam, 2015
Durairajanayagam, 2015
Testicular heat stress: contributing factors
 Life style
• Clothing and posture
• Hot baths and sauna
• Laptop use
• Cycling
• Obesity
 Occupational and environmental factors
• Radiat heat
• Ambient heat
 Clinical factor
• Cryptorchidism
• Varicocele
• Febrile episodes
Durairajanayagam, 2015
Clinical insight

Androgen-Insensitivity Syndrome

Undescensus testis:
Patophysiology – Treatment - Outcome

Failure of testis descent into the scrotum is one of the two

most frequent male reproductive pediatric complications.
3% mature male newborns (up to 4-5%)
1% in 1 year old boys
30% prevalence in premature boys
The End
 FAKULTAS KEDOKTERAN
UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 9- HPA axis and hormonal regulation

Raden Argarini

raden-a@fk.unair.ac.id
Hypothalamic–Pituitary–Adrenal (HPA)Axis
Hypothalamic-Pituitary-Gonadal (HPG) Axis

Barati, 2020
Hypothalamic–Pituitary–Adrenal (HPA)Axis
 Complex system of neuroendocrine pathways and
feedback loops that function to maintain physiological
homeostasis
 Consists of a cascade of endocrine pathways that respond to
specific negative feedback loops involving the hypothalamus,
anterior pituitary gland, and adrenal gland

Hypothalamic–Pituitary–Gonadal (HPG)Axis
 Comprised of the hypothalamus, the pituitary gland and the
testes.
Adrenal androgen

 Steroid hormones that are

secreted by the adrenal
cortex (zona reticularis).
 derived from cholesterol
 AA includes:
 dehydroepiandrosterone
(DHEA)
 dehydroepiandrosterone
sulfate (DHEAS)
 androstenedione (A4)
 androstenediol (Α5)
 11β-
hydroxyandrostenedione
(11βOHA4)
georgiahealth.edu
Adrenal androgen
Adrenal androgen
 Functions
 have little androgenic activity
 a pool of circulating precursors for peripheral conversion to
more potent androgens (e.g. testosterone) and estrogens,
(e.g. estradiol)
 play a role before puberty

Hirsusitism
 Hormones and Brain Testicular (HPG)
Hypothalamic-Pituitary-Gonadal Axis Axis
Saladin
Hypothalamic–Pituitary–Gonadal (HPG)Axis
 secretes gonadotrophin releasing hormone (GnRH) in a
pulsatile fashion
 stimulates the anterior pituitary gland to secrete two hormones
vital for reproduction, follicle-stimulating hormone (FSH) and
luteinizing hormone (LH)
 LH and FSH act on cells in the testes including Leydig, Sertoli
(sustentacular/nurse) and germ cells.
 Leydig cells are the testosterone producing cells in the testicle
 Sertoli cells produce inhibin B
 Both hormones feedback onto the anterior pituitary and the
hypothalamus
 Testosterone, once released into the peripheral circulation
may be converted to estradiol by the enzyme aromatase,
which can have effects on fertility
Hypothalamic physiology—GnRH signaling
 GnRH is a short peptide hormone secreted by neurons that
originate in the nasal placode
 Secreted by neuronal endings directly into the hypophyseal
circulation
 Binds to GnRH receptors located on pituitary gonadotrope
cells in the anterior pituitary
 GnRH activity is low in childhood and pulsatile secretion
begins at puberty
 Fast GnRH pulses (>1 pulse per hour)  induce LH synthesis
 Slower pulse frequencies (<1 pulse per 2–3 hours)  induce
FSH synthesis
 Key regulator: Kisspeptins
Key regulator of GnRH pulses generator
 Kisspeptin fibers project to GnRH cell
bodies as well as GnRH fibers
 GnRH neurons express KISS1-Receptor

KNDy (Kisspeptin-Neurokinin B and Bhattacharya, 2019

Kisspeptins

 a group of neuropeptides encoded by the Kiss1 gene

(essential gatekeeper of puberty and fertility)
 acts via the KISS1-Receptor, a G protein-coupled receptor 54
(GPR-54)
 potent inducer of GnRH secretion

Bhattacharya, 2019
Pituitary physiology—FSH/LH signaling
 FSH/LH  maintaining spermatogenesis
 LH  testosterone production
Sertoli and Leydig (interstitial) cells
Gonadal - Testosterone
 Produced by Leydig cells
 Stimulate spermatogenesis in the presence of ABP
 Spermatogenesis could be stimulated with the LH analog hCG
in patients who had active spermatogenesis prior to pituitary
suppression
 Inhibit GNRH secretion by the hypothalamus
 Reduces the GnRH sensitivity of the pituitary
 Development of secondary sexual characteristics and other
somati changes related to the puberty
 Stimulate growth hormone secretion  growth spurt, ↑
muscle mass, ↑ BMR, larger larynx
 Stimulate eritropoesis
 Stimulate the brain and awakens the libido or sex drive
Inhibin

 Produced by
sertoli/sustantecular
cells
 Suppress FSH output
from the pituitary
(negative feedback)
 Sperm production ↓
below 20 mill
sperms/ml 
inhibin↓, FSH↑
Activin

 Produced by
sertoli/sustantecular
cells
 Stimulate FSH output
from the pituitary
Abnormalities of HPA Axis

