Gonadal Hormones Flashcards
GnRH:
- ______ release stimulates pituitary gonadotrophins to release LH and FSH
- sustained ______ release inhibits LH and FSH release
pulsatile
nonpulsatile
_____ promotes spermatogenesis/follicular development, and ______ promotes steroidogenesis
FSH
LH
GnRH agonist
gonadorelin
leuprolife, goserelin, nafarelin (-relin)
GnRH analog
ganirelix
GnRH antagonist
- agonists stimulate gonadotropins –> infertility, dx of LH responsiveness
- suppression of gonadotropins by controlled ovarian stimulation (suppress premature LH surge), endometriosis, fibroids, prostate cancer, precocious puberty
- toxicity: hypersensitivity, menopause like, gynecomastia
Gonadotropins (agonists and antagonists)
urofillotropin, fillotropic alpha
FSH
lutropin alpha
recombinant LH
hCG and choriogonadotropin alpha are produced by the ______, LH > FSH
placenta
- assisted reproduction
- protocols mimic phsyiological stimulation of ovulation
- risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies
-ovulation induction by gonadotropins
- start with hCG, then hMG
- require 4-6 months to detect sperm
- black box: obesity
male infertility, tx by gonadotropins
major estrogen product of the ovary?
estradiol (E2)
purified crystalline estrone?
estropipate
metabolically resistant prophormones with improved bioavailability and half life, readily hydrolyzed into active form
estrogen esters (acetate, cypionate)
equine estrogen sulfate sodium salts, high potency
conjugated estrogen
synthetic estrogen that undergoes extensive hepatic metabolism, more active than natural estrogens
ethinyl estradiol
nonsteroidal, caused variety of complications in exposed female offspring including clear cell carcinoma of vagina
DES
-manufactured from soybeans and yams consisitng of primarily estrone and equilin, activity depends largely on metabolic conversion to estradiol
esterified estrogens
estrogenic compound that leaches from plastics
BPA
- estrogens bind intracellular estrogen receptors, in nucleus
- receptor ligand complex initiates gene transcription by bining ______
- used for primary hypogonadism, hormonal contraception, ovarian suppression for endometriosis, postmenopausal hormone therapy
- non oral preps avoid _____
ERE
first pass metabolism
- nausea
- breast tenderness
- hyperpigmentation
- migraine
- cholestasis, gallbladder disease
- HTN
- accelerated blood clotting
- cancer: uterine and breast with HRT, adenocarcinoma from DES
- uterine bleeding (do NOT use unopposed estrogen for hormone replacement therapy in women with a uterus )
estrogen side effects
- bind IC receptor and initiate transcription at PRE
- used for hormonal contraception, ovarian suppression, postmenopause HRT
- may increase BP
progestins
progesterone, norethindrone, levonorgestrel, desogestrol, drospirenone
progestins
most oral contraceptives are ______
ethinyl estradiol
mechanism of hormonal contraception?
suppress FSH/LH surge through negative feedback, decreased fallopian tube motility, thicken cervical mucus
adverse effects of contraceptives?
venous thromboembolism
SERM used for breast cancer?
tamoxifen, toremifene
SERM used for osteoporosis?
raloxifene
SERM used for ovulation induction, increases LH and FSH release by blocking negative feedback by estrogen
clomiphene
SERM used for menopausal symptoms in combo with conjugated estrogens
bazedoxifene
estrogen antagonist used in tamoxifen resistant breast cancer?
fulvestrant
progesterone antagonist, used as postcoital contraceptive, abortifacient in combo with misoprostol, glucocorticoid antagonist
mefipristone
- anstrazole, letrozole, exemestane
- used for breast cancer in postmenopausal women to block estrogen production by peripheral tissues
aromatase inhibitors
-derivative of 17a-ethinyl-testosterone with weak progestin/androgen/glucocorticoid activity used to suppress ovarian function
danazol
methyltestosterone, fluoxymetstrone, oxandrolone
oral antiandrogenics
testosterone esters
IM antiandrogen
testosterone given in what form?
transdermal patch
- used for replacement
- gynecologic disorders
- anabolic agents
- growth stimulation (boys w/ delayed puberty)
- osteroporosis in men
- aging
androgens
acne sleep apnea gynecomastia testicular atrophy (feedback inhibition) masculinization in females sodium retention, edema hepatic dysfunction, cholestasis increased aggression
androgen side effects
inhibits adrenal and gonadal steroid synthesis, increases estrogen:testosterone –> gynecomastia
ketoconazole
17 alpha hydroxylase inhibitor
abiraterone
5alpha hydroxylase inhibitor, decreases DHT
finasteride
5alpha hydroxylase inhibitor with longer half life
dutasteride
angrogen receptor inhibitor used for hirsutism in women and excessive sexual desire in men
cyproterone
competitive antagonist of androgen receptor
flutamide
competes with DHT as well as aldosterone
spironolactone
