LM 16.2: Pharmacology of Contraception Flashcards
what does progesterone do to the endometrium?
it stimulates the endometrial glands to dilate, fill with glycogen, and become secretory while stromal vascularity increases
how long does the corpus luteum persist?
if the oocyte is fertilized, then the hCG produced from the new embryo will rescue the corpus luteum and allow it to continue progesterone production until the 9th or 10th gestational week –> then, the fetal placenta will take over progesterone production throughout pregnancy
if progesterone levels are not maintained by the rescued corpus luteum, estradiol and progesterone levels decrease late in the luteal/secretory phase, the stroma becomes edematous, and the endometrium and its blood vessels necrose, leading to bleeding and menstrual flow
how do combined hormonal contraceptives work?
the interplay of the steroid hormones, estradiol and progesterone, with the gonadotrophs, LH and FSH, is the principle mechanism by which combined hormonal contraceptives work
the constant level of steroid hormones allow for continuous negative feedback on gonadotroph production from the pituitary – so with OCPs, stable levels of estradiol and progestin result in negative feedback on GnRH and then during the placebo week when estradiol and progesterone levels drop, you get menstration!
this inhibition provided by hormonal contraceptives prevents the rise in FSH that is necessary to initiate follicle development and selection of a dominant follicle – this inhibition also prevents the LH surge that is necessary to trigger ovulation!
how does ethinyl estradiol function as hormonal contraception?
it suppresses FSH continuously, inhibiting dominant follicle growth
it also potentiates progesterone receptors which stabilizes the endometrium
ethinyl estradiol has greater bioavailability than estradiol and is metabolized through the liver
what are side effects of ethinyl estradiol?
MINOR
1. breast tenderness
- nausea
- HA
- fluid retention
MAJOR
dose-related side effects of increasing clotting factors and thereby risk of thrombosis (arterial and venous) and cardiovascular events (MI/stroke)
how does ethinyl estradiol effect acne?
higher doses result in increased steroid hormone binding globulin (SHBG) therefore decreased circulating androgens and subsequent decreased androgenic side effects, like acne
how do progestins function as hormonal contraception?
it suppresses LH surge and prevents ovulation
it also causes endometrial decidualization and thinning, thickens cervical mucus, may decrease tubal peristalsis
what are the side effects of progestins?
- menstrual irregularities
- hair changes
- loss of bone mineral density
- mood changes
- increased appetite
- weight gain
also, based on which progestin derivative you’re using, it might have androgenic, estrogenic, glucocorticoid, anti-mineralocorticoid or anti-androgenic properties
how do progestins effect bone mineral density?
loss of bone mineral density
progestins significantly inhibits estrogen production and therefore limits the effect of estrogen on inhibiting bone resorption by osteoclasts
this effect is however reversible with discontinuation of the long acting progestin
what are the progesterone derivatives?
- progesterone
- hydroxyprogesterone caproate
- medroxyprogesterone acetate
- 19-nortestosterone
- norethindrone
- norethynodrel
- norgestrel
- desogestrel
- norgestimate
which drugs are first generation progesterones?
- megestrol acetate
- medroxyprogesterone acetate (MPA)
pregnanes have an extra methyl group at C6, which decreases first-pass hepatic metabolism and thus makes these formulations orally available
which drugs are second generation estranes?
- norethindrone
- norethindrone acetate
- ethynodiol
- lynestrenol
estranes have lost the methyl group at C19, which decreases androgenic activity
which drugs are third generation gonanes?
- norgestrel
- levonorgestrel
- desogestrel
- norgestimate
- gestodene
- dienogest
gonanes have replaced the methyl group at C13 with an ethyl group, which again decreases androgenic activity
what is drosperinone?
a synthetic progestin that is an analog to spironolactone and therefore has anti-mineralocorticoid and anti-androgenic activity
what are the 3 mechanisms by which combined hormonal contraceptives provide contraception?
- progestin thickens cervical mucus, inhibiting sperm transit
- estradiol component negatively feeds back to inhibit FSH and subsequent development of dominant follicle
- progestin component causes decidualization of endometrium, creating an unfavorable environment for implantation
what are the contraindications to estrogen based contraceptives?
