2/24 Male Hypogonadism - Lubitz Flashcards
phenotypic differentiation of female/male urogenital tracts
phenotypic differentiation of male/female external genitalia
male sexual devpt
Y chromosome: SRY gene → testis determining factor
- SRY encodes tf → incr expression of SOX9 → formation of Sertoli cells, testes differentiation
- Sertoli cells → antiMullerian hormone → regression of Mullerian ducts (no uterus, fallopian tubes, etc)
- 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)
Mullerian/Wolffian spectrum of sex devpt
disorders of sex devpt
defects in androgen action
- complete androgen insensitivity
- partial androgen insensitivity
- 5alpha-reductase deficiency
complete androgen insensitivity
(formerly: testicular feminization)
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)
partial androgen insensitivity
can have variety of phenotypes:
- female w mild virilization
- predom male
- infertile male syndrome
- undervirilized fertile male syndrome
5 alpha reductase deficiency
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
hypothalamic-pituitary gonadal axis
testosterone
(and downstream products)
testosterone
estradiol
DHT
hypogonadism
physical exam
- eunuchoidal proportions
- testicular size and consistency
- visual fields
- gynecomastia
- pubic and axillary hair
- hypospadias
eunuchoidism
- 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
causes of gynecomastia
-
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
sx of male hypogonadism
later risks
- 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
hypogonadotropic hypogonadism
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
Kallmann’s syndrome
idiopathic hypogonadotropic hypogonadism with anosmia
(failure of GnRH secretion and neuronal devpt)
- eunuchoidal proportions
- absent olfactory tracts (anosmia)
- color blindness
- midline defects
hypergonadotropic hypogonadism
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
Klinefelters syndrome
47XXY
- small firm testis
- azoospermia
- variable secondary sexual devp
- variable secondary sexual devpt
dx: low testosterone, high FSH/LH
incr risk for breast cancer
testosterone and aging
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
side effects of testosterone replacement
contraindications
- 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
*
- 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
ED and hypogonadism
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