Etiology:
Abnormal development ==>long-term alterations in neuropeptide
and neurotransmitter synthesis in CNS and glucocorticoid
hormone synthesis in the periphery
Hypogonadotropic hypogonadism: Kallman’s syndrome (KS):
prototypical form of HH
Etiology:
1. loss of Gpr54 and/or Kiss1 genes
2. loss of function mutations in man in either Neurokinin B or its
receptor (Tac3-Receptor)
Effects:
• delay puberty
• a defect in GnRH signaling leading to deficits in FSH and LH
• azoospermic
Abnormalities of HPG Axis

Testosterone deficiency syndrome (TDS)

generally total testosterone
decrease or loss of muscle strength, libido, memory, vitality,
alterations in mood, and erectile dysfunction (ED)
typically considered exclusively in older men
Anatomy structure of HPA Axis

Paraventricular Nucleus (PVN)  parvocellular, neurosecretory

magnocellular, and long-projecting neurons.
a. Neurosecretory parvocellular neurons:
• axons to the external zone of the median eminence to
regulate the secretion of releasing factors (CRH, TRH)
into the hypothalamohypophyseal portal vasculature
• Control the secretion of corresponding anterior pituitary
hormones
Development of HPA Axis

Develop as early as fetal life

Becomes sexually dimorphic during puberty due to differing
levels of gonadal hormones
Regulation of HPA Axis

Etiology: Abnormal development

o Prenatal stress
o Prenatal exposure to the periphery excess fetal glucocorticoid
(GC) hormones or environmental perturbations
o stress-related neuropathologies: such as maternal stressors

Impact:
long-term alterations in neuropeptide and neurotransmitter
synthesis in CNS and glucocorticoid
 FAKULTAS KEDOKTERAN
UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 10- Spermatogenesis and accessory glands

Raden Argarini

raden-a@fk.unair.ac.id
Spematogenesis

Definition: process by which sperm cell production occurs.

This is a highly organized and complex sequence of
differentiation events that yields genetically distinct
male gametes for fertilization.
Inside the seminiferous tubules
initiated at puberty and continuing throughout life (age 12-
14 y.o)
Seminiferous tubules
Young sperms
The schematic process of spermatogenesis

Germ cells (Spermatogonia) (46 chromosome)

mitosis
Androgen
Primary Spermatocytes (46 chromosome : 44 + X+ Y)
independent
(42-76 days) Meiosis I

Secondary Spermatocyte (23 chromosome : 22 + X/Y)

Meiosis II
Spermatid (23 chromosome : 22 + X/Y)
Androgen
dependent Spermiogenesis

Spermatozoa (23 chromosome : 22 + X/Y)

Maturation
Germ cells :

around 50–70% of developing GCs are discarded during

spermatogenesis

Spermatogonia
 Diploid progenitors of all other GCs types
 Located in the basal compartment of the STs
 dual responsibility
 meiosis to produce the male gamete,
 mitosis to self-renew
 Structure: ovoid nucleus and a dense cytoplasm containing a
small Golgi apparatus, few mitochondria, and many free
ribosomes.
Spermatocytes and spermatids

Primary spermatocytes (diploid):

 mitotic division of type B SPG
 the first GCs to cross the BTB to the adluminal compartment
 proceed to meiosis

Secondary spermatocytes and spermatids (haploid):

 lactate as their principal energy source

Spermiogenesis: spermatid  spermatozoon

 a series of cytoplasmic and nuclear changes
 acrosome is formed from the Golgi apparatus with participation
of a cytoskeletal structure called perinuclear theca
Spermiogenesis

Spermiogenesis: spermatid  spermatozoon

 a series of cytoplasmic and nuclear changes
 acrosome is formed from the Golgi apparatus with participation
of a cytoskeletal structure called perinuclear theca
 nucleus becomes more condensed and migrates to an eccen-
tric position
Spermiogenesis

Spermiogenesis: spermatid  spermatozoon

 The sperm tail arises from the centriole, gradually elongating
the spermatid shape, and is formed of microtubules disposed in
a2 + 9 formation
 Mitochondria increase in number and gather around the tail
basis, forming the mid piece
 excess of cytoplasm containing the remnants of Golgi
apparatus and other organelles is removed
Seminiferous tubules

 The functional unit of the testis

 Occupy two-thirds of the testis
 Length: 70-80 cm, total length is 250 m /testis
 consist of: basement membrane, sertoli cells, germs cells
 Surrounded by peritubular tissue (myoid cells, fibrocyte-like
adventitial cells, and collagen matrix)
 paracrine regulations of SCs (transferrin, inhibin and
androgen-binding protein )
 Characteristic of STs fluids:
 Thick consistency
 Low PH (high metabolites)
 Consist of:
 Estrogen
 K+
 Inositol
 Glutamic acid
 Aspartic acid
 Protein dan glucose : sangat sedikit
Blood Testis Barrier (BTB)

 anatomical and functional barrier that divides the

seminiferous epithelium in two separate spaces, the basal
and adluminal compartments
 Formed by cellular junctions
between adjacent SCs (tight
junctions, basal ectoplasmic
specialization, gap junction,
and desmosomes) and
peritubular tissue (myoid cells
and endothelial cells )
 restricts the paracellular
transit ofsubstances
Support system of spermatogenesis

1. Scrotum

2. Sertoli cells

3. Leydig cells

4. Hormones
Sertoli cells (SCs)

• It is surrounding the
seminiferous
tubulus.