- increased risk of thrombosis so contraindicated in patients with HTN
- increased risk for MI with contraceptive use –> the highest risk is in those women who use combination OCPs and are over the age of 35, with hypertension
- tobacco use –> to consider removing this risk factor, one must have quit smoking for a minimum of 6 months
- abnormal liver function
- migraines with auras (related to risk of stroke)
- DM with vascular disease
- estrogen sensitive breast cancer
- pregnancy
- sever hypercholesterolemia/hypertriglyceridemia
it is important to screen a patient’s vital signs, tobacco use and personal and family history of known thrombogenic mutations, CVA, TIA, heart disease, hypertension, MI, vascular disease and VTE, prior to prescribing CHC
what is the usual dosage for estrogen CHC?
more standard doses are 30-35 mcg EE, with lower doses ranging from 20-25 mcg EE
what are the benefits to lowering estrogen dosage in CHC?
lowering doses of ethinyl estradiol includes minimizing:
- nausea
- breast tenderness
- fluid retention
- headaches
however higher doses result in increased steroid hormone binding globulin (SHBG) and therefore decreased circulating androgens with subsequent decreased androgenic side effects, like acne
what are the routes of delivery for ethinyl estradiol CHC?
- oral
- transdermal
- vaginal
how are oral CHC metabolized?
via the liver
so they’re avoided in those with significant hepatic disease
what are monphasic, biphasic vs. triphasic OCPs?
they have varying doses of ethinyl estradiol
they typically having lower doses in the beginning of the regimen, reducing estrogen-related side effects like nausea then increasing doses through the month, therefore increasing SHBG, decreasing free androgens and decreasing androgen-related effects (like acne)
what are extended regimen OCPs?
pills with active steroid hormones for 24 day with a 4 day pill free interval
extended regiments reduce the pill free interval to decrease breakthrough bleeding and better suppress ovarian activity
what are continuous regimen OCPs?
active steroid hormones for a consecutive 84 days followed by a 7 day pill free interval, resulting in better suppression of ovarian activity
what are the non-contraceptive uses of CHCs?
- abnormal uterine bleeding
- dysmenorrhea
- endometriosis
- PCOS
- hirsutism
- acne
- menstrual migraines
what are the beneficial effects of contraception?
- with 12 months of use, there is a 50% reduction in risk of endometrial cancer for up to 20 years
- with as little as 3-6 months use, there is a 40% reduction in ovarian cancer risk
what are the cons of contraception?
- OCPs may result in behaviors that lead to a 3-fold increase in cervical cancer in HPV positive individuals after 5 years of use
- current and recent use may increase rates of premenopausal breast cancer
when should you initiate CHCs?
they should typically be started immediately (“quick start” method), provided that there is reasonable certainty of negative pregnancy and with the advice to use backup contraception for the first week of use
how can you be reasonably certain that a woman is not pregnant?
- if a patient’s last menstrual period was within 5 days
- if there was no unprotected intercourse since the time of her last menstrual period with a negative pregnancy test
if patient has not had a LMP within 5 days and has had unprotected intercourse but has a negative pregnancy test, contraception may be initiated with the caveat that pregnancy is not ruled out but that contraception is unlikely to have deleterious effects on pregnancy
what do you do if a dose of CHC is missed?
when a dose is missed, patient’s should immediately take a missed pill and continue usual use –> if another dose is due that day, it should be taken
when do you start CHC postpartum?
CHC planned in the postpartum period should be initiated at the third week postpartum to minimize risks of VTE
CHC is typically avoided in the initial 6 months following delivery in breastfeeding mothers, as there is some low-quality evidence that steroid hormone use may affect liver and brain development in neonates and may affect quality and quantity of breast milk production
however, CHC is commonly used after 6 months postpartum in the breastfeeding mother as the newborn begins solid foods
which patient is NOT at increased risk for thrombosis while using estrogen-containing contraception?
A. age 24, history of tobacco use, last use 3 years ago
B. age 37, uncontrolled HTN, diabetic retinopathy
C. age 25, migraines with neurosensory aura
D. age 23, postpartum 2 weeks after pregnancy complicated by preeclampsia, normal current bP
E. age 25, history of postpartum DVT requiring extended anticoagulant therapy
A. age 24, history of tobacco use, last use 3 years ago
all the rest are at risk for thrombosis!!
what are progestin only pills?
