gonadal Flashcards
primary female steroid hormone
increase feedback inhibition of FSH and LH
estrogen
MOA
1) developmental actions - 2nd sex organs/ characteristics and menstrual cycle
2) metabolic - bone
3) blood coagulability increase (Factors 2, 7, 9, 10)
4) lipid profile - decrease LDL cholesterol
5) sensitizes myometrium to oxytocin at term
6) maintain normal structure of skin and blood vessels
estrogen
estrogen receptors
ER alpha and ER beta
nuclear receptor
natural estrogen preparations
estradiol
estrone
estriol
synthetic steroidal estrogen preparation
ethinylestradiol
synthetic non steroidal estrogen preparation
diethylstilbestrol
therapeutic uses of estrogen
1) gonadal dysgenesis
2) hormone replacement therapy (HRT) - conj. estrogens, ethinylestradiol, progestin, tibolone
3) combo oral contraceptives
ADR
1) hepatic adenoma
2) thromboembolism, stroke
3) breast cancer (prolonged use)
4) endometrial cancer
estrogen
used in pregnant women - increase in clear cell adenocarcinoma of vagina and cervix in female offspring
diethylstilbestrol
breast cancer, endometrial cancer, pregnancy, liver dz, heavy smoker, hx of thromboembolic disorders
estrogen CI
selective estrogen receptor down regulator (SERD)
fulvestrant
MOA: inhibits ER dimerization - ER interaction with DNA prevented receptor degradation enhanced
fulvestrant
Use: tx of metastatic treats cancer unresponsive to tamoxifen
fulvestrant
estrogen antagonists
anastrozole
letrozole (reversible)
exemestane (irreversible)
MOA: aromatase inhibitor - decrease estrogen synthesis
estrogen antagonists
Use: estrogen - dependent, post menopausal breast cancer (ER +), advanced breast cancer: in case tamoxifen failure
estrogen antagonists
partial estrogen agonist
clomiphene
MOA: decrease feedback inhibition - increase FSH and LH - increase ovulation - pregnancy (follicular maturation enhanced)
clomiphene
Use: fertility drug
ADR: increase multiple births, ovarian hyper stimulation syndrome, increase risk of ovarian/endometrial cancer
clomiphene
Selective estrogen receptor modulators (SERMS)
tamoxifen
raloxifene
estrogen antagonists in breast, blood vessels
anti estrogen action - inhibit breast cancer cells and hot flashes
tamoxifen
E receptor agonists (bone)
antagonist (breast)
partial agonist (endometrium, uterus bone, liver, pituitary)
estrogen agnostic action: stimulation of endometrial proliferation (cancer risk)
tamoxifen
ADR: increase risk of endometrial cancer, hot flashes, increase risk of venous thromboembolism
tamoxifen
Used: estrogen dependent breast cancer (post mastectomy) and for prophylaxis in high risk patients
tamoxifen
E receptor agonist (bone)
antagonist breast and uterus
estrogen partial agonist in bone and CVS
distinct DNA target - raloifene response element
raloxifene
Use: postmenopausal, breast cancer, no increase cancer risk
raloxifene
ADR: hot flushes, DVT, pulmonary embolism
raloxifene
major natural progestin
increase body temp (.5-1 degrees C)
regular maturation of the endometrium
increase feedback inhibition of gonadotropins especially LH
progesterone
synthetic progestin
medroxyprogesterone
norethindrone
desogestrel
megesterol acetate
Uses: contraception, HRT, dysfunction uterine bleeding, endometriosis, threatened/habitual abortion
progesterone
SE: increased HDL and decreased LDL, glucose intolerance, break through bleeding, androgenic (hirsutism and acne), weight gain, depression
progesterone
anti progestin
1) antiprogestional +
2) antiglucocorticoids +
3) anti androgenic activity
mifepristone
MOA:
1) partial agonist and competitive antagonists at progesterone receptor
2) attenuates midcycle Gn surge from pituitary - delay in follicular develop - delay/failure of ovulation
3) blocks progesterone support to endometrium
4) induces menstruation
mifepristone
