female reproductive and infertility Flashcards
target cells of FSH and LH
FSH: Sertoli and granulosa cells
LH: Leydig and theca cells
inhibin and activin
inhibin: from Sertoli and granulosa cells, inhibits anterior pituitary release of FSH (not LH)
activin: same source, but activate ant pit release of FSH (not LH)
PCOS sx and cause
anovulation, oligo-ovulation, inc plasma androgen -> hirsutism, dysmenorrhea, acne
theories:
1- inc freq and amplitude of LH pulses = stimulates theca cells to make androgen
2- inc insulin secretion = dec sex hormone binding globulin = inc free testosterone
3- theca cell dysregulation of sex steroid synthesis
prolactinoma
benign lactotroph adenoma in ant pit -> suppressed estrogen synth by GnRH-block, dec gonadotroph sensitivity to GnRH
sx: gynecomastia, galactorrhea, dysmenorrhea, etc.
hypogonadism
sex hormone production impaired before adolescence -> no sexual maturation
inc FSH and LH
menopause
exhaustion of ovarian follicles -> dec estrogen and inhibins, inc FSH and LH
GnRH agonist MOA
continuous administration suppresses FSH and LH since they are released in a pulsatile manner
*R is in ant pit
leuprolide
continuous GnRH agonist
goserelin
continuous GnRH agonist
naferelin
continuous GnRH agonist
cetrorelix
GnRH antagonist
ganirelix
GnRH antagonist
uses of GnRH replacements
hormone-dep tumors: prostate, some breast ca endometriosis pain ? central precocious puberty PCOS controlled ovarian hyperstimulation
anastrozole
competitive aromatase inhibitor
reversible
letrozole
competitive aromatase inhibitor
reversible
exemastene
covalently-binding aromatase inhibitor
irreversible
formestane
covalently-binding aromatase inhibitor
irreversible
uses and ADR of aromatase inhibitors
ER+ metastatic breast ca: tx and prevention of recurrence
ADR: estrogen suppression -> osteoporosis
tamoxifen
SERM w agonistic effect on endometrium and bone, antagonistic effect on breast
for breast ca
4-6x inc risk endometrial ca, so not given >5 yr (switch to aromatase-inh)
raloxifene
SERM w agonistic effect on bone, antagonistic effect on endometrium and breast
mgmt of post-meno osteoporosis and breast ca prevention
clomiphene
SERM w antagonistic effect in hypothal and ant pit, partial agonist in ovaries = inc release GnRH and gonadotropins -> stimulates follicle growth and ovulation
use: ovulation induction
ADR: inc ovary stimulation, multiple pregnancies
locations of ER receptors
all are cytoplasmic/ nuclear
ERa - endometrium, breast ca cels, ovarian cells, hypothalamus
ERb - kidney, brain, bone, heart
flutamide
androgen-R antagonist
spironolactone
androgen-R antagonist
MOA androgen-R antagonist
competitively inhibit binding of endogenous androgens to receptor = blocks action of DHT and testosterone
uses of androgen-R antagonists
metastatic prostate ca, severe BPH
spironolactone: K-sparing diuretic (aldosterone blocker), female hirsutism, male pattern baldness (but causes loss of libido)
mifepristone
progesterone-R antagonist to induce abortion up to 63 days of pregnancy
prog stabilizes uterine lining, promotes decidua prep - inhibition -> decay of decidua, detachment of blastocyst
misoprostol
PG analogue given with mifepristone to stimulate uterine contractions
ethinyl estradiol and mestranol
estrogens for HRT and acne, also in combo OCPs
ADR: HTN (inc AT2 d/t inc angiotensinogen activity), thomboembolic d/o (inc hepatic synth of clotting factors), gall bladder dz (inc cholesterol excretion in bile)
2 types of OCP
combo estrogen-progestin pills
progestin-only pills
MOA of estrogen-progestin pills
suppress GnRH, LH, FSH = no follicular development or ovulation
also altered tubal peristalsis, dec endometrial receptivity, dec cervical mucus secretions
ADR of estrogen-progestin pills
unopposed estrogen: inc risk endometrial ca (reduce risk w progestin), DVT, and PE
inc risk GB d/z (stasis)
don’t give to women >45 and smoke
androgenic activity of estrogens
highest: norgestrel, levonorgestrel
lower: norethindrone
lowest: norgestimate, ethynodiol
anti-androgen: drosperinone (inc CV/ thromboembolic risk)
combo OCP drug interactions
abx like penicillin, tetracyclines - dec effect estrogen
estrogen can inh metabolism of: cyclosporine, antidepressants, glucocorticoids
estrogen inc synthesis of vit-K-dep clotting factors, antagonizes warfarin effect
norgestrel and norethindrone
progestin-only pills, used when estrogen contraindicated
pts won’t menstruate but may have spotting
medroxyprogesterone acetate
“depot” progestin, used for sex offenders to dec sexual drive and stop spermatogenesis
levonorgestrel and etonorgestrel
progestin implants
*levo also emergency contraception (plan B) - most efficacious with fewest ADRs
ADR progestin only
androgenic effect -> acne, hirsutism, inc libido, oily skin
MOA plan B (levonorgestrel)
blocks LH surge, disrupting ovulation and produces endometrial changes not conducive for implantation
PCOS tx
estrogen-progestin contraceptive (stop ovarian testosterone production)
anti-androgen (spironolactone)
metformin to reduce insulin resistance -> regular ovulation and T levels
GnRH analogues
female infertility tx
clomiphene citrate
prolactinoma tx
DA-R agonist: cabergoline, bromocriptine
breast and endometrium ca tx
SERM, aromatase inhibitors
endometriosis tx
OCP, GnRH analogs (continuous)
Danazol - androgen analog (suppresses FSH, LH -> hypoestrogenic state)
menopause tx
hormone replacement therapy
