2. HYPOGONADISM

3. Chromosomal sex
(46 XY male _ 46 XX female)
gonadal sex
phenotypic sex

8. Increased FSH suggests damage to the seminiferous tubules low testosterone level high LH = hypergonadotropic hypogonadism low testosterone low or inappropriately normal LH = hypogonadotropic hypogonadism

11. nocturnal surges of LH and FSH
Puberty
Sensitivity to steroid inhibition is gradually lost
GnRH reactivation
nocturnal surges of LH and FSH
Leptin, a hormone produced by adipose cells, may play role

12. -breast budding in girl -increase in testicular volume in boys
PUBERTY
First signs of pubertal maturation is :
-breast budding in girl
-increase in testicular volume in boys 12

13. Lab tests

14. Total testosterone unbound or free testosterone (1-3%)
SHBG-bound testosterone (30-45%)
albumin-bound testosterone (50-70%)
Bioavailable testosterone:
( both free and albumin-bound testosterone)
dissociates readily in the capillaries

15. low SHBG : androgens - obesity - insulin - nephrotic syndrm - congenitaly high SHBG : estrogen - hyperthyroidism - chronic inflammatory dis - aging

16. Measuring Testosterone Levels
when total testostrone is borderline:
Calculate free testosterone from total testosterone and SHBG
FSH, LH , prolactin , thyroid tests

17. Chronic illness Taking medications Androgens and Ageing
Measuring total testosterone is unreliable (increased SHBG )
Chronic illness
Taking medications

18. Free testostron All levels of hypothalamic-pituitary-testicular axis Testis dysfunction ( andropause )

19. GnRH test
in Prepubertal period or severe GnRH deficiency only for secondary hypogonadism with false positive

20. hCG stimulation test in prepubertal boys increase in testosterone indicates the presence of testicular tissue

21. 2 to 6 mL sperm counts >20 million/mL motility of >50% >50% normal morphology liquification
Spemen analyses

22. TESTICULAR BIOPSY
* normal biopsy in azoospermic man & normal FSH level =obstruction of vas deferens, (correctable surgically) *for intracytoplasmic sperm injection (ICSI)

23. MALE HYPOGONADISM
Sperm production or Testosterone production

24. Primary = hypergonadotrophic Androgen insensitivity
Hypothalamic-pituitary  
Secondary = hypogonadotrophic
  Gonadal
Primary = hypergonadotrophic
Androgen insensitivity

25. Primary or hypergonadotrophic
Testosterone & sperm count low
High FSH and LH
Sperm count is more damaged than testosterone levels
Secondary or hypogonadotrophic
Testosterone & sperm count low
Low or normal FSH, LH
Sperm count level is proportional to testosterone levels

26. History Puberty Growth spurts Systemic illness Eating disorders, excessive exercise Social and psychological problem Decreased libido ,Erectile dysfunction, Infertility Osteoporosis/fractures/Asthenia

27. Physical examination Secondary sex characteristics hair growth (face, axilla chest , pubic ) Gynecomastia Testicular volume Testicular size >2.5 cm indicates child entered puberty Varicocel Phallic size, and scrotal reddening and thinning. Height & body proportions Eunuchoidal =arm span >2 cm greater than height (when androgen deficiency occurred before epiphyseal fusion.)

28. PRIMARY MALE HYPOGONADISM
Congenital
Klinefelter
Cryptorchidism undescended testes
Varicocele
anorchia
Acquired
Mumps Orchitis  
Trauma
Radiation
Chemotherapy
drugs
Chronic diseases

29. Undervirilized Males (46 XY DSD) =Male Pseudohermaphroditism defect in androgen production or action

30. Disorders of testis development   True hermaphroditism (46,XY)   testicular dysgenesis   Disorders of androgen synthesis   LH receptor mutations   enzyme defects   5α-Reductase 2 deficiency   Aromatase overexpression

31. Disorders of androgen action Androgen Insensitivity Syndrome Other disorders of male reproductive tract Persistent müllerian duct syndrome Isolated hypospadias Cryptorchidism

32. Klinefelter Syndrome Extra X chromosome. common genotype is 47 XXY
Mosaic forms has less severe phenotype.

33. Klinefelter Syndrome Decreased penile length
Small firm testes , azoospermia
Decreased penile length
Decreased facial, axillary hair
Decreased libido
Tall stature & increased leg length
= eunuchoid habitus
Gynecomastia high Breast cancer risk
Varicose veins

35. Drugs interfere with testicular function
radiation damage
Mump
unilateral or bilateral
atrophy 6 months after acute ilness
Direct + ischemia due to edema pressure
Drugs interfere with testicular function
ketoconazole inhibition testosterone synthesis
spironolactone blockade of androgen action
marijuana increased estrogen
Cyclophospham Direct inhibition of spermatogenesis
Alcohol decreases testosterone
( independent of liver disease or malnutrition )
digitalis Elevated estradiol & decreased testosterone

36. Environmental hazards
microwaves and ultrasound
Chemical nematocide dibromochloropropane
Cadmium
lead
Environmental estrogens or antiandrogens
Polyglandular autoimmune insufficiency

37. Granulomatous diseases
Sperm antibodies
isolated male infertility
in some , secondary phenomena to duct obstruction or vasectomy.
Granulomatous diseases

38. Systemic disease Cirrhosis - primary testis dysfunction
- Suppressing gonadotropin production.
Cirrhosis
Impaired hepatic extraction androstenedione leads to extraglandular conversion to estrone
(gynecomastia)
suppresses LH
(Testicular atrophy)

