Hormonal Contraceptives Flashcards
Hormonal Contraceptives (HCs)
General
Contain synthetic analogs of the reproductive hormones (estrogen and/or progesterone)
Act synergistically to produce anti-ovulatory effects
Suppression of GnRH
Affect the endometrial lining (↓ bleeding and pain associated with menstruation)
Available formulations:
Oral contraceptive pills (combined and progestin-only)
Transdermal patches
Vaginal rings
Progestin injections
Subdermal implants
Intrauterine devices
Choice of Contraception
The choice of contraceptive method is individualized and often is dictated by a variety of factors:
Ease of access and use (dosing regimen, required procedures)
Affordability
Efficacy rate
Reversibility or permanence
Prevention of STIs
Adverse effects
Medical contraindications
Ethical and moral beliefs
Chemistry review
Ethinyl estradiol (EE)
Both estrogens and progestins are steroidhormones, making them fat-soluble and highly protein-bound
Ethinyl estradiol (EE):
Very similar in structure to natural estradiol
Addition of an ethynyl group (C2H) makes it significantly more stable than estradiol
↑bioavailability as compared with estradiol when taken orally
~50% (natural estradiolis only ~5%)
Only estrogen used in hormonal contraception (variable doses)
chemsirty review
progestins
Progestins:
Similar in structure to progesterone
Addition of a triple bond in most cases makes the molecules more stable
Androgenic effects:
Most are derived from testosterone → have stronger androgenic effects than natural progesterone
Less androgