Reproductive Flashcards
Estrogens include
estradiol
estrone
ethinyl estradiol
SERMs include
Clomiphene
ospemifene
raloxifene
tamoxifen
toremifene
Anti- progestin
mifepristone
Progesterone agonist/ antagonist
ulipristal acetate
Physiology of menstrual cycle
hypothalamus - gonadotropin releasing hormone is secreted
Anterior pituitary - GnRH stimulates FSH and LH by the anterior pituitary
FSH and LH downregulates the release of GnRH from the hypothalamus
Days of menstrual cycle
days 1-5 - menstruation
days 6-14 - follicular phase (estrogen driven)
day 14 - ovulation (LH driven)
days 15-28 - luteal phase (progesterone driven)
MOA of estrogens
agonist to the estrogen receptor
Use of estrogens
oral contraceptive
menopausal hormone therapy
gynecologic disorders
Estrogens are most often administered with a _______ in combination oral contraceptives (COC)
progestin
COC MOA
suppresses LH and FSH by interfering with hypothalamic gonadotropin-releasing hormone and pituitary gonadotropin secretion
Ovulation is suppressed by inhibition of the mid-cycle LH surge
Suppression of ovarian folliculogenesis via suppression of pituitary follicle stimulating hormone secretion
Why we give estrogen and progesterone
estrogen - potentiates progesterone so lower doses can be used, allows for endometrial growth so less breakthrough bleeding
progesterone - protects against estrogen-induced endometrial hyperplasia
Progestin related mechanisms:
endometrium becomes less suitable for implantation
cervical mucus thickens and becomes less permeable to penetration by sperm
Level of activity: High
Norgestrel
Levonorgestrel
Level of activity: Moderate
Norethindrone
Norethindrone acetate
Level of Activity: Low
Ethynodiol
Norgestimate
Desogestrel
Drospirenone
Dienogest
Benefits of COCs (Noncontraceptive)
Abnormal or dysfunctional uterine bleeding
Dysmenorrhea
PMS and PMDD
Endometriosis
Adenomyosis
Functional ovarian cysts
PCOS
Hormone replacement in women with primary hypogonadism
Potential adverse effects of COC
HTN
Thromboembolism: DVT, PE, stroke
Changes in lipids (decreased HDL)
Bleeding irregularities
Nausea
Mood changes
Breast changes
Wt gain
HA
Estrogen Deficiency can cause
vasomotor symptoms
Estrogen Excess can cause
chloasma (melasma)
Menorrhagia and clotting
increased breast size
Progestin Deficiency
breakthrough bleeding
delayed withdrawal bleeding
dysmenorrhea
heavy flow/ clots
Progestin Excess can cause
Candidiasis
appetite increase
depression
fatigue
libido decrease
Androgen Excess can cause
acne
Hirsutism
libido increase
oily skin and scalp
edema
Contraindications to estrogen-containing contraception
Thromboembolic disorders
smokers > 35 yo
impaired liver function
abnormal vaginal bleeding
pregnancy
cardiac disease
migraine
Consider progestin only contraceptive options
Drug interactions
Anticonvulsants - phenytoin, carbamazepine, barbiturates, topiramate
Antibiotics - rifampin
Drugs used to treat HIV
Emergency Contraception MOA
works by delaying or blocking ovulation
Emergency contraceptives must be used within
72 hours of unprotected intercourse
Emergency Contraception is ineffective once
implantation has occurred
Options for emergency contraception include
levonorgestrel (Plan B)
Ulipristal (high dose progestin)
COC (higher dose hormones)
Copper IUD
Levonorgestrel MOA
prevents ovulation or fertilization, alters endometrium
Levonorgestrel is contraindicated in
known or suspected pregnancy
Levonorgestrel adverse reactions
generally well tolerated, may cause GI upset, re-administer if vomiting within 2 hours
Ulipristal is a
selective progesterone receptor modulator (progesterone agonist/ antagonist)
Ulipristal MOA
binds to progesterone receptor and inhibits or delays ovulation, alters endometrium
Ulipristal contraindicated in
known or suspected pregnancy
Ulipristal adverse reactions
generally well tolerated, may cause HA, nausea, dysmenorrhea, dizziness, fatigue
Mifepristone is a
synthetic steroid compound, antiprogesterone
Mifepristone use
medical abortion
Mifepristone MOA
Competitively binds progesterone receptor (blocks progesterone receptor)
Antagonizing endometrial and myometrial effects leads to contraction inducing activity - disrupts implanted embryo
Mifepristone used for pregnancies less than
49 days (7 weeks)
Mifepristone is followed by
Misoprostol for expulsion of the products of conception
HRT goals of therapy
decrease symptoms which may include vasomotor symptoms (hot flashes), mood lability, vaginal atrophy, sleep disturbance
HRT is given as
estrogen only - women that have had a hysterectomy
estrogen-progestin - women with a uterus
HRT is only given for approximately
< 5 years - considered safe
and not beyond the age of 60
