• GnRH released from hypothalamus
• anterior pituitary release FSH and LH
• gonads make hormones

Primary failure- problem with testes/ovaries

Secdondary failure- problem with pituitary, hypothalamus

• peak in second trimester
• peak at birth
• declind until 10
• begin to rise continually and tonic high levels until age 80

• young men- higher then older men and peak at 8 AM
• older men- tonic levels, lower than young men

• SHBG
• albumin (less tightly bound, so more bioavailable)

Remember, very small fraction is free

• free testosterone goes down with age due to slight increases in SHBG

Note also LH does go up with age

• total
  • widely available
  • inexpensive
  • simple to perform
  • reliable
• free testosterone
  • equilibrium dialysis is gold standard
  • analog method inaccurate
• bioavailable testosterone- gives most info

• obesity
• hypoT
• androgen abuse
• progestin abuse
• glucocorticoids
• nephrotic syndrome

• aging
• hyperT
• androgen deficiency
• estrogens
• anticonvulsants
• hepatitic cirrhosis
• HIV

• decrease libido
• erectile dysfunction
• regression of secondary sex characteristics
• osteoporosis
• decrease muscle strnght
• depression
  • lethargy
  • inability to concentrate
  • sleep disturbance
  • irritability
  • decrease interest in activities
• additional signs/symptoms
  • incomplete sexual development
  • breast discomfort, gynecomastia
  • very small or shrinking testes
  • infertility
  • mild anemia
  • decrease spontaneous erections
  • hot flashes, sweats

• Klinefelter's syndrome
• mumps orchitis
• testicular trauma (bicycle accident)
• radiation
• autoimmune disease
• drugs
  • chemotherapy
  • cyclophosphamide

• sparse facial and body hair
• gynecomastia
• firm testes less than 4 mL
• female body habitus
• long arms and legs
• present at puberty when semineferous tubules undergo fibrosis and hyalinization resulting in firm testes

• chronic pulmonary disease
• varicose veins
• cerebrovascular disease
• osteoporosis
• glucose intolerance
• primary hypothyroidism
• breast cancer
• taurodontism (early tooth decay)

• pituitary disorder
  • hemachromatosis (bronze diabetes)
  • tumor, trauma, infiltrative
  • hyperPRL
  • hypopituitarism
• hypothalamic tumor/trauma
• critical illness
• congential disorder of gonadotropin secretion
  • ex: Kallmann's syndrome with anosmia
• drugs- marijuana, heroin, opiates, progesterone

• morning total testosterone or bioavailable testosterone
• if low T, you must figure out why
• check gonadotropins
  • if low, secondary
  • if high, primary

Dont make this dx of androgen deficiency during acute or subacute illness

• increase muscle mass
• decrease fat mass
• no change in strength
• no change in physical function
• some experience increase in bone mineral density at lumbar spine
  • depends on androgen dose and degree of baseline testosterone deficiency

• low testosterone on consistent level
• symptomatic

• T gel
• buccal testosterone
• IM testosterone undecanoate (not in US)

• gels- it will give you a steady state level
• intramuscular injection- causes peaks and valleys from point of injections

• infrequent acne
• skin rxns (high with patch and low with gel)

• transdermal gel (less often)
• transdermal patch (less often)
• IM injections it is very much a problem

• erythrocytosis hyperviscocity
• breast cancer
• prostate cancer or nodule
  • severe UT symptoms
• heart failure
• untrated obstructive sleep apnea

• monitoring
  • IM- midway btw injections
  • patch- 3-12 hrs after application
  • gel: 1-2 wks on tx
• physical- acne, gynecomastia, palpable prostate
• blood test- hematocrit, PSA
• questionare- sleep apnea
• follow Hct and PSA 3 months after starting than yearly
• if Hct greater than 52, reduce dose
• PSA greater than 4, refer to urologist

• theca cells- make androgens
• granulosa cells- make estrogen

• decline in total testosterone was greatest in early reproductive years
• no decline of testosterone across menopause
• highest levels at 18-24

• hirsutism
• acne
• clitoromegaly
• male pattern baldness

• excessive terminal hair in male pattern on women (hair on abdomen, chest)
• due to interaction between androgen and hair follicle sensitivity to androgen
  • become oily
• grade via Ferriman Gallwey scale

• history
  • hirsutism in other female family member
  • ethnicity
  • PCOS risk factors (irregular menses)
  • rate of onset
  • any virilization
• labs
  • no labs if mild hirsutism with regular menses and no features suggestive of secondary cause, as is most likely idiopathic
  • otherwise, free testosterone best initial lab

• cosmetic and physical measuring
  • bleach, wax, shave
  • electrolysis and laser therapy (long term may be the best option)
• cell cycle inh (cream applied to face but not much improvement)
• antiandrogens
• oral contraception (max effect in 9-12 months)

• at least 2 of 3
  • oligo/amenorrhea
  • hyperandrogenemia/hyperandrogenism
    • hirsuitism, acne, male pattern hair loss)
  • polycystic overies on US
• usually manifst in teenage years

• hyperinsulinemia (insulin R)
• obesity
• impaired glucose tolerance
• dyslipidemia
• increase coronary calcifications on electron beam CT
• obstructive sleep apnea
• endometrial hyperplasia/carcinoma

• Cushings
• acromegaly
• hyperPRL
• nonclasical congenital adrenal hyperplasia
• androgen secreting tumor

• oral contraception
  • use progestin so antiandrogenic
  • estrogen increase SHBG so there is less frequent testosterone
  • estrogen suppress LH and androgens
• wt loss
• antiandrogens
• insulin sensitizers (DM)

• ovarian (chemo, radiation, oophorectomy)
• adrenal (insufficiency, -ectomy)
• hypothalamic/pituitary- hypopituitarism
• medication related- corticosteroids, oral contraception
• idiopathic

• beware of DHEA products (not regulated)
  • some dont have any DHEA
  • some have much less than what they claim
  • one had 50% higher

• in men, bicalutamide used as GnRH agonist to tx prostate cancer
• women, spironolactone in low ose prevent androgen binding to R< at high dose inhibits testosterone synthesis
• Finasteride (alpha 5 reductase inhibitors)
  • for male pattern balding or decrease prostate size in BPH

• 17 alpha alkalated substiution
• esterfication (longer carbon chain means greater half life)
• steroid nucleus

• muscle hypertrophy
  • increase muscle fiber diameter
  • increase lean body mass
  • positive nitrogen balance
  • retention o potassium, sulfates, phosphates
• increase RBC mass
• CNS- dont know effect on brain
• glucocorticoid R antagonist (inh. catabolism)

• CV
  • increase LDL
  • decrease HDL
  • fluid retention
• hepatic
  • liver cancer
  • LFT elevations
• endocrine/reproductive
  • decrease FSH, LH
  • in males, infertility, testicular atrophy
  • in females, hirsutism, voice deepening, amenorrhea, clitoral hypertrophy, male pattern baldness
• dermatology- acne

• euphria
• energy
• sexual arousal
• negative mood
  • irritability
  • mood swings
  • violent feelings
  • hostility
• cognitive impairment
  • distractibility
  • forgetfulness
  • confusion

• lab monitoring
  • testosterone, estradiol
  • lipids
  • LFT's
  • glucose
  • hematocrit
• screening
  • pelvic exams
  • pap smears
  • endometrial US
  • DXA bone density

tx for transexual (female to male)

• testosterone esters 200 mg IM
• trasndermal testosterone 5g/day (with or w/o testosterone)