• occupy 17–20% of
the STs epithelium
in adult man

• Spermatogenesis
occurs in between 2
adjacent SCs.
Vander (2001)
The functions of Sertoli cells (SCs)

 A single SC can support up to 30–50 GCs at different stages

of development  energy sources for GCs
 Produce:
o an Androgen-binding protein (ABP)
o inhibin B is a glycoprotein hormone that regulates the production
and secretion of FSH in the anterior pituitary gland, in a classic
negative feedback loop
o Embrio : produce Műllerian inhibiting substance (MIS)
 Act as macrophages, using phagocytosis to clean any
degenerating GCs or residual bodies from spermatids
Leydig cells

 located in clusters usually found in strategic positions between

blood vessels and ST
 the primary source of testosterone (3 and 10 mg/day of T,95%
of total T )
 the predominant testicular source of estrogens afterpuberty
(microsomal P450 aromatase )

Sel Leydig
Post-testicular sperms maturation (Spermiation)

Dari lumen tubuli seminiferi

Epididymis (Panjang ± 6 m )

Vas deferens

Ampula Vas deferens

Tempat penyimpanan spermatozoa

Bertahan ± 1,5 bulan

Hormonal and paracrine control of sprematogenesis

F.T.L. Neto et al. / Seminars in Cell & Developmental Biology 59 (2016) 10–26 13
HOMEWORK

azoospermia

Globozoospermia

Sertoli-cell–only syndrome
4. Hormon-hormon
spermatogenesis

Testoteron : untuk pertumbuhan dan pembelahan

germ cells

LH : merangsang sel Leydig

FSH : merangsang sel sertoli guna

spermiogenesis dan memicu produksi
androgen binding protein (ABP)

Estrogen : dibentuk dari testosteron dalam sel

sertoli (dipicu oleh FSH)

GH : mengatur fungsi metabolik testis

terutama mempromosi pembelahan
spermatogonia yang pertama
 KELENJAR - KELENJAR

a. Vesica Seminalis
Merupakan kelenjar sekretorik
(bukan tempat penyimpan spermatozoa
Fungsi :

1. Nutrisi terhadap spermatozoa

(oleh adanya fruktosa >>)

2. Alkalinisasi eyakulat  pH

3. Mengandung Prostaglandin
• Mempercepat gerakan sperma
• Mempengaruhi motilitas uterus & tuba fallopii
b. Prostat
 merupakan kelenjar yang mengitari uretra bagian atas dan
mensekresi cairan ke dalam uretra

 sekresi cairan basa  menetralkan sekret vagina yang

asam
 mengandung enzim proteolitik

Mencairkan eyakulat Sperma lebih mudah bergerak

C. Kelenjar bulbouretra (Cowper’s)

Sekresi mukus untuk pelumasan
EYAKULAT = SEMEN
 Cairan yang dikeluarkan pada saat ejakulasi
(spermatozoa + sekret kelenjar-kelenjar)

 Warna putih opalescent

 pH = 7.2 – 7.8
(di vagina 6.5 – optimal untuk mobilitas)

 Jumlah sperma rata-rata 100 juta/ml

 Komponen semen
 Komponen dari vesika seminalis
(60%)
total volume
 Komponen dari prostat (20%) total
Volume
 Buffer
Sifat-sifat semen (kesuburan pria) :

 Volume
Rata-rata 2 – 3 ml (cc)
Kurang 1 cc mandul
Berlebihan kurang subur
 Jumlah sperma
kurang dari 20 juta / mL mandul
lebih dari 40 juta / mL fertil
20 – 40 juta / mL subfertil

 Motilitas
Spermatozoa harus bergerak “maju”
Sarana bergerak adalah melalui ekornya.
Ekor utama spermatozoa mengandung mitokondria
Kurang dari 60 % Mandul
Sperms
 Daily production: 150-275 million/day
 Shape: kepala mengandung inti (nukleus)
 Yang dilapisi oleh acrosome
 Kurang 75 %  Mandul
 HORMON ANDROGEN

LH (=ICSH) ACTH

Sel Leydig Cortex adrenalis

(interstitial) pars reticularis

ANDROGEN :
 Testoteron


Dihydrotestosteron

 Androstenedion
Merupakan senyawa steroid dengan efek maskulinisasi
Reseptor hormon steroid: intraseluler
WHO, 2010: reference limit
 FAKULTAS KEDOKTERAN
UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 11- Ejaculation, Male In/Fertility, Fertilisation

Raden Argarini

raden-a@fk.unair.ac.id
Ejaculation

 Definition: ‘ejaculari’ meaning to project, to throw forcefully 

forceful propulsion of seminal fluid out of the body
 is the final stage of coitus and is mandatory for natural
procreation
 Two synchronized phases:

 Emission  secretion of the spermatozoa mixed with different

components of the seminal fluid from testes and accessory sex glands

 Expulsion  forceful expulsion of semen through the urethral meatus

 is triggered by intense rhythmic contractions of pelviperineal striated
muscles and striated urethral sphincter
Ejaculation: anatomical structures

Organs of emission:
1. Epididymis: maturation
and storage of
spermatozoa
2. Vas deferens: transport
spermatozoa from the
epididymis to the urethra
3. Seminal vesicles:
produce 50–80% of the
entire ejaculatory volume
4. Prostate gland: 15–30%
of the seminal fluid
5. Bulbourethral glands:
very small amount of fluid
Ejaculation: anatomical structures
Organs of expulsion:
1. Bladder neck/internal
urethral sphincter smooth
muscle cells that firmly
contract prevent sperm to
flow backward
2. Urethra: exhibits intense
contractions interrupted by
silence periods
3. pelviperineal striated
muscles: levator ani,
ischiocavernosus and
bulbospongiosus
muscles:rhythmically
contract: to propel semen
throughout
Ejaculation: nerve control

