Gangguan Hormon

Sex Pria

Nanang Miftah Fajari

Div. Endocrine Metabolic and Diabetes
Faculty of Medicine – Lambung Mangkurat University
Banjarmasin
Pengaturan Fungsi Hormon
Reproduksi Pada Pria
Sintesa Hormon Testosteron
Metabolisme Testosteron
Normal androgen sources

Greenspan FS, Gardner DG. Basic & Clinical Endocrinology. Lange, NY,
2004:482.
Testosterone Level Sesuai Usia
Fungsi Hormon
Testosterone

 Male sexual differentiation

 Pembentukan Organ Sex Sekunder
pada pubertas dan dewasa
 Spermatogenesis
 Muscle strength, Muscle volume
 Bone density
 Erythropoisis
Male Sexual Differentiation
HUMAN GAMETOGENESIS
AND FERTILIZATION
Disorders of Sex Development
and their Characteristics
Male Hypogonadism

 Penurunan salah satu / kedua fungsi

dari testis :
 Produksi sperma
 Produksi testosterone
 Androgen Deficiency
Symptoms
Metabolic Effect :
Musculoskeletal  Menurunkan HDL dan
 Decreased vigour and physical
energy Meningkatkan LDL
 Diminished muscle strength cholesterol
Sexuality  Gangguan Metabolisme
 Decreased interest in sex
 Reduction in frequency of Glucosa DM
sexual activity  Peningkatan total body fat
 Poor erectile function/arousal
 Loss of nocturnal erections (change in lean:fat ratio)
 Reduced quality of orgasm  Osteopenia
 Reduced volume of ejaculate
 Osteoporosis
 Berkurangnya red cell
volume
 Androgen Deficiency
Symptoms
Mood disorder and cognitive Vasomotor and nervous
function  Hot flushes
 Irritability & lethargy  Sweating
 Decreased sense of well-
being
 Lack of motivation
 Low mental energy
 Difficulty with short-term
memory
 Depression
 Low self-esteem
 Insomnia
 Nervousness
Physical Signs

 Diminished muscle mass

 Loss of body hair
 Abdominal obesity
 Gynæcomastia
 Testes frequently normal, occasionally
small
Tanner staging
 Androgen Disorders
 Primary
 Testicular dysfunction
 Low testosterone,
elevated LH/FSH
 Secondary
 Hypothalamic-pituitary
dysfunction
 Low testosterone, low
LH/FSH
 Mixed
 Can be observed with age
associated testosterone
deficiency
Bhasin S and Jameson JL. Disorders of the testes and male reproductive system. In: Harrison’s principles of internal medicine. EdsFauci AS, et al. McGraw-
Hill Companies, 2008.
Male hypogonadism: Onset
 Prepubertal onset: Eunuchoidism
 Lack of adult male hair distribution
 Sparse axillary, pubic hair
 Lack of temporal hair recession
 High-pitched voice
 Infantile genitalia
 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
Obat Obat Penyebab
hypogonadism

 ↓ Leydig cell production of testosterone

 Corticosteroids, ethanol, ketoconazole
 ↓ Conversion of testosterone to DHT
 Finasteride
 Androgen receptor blockers
 Spironolactone, flutamide, cimetidine
Secondary hypogonadism:
Cause

 Prepubertal onset
 Isolated idiopathic hypogonadotropic
hypogonadism
 Kallmann's syndrome
 Idiopathic hypogonadotropic hypogonadism
associated with mental retardation
 Abnormal ß-subunit of LH
 Abnormal ß-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,

Cupid’s-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
Secondary hypogonadism:
Cause
 Postpubertal onset
 Sella or suprasellar tumor
 Infiltrative disease
 Sarcoidosis, eosinophilic granuloma → hypothalamic
hypogonad
 Hemochromatosis → pituitary hypogonad
 Infection: meningitis
 Trauma
 Critical illness: surgery, MI, head trauma
 Chronic systemic illness : cirrhosis, CKD, HIV
 Drugs
Drugs: 2° hypogonadism

 ↓ Pituitary secretion of gonadotropins

 corticosteroids
 ethanol
 GnRH analogs
 estrogen, progestrins
 medication that raise prolactin levels
( opiate, metoclopramide )
 Investigation
 Serum testosterone : 8.00 AM
 Free testosterone: Equilibrium dialysis
 Bioavailable testosterone
 Total testosterone

SHBG ↑ SHBG ↓
 moderate obesity  aging
 nephrotic syndrome  cirrhosis

 hypothyroidism  hyperthyroidism

 use of glucocorticoids,  use of anticonvulsants,

progestins, androgenic estrogen
steroids  HIV
Investigation

 Serum FSH,LH
 Semen analysis
 Others
 Peripheral leukocyte karyotype
 Other pituitary hormones
 Serum prolactin
 Iron saturation
 MRI brain
Scheme for evaluation of clinical hypogonadism
Evaluation of hypogonadism
 Hx + PE

Morning Total T Normal T

Low T (< 300 ng/dL) Follow up

Exclude reversible illness, drugs, nutritional deficiency

Repeat T ( use free or bio T, if suspect altered SHBG )
LH + FSH

Confirmed low T Normal T, FSH + LH

Low T, Low or normal FSH + LH Low T, High FSH + LH

Secondary hypogonadism Primary hypogonadism

Treatment

 Testosterone replacement
 Rx. Underlying disease
Testosterone replacement
 Intramuscular preparations
 Transdermal patch
 Transdermal gel
 Oral agent
 Testosterone pellet
 Buccal testosterone tablets
Intramuscular injection

 Short-acting:
 Testosterone propionate
 Intermediate-acting:
 Testosterone enanthate
 Testosterone cypionate
 Long-acting:
 Testosterone undecanoate
Monitoring treatment

 Desirable effect
 Normal and maintained virilization
 Improvement of libido
 Improvement of energy
 Improvement of muscle strength
 Improvement of BMD
Monitoring treatment

 Undesirable effects
 Effects on the prostate
 Benign prostatic hypertrophy
 Prostate cancer

 Effect on cardiovascular risk

 Lipids

 Effect on haemopoiesis
 Polycythaemia

 Effects on the liver