2/24 Male Hypogonadism - Lubitz

Question 1

phenotypic differentiation of female/male urogenital tracts

Answer 1

Question 2

phenotypic differentiation of male/female external genitalia

Answer 2

Question 3

male sexual devpt

Answer 3

Y chromosome: SRY gene → testis determining factor

• SRY encodes tf → incr expression of SOX9 → formation of Sertoli cells, testes differentiation

1. Sertoli cells → antiMullerian hormone → regression of Mullerian ducts (no uterus, fallopian tubes, etc)
2. Leydig cells → testosterone → differentiation of Wolffian ducts (ejac ducts, epididymis, seminal vesicles, vas deferens)

also…

testosterone → DHT [5alpha reductase]

• differentiation of external genitalia (penis, scrotum, prostate)

Question 4

Mullerian/Wolffian spectrum of sex devpt

Answer 4

Question 5

disorders of sex devpt

defects in androgen action

Answer 5

1. complete androgen insensitivity
2. partial androgen insensitivity
3. 5alpha-reductase deficiency

Question 6

complete androgen insensitivity

(formerly: testicular feminization)

Answer 6

dysfunctional androgen receptor @ internal genitalia, ext genitalia, pituitary gland

XY w female phenotype

• elevated testosterone (male ref range)
• elevated LH/FSH
• elevated estrogen (male ref range)

features

• primary amenorrhea
• normal breast devpt
• blind vaginal pouch
• absent uterus
• absent pubic/axillary hair
• testes absent/poorly devpd (in abdomen, inguinal canals, labial folds)

Question 7

partial androgen insensitivity

Answer 7

can have variety of phenotypes:

• female w mild virilization
• predom male
• infertile male syndrome
• undervirilized fertile male syndrome

Question 8

5 alpha reductase deficiency

Answer 8

have testosterone, DONT have DHT

testosterone → Wolffian stimulation

no DHT → no differentiation of external genitalia

• variable phenotype as child
• normal testes → adolescence leads to boost in testosterone → male phenotype body habitus BUT no DHT

dx: high testosterone/DHT ratio

Question 9

hypothalamic-pituitary gonadal axis

Answer 9

Question 10

testosterone

(and downstream products)

Answer 10

testosterone

estradiol

DHT

Question 11

hypogonadism

physical exam

Answer 11

• eunuchoidal proportions
• testicular size and consistency
• visual fields
• gynecomastia
• pubic and axillary hair
• hypospadias

Question 12

eunuchoidism

Answer 12

• no pubertal growth spurt
• eunuchoid proportions/eunuchoid habitus
  
  • lower body seg >2cm longer than upper body seg
  • arm span >5cm longer than height
• high pitched voice
• microgenitalia

Question 13

causes of gynecomastia

Answer 13

• increased free estrogen:testosterone ratio
  
  • aging
  • hyperthyroidism → high levels of SHBG
  • liver disease → high levels of SHBG
  • incr body fat → adipose aromatization
• hypogonadism
• meds that block male hormones or androgen receptors or raise prolactin
  
  • spironolactone
• tumors of gonads, adrenal, pit gland

Question 14

sx of male hypogonadism

later risks

Answer 14

• decr energy
• poor libido
• decr erectile fx (not eliminated)
• decr strength and edurance
• decr secondary hair growth (facial hair)
• infertility
• hot flashes (when testosterone low)

if have hypogonadism, worry about

• infertility
• osteoporosis
• incr CV risk factors

Question 15

hypogonadotropic hypogonadism

Answer 15

low testosterone

low FSH/LH

• genetic
  
  • Kallmann’s syndrome
  • Prader-Wili syndrome
• pituitary dysfx
  
  • hyperPRLemia
  • panhypopituitarism
  • pituitary tumor
  • lymphocytic hypophysitis
  • sarcoidosis
  • hemachromatosis
• other
  
  • isolated LH def
  • opiate/anabolic steroid use
  • chronic systemic illness (ex. HIV)
  • anorexia/intense exercise
  • stress fxal hypogonadism
  • aging/obesity

Question 16

Kallmann’s syndrome

Answer 16

idiopathic hypogonadotropic hypogonadism with anosmia

(failure of GnRH secretion and neuronal devpt)

• eunuchoidal proportions
• absent olfactory tracts (anosmia)
• color blindness
• midline defects

Question 17

hypergonadotropic hypogonadism

Answer 17

low testosterone

high FSH/LH

• genetic
  
  • Klinefelter syndrome
  • myotonic dystrophy
  • Noonan syndrome
• congenital
  
  • bilateral anorchia (vanishing testes syndrome)
  • cryptorchidism
  • Leydig cell aplasia
• orchitis
  
  • mumps
  • HIV
• gonadal trauma
  
  • trauma
  • radiation
  • chemotx
  • alcohol

Question 18

Klinefelters syndrome

Answer 18

47XXY

• small firm testis
• azoospermia
• variable secondary sexual devp
• variable secondary sexual devpt

dx: low testosterone, high FSH/LH

incr risk for breast cancer

Question 19

testosterone and aging

Answer 19

testosterone drops approx 1%/yr after 30

• sperm production does not stop
• all men do NOT develop low testosterone levels as they age
  
  • illness meds, injury, lifestyle → hypogonadism
• only treat for symptomatic hypogonadism

Question 20

side effects of testosterone replacement

contraindications

Answer 20

• dyslipidemia
  
  • high TG, low HDL
• HTN w salt/fluid retention
• polycythemia
• acne
• gynecomastia
• worsening of sleep apnea
• growth of prostate: potential growth of hormone-sensitive prostate cancer

testosterone replacement: contraindications

• breast cancer, prostate cancer
• untreated severe sx of prostate enlargement
• untreated obstructive sleep apnea
• men desiring short term fertility
  
  • low testosterone + testosterone is going to give you feedback! → downreg of FSH/LH → FSH won’t hit the testes and tell it to make sperm
    *

Question 21

ED and hypogonadism

Answer 21

hypogonadism (low test) can cause ED

• low test → low libido, but usually doesnt cause difficulty achieving/maintaining erection
• i.e. testosterone only a good tx if pt also has significant hypogonadism

ED can be early manifestation of endothelial dysfx and predictor of subsequent CV events

tx: phosphodiesterase inhibitors