Input: strong influence of

stimulating or inhibiting genital
sensory and supraspinal inputs
pudendal nerve
Central control: serotonin
neurotransmission
Peripheral control: spinal nuclei
(thoracolumbar and
lumbosacral segments) 
autonomic (sympathetic and
parasympathetic)
 somatic divisions of the
nervous system
Clement and Giuliano, 2015
Ejaculation: peripheral nerve control
Clement and Giuliano, 2015

Spinal control:
orchestrated by spinal
generator of ejaculation (L3–
L5)
Autonomic
 Sympathetic:
intermediolateral cell column
and dorsal grey column of
thoracolumbar (12th thoracic
- 2nd lumbar) contractile
activity
 Parasympathetic:
Somatic motoneurons: Onuf's nucleus): intermediolateral cell column
ventral horn of S2–S4 segments  of sacral segments (2nd - 4th
pelviperineal striated muscles and urethral sacral) epithelial secretion
sphincter
Ejaculation: cerebral control

• SPFp: parvicellular part of

the subparafascicular
nucleus.
• BNSTpm: posteromedial part
of the bed nucleus of the
stria terminalis
• MeApd: posterodorsal part of
the medial amygdala
• MPOA: medial preoptic area;
• PNpd: posterodorsal part of
the preoptic nucleus
• PVN: paraventricular nucleus
• Gi, gigantocellular nuclei
• LH, lateral hypothalamus;
Clement and Giuliano, 2015
Ejaculation: neuroetransmitter

Peripheral:
• Noradrenaline: seminal tract and sex glands contractions,
mainly mediated by α-1 adrenoreceptors expressed by
smooth muscle cells
• Acetylcholine: contractions of sex glands through the
activation of muscarinic receptors, muscarinic receptors
triggers seminal fluid secretion from seminal vesicles
• NO: major component of the NANC autonomic system 
reduced smooth muscle contractile activity
• Oxytocin: induces contraction of smooth muscle cells in the
genital tract, promote spermatozoa transport in the vas
deferens
Ejaculation: neurotransmitters

Spinal cord:
• γ-aminobutyric acid (GABA) spinal generator of
ejaculation
• Oxytocin: ejaculatory response
• Serotonin: multi-level and multi-modal action in spinal
mechanisms of ejaculation (triggering/facilitation of
ejaculation, inhibition of expulsion)
• Substance P: produced by primary sensory neurons
transmission of sensory information from the periphery to
the spinal cord
Ejaculation: neurotransmitters

Brain:
• Serotonin: control of the ejaculatory response has received
particular attention
• Dopamin: pro-ejaculatory activity
• Oxytocin: facilitated ejaculatory behaviour
Ejaculatory disorders

Abnormalities:
1. retrograde ejaculation
2. Anejaculation
3. failure of emission
Charaterized by: absence of antegrade semen propulsion
Etiology:
 possible consequences of disruption of sympathetic efferents
 neuropathy in diabetics
Male in/sub-fertility

WHO: 9% of couples worldwide struggle with fertility issues

Male factor contributes to 50% of the issues
Idiopathic sperm abnormalities still account for about 30% of
male infertility
Etiology:
 genetic mutations
 lifestyle choices
 medical illnesses
 medications
Pandruvada, 2021
Pandruvada, 2021
• Male factor infertility (infertile males with abnormal semen analyses)
• Unexplained male infertility (infertile males with “normal” semen
analyses).
Pandruvada, 2021
Sperm Production Issues:
 Varicocele: 40%
 An undescended testicle
 Testicular disorders and hormonal
imbalances
 Genetic variations
 Various infections: STD’s

Sperm Delivery Issues

 Sexual issues: erectile dysfunction
(ED), improper technique, or pain
during intercourse
 Retrograde ejaculation: diabetes, or
certain surgeries involving the
bladder, prostate, or urethra.
 A blockage in certain areas of the
testicles or ejaculatory ducts
 do not produce ejaculate (semen),
which delivers the sperm
Environmental Factors:
 excessive consumption of
alcohol or other substance
abuse
 smoking tobacco
 Obesity
 emotional stress
 excessive exposure to heat
 exposure to pesticides or
other chemicals
Kategori distribusi penyebab infertilitas pria

Kategori Jumlah Persentase

Varicocele 603 42.2
Idiopatik 324 22.7
Obstruksi 205 14.3
Normal/Faktor wanita 119 7.9
Kriptorkidisme 49 3.4
Immunologi 37 2.6
Disfungsi ejakulasi 18 1.3
Gangguan testis 18 1.3
Obat/radiasi 16 1.1
Endokrinologi 16 1.1
Lain2( <1%) 31 2.1
TOTAL 1430 100.0

Sumber: Sigman, M., in Infertility in the Male, 3rd Edition, 1997

 FAKULTAS KEDOKTERAN
UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 12- Penile Erection and Disorder

Raden Argarini

raden-a@fk.unair.ac.id
PENILE ERECTION

Corpora Cavernosa: penile erectile tissue

Cavernous smooth musculature and muscles of the arteriolar and
arterial walls plays a key role in the erectile process
 Penile Erection Nerve involved:
1. Somatic 
sensory neuron
2. Autonomic 
sympathetic and
parasympathetic

