Gonadal Hormones Flashcards
Hypothalamic- pituitary-gonadal axis
Hypothalamus secretes Gonadotropin releasing GnRH
Anterior pituitary releases gonadotropins- FSH and LH
Gonads- ovaries release estrogen and progesterone and testes release testosterone
GnRH
pulsatile release stimulates pituitary gonadotrophs to release LH and FSH
GnRH non pulsatile release
inhibits LH and FSH
FSH
spermatogenesis, follicular development
LH
steroidogenesis
testosterone secretion
Gonadorelin
synthetic GnRH
Peptide- 1/2 life 4 minutes
Must be administered parantally
Analogs of GnRh
more potent and longer acting
Leuprolide, goserelin, dafarelin (and other relins)
t1/2- 4 hrs
parenteral adminstration
Antagonists of GnRH
Ganirelix (and other relix’s)
parenteral administration
Usage of GnRH analogs
stimulation of gonadotropins
female and male infertility
or suppression of gonadotropins (agonist and antagonists)- endometriosis, uterine fibroids, prostate cancer, precocious puberty
Toxicity- hypersensitivity, menopausal symptoms, gynecomastia
Urofillotropin
Derived from urine of post menopausal women
FSH analog
parenteral
Fillotropin alpha
recombinant FSH
parenteral
Lutropin alpha
recombinant LH
parenteral
Chorionic gonadotropins
produced by placenta LH»_space; FSH
- hcg
- choriogonadotropin alpha is recombinant version
parenteral
hMG
human menopausal gonadotropin
menotropin with FSH and LH activity
parenteral
Gonadotropin use
ovulation induction- collecting eggs, infertility, obesity, assisted reproduction. risk of ovarian hyperstimulation syndrome and multiple pregnancies
male infertility- start with hCG (less expensive) and then hMG
requires 4-6 months of treatment to detect sperm
Estradiol
E2
major product of ovary
other estrogens are estrone and estriol
estropipiate
purified crystalline estrone
estrogen esters
metabolically resistant prohormones with imrpoved bioavailability and t1/2
conjugated estrogens
equine estrogens (horses) sulfate sodium salts blended to standardized activity. high potency
ethinyl estradiol
synthetic estrogen
undergoes extensive hepatic metabolism
more active than natural estrogens
diethylstilbesterol
nonsteroidal estrogen
was used to prevent pregnancy complications but caused teratogenic effects - adenocarcinoma of vagina in daughters of pts who were treated with this
esterified esterogens
manufactured from soybeans and yams consisting primarily of estrone and equiline
metabolic conversion of estrone to estradiol
bisphenol
estrogen
leaches from plastics
genistein
isoflavone phytoestrogen
derived from soybeans
estrogens mechanism
bind to intracellular estrogen receptors- alpha and beta located in nucleus
receptor ligand complex initiates gene transcription by binding to estrogen response element (ERE)
-activity varies by tissue, interaction of estrogen with receptor, ERE, concentration of estrogen
Uses for estrogen
primary hypogonadism
hormonal contraception
ovarian suppression for dysmenorrhea, endometriosis
post menopausal hormone therapy
Formulations of estrogen
often with progestin
oral, injxn, transdermal, vaginal ring, troche
oral will have 1st pass metabolism
estrogen side effects
nausea, breast tenderness, hyperpigmentation, increased migrains, accelerated blood clotting
cancer- uterine and breast cancer
uterine bleeding in post menopausal bleeding (only use estrogen + progestin for post menopausal with uterus)
Progestins
all progesterin agents also have antiestrogenic activity and antimineralocorticoid activity
bind to intracellular progesterone receptors and initiates gene transcription
Use of progestins
hormonal contraception, ovarian suppression for dysmenorrhea, endometriosis, post menopausal hormone replacement
Progestins AE
increase blood pressure
androgenic agents may decrease plasma HDL
Progestin agents
progesterone- IM medroxyprogesterone acetate- long doa, IM or PO norethindrone levonorgesterl desogestrol drospirenone
Mechanism of hormonal contraception
suppress FSH and LH surge through negative feedback (except progestin only mini pill)
Thicken cervical m ucus
Decrease fallopian tube motility
Oral contraceptives
21 days on, 7 days placebo
Most are thinyl estradiol
progestins include norethindrone, l-norgesterel, desogestrel
AE of oral contraceptives
venous thromboembolism
peri- and postmenopausal hormone therapy
decrease hot flashes, vaginal dryness, prevent osteoporosis, prevent atherosclerosis, prevent dementia
risks- heart disease, stroke, breast cancer (esp E + P), uterine cancer (unopposed E), inc triglycerides
use for shortest period and lowest dose to achieve treatment goals
Selective estrogen receptor modulators (SERMS)
partial agonist-antagonists
Tamoxifen
SERM
breast cancer
also Toremifene
Raloxifene
used for osteoporosis
Bazedoxifene
SERM
menopausal symptoms
Clomiphene
ovulation induction, oral drug (compared to other drugs)
increase LH and FSH release by blocking negative feedback by estrogen
Estrogen antagonist
fulvestrant- used in tamoxifen resistant breast cancer
Mefipristone
Progesterone antagonist
Postcoital contraceptive
Abortifacient, in compination with misoprostol or PGE1
Also a glucocorticoid antagonist
Aromatase inhibitor
Used for breast cancer in post menopausal women to block estrogen production by peripheral tissues
Anstrazole- nonsteroidal
Letrozole-nonsteroidal
Exemestane-steroid, irreversible
Danazol
Derivative of 17a ethinyl testosterone with weak progestin, androgen, and glucocorticoid activity used to suppress ovarian function
Androgenic agents
difference is between routes of administration and how much anabolic activity relative to androgenic effects
testosterone has equal anabolic and androgenic effects
Oral androgenic agents
methyltestosterone
fluoxymetstrone
oxandrolone (more anabolic)
IM androgenic agents
testosterone esters
Transdermal patch androgenic agents
testosterone
Use for androgens
androgen replacement
gynecologic disorders
anabolic agents after trauma (oxandrolone)
growth stimulation (boys with delayed puberty, but can cause premature closure of epiphyses) , osteoporosis in men, aging
AE of androgens
acne, gynecomastia (aromatase makes testosterone into estradiol), testicular atrophy via feedback inhibition, masculinization in females, sodium retention, psych dependence, inc aggression
Androgen suppression and antiandrogens used for
prostate cancer
Steroid synthesis inhibitors
ketoconazole, abiraterone, finasteride, dutasteride
used for prostate cancer and in men with excess testosterone secretion
cyproterone
androgen receptor inhibitors
used for hirsutism in women and excessive sexual desire in men
flutamide
competitive androgen receptor antagonist
spironolactone
androgen receptor inhibitor
competes with DHT and aldosterone