POPs are an oral alternative but they are not as effective as CHCs
its effectiveness depends on its ability to thicken cervical mucus, the progestin-only pill can only be relied upon as long as plasma progestin levels remain sufficient to affect cervical mucus –> in order to do so, they must be taken at the same time every day, or within a consistent 3 hour window
progestin-only pills are also a useful adjunct in exclusively breastfeeding women as they are safe in this context and in combination with lactational amenorrhea, may afford acceptable contraception
what are LARCs?
long-acting reversible contraceptives
they are the most effective method of hormonal contraception!
they involve an injection (Depo-Provera) that is given once every 3 months, an implantable rod that releases a progestin (Nexplanon), and an intrauterine device (IUD) that releases a progestin
what is the nexplanon?
a subdermal implant in the medial aspect of the patient’s non-dominant arm and provides reliable contraception for 3 years with a failure rate of <1%
one of the most effective reversible contraceptives
what are the risk involved with the nexplanon?
- bleeding/bruising/pain at placement site
- migration of device
- fracture of implant
- damage to surrounding structures
what is the depo provera?
intramuscular injection of medroxyprogesterone acetate administered every 12 weeks
what are the non-contraceptive benefits of the depo provera?
- decreased risk of anemia, PID, and fibroids
- decreased risk of seizures in women with epilepsy
- decreased incidence and severity of sickle cell crisis
- reduced risk of endometrial cancer
what are the side effects of the depo provera?
- irregular bleeding
- amenorrhea
- depression
- weight gain
- hair loss
- breast tenderness
- reversible decrease in bone mineralization
- a delay in return of regular ovulation of approximately 6-18 months
what are the non-contraceptive indications for levonorgestrel IUDs?
- reduction of dysmenorrhea
- reduction of abnormal uterine bleeding
- treatment and prevention of endometrial hyperplasia
- treatment of endometriosis
- protection from PID
what are the contraindications for IUDs
- uterine anomalies
2. distorted uterine cavity
what are the contraindications to LARCs?
- known or suspected pregnancy
- history of thrombosis
- hepatic disease
- undiagnosed abnormal genital bleeding
- known/suspected breast cancer
- hypersensitivity to progesterone
which women are good candidates for progestin-only contraception?
- women who can’t use estrogen
- those seeking long-acting and reversible contraception
- those with medical conditions which may benefit from long-term ovulation and menstrual suppression including AUB, primary dysmenorrhea, endometriosis and endometrial hyperplasia
LARCs can be used for the following indications except:
A. abnormal uterine bleeding (AUB)
B. effective long-term contraception
C. uncontrolled HTN
D. dysmenorrhea
C. uncontrolled HTN
which contraception can be used as an emergency contraception?
the copper IUD aka Paragard can be used for emergency contraception within 5 days of unprotected intercourse
how does the copper IUD act as a contraceptive?
- copper hampers sperm motility
- reduced tubal peristalsis
- decreases implantation due to endometrial irritation
what are the contraindications to a copper IUD?
- severe uterine distortion
- active pelvic infection
- known/suspected pregnancy
- Wilson’s disease
- copper allergy
- unexplained uterine bleeding
which contraceptives are barrier methods?
- male condom
- female condom
- diaphragm
- cervical cap
- sponge
how effective is a male condom?
80%
condoms break 2% of the time as well
what are the types of male condoms?
- rubber
- natural membrane (made from intestinal cecum of lambs)
- synthetic (polyurethane)
- spermicidal condoms
what is a female condom?
the female condom covers the cervix, vagina and shields the introitus
effective against STIs but difficult to use
21% pregnancy rate
what is a diaphragm?
the diaphragm fits over the cervical opening, preventing sperm from entering the uterus –> requires spermicide
must be fitted and retained for 6-8 hours
15-20% failure rate
what is a cervical cap?
the cervical cap fits snugly over the cervix, preventing sperm from entering the uterus
requires spermicide and may be left in pace for up to 48 hours
sizing is based off of obstetric history
less effective than the diaphragm due to dislodgment
what is the sponge?
it’s a 2 inch circular disk with spermicide that is moistened with water and then inserted deep in the vagina
does not require fitting or prescription
can be used repeatedly and left in place for up to 24 hrs
less effective tan the diaphragm
what is natural family planning? what are the 3 methods?
methods not requiring medications or surgery but which confer contraception based on:
- avoiding intercourse during peak fertile times in the cycle,
- withdrawal of penis prior to ejaculation and
- the interruption in ovulation related to exclusive breastfeeding and prolactin’s negative feedback on the pulsatile release of GnRH from the hypothalamus and subsequent LH release from pituitary
what is the rhythm method/period abstinence?
- avoid intercourse during greatest time of fertility
- requires menstrual regularity and monitoring for ovulation
high failure rate; 15-25%
what is coitus interruptus?
aka the pull out method
20% failure rate
what is lactational amenorrhea?
breast feeding causes hypothalamic suppression of ovulation via prolactin-induced inhibition of pulsatile GnRH release
failure rate is low, only 2%, as long as the baby is feeding on demand 5-10 times a day and there’s no supplemental feeding of the infant
what is the only surgical contraceptive option?
sterilization
what is male sterilization?
vasectomy
the removal of a portion of the vas deferens, which then prevents sperm produced by the testes from joining semen and passing into ejaculate from the urethra
sperm produced in the testes instead reabsorb
the procedure is performed under local anesthesia and is safer and less expensive than tubal sterilization
must confirm azoospermia after 15-20 ejaculations or 3 months but it’s reversible in 60-70% of patients
what is female sterilization?
procedures which focus on interruption of the passageway by which sperm and the oocyte meet in the fallopian tube
the procedure can be immediately postpartum (via mini-laparotomy), as an interval procedure(> 6 weeks postpartum, via laparoscopic approach) and as a separate elective procedure
what is hysteroscopic sterilization?
aka Essure procedure
the tubal ostia are blocked with nickel cadmium coils from the uterine cavity-side and cause scarring of the tubal ostia over time aka it’s irreversible
requires back-up contraception for a minimum of 3 months following the procedure and can only be relied upon after confirmatory hysterosalpingogram (HSG) confirms correct placement of the coils and tubal occlusion
what are the contraindications for a hysteroscopic sterilization?
- pregnancy or suspected pregnancy
- less than 6 weeks out from delivery or abortion
- active or recent pelvic infection
- pathology that impedes accesss to one or both tubal ostia
- hypersensitivity to nickle
- known allergy to contrast media
- gynecology malignancy
what is the most reliable long term surgical female contraceptive?
salpingectomy = removal of fallopian tubes
what is the purpose of emergency contraception?
they’re intended to prevent pregnancy in patients who have had unprotected or inadequately protected intercourse, as well as those victims of sexual assault
emergency contraception should be offered or made available to women who have had unprotected or inadequately protected sexual intercourse and who do not desire pregnancy
there are no conditions in which the risks of emergency contraception use outweigh the benefits –> even women with previous ectopic pregnancy, cardiovascular disease, migraines, or liver disease and women who are breastfeeding may use emergency contraception
what are the various regimens for emergency contraception?
these can be administered without an exam although some do require prescription or provider placement:
- combined oral contraception
- progestins only pills
- selective progesterone receptor modulators
- copper IUD (most effective form of emergency contraception)
which combined oral contraceptives are specifically for emergency contraception and FDA regualted?
- ella
- levonorgestrel
in the U.S., levonorgestrel EC, like Plan B One-Step and Take Action, is available on the shelf with no restrictions. ella is available by prescription only
how do progestins only pills work as emergency contraceptives?
levonorgestrel in either 2 doses or a single dose within 72 hours of unprotected intercourse, to delay or inhibit ovulation
when administered prior to the LH surge of the menstrual cycle, may also prevent follicular development
aka Plan B
how do selective progesterone receptor modulators work as emergency contraceptives?
ulipristal acetate is used as an oral regimen to delay or prevent ovulation and is effective in preventing ovulation even after the LH surge of the menstrual cycle
available by prescription only and is marketed as Ella
efficacy is superior to levonorgestrel regimens, and it is effective up to 5 days following unprotected intercourse
how effective are emergency hormonal contraceptives around the time of ovulation?
levonorgestrel has been shown to be no better than placebo at inhibiting ovulation when giving immediately prior to ovulation
ulipristal (ella) however, is effective right up to the point of ovulation even if LH levels have already begun to rise
emergency contraception can be used in the following conditions except:
A. unprotected intercourse last night
B. broken condom during vaginal intercourse 2 days ago
C. undesired 5 week intrauterine pregnancy
D. non-consensual vaginal intercourse 65 hours ago
C. undesired 5 week intrauterine pregnancy