Sexual stimulation  release of neurotransmitters from the

cavernous nerve terminals  relaxation of these smooth muscles
Nerve pathway during PENILE ERECTION?
1. Somatic:
• Sensation : sensory receptors in the penile skin, glans, and
urethra and within the corpus cavernosum
• contraction of the bulbocavernosus and ischiocavernosus
muscles
2. Autonomic:
• Sympathetic: T10 to T12 segments  white rami to the
sympathetic chain ganglia (sacral and caudal ganglia) 
lumbar splanchnic nerves hypogastric nerves to the pelvic
plexus  detumescence
• Parasympathetic pathway: S2 to S4 segments 
preganglionic fibers pass in the pelvic nerves to the pelvic
plexus  tumescence
What happen during PENILE ERECTION?
1. Dilatation of the arterioles and arteries by increased blood flow in both
the diastolic and the systolic phases
2. Trapping of the incoming blood by the expanding sinusoids
3. Compression of the subtunical venular plexuses between the tunica
albuginea and the peripheral sinusoids, reducing the venous outflow
4. Stretching of the tunica to its capacity, which occludes the emissary
veins between the inner circular and the outer longitudinal layers and
further decreases the venous outflow to a minimum
5. An increase in PO2 (to about 90 mmHg) and intracavernous pressure
(around 100 mm Hg), which raises the penis from the dependent position
to the erect state (the full-erection phase)
6. A further pressure increase (to several hundred millimeters of mercury)
with contraction of the ischiocavernosus muscles (rigid-erection phase)
PENILE ERECTION DISORDER (Priapism)
• Definition: a prolonged erection of the penis
• Incidence: 0.34 to 5.34 cases per 100,000 male individuals per
year
• Type: ischemic and non ischemic
• Ischemic  compartment syndrome  absence of blood flow
within the penis is affirmed to lead to metabolic abnormalities and
penile pain
• Etiology:  suppressed NO/cGMP signaling
– Hematologic disorders: sickle cell disease, thalassemia, G-6PD,
deficiency, and hereditary spherocytosis
– Neurologic: spinal cord injury, syphilis,
– pharmacologic exposures: phosphodiesterase type 5 (PDE5) inhibitors
such as sildenafil
– metabolic disorders
– anxiety disorders
– genital trauma
PENILE ERECTION DISORDER (Rare)
• Painful nocturnal erections (sleep-related painful erections/
SRPE) clinical disorder of penile pain occurring during
erections in association typically with rapid eye movement
(REM) sleep episodes
• Prevalence: <1% of patients
• all ages including boys, with a mean age of onset of 40 years
• Etiology:
– psychogenic, related to sleep loss and anxiety
– pain sensations  associated with ischemia and a penile
‘‘compartment syndrome”
PENILE ERECTION DISORDER (Priapism)
• Idiopathic stuttering priapism
– a variant of a disorder of repetitively prolonged penile erection that
occurs with or without pain during wakefulness, involuntarily and in
the absence of sexual excitement or stimulation
 FAKULTAS KEDOKTERAN
UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 13- Puberty and procreation

Raden Argarini

raden-a@fk.unair.ac.id
Introduction
• Physical development of sexually mature adults
• Changes during puberty:
– Hormonal
– Physical
– emotional

MacKelvie, et al. Br. J. Sports Med. 2012;36:250–257

Wet dream/nocturnal emission
• spontaneous, uncontrolled
orgasm with ejaculate
(semen) emitting from the
penis during sleep— hence
the technical term “nocturnal
emission.”
• hormonal changes of puberty,
• one-time, occasional, or
frequent feature
Hormonal changes during puberty
• ↑ stimulation of HPG-axis
• Initiated by GnRH
neurons of the
hypothalamus 
pulsatile secretion of
GnRH (LnRH)release
of LH and FSH from the
gonadotropic cells of the
anterior pituitary gland
• Extragonadal hormonal
changes (↑ IGF-1 and
adrenal steroids)
Onset of puberty: 9.5-14 y.o (11.5)
Caucasian Boys

Tinggaard et al.
Tanner Stage
Physical changes during puberty
• Adrenal/testis derived androgens DHEA and DHEAS
pubic,axilla,and facial hair development; voice changes
• growth spurts: 11 – 12 y.o
• Total body fat, voice break and change, and an increase
in muscle mass
Abnormalities of puberty: Premature puberty
• Prematur/Precocious puberty  the development of
secondary sexual characteristics before age 9.
• Etiology:
– benign premature adrenarche  premature presence of pubic
or axillary hair and possibly increased sebaceous gland
activity without other signs of puberty present, usually before
6 years of age.
– central nervous system and pituitary lesions
– constitutional and idiopathic precocious puberty
– McCune-Albright syndrome
– exogenous sex hormones
– Unique to male only: gonadotropin secreting tumors, benign
gynecomastia of adolescence, and familial gynecomastia
Abnormalities of puberty: Premature puberty
– benign premature adrenarche
• premature presence of pubic or axillary hair and possibly increased
sebaceous gland activity without other signs of puberty present, usually
before 6 years of age.
• isolated abnormality
– central nervous system and pituitary lesions:
• normal stages of puberty but occurring prematurely
• Children may have a bone age greater than their chronological age
• may come with other problems, such as visual field defects
– constitutional and idiopathic precocious puberty
• more often in females but can occur in both boys
• can be linked to a familial tendency toward early development
– McCune-Albright syndrome
• associated with cafe-au-lait spots, polyostotic fibrous dysplasia, and
precocious puberty
– exogenous sex hormones: oral contraceptives and anabolic
steroids
Abnormalities of puberty: Premature puberty

