Male

hypogonadism

Definition

A decrease in either of the two major

functions of the testes:

sperm production
testosterone production

Hypothalamic-Pituitary-Testis Axis

Inhibin B

Testosterone function

Male sexual differentiation

Secondary sex characteristic in
puberty and adult
Spermatogenesis
Muscle strength, Muscle volume
Bone density
Erythropoisis

Androgen Deficiency
Symptoms
Musculoskeletal

Decreased vigour and physical energy

Diminished muscle strength

Sexuality

Decreased interest in sex

Reduction in frequency of sexual activity
Poor erectile function/arousal
Loss of nocturnal erections
Reduced quality of orgasm
Reduced volume of ejaculate

Androgen Deficiency
Symptoms
Mood

disorder and cognitive function

Irritability & lethargy

Decreased sense of well-being
Lack of motivation
Low mental energy
Difficulty with short-term memory
Depression
Low self-esteem
Insomnia
Nervousness

Androgen Deficiency
Symptoms
Vasomotor

and nervous

Hot flushes
Sweating

Physical Signs

Diminished muscle mass

Loss of body hair

Abdominal obesity

Gyncomastia

Testes frequently normal, occasionally

small

Tanner staging

Metabolic and Other Effects

Reduction in HDL and increase in LDL cholesterol

Impaired glucose metabolism

Increase in total body fat (change in lean:fat ratio)

Osteopenia

Osteoporosis

Reduction in red cell volume

Male hypogonadism

Primary hypogonadism

Testes
Serum Testosterone, FSH & LH

Secondary hypogodism

Pituitary gland or Hypothalamus

Serum Testosterone, FSH & LH ,

Male hypogonadism: Onset

Prepubertal onset: Eunuchoidism

Lack of adult male hair distribution

High-pitched voice
Infantile genitalia

Sparse axillary, pubic hair

Lack of temporal hair recession

Small penis, testes and scrotum

fat deposition in pectoral, hip, thigh and lower

abdomen
Eunuchoidal proportion

Arm span > Height > 5 cm

Upper/ lower segment ratio < 1

Male hypogonadism: Onset

Postpubertal onset

Loss of libido
Impotence
Infertility

Primary hypogonadism:
Cause

Prepubertal onset

Klinefelter's syndrome
Other chromosomal abnormalities
Mutation in the FSH and LH receptor genes
Cryptorchidism
Disorders of androgen biosynthesis
Myotonic dystrophy
Congenital anorchia
Varicocele

Klinefelter's syndrome

Most common congenital abnormality

causing primary hypogonadism
Male who has an extra X chromosome
Genotype

47,XXY (most common)

48,XXXY
46,XY/46,XXY mosaicism
46,XX

Klinefelter's syndrome

Testes

Hyalinization & fibrosis of seminiferous

tubule
Sertoli cell inhibin FSH

Gynecomastia

peripheral conversion of testosterone

clearance of estradiol
Intraductal hyperplasia

Klinefelter's syndrome

Klinefelter's syndrome:
Associated syndrome

Cancer: CA breast, extragonadal germ cell

tumor
Autoimmume: SLE, SS, RA
Intelligent & psychology: IQ score,
development, memory, depression,
psychosis
Others: DM, DVT, Pulmonary dz. (chronic
bronchitis, bronchiectasis, emphysema)

Primary hypogonadism:
Cause

Postpubertal onset

Infections Mumps orchitis

Radiation
Drugs
Trauma
Bilateral orchiectomy
Autoimmune damage
Chronic systemic diseases

Cirrhosis
Chronic renal failure
HIV

Secondary hypogonadism:
Cause

Prepubertal onset

Isolated idiopathic hypogonadotropic

hypogonadism
Kallmann's syndrome
Idiopathic hypogonadotropic hypogonadism
associated with mental retardation
Abnormal -subunit of LH
Abnormal -subunit of FSH
Idiopathic hypogonadotropic hypogonadism
associated with other hypothalamic pituitary
hormonal deficits

Kallmann's syndrome

Hypogonadotropic hypogonadism
Sporadic (most common)
Familial; X-linked, AD, AR
X-linked; deletion in KAL gene(Xp22.3)

Lack of expression of anosmin ( neural cell adhesion-like

molecule )
inability of GnRH-secreting neurons, which arise in the
olfactory placode early in embryogenesis, to enter the
brain and occupy either the olfactory bulb or arcuate
nucleus of the hypothalamus
anosmia and hypogonadotropic hypogonadism

Kallmann's syndrome

Hypogonadotropic hypogonadism
Anosmia or hyponosmia
Somatic abnormality

cleft lip, cleft palate, short metacarpal bone, pes

carvus, renal agenesis, urogenital tract defect

Neurological abnormality

Uncoordinated eye movement, synkinesia,

spatial attention, mental retard, sensoryneural
deafness, seizure, cerebellar ataxia, red green
color blinness

Genetic hypogodadotropic
hypogonadal syndromes
Syndrome

Clinical manifestation

Prader-Labhart-Willi

hypomentia, hypotonia,short stature,

Cupids-bow mouth, DM, obesity

Laurence-Moon Biedl

retinitis pigmentosa, obesity, polydactyly,

MR

Multiple lentigines

multiple lentigines, cardiac defect,

hypertelorism, short stature, deafness,
genital and uro. defect

Rud

MR, epilepsy, congenital icthyosis

History and Physical

Examination

Workup

Management

HRT
Pulsatile LHRH or hCG = stimulate testicular growth, more complex
than testosterone replacement
When fertility desired, pulsatile luteinizing hormone-releasing
hormone (LHRH) or (more commonly) with a schedule of injections of
human chorionic gonadotropin (hCG) and follicle-stimulating hormone
(FSH).
Removal of gonadal tissue (significant risk of gonadoblastoma and
carcinoma)
- Males with nonfunctioning testicular tissue should undergo
orchiectomy and replacement with prostheses
Reevaluate patients with hypogonadism receiving HRT every 6-12
months.