GYN/Final: contraceptives, HRT, etc Flashcards
Estrogen’s effect on
- women
- men
WOMEN
- developmental effects
- neuroendocrine actions on ovulation
- preparation of reproductive tract for fertilization and implantation
- mineral, CHO, protein and lipid metabolism
MEN:
- effects on bone
- spermatogenesis
- behavior
list the three clinically significant estrogens
- 17-b estradiol
- estrone
- estriol
which estrogen is most potent
estradiol
Estradiol
- natural or synthetic
- priimary circulating estrogen in who
natural–>secr by ovary
primary circulatng estrogen in PRE-menopausal
what is the primary estrogen circulating in pre-menopausal women
estradiol
Estriol
- more or less potent than estradiol
- secreted and synthesized?
less potent—its a metabolite of estradiol
synthesized and secretd by placenta during pregnancy
estrone
- potent?
- circulates predominanly in who
metabolite of estradiol
1/3 potent as estradiol
primary circulating estrogen in post-menopausal women
what is the primary circulating estrogen in post-menop women
estrone
do we use synthetic or natural estrogens in contraceptives and HRT?
synthetic
mainly ethinyl estradiol
MOA of estrogen
- protein bound
- diffuses acrross CM to bind with receptor proteins
- causes RNA synthesis of proteins specific to target tissues
list the 3 main clinical uses of estrogen
- HRT
- contraception
- stimulation of sexual chacteristics
benefits of estrogen in HRT (2)
- in PM women— rid of vasomotor challeneges of menopause
- hot flahses
- rid of genitourinary s/s too
- vaginal atrophy
risk of estrogen in HRT (5)
- decrrs bone resoprtion— incrs risk of bone fx
- 3-10x incr risk of endometrial CA (esp with unopposed estrogen)
- 2.5x incr risk of VTE (transdermal patches asoc with decr risk)
- incr risk of BCA
- incr risk of gallstones
in women with intact uterus—- what are they at risk of with unopposed estrogen tx
-how can this risk be reduced?
endometrial CA
risk can be reduced by adding progestin with estrogen
what patient would it be indicated to give estrogen tx alone for HRT?
s/p hysterectomy
what is very imp to do before HRT
- **evaluate risks vs benefits
* **each woman is diff and therefore tx will be individualized
estrogen preparations
oral
transdermal
topical
oral preps of estrogen
indications?
OCPs and HRT
transdermal estrogen
- which estrogen is used
- inds
estradiol
INDS
- both PM osteoporosis and menopausal symptoms
- contraception
- control ovulation in preparation for assisted reproductive therapy
topical preps of estrogen are used for
vaginal atrophy
Kinetics for natural estrogens (estradiol)
- abs
- met
well abs– orally, skin, and mucous mems
partially met by first pass effect, metabolites still effective
synthetic estrogens
-list them
ethinyl estradiol and estradiol valerate
kinetics for synthetic estrogens
- ___ soluble
- stored where
- released how
- more or less potent than natural
- DOA
fat solube stored in adipose tissue released slowly more potent than natural longer acting
SE of estrogen (7)
- nausea
- HA
- breast tenderness
- thromboembolic events
- MI
- incr risk of BCA
- incr risk of endo CA (estrogen unopposed)
define progestogens
compounds with bioligc activities similar to progesterone
progestin
synthetic progesterone
MC progestogen
progesterone
what secreted progesterone
-secreted in resp to?