– Gonadotropin secreting tumors secrete hCG-like

components signaling LH  incomplete type of premature
puberty in boys
– Benign gynecomastia of adolescence gynecomastia in boys in
mid to late puberty
– Familial gynecomastia has a genetic link, usually either x-
linked recessive or sex-linked dominant
Abnormalities of puberty: Delayed puberty

• Definition: lack of physical evidence of puberty by 2 to 2.5

standard deviations above the mean age for the initiation of
puberty
– a period longer than four years between the first signs of testicular
enlargement and the end of puberty, or
– the absence of testicular growth by 14 years old.
• Etiology:
– Hypergonadotropic hypogonadism
– Hypopituitarism
– Constitutional delay of puberty
– Chromosomal abnormalities
Abnormalities of puberty: Delayed puberty
• Hypergonadotropic hypogonadism:
– failure of the gonads to produce sex hormones
– FSH and LH will be elevated
– causes of gonadal failure
• genetics and physical trauma (testicular torsion or cryptorchidism)
• Noonan syndrome and myotonic dystrophy
• LH beta-receptor mutations
• Hypopituitarism:
– lack of release of hormones from the pituitary gland: Kallmann
syndrome
• Constitutional delay of puberty
• Chromosomal abnormalities:
– Klinefelter syndrome (48, XXXY, 48, XXYY, and 49 XXXYY)
– small testes, gynecomastia, tall stature, long legs, and short arms.
This disorder will cause puberty to not come to completion rather
than a complete delay
Task:
1. Contrasexual Development
 FAKULTAS KEDOKTERAN
UNIVERSITAS AIRLANGGA

The Male Reproductive System

Week 13- Andropause, Climateric and Contraceptive

Raden Argarini

raden-a@fk.unair.ac.id
Definition

• “Andras” in Greek meaning human male

• “Pause” in Greek meaning a cessation

• A syndrome in which the changes accompanying

ageing are associated with the signs and symptoms
of androgen deficiency in the older male
(traditionally age >50). Signs and symptoms are
accompanied by a low serum testosterone level.
• Other terms: Male Menopause; Male Climacteric;
Androclise; Androgen Decline in the Ageing Male
(ADAM); Ageing Male Syndrome (AMS); Late Onset
Hypogonadism
 AOH – Adult-Onset Hypogonadism

Clinical and biochemical syndrome characterized by a

deficiency of testosterone with associated signs and
symptoms as well as failure of the body to produce an
adequate compensatory response

Khera, et al. Mayo Clin Proc. July 2016;91(7):908-926

History

• 1935, Butenandt & Ruzicka received the Nobel

Prize in Chemistry after synthesizing testosterone
in the laboratory.
• 1946, Werner published a landmark paper in JAMA
entitled, “The male climacteric”. Climacteric
characterized by nervousness, reduced potency,
decreased libido, irritability, fatigue, depression,
memory problems, sleep disturbances, and hot
flushes.
Epidemiology – Low T
• Up to 38.7% of men
older than 45 years
have hypogonadism
• The Baltimore
Longitudinal Aging
Study reported 20% of
men in their 60s and
50% of men in their 80s
to have hypogonadism
(International Journal of Clinical Practice
2006; 60: 762–769)
– 1.6% per year decline in
serum testosterone with
increase in LH & FSH
Physiology of Testosterone
–and clinical effects of low levels of Testosterone

Khera et al. Mayo Clinic Proceedings. 91-7. 908-26

Signs and Symptoms of the Andropause

• Endocrine symptoms: erectile dysfunction, reduced

erectile quality; diminished nocturnal erections; increased;
abdominal fat/increased waist size
• Physical symptoms: decreased vigor; easily fatigued; poor
exercise tolerance; diminished strength and muscle mass;
decrease in bone mineral density; decreased body hair
• Sexual symptoms: decreased libido; decreased sexual
activity; limited quality of orgasm; reduced ejaculate
strength; reduced ejaculate volume
• Psychological symptoms: mood changes; poor
concentration; loss of motivation; reduced initiative; memory
impairment; anxiety; depression; irritability; insomnia;
general reduction in intellectual activity; poor work
performance
Patophysiology of Andropause

Hypothalamus Lower GnRH pulse amplitude

Attenuation of diurnal pulsatility
More sensitive to negative feedback

Pituitary

E
Reduced Leydig cell number
Impaired Leydig cell function
Testes

T
Patophysiology of Andropause cont..