Uses:
1) termination of pregnancy (<7 wks)
2) cervical ripening
3) induce labor
4) postcoital contraceptive
5) cushings syndrome
mifepristone
inhibits LH and FSH surge
inhibits steroid enzymes and gonadal fxn
danazol
Uses:
1) endometriosis
2) fibrocystic breast dz
3) hereditary angioneurotic edema
danazol
oral contraceptives
estrogen + progestin - suppresses midcycle LH surge - prevent ovulation
interactions of oral contraceptives
decrease contraceptive effectiveness when used with antimicrobials and enzyme inducers
benefits of oral contraceptives
decreases risk of endometrial and ovarian cancer, dysmenorrhea, endometriosis, pelvic inflammatory dz, osteoporosis
serious A/E of oral contraceptives
thromboembolism
hepatomas
increase risk of breast cancer
natural androgens
testosterone
dihydrotestosterone
weak androgens
androstenedione
dihydro androstenedione
Uses for androgens
1) testicular failure
2) delayed puberty (to achieve grow spurt)
3) hypopituitarism
4) male hypogonadism (increase muscle mass and RBC)
5) anemias (fanconi, sickle, hemolytic, aplastic)
6) illicit in athletes
7) hereditary angioneurotic edema
PK: converted to dihydrotestosterone by 5 alpha reductase
phys: large doses - suppress gonadotropins
androgens
SE: excessive masculinization, premature closure of epiphysis, cholestatic jaundice, aggression, dependence, oligospermia, azospermia
androgens
17- alkyl derivatives: resist 1st mass
lipid soluble esters of testosterone
transdermal testosterone: by pass 1st pass
gels, buccal tablets, implanted pellets
use with caution in CHF, epilepsy, migraine
testosterone preparations
17 alkyl derivatives testosterone preparations
methyl testosterone
fluoxymesterone
lipid soluble ester of testosterone preparations
undecanoate
propionate
enathate
androgen antagonists
flutamide
leuprolide
finasteride / dutasteride
competitive androgen receptor blocker
used for androgen receptor positive prostate cancer
increases LH secretion by blocking feedback inhibition
flutamide
GnRH analog: repository form used for androgen receptor positive prostate cancer
increase androgen levels in combo
leuprolide
inhibit both type 1 and 2 5 alpha reductase enzyme - preventing conversion of testosterone to dihydrotestosterone
finasteride / dutasteride
Uses in BPH and male pattern baldness
finasteride / dutasteride
non competitive androgen receptor antagonists
cyproterone acetate - used fro hirsutism in females
anabolic steroids
nandrolone
oxymetholone
stanozolol
methandienone
uses for anabolic steroids
1) catholic state: severe trauma, major surgery
2) renal insufficiency: decrease urea prod and dialysis freq
3) osteoporosis: elderly males
4) anemia: hypoplastic, hemolytic, malignancy associated
5) to improve athletic performance (illegal)
1) Gn preparations: menotropins, urofollitropin, HCG, recombinant FSH
2) GnRH antagonists: cetrolrelix
3) GnRH agonists: clomiphene and leuprolide
TX for aiding IVF
synthetic Gn: gonadorelin
GnRH agonist: leuprolide
tx for infertility pulsatile tx
prostate cancer drugs
GnRH antagonists: cetrolrelix
GnRH agonists: flutamide and leuprolide
Breast cancer drugs
SERMs: tamoxifen
SERDs: fuluestrant
aromatase inhibitor: letrozole
endometrial cancer drugs
progesterone
Used in premenopausal breast cancer endometrial hyperplasia endometrial cancer risk no bone loss, fractures venous thromboembolism risk improves lipid profile
SERMS
not used in premenopausal women
no cancer risk
accelerates bone loss, predisposes to fractures
no increase of such risk
AIs
Why does exogenous androgen cause infertility?
it inhibits FSH and LH
leydig cells synthesize less androgen
Sertoli cells then reduce synthesis of androgen binding protein
seminiferous tubules degenerate - no sperm
prevention: transdermal androgen patches applied to scrotum
