Progestins, estrogens & androgens Flashcards
Role of FSH
stimulate estrogens and follicular growth
-always inhibitory to Pit/Hypothalamus
Role of LH
stimulate ovulation, progesterone
-inhibitory early, stimulatory mid-cycle
aromatase enzyme
present in granulosa cells of ovaries
- synthesizes estradiol and estrone from testosterone and androstenedione
- also called CYP19A1
estrogens: main and action
- estradiol-17B
actions: stim growth and dev of the mammary gland - promote endometrial proliferation during follicular phase
- promote proliferation of the vag epithelium
- block reabsorption of bone
- increase HDL and decrease LDL
- increase risk of thromboembolism
- increase incidence of endometrial/breast ca
- increase progesterone receptors
progestins: main and actions
- progesterone
- promotes endometrial dev during luteal phase
- main determinant of the onset of menstration
- decreases amt of cervical mucus and increases viscosity
- increases body temp
- stim growth and dev of mammary gland during pregnancy
- uterine effects are essential for maintenance of preg
- weak mineralocortiocoid antagonist
general properties of estrogens and progestins
progesterone and estradiol are rapidly inactivated when taken orally
- synthetic analogs are more useful but then cross-rxn with other steroid receptors and act as agonists or antagonists
- many routes
drospirenone
-progesterone analog with increased activity as MC antagonist and androgen antagonist
ulipristal
- selective progesterone receptor modulator (SPRM)
- postcoital contraceptive
- more effective than norgestrel and maintains efficacy longer
- can be agonist or antagonist, dep on tissue
diethylstilbestrol (DES)
-non-steroidal estrogen, 1st
Hormones that can be used for contraception
-P, E, SPRM
Hormones that can be used for suppression of the hypothalamic-pituitary gonadal axis
P, E
hormones that can be used for hormone replacement therapy
P, E, SERM
hormones that can be used for abortion
P antagonists
hormones that can be used for ovulation induction
E antagonists, aromatase inhibitors
hormones that can be used for breast ca therapy
SERM, aromatase inhibitors
copper IUD
- among the most effective methods of contraception
- copper is spermicidal
- in theory, could prevent implantation, but fertilization would have had to occurred prior to insertion
norethrindrone
a progesterone analog
- used as an oral contraceptive agent
- also present in IUD
medroxyprogesterone acetate
Depo-provera
- IM injection q 3 mo
- progesterone analog used as contraception
- decreased bone density
norgestrel
-progestin analog
-present in IUD
-present in post coital contraceptives (plan B)
(higher dose than routine contraception, prevents ovulation)
progestin analog MOA
- prevent fertilization by decreasing amount and increasing the viscosity of cervical mucous
- prevent ovulation by inhibiting gonadotropin secretion
progestin analog SE
- h/a
- abnormal bleeding
progestins and estrogens as contraceptive agents
-oral
21 on, 7 off
-usually contain norethindrone and ethinyl estradiol
-monophasic (constant E & P for 21 days)
-biphasic (constant E for 21 days, progesterone low for 1-10, increased 11-21)
-triphasic (constant E 21 days, low P 1-7, increased 7-14, increased again 15-21)
drospirenone/ethinyl estradiol
oral drug
- Yaz
- can prevent acne?
MOA of P& E combos
- P and E prevent ovulation by inhibiting the hypothalamus and pituitary
- no change in LH/FSH
- progestins prevent fertilization by decreasing the amount and increasing the viscosity of cervical mucus
P & E combos
SE
- nausea, h/a
- not recommended for migraines
- CV effects like thromboembolism and MI, mostly smokers and those 35 yo and older
- decreased glucose tolerance, (weight gain, acne, hirsutism d/t androgen activity)
health benefits of P & E combos
- decreased ovarian cysts and benign fibrocystic breast disease
- decreased endometrial and ovarian ca
- increased HDL and LDL
which drugs reduce efficacy of contraceptives
- rifampin antibiotics
- some anticonvulsants
MOA for postcoital contraceptive
- suppresses hypothalamic-pituitary-gonadal axis and inhibits ovulation
- may prevent implantation and promote bleeding
SE for postcoital contraceptives
N/V
- h/a
- dizziness
- breast tenderness
- leg cramping
MOA of ulipristal as post coital
- inhibits ovulation by antagonizing actions of progesterone on the granulosa cell progesterone receptor, needed for follicular rupture
- also a progesterone agonist in the HP axis and delays LH surge
- need rx
other uses for progestins
-suppress HPG axis in rx of dysmenorrhea, endometriosis
other uses for P/E combos
- replacement therapy in ovarian dysfunction
- replacement in postmenopause and postmenopausal osteoporosis
clomiphene/fulvestrant
antagonist of estrogen receptors
- all antagonists
- induction of ovulation. when given in the early follicular phase of the menstral cycle, they antagonize the inhibitory effects of estrogen on the pituitary and hypothalamus
tamoxifen
SERM, antagonist at breast
-used for relief of post menopausal symptoms, rx osteoporosis, estrogen-dep breast ca.