Partition of testosterone in the circulation in young and old men

Diagnosis of Late Onset Hypogonadism

 Screening beginning age 50 or 55

ADAM, MMAS

 Positive screen should be followed by check of total

testosterone

 If total testosterone (T) <200ng/dL, hypogonadism is present

regardless of age

 For total T 200ng/dL-400ng/dL, repeat and then obtain

calculated free T or obtain free T by equilibrium dialysis if
available

 Once T defficiency is established, obtain LH and prolactin

Other causes of post-pubertal hypogonadism

Pituitary adenomas
Uremia
Systemic illness
Hyperprolactinemia
Hemochromatosis
Cushing’s Syndrome
Cirrhosis
Morbid obesity
Cranial irradiation
Medications and low T

Decrease Leydig Cell T Production

corticosteroids
ethanol
ketoconazole
Bind to the Androgen Receptor
spironolactone
flutamide
cimetidine
Decrease Gonadotropin Secretion
corticosteroids
ethanol
estrogens
progestins (Megace)
Rx that raise prolactin (opiates, metoclopramide, psych meds)
Decreases Conversion of T to DHT
finasteride
Contraindications to Testosterone Replacement
Therapy (TRT)

Absolute Relative

 Documented hx of prostate  Hct 52% or more

CA
 Untreated sleep apnea
 Hx of breast CA
 Severe obstructive sx of
 Hct 55% or more BPH

 Sensitivity to ingredients in T  Advanced CHF (NYHA III/IV)

formulations
Trial Data - CV risk factors

o A number of trials have shown T replacement to

improve CV risk factors including:
o Type 2 DM
Haider A, et al. Int J Endocrinol. 2014;2014:683515
o Metabolic Syndrome Jones et al., Diabetes Care. 2011;34:828-837
Aversa A, et al. J Sex Med. 2010;7:3495-3503
Kalinchenko SY, et al. Clin Endocrinol. 2010;73:602-12
o Waist Circumference Mulligan T, et al. Int. J Clinical Practice. 2006;60: 762–769
Basaria, et al. JAMA. 2015;314(6):570-581

o Fat Mass
o Carotid Intimal Thickness
o Lean muscle mass
Trial Data – CV Risk

In addition, meta-analyses from 2011 have

shown
increased CV events in men with low T levels…
Kloner, et al. J Am Coll Cardiol 2016;67:545–57
 Meta-analyses

o Meta-analysis of 75 randomized placebo controlled trials

o No increase in CV adverse events for T-treated patients
o Since 2013, there have been at least 16 meta-analyses showing
no increase in CV events with T therapy
o The conclusions were that we have very low-quality evidence,
especially with observational studies
o RCTs need to be done to look more closely at risks and benefits
of T replacement in our male population…

Corona G, Rastrelli G, Monami M, Guay A, Buvat J, et al. (2011).

Eur J Endocrinol 165: 687–701
Male contraceptive

1. Permanent methods
• Male sterilization (Vasectomy)
• Female sterilization (tubal ligation)
2. Emergency contraception (EC) or postcoital contraception
• Emergency contraceptive pills (ECPs)
• Copper-bearing IUDs (Cu-IUD) for EC
3. Lactational amenorrhea method
4. Fertility awareness methods
• Standard Days Method (SDM)
• Others
•5. Withdrawal
 Comparing Effectiveness of Family Planning Methods

More effective
Less than 1 pregnancy per
How to make your
100 women in one year method more effective
Implants, IUD, female sterilization:
After procedure, little or nothing to do or
remember
Vasectomy: Use another method for first
3 months
Injectables: Get repeat injections on time
Lactational Amenorrhea Method (for 6 months):
Breastfeed often, day and night
Pills: Take a pill each day
Patch, ring: Keep in place, change on time

Male condoms, diaphragm: Use correctly every

time you have sex
Fertility awareness methods: Abstain or use
condoms on fertile days. Standard Days Method
and Two-Day Method may be easier to use.

Female condoms, withdrawal, spermicides:

Use correctly every time you have sex
Less effective
About 30 pregnancies per
100 women in one year

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 Vasectomy
(Male Sterilization)
 What Is Vasectomy?
• A permanent method of contraception for men who do
not want any more children
• A safe, simple, and short surgical procedure
• Also referred to as male sterilization or male surgical
contraception
• Procedure requires a trained health care provider
• Two techniques for performing vasectomy
• Conventional or incisional vasectomy
• No-scalpel vasectomy (NSV)

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Relative effectiveness of vasectomy to
other FP methods
Method No. of unintended pregnancies among
1,000 women in 1st year of typical use

No method 850
Withdrawal 220
Female condom 210
Male condom 180
Pill 90
Patch 90
Injectable 60
IUD (Copper T 380A/LNG-IUS) 8/2
Female sterilization 5
Vasectomy 1.5

Implant 0.5
Source: Trussell, J. 2011. Contraceptive failure in the United States. Contraception 83(5):397–404.

Adapted from Training Resource Package for Family Planning: https://www.fptraining.org/

Vasectomy: Method of action

Engrenderhealth NSV Training Curriculum 2007

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Characteristics of vasectomy
• The method must be offered by a provider and involves a
simple surgical procedure.
• The procedure is much simpler than female sterilization.
• No user action is required.
• The procedure can be performed at any time the man makes
an informed and voluntary decision.
• After the procedure, there may be discomfort or some pain
during recovery.
• It may require semen analysis to measure effectiveness.
• It is not reversible. (Where such reversal services are offered, it
is expensive, and success is not always guaranteed.)

Adapted from Training Resource Package for Family Planning: https://www.fptraining.org/

Health benefits, non-health benefits and
risks of vasectomy
• Is a cost-effective, one-off event, with no need for
resupply
• Does not interfere with sex
• May enhance enjoyment and frequency of sex
• Allows man to play significant role in FP
• Is a safe procedure
• Carries a small risk of failure
• Carries risk associated with pain management drugs
and surgical procedure

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Possible side effects and complications
of vasectomy
• Headaches and mild dizziness • Surgical site/wound infection
• Nausea • Abscess formation
• Fever • Sperm granuloma
• Pain • Anti-sperm antibodies
• Injury to other structures • Regret
• Hemorrhage • Failure
• Hematoma

129
Adapted from Training Resource Package for Family Planning: https://www.fptraining.org/
Physiological changes after vasectomy

• Sexual and reproductive physiology remains unaffected except

for desired change in fertility.
• Erection is not affected.
• Ejaculation is not affected.
• Sexual drive is not affected.
• Sperm production is not affected.
• Sperm count in the ejaculate semen is drastically reduced by
three months afterward.
• Serum antisperm antibodies rises.
• There are no long-term negative health effects.