in the ovary— by corpus luteum
in response to LH in 2nd phase of menstrual cycle
imp functions of progesterone
- development of secretory endometrium—allows implantation
- maintain endometrium after implantation
- decline in progesterone stimulates menstruation— shedding the basilar layer of endometrium
decline in progesterone levels causes
menstruation
list the physiologic functions of progesterone (7)
- develops secretory endometirum
- affects endocerivcal glands–leading to changes decreasing sperm penetration into cervix
- maintains pregnancy by suppressing menstruation and uterine contractility
- invovled in preparing mammary glands for lactation
- slightly elevates body temp during menstruation
- incr ventilatino in lueteal phase and pregnancy–>reducing CO2
- incrs basil insulin levels and enhances fat deoposition
wht is the primary hormone hat maintains pregnancy
progesterone
routes of admin/uses for Medroxyprogesterone
PO for HRT
injectable for contraception
clinical uses for progesterone (6)
- contracption (with estrogen)
- HRT (with estrogen)
- DUB
- tx of dysmenorrhea
- management of endometriosis
- interfitlity
kinetics of progestogens
- met
- bioavail
- half lives
rapidly met (t 1/2 is 5 min) -first pass affect-->gives it poor bioavail
kinetics for progestins
- t 1/2
- stability vs progestogens
more stable to first pass effect
half life=7-30 hours
Medroxyprogesterone
- synthetic or natural
- routes and their diff metabolisms and half lives
- uses
synthetic
PO with a short half life– of hours—due to extensive hepatic metabolism
IM injection half life for 40-50 days
uses;
*IM for prolonged contraception (3 MO)
Norethidrone, Norethidrone acetate, Norgestrel and Levonorgestrel
- natural or synthetic
- MOA
- SEs
androgenic activity bc their structures are similar to testosterone
SEs= acne and hirsutism
Norgestimate and Drospirenone
- good for PT with what?
- uses
good for PTs with acne
*found in combined oral contraceptives
SE of progestins
HA
Depression
Wt gain
Libido changes
Mifepristone RU-486
- drug class
- MOA
- uses
- route
- se
Anti-progestin
MOA
*Progesterone antagonist–resulting in inability to maintain pregnacy
INDS= termination of preg
*combined with prostaglandin analog (Misoprostol)– which causes uterine contractions
PO
SE
- uterine cramps
- bleeding
- abd pain
- incomplete abortion
list the non-hormonal contraceptives
diaphgram
contraceptive sponge
copper IUD
in combined OCPs, name the MOA for
- estrogen
- progestin
ESTROGEN MOA
*prevents (-) feedback to PG–>prevents released of FSH–>preventing selection of dominant follicle
PROGESTIN MOA
*inhibits LH secretion—>preventing ovulation
for the biphasic or triphasic COCs, what hormone is varying doses
progestin
places to put the transdermal patch
- abdomen
- upper torso
- buttock
- upper outer arm
which contraception has greatest estrogen exposure
transdermal patch (vs PO)
who is NOT a good candidate for transdermal patch
PT over 200 pounds
who is GOOD candidate for transdermal patch
woman who is non-compliant with taking a pill everyday
major SE with transdermal patch
higher breakthrough bleeding, spotting
- breast tenderness in the first two cycles
- *rash/site rxn
with the vaginal ring, when do you need to use backup protection
for the first 7 days
if ring has been out for >3 hours
main SE with vaginal ring
breakthrough bleeding
incr vaginal secretions
progestin only pills “mini-pills”
- who gets them
- MOA
- cons
- pros
BREASTFEEDING moms (never give then estrogen OCPs in PP phase) or any woman who has a contra to estrogen
MOA
- suppress ovulation
- thicken cervical mucus
- alter endometrium
- inhibit tubal transport
CONS
- less effective
- more room for error–has to be taken SAME EXACT TIME every day
- breakthrough bleeding
PROS
*no incr risk of thromboembolic evvents
list the 3 long acting forms of contraception and how long each lasts
- depo shot– 3 MO
- IUD
* progestin ones: 3-5 yrs
* copper: 10 yrs - Implants–3 yrs
Injectable contraception
- what hormone is in it
- how is it administered
- effectiveness
- SE
- not recc for?