raloxifene
SERM, antagonist at breast. neutral at endometrium and vag
-used for relief of post menopausal symptoms, rx osteoporosis, estrogen-dep breast ca.
ospemifene
SERM, antagonist at breast, neutral and endometrium
-recently approved for rx of vag atrophy in post-menopausal women,
bazedoxifene
SERM, antagonist at breast, endometrium. neutral to CV system.
-with conjugated estrogens, approved for rx of postmenopausal symptoms. takes advantage of agonist on bone and antagonist on breast and endometrium
anastrazole
- aromatase inhibitors
- inhibit conversion of androgens to estrogens
- oral
- useful in the rx of breast ca or other d/o where estrogen action needs to be inhibited
- only post menopausal women
- can also induce ovulation
exemestane
- aromatase inhibitors
- inhibit conversion of androgens to estrogens
- oral
- useful in the rx of breast ca or other d/o where estrogen action needs to be inhibited
- only post menopausal women
- can also induce ovulation
SE of aromatase inhibitors
arthralgia, hot flashes, post menopausal symptoms
mifepristone/RU 486
oral progesterone receptor antagonist
- used for abortions and post coital contraception: antagonizes progesterone actions everywhere
- GC antagonist and can be used in rx of cushings/dm II
role of aromatase in males
converts testosterone to estradiol
how do males produce dihydrotestosterone
-5 a reductase (SRD5A2)
actions of androgens
- virilization of the urogenital tract during dev
- puberty
- maintenance of secondary sexual characteristics and accessory organs
- essential for spermatogenesis
- promote anabolic reactions
testosterone oral/transdermal vs IM
-esters must be given IM
which androgens have increased SE
- 17A alkylated androgens (such as danazol, methyltestosterone)
- more SE, includes hepatic toxicity
uses of androgen therapy
- replacement therapy in male hypogonadism
- rx of some catabolic stats such as muscle wasting in AIDS
SE of androgen therapy
- virilization for pre-pubertal males
- feminization of males bc precursors to androgens
- azoospermia and decreased testicular size (bc decreased FSH)
- edema, jaundice, hepatic ca (exacerbated by 17alpha agents)
finasteride
- 5alpha reductase inhibitor used to treat syndromes of androgen excess or androgen dependent d/o: BPH, prostate ca, hirsutism, congenital adrenal hyperplasia, precocious puberty
- may cause persistent sexual dysfunction
dutasteride
- 5alpha reductase inhibitor used to treat syndromes of androgen excess or androgen dependent d/o: BPH, prostate ca, hirsutism, congenital adrenal hyperplasia, precocious puberty
- may cause persistent sexual dysfunction
flutamide
androgen receptor antagonist used to treat syndromes of androgen excess or androgen dependent d/o: BPH, prostate ca, hirsutism, congenital adrenal hyperplasia, precocious puberty
bicalutamide
androgen receptor antagonist used to treat syndromes of androgen excess or androgen dependent d/o: BPH, prostate ca, hirsutism, congenital adrenal hyperplasia, precocious puberty
nilutamide
androgen receptor antagonist used to treat syndromes of androgen excess or androgen dependent d/o: BPH, prostate ca, hirsutism, congenital adrenal hyperplasia, precocious puberty
LH and CG as diagnostic agents
LH: ovulation
CG: pregnancy
FSH as therapeutic agents
-induce follicular growth. IM
CG as therapeutic agent
-induce ovulation, IM inj
gonadorelin
- synthetic GnRH, wild-type
- stim gonadotropin secretion. for ex, delayed puberty in boyd and girls, anovulatory d/o in women
- admin single injection or in pulsatile (stimulatory)
cetrorelix
GnRH antagonist
- rx of precocious puberty in boys and excess androgens
- rx endometriosis and dysmenorrhea
- stop gonadotropin secretion in ovulation-induction protocols
luprolide
- long acting GnRH agonist
- after initial stimulation of gonadotropin secretion, suppresses it
- used to suppress gonadotropin secretion like antagonist