130
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Who can have vasectomy?
• Most men can have a vasectomy.
• But they may need to wait if:
• They have problems with their genitals, such as infections, swellings or lumps, or
injuries in the penis or scrotum.
• They have other serious health conditions or infections (e.g., diarrhea).
MEC categories for male sterilization (vasectomy)

Category Description When Clinical Judgement is Available

A=Accept There is no medical reason to deny the client Use the method.
a vasectomy.
C=Caution The procedure can normally be conducted in May have some risks, but advantages
routine settings, but with extra preparations outweigh any risks.
and precautions.
D=Delay Delay the procedure until the condition is The theoretical or proven risks may
evaluated or corrected. outweigh benefits of the procedure if
the condition is not corrected.
S=Special The procedure should be undertaken in Theoretical or proven risks may
settings with an experienced surgeon, staff, outweigh the benefits of the
and equipment for anesthesia and other procedure if it is not performed in
back-up support. settings that have the capacity to
manage complicated cases.

131
Adapted from Training Resource Package for Family Planning: https://www.fptraining.org/
Eligibility criteria for vasectomy
WHO Category Conditions (Selected Examples)
A=Accept Sickle cell disease, mild hypertension, clients at
risk of HIV or STIs
C=Caution Young men, varicocele, hydrocele, previous
surgery, depressive mental disorders, diabetes
D=Delay Systemic infections such as diarrhea, local
infection of the penis or scrotum (balanitis),
scrotal skin infection or ulcers, STIs,
elephantiasis, intrascrotal mass
S=Special Undescended testis or cryptorchidism, inguinal
hernia, coagulation disorders

132
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Vasectomy use by men with HIV
• Men with asymptomatic or mild HIV clinical disease or severe,
advanced HIV disease on antiretroviral drugs can SAFELY have
vasectomy. (Special arrangements are needed for advanced
clinical disease.)
• Patients need to be aware that vasectomy does not protect
against HIV infections or STIs.
• Promote consistent condom use to prevent transmission of
infections.
• No one should be coerced or pressured to accept vasectomy,
whether or not they are seropositive.

133
Adapted from Training Resource Package for Family Planning: https://www.fptraining.org/
Timing of the vasectomy procedure
When can a client have a vasectomy?
• The procedure can be performed at any time if:
• The client has made the request and is prepared.
• No medical conditions warrant delay of the vasectomy.
• The client has made an informed and voluntary decision (provided
written informed consent).
• The provider is prepared and ready, with the right equipment and
supplies to perform the procedure.
• If any of the above conditions are not met, there can be a delay.
• The client may need to be referred if he has a condition that
needs special attention.

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Correcting rumors and misunderstandings about
vasectomy
1. In rare instances, vasectomy may cause testicular cancer. (False)
2. The volume of ejaculate from vasectomized men is always significantly
lower than that of nonvasectomized men. (False)
3. Vasectomy causes vascular problems for men, especially those who
have chronic hypertension. (False)
4. Vasectomy is not castration. (True)
5. Vasectomy does not interfere with manhood or sexuality in any way.
(True)
6. It is easier to perform female sterilization on a female client than to
perform a vasectomy on a man. (False)
7. Vasectomy makes men obese and weak. (False)

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Vasectomy: Summary
• With proper counseling and informed consent, any man can
have a vasectomy safely
• Involves a safe, simple surgical procedure
• Is permanent and convenient
• 3-month delay in taking effect
• The man takes responsibility for contraception; takes burden off
the woman
• Does not affect male sexual performance
• Does not prevent transmission of sexually transmitted
infections, including HIV
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Family Planning: A Global Handbook for Providers (3rd Edition, 2018)
A barrier form of contraception Barrier
that (Condom)
stops sperm from reaching and
fertilising an egg
When used correctly every time you have sex, male condoms
are 98% effective
Withdrawal
 What is withdrawal?
• Just before ejaculation, the man withdraws his penis from
his partner’s vagina and ejaculates outside the vagina,
keeping his semen away from her external genitalia.
• Also known as coitus interruptus and “pulling out.”
• Works by keeping sperm out of the woman’s body.
• No side effects, health benefits and health risks.
• Can be used at any time and by all men.
• May be especially appropriate for couples who:
– have no other method available at the time
– are waiting to start another method
– have sex infrequently
– have objections to using other methods
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Family Planning: A Global Handbook for Providers (3rd Edition, 2018)
Effectiveness of withdrawal
• Depends on the user.
• One of the least effective methods, as commonly used.
• As commonly used, about 20 pregnancies per 100 women
whose partners use withdrawal over the first year. This means
that 80 of every 100 women whose partners use withdrawal
will not become pregnant.
• When used correctly with every act of sex, about 4
pregnancies per 100 women whose partners use withdrawal
over the first year.
Effectiveness depends on the
• No delay in return of fertility. willingness and ability of the
• No protection against sexually couple to use withdrawal with
transmitted infections. every act of intercourse.

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Research into male
contraception
• Male pill

141