39. chronic renal failure * Androgen synthesis &sperm production decrease
*Hyperprolactinemia (reduced clearance)
but Elevated LH due to reduced clearance

40. Sperm density decrease temporarily Infertility in celiac disease
sickle cell anemia
testicular or hypothalamic-pituitary
Acute febrile illness
Sperm density decrease temporarily
Infertility in celiac disease
Androgen resistance

41. myotonic dystrophy small testes (impairment spermatogenesis , Leydig cell function ) paraplegia _temporary decreased testosterone & spermatogenesis _some retain capacity for erection & ejaculation

42. Secondary hypogonadism
Congenital
Isolated idiopathic
Kallman Syndrome
Prader-Willi , Laurence-Moon syndrome

43. Acquired Pituitary tumors , Mass , Hyperprolactinemia
Infiltrative diseases , Apoplexy ,Trauma
Critical and chronic illness
STRESS ,MALNUTRITION ,EXERCISE
Marijuana (decreased GnRH secretion)
obesity

44. Kallmann syndrome : X-linked mutations in KAL1 gene GnRH deficiency anosmia , renal defects , neurologic abnormalities

45. OBESITY SHBG decrease =lower total testosterone
insulin inhibits SHBG production
higher Estradiol in obese men
hypothalamic-pituitary axis defect

46. DELAYED PUBERTY boys age 14 Constitutional delay of growth & puberty ( 60%) Functional hypogonadotropic hypogonadism (20%( systemic illness ,Chronic disease - Malnutrition,Anorexia nervosa Hypergonadotropic hypogonadism ( 15%) Hypogonadotropic hypogonadism ( 10%)

47. Constitutional delay PUBERTY + delayed bone age and short stature : family history blunted responses to exogenous GnRH diagnosis of exclusion requires ongoing evaluation until onset of puberty &growth spurt.

48. ANDROGEN INSENSITIVITY SYNDROMES (AIS)
Resistance to action of testosterone and DHT , 5α-reductase
X-linked mutations
Variable degrees of defective male phenotypic development and undervirilization
tall stature , eunuchoidal proportions

49. High Gonadotropins and testosterone levels
complete AIS
(testicular feminization syndrome)
Female phenotype
breast development
short vagina
but no uterus , because MIS production Is normal
scanty pubic and axillary hair
High Gonadotropins and testosterone levels

51. Partial AIS ( Reifenstein syndrome ) hypospadias , cryptorchidism Gynecomastia More severely undervirilized patients present with clitoral enlargement and labial fusion as females.

52. Mild mutations in the androgen receptor: Azoospermia , infertility gynecomastia

54. Metabolic and Other Effects in androgen deficiency
Reduced HDL , increased LDL
Increased total body fat = viceral fat
Impaired glucose metabolism (ins. Resistance)
Osteopenia , Osteoporosis
Reduction in red cell volume

55. Consequences for Health
Increased risk of
Osteoporotic fracture
cardiovascular disease
diabetes
Reduced wellbeing ,Depression
Reduced physical strength
Sexual dysfunction

56. Risks of Therapy Effects on the prostate Benign prostatic hypertrophy
Prostate cancer
Effect on cardiovascular risk (unknow)
HDL (depend on dose , route of administration & formulation)
haemopoiesis ,Polycythaemia
( less common with transdermal)
Effects on the liver Only alkylated testosterone

57. Gynecomastia
Testicular atrophy & inhibition spermatogenesis
Early fusion of epiphisial plate
Hepatoma , pleosis hepatis
Sodium , water retention
Priapism,Acne

58. Contraindications for Androgen
presence of prostate cancer
Baseline PSA ≥ 4 ng/mL
Palpable abnormality of prostate
Severe symptoms of lower urinary tract obstruction
Baseline hematocrit > 52%
Severe sleep apnea
Class IV congestive heart failure

60. PRECOCIOUS PUBERTY Puberty in boys before age 9 Isosexual precocity =premature sexual development with phenotypic sex such as the development of facial hair and phallic growth. 1- gonadotropin-dependent 2- gonadotropin-independent causes of androgen excess. Heterosexual precocity =premature development of feminizing features in boys, such as breast development

61. Gonadotrop dependent central precocious puberty (CPP) gonadotropin levels inappropriately elevated for age Idiopathic    2. Hypothalamic hamartoma or other lesions CNS tumor or inflammatory state  

62. Gonadotropin independent  CAH HCG-secreting tumor  Hormon producing tumor(adrenal ,testis)   Exogenous androgens McCune-Albright syndrome   Familial male-limited precocious puberty (testotoxicosis)  

63. FAMILIAL MALE-LIMITED PRECOCIOUS PUBERTY
autosomal dominant or mutations in the LH receptor, leading to stimulation of the cyclic AMP and testosterone production called testotoxicosis
premature virilization in boys, growth
acceleration in early childhood, advanced bone age followed by premature epiphyseal fusion.
Testosterone elevated and LH suppressed.

64. McCUNE-ALBRIGHT SYNDROME sporadic disorder mutations in the Gsα subunit. impair guanosine triphosphatase activity leading to activation of adenylyl cyclase. Like activating LH receptor mutations, stimulates testosterone production sexual precocity autonomy in adrenals, pituitary, and thyroid - Café au lait spots. - Polyostotic fibrous dysplasia is caused by activation of parathyroid hormone receptor in bone

65. Heterosexual Sexual Precocity Breast enlargement in prepubertal boys ( gynecomastia ) Familial aromatase excess Estrogen-producing tumors in the adrenal Sertoli cell tumors in the testis Germ cell tumors that secrete hCG excessive stimulation of estrogen production Marijuana, Smoking ,Estrogen use