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41 Cards in this Set

  • Front
  • Back
function of GnRH
stimulated release of FSH and LH from the pituitary to regulate androgens, estrogens, and progestins
GnRH replacements
GnRH itself, leuprolide, nafarelin, buserelin, desorelin, histrelin, goserelin
GnRG as a diagnostic tool
-distinguish between constitutionally delayed puberty (low LH) and hypogonadotropic hypogonadism
GnRH as a drug
stimulation of gonadal function in hypogonadotropic hypogonadism, delayed puberty or cryptorchidism
-must be given in pulses by an IV pump
-not used due to cost and inconvenience of pump
GnRH analogues used for:
-suppression of gonadal function--"chemical castration"
-continuous administration block gonadotropin release by downregulating GnRH receptors
-also in precocious puberty and prostate/breast cancer
problems associated with using GnRH analogues
-initial increase in gonadotropins
-hot flashes in men and women
-headache and abdominal discomfort
-vaginal dryness and atrophy
-osteoporosis in women
GnRH receptor antagonists
-now imporved so they don't release histamine
-able to avoid initial gonadotropin release
-EX: ganirelix for androgen replacement therapy
Natural Gonadotropins
-follicle-stimulatin hormone
-leutinizing hormone
-human chorionic gonadotropin
Urofollitropin (Fertinex)
FSH, no LH
menotropin OR human menopausal gonadotropins
purified FSH and LH
Human Chorionic Gonadotropin
LH like activity
follitropin alpha and beta
recombinant FSH
uses of urofollitropin or menotropins
-stimulation of follicular growth for ovulation
-urofollitropin used only after clomiphene
-used daily then use hCG to induce ovulation
-urofollitropin used in polycystic ovary syndrome
-both also used to stimulate spermatogenesis
uses of hCG
-induce ovulation
-induce masculinization in men
-with menotropins to induce spermatogenesis
-treat cryptochidism
-test Leydig cell function for testosterone production
adverse effects of gonadotropins
-ovarian enlargement or hyperstimulation
-ectopic pregnancy
-pulmonary and vascular complications
contraidications of gonadotropin use
-primary ovarian failure
-ovarian cysts
-dysfunctional abnormal bleeding
adverse effects of hCG
-ovarian enlargement
-ovarian hyperstimulation syndrome
-pelvic pain
contraindications for hCG
-dysfunctional abnormal bleeding
-ovarian failure
-prostate carcinoma
major androgens
testosterone and dihydrotestosterone
testosterone production
-from androsenedione
-by 17 beta hydroxysteroid dehydrogenase
-controled by LH
5 alpha reductase
-produces dihydrotestosterone from testosterone
-two forms: 5 alpha R1 (liver, non-genital skin, and brain), 5 alpha R2 (liver and urogenital tract)
site of testosterone production
-testes in male
-adrenal gland in females and children
testosterone feedback
-must be converted to estridiol by aromatase
-estradiol blocks GnRh
-inhibin block FSH
androgen administration
-transdermal patch: Testoderm and Androgel
-esters at C17: prepionate, cypionate, enanthate groups
-17 alpha aklyl derivatves: Danazol, Fluoxymesterone, Stanozolol, Methyltestosterone
androgen pharmacokinetics
-11 min half life
-98% bound to albumin or sex hormone binding globulin
-conjugated in liver for urine escretion
-most in urine from adrenal production
testosterone esters pharmacokinetics
-parentteral admin. slows absorption and lengthens duration
-proprionate: 2-3 days
-cypionate and enanthate: 1-2 weeks
-esterases remove esters and metabolized like testosterone
17 alpha alkyl derivatives pharmacokinetics
-derivatives-specific metabolism
-modifications alter absorption and excretion
-some excreted unmetabolized
actions of androgens
-depends on age and gender
-males: secondary sex characteristics, anabolic growth, epiphyseal closure (by 17 beta estradiol), thinkening of skin, sebum production
-female: virilization
androgen therapeutic for hypogonadism
-male hypogonadism to allow noraml development
--prepubertal: vigorous and prolonged treatment with long acting testosterone ester
--adult: less intense regimen
androgen therapeutic for hypopituiarism
-for boys only
-thyroid and cortisol therapy must be started first
-GH should be started first in dwarfism
-use gradual increase for max anabolic effect
androgen therapeutic for refractory anemias
-oxymetholone derivative has high anabolic activity
-stimulates erythropoietin
-not used so much becasue of erythropoietin use
androgen therapeutic for wasting states
-use testosterone esters, oxymetholone, oxandrolone
-for reversal of protein loss
-does well in AIDS-related wasting
minor therapeutic uses of androgens
-gynecological disorders
--synthetic androgens with estrogen reduce breast engorgement
-prevent postmenopausal endometrial bleeding due to use of estrogen alone
-anti-estrogen action of high doses can treat breast cancer
uses of 17 alpha alkyl derivatives
treatment of hereditary angioneurotic edema
-danazol is most effective
-stanozolol is used prophylactically
-promotes production of C1 esterase inhibitor--a non-androgen activity
effects of anabolic androgen abuse
-usually use veterinary or designer drugs
-reduction of testosterone and gonadotropins
-leades to low sperm count, testicular atrophy, gynecomastia, liver damage/tumor, increased LDL, decreased HDL
adverse effects of androgens
-usually due to pharmacodynamics
-most noticeable in women and children
-premature epiphyseal closure
-hirsutism, deep voice, baldness, clitoral hypertorphy in women
-edema from Na and water retention
adveres effects of 17 alpha alkyl derivative
-endometrial bleeding
-jaundice, hepatic tumors, frank liver damage
contraindications of androgen use
-prostatic cancer
-heart failure
-liver cirrhosis
-renal disease
GnRH and analogues as anti-androgens
-block androgen syntesis
-gonadorelin, leuprolide, naferelin block LH by continuous administration
--receptor down regulation
-lowers testosterone production to castration levels
-5 alpha reductase inhibitor
-blocks testosterone to DHT
-reduces prostate volume and prevents hair loss
-careful because lowers PSA, indicator of BPH
androgen receptor antagonists
-flutamide: treat prostate cancer with GnRH blockade
-bicalutamide: less hepatotoxic than flutamide
-cyproterone acetate: orphan drug for severe hirsutism
-spironolactone: weak antagonist, hirsutism