HRT is associated with an increased risk of
coronary heart disease
stroke
DVT/Pulmonary embolism
invasive breast cancer
HRT appears to be protective against:
Osteoporosis
colon cancer
Contraindications for HRT
Hx of breast cancer
Hx of coronary heart disease
Previous hx of DVT/PE
Hx of CVA or TIA
Active liver disease
Unexplained vaginal bleeding
Risk of endometrial cancer
HRT side effects
breast soreness
mood symptoms
bloating (progestin)
vaginal bleeding
HRT types that are effective in relieving menopausal symptoms
all types and routes of estrogen are effective
SERMs (selective estrogen receptor modulators) affect different parts of the body:
Tamoxifen
raloxifene
ospemifene
toremifene
Clomiphene
Tamoxifen - breast cancer tx, antagonist in breast, agonist at bone and endometrium
raloxifene - osteoporosis tx, antagonist in breast and endometrium, agonist at bone
ospemifene - antagonist in breast, agonist in vaginal tissue and endometrium
toremifene - antagonist in breast, agonist in bone and endometrium
Clomiphene - ovulation induction, antagonist at hypothalamus, weak agonist in other tissues
SERMs Adverse reactions
flushing, hot flashes
mood changes, depression
GI upset
vaginal bleeding
bone marrow suppression
Contraindications of SERMs
Warfarin therapy
Hx of DVT/PE
Hx of CVA/TIA
Endometrial cancer
Leuprolide MOA
inhibitor of gonadotropin secretion - results in transient increase in LH/FSH which leads to transient increase in testosterone and estrogen BUT continuous GnRH agonist use results in decrease in LH/FSH and suppression of testosterone/ estrogen production
Adverse effects of Leuprolide
HA
Depression
GI
decreased libido
Leuprolide indications
prostate cancer
endometriosis
uterine fibroids
used for some IVF protocols
Flutamide is a
synthetic, nonsteroidal anti-androgen
antagonist at androgen receptor - competes with natural hormone for binding to the androgen receptor - blocks effect of androgens on target organs
Flutamide adverse reactions
GI distress
Gynecomastia
impotence
hot flash
liver failure
Contraindications Flutamide
Severe hepatic impairment
Phosphodiesterase Type V inhibitors include
sildenafil
tadalafil
vardenafil
Alpha-1 Blockers nonselective includes
Doxazosin
Prazosin
Terazosin
Alpha-1 Blockers selective include
alfuzosin
tamsulosin
Tadalafil lasts longer than both Vardenafil and Sildenafil
up to 36 hours in some cases (only take once a day or every other day)
Phosphodiesterase Type V inhibitors should be taken on
an empty stomach
Phosphodiesterase Type V inhibitors: Contraindicated in patients taking
nitrates - can cause severe hypotension
do not administer nitrate if they have taken PDE5 inhibitors in the past 24-48hrs
Avoid taking in combination with drugs use to treat BPH
Side effects of Phosphodiesterase Type V inhibitors
Hypotension
Flushing
HA
heartburn
visual effects (blue vision)
priapism
5-alpha reductase inhibitors include
finasteride
dutasteride
anticholinergic agents include
tolterodine
oxybutynin
darifenacin
Alpha-1 receptor cause inhibition of
contraction of smooth muscle of:
ureter
vas deferens
urethral sphincter
most common side effect of alpha-1 adrenergic antagonists
orthostatic hypotension
how to take alpha-1 adrenergic antagonists
initiate at bedtime, low doses and titrate up over weeks
Other side effects of alpha-1 adrenergic antagonists
interaction with phosphodiesterase-5 inhibitors
ejaculatory dysfunction
reflex tachycardia, HA, dizziness, vertigo, nausea, nasal congestion/rhinitis
intraoperative floppy iris syndrome during cataract surgery (tamsulosin)
5-alpha reductase inhibitor MOA
inhibits type 2 5-alpha reductase -> interfering with the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT stimulates prostate growth)
5-alpha reductase inhibitor adverse reactions
erectile dysfunction
decreased libido
abnormal ejactulation
Drugs used to treat androgen deficiency
methyltestosterone
fluoxymesterone
testosterone
Indications for androgen deficiency
primary or secondary hypogonadism
delayed puberty
menopausal symptoms
occasionally used for metastatic breast cancer
Contraindications of methyltestosterone/ fluoxymesterone
prostate cancer
women who are or may become pregnant
caution if cardiovascular risk
Adverse effects of methyltestosterone/ fluoxymesterone
Males: Priapism, impotence, gynecomastia, BPH
Females: masculinization, acne, facial hair
may increase risk of MI or stroke
Anabolic Androgenic steroids include
synthetic - stanozolol, oxandrolone, nandrolone (many more)
indications of Anabolic Androgenic steroids include
AIDS wasting
low testosterone state
transgender
also used at high doses by athletes for:
-increasing lean muscle mass and improve performance
-faster recovery
-appearance