only progestin—Medroxyprogesterone
given IM or SC every 3 MO
effectiveness= as close as sterilization
SE
- wt gain
- menstrual irregularity
NOT recc for
* treatment > 2 years bc it can decr bone density
Implants
- what hormone
- MOA
- pros
- cons/se
progestin only–>etonogestrol
LARC– long acting reversible contraceptive
MOA
- inhibs ovulation
- thickens cervical mucous
PROS
- good for compliance
- good for effectiveness
- not assoc with decr bone density or thromboembolic events
SE/CONS
*irregular menses and HA
IUDS
- what hormone is released
- duraton
Progestin IUDS
LARCs
also have copper only ones– no hormones
Release Levonorgestrel for 3-5 years
MOA
*prostaglandin release–>alters urterine and tubual activity–>drectly toxic to sperm–>
PROS
- effective
- little systemic SE
- helps with heavy menses (copper)
which contraceptive is one of the most effective with least systemic SEs
IUDS
most effective method for EC?
copper IUD
Plan B, Next step
- hormones
- how to take
- effecetivenss
Progestin ONLY– levonorgestrel
take 1 or 2 doses wihtin 72 hrs
75-89% effective
Ella/Ulipristal
- hormones
- MOA
- directions to take
Progesterone agonist/antagonists
MOA: delays or inhibis ovulation
take within 5 days
Yuzpe Method
-hormones
COC–estrogen and progestin
one dose— then 2nd dose 12 hrs later
-decrs pregnancy by 75%
copper IUD insertion for EC
- timing of insertion
- contra
inserted within 5 days
CONTRA
- PT with STDs
- risk of ectopic pregnancy
list the four EC
- progestin only pills
- Progestin antagonist/agonist pills
- COCs
- Copper IUD
SE of contraceptives depends on?
[ ] of estrogen and progestin in individual formulations
list the serious SE of combined hormonal contraceptives
-esp in women who——
ESP IN WOMEN WHO ARE >35 and SMOKERS ::
- incr BP
- migraines with aura
- thromboemobism
- MI
- Stroke
- incr risk of cerivcal CA
BUT decr risk of endometrial and ovarian CA
AKA— ACHES
Abominal pain Chest pain Headaches Eye problems Severe leg pain
COCs
- incr risk of what CA
- decr risk of waht CA
INCR risk of cervical CA
DECR risk of ovarian and endometrial CA
red flags for OCPs/contras
>35 smokerrs hx of: thromboembolic dz, MI, stroke HTN migranes with aura
SERMS?
- moa
- list the drug
selective estrogen receptor modulators
**class of estrogen-related drugs that display selective agonism or antiagonism on estrogen receptors dep on target tissue
DRUGS
- Tamoxifen
- Raloxifen
- Clomiphene
Tamoxifen -MOA -kinetics--routes, met, -uses -SE -
MOA
*estrogen receptor modulator—competes with estrogen for binding in breast tissue
KINETICS
- PO
- extensively met by CYP450— so drug-drug interactions can reduce efficacy
USES
- BC that is estrogen rec receptive
- endometrial CA
- prophylaxis in high-risk PT after they finish tx
SE *flushing *periphereal edema *HTN *N/V/D *irreg menses *endometrial hyperplasia BBW******* stroke, thromboembolic events--PE, uterine malignancies
post-menopausal osteoporosis
Raloxifene
Climiphene
- MOA
- Kinetics–how to adminsiter, rtoue
- uses
- SE
- incr risk of?
MOA:
*estrogen agonist interfering with negative feedback of estrogens on the hypothal—- incrs secretion of GnRH–leading to ovarian stimualtion and ovulaiton
KINETICS
- PO
- given on or about 5th day of cycle with a 5- day course of medication
USES
*anovulation— stimualtes ovulation in infertility
SE
- Hyperstimulation of ovary
- ovary enlargement
- HA
- ****Very high risk of multiple gestation
what is the most imp androgen in huans
testosterone
what organs synthesize testosterone
ovaires
testes
adrenal gland
clinical uses of testosterone
- primary hypogonadism or secondary
- wasting due to CA or HIV
- controlled substances to incr lean body mass– muscles stregnth, endurance—UNAPPROVED USE
is testosterone active if taken PO
no—– highly effected by first pass metabolism
two uses for anti-androgens
Prostate CA
BPH
Flutamide
-use
0moa
prostate ca
MOA: inhibits androgens at target cell
Finasteride use and MOA
BPH
*inhibits 5-alpha reductase–which converts testosterone to DHT– which can bind to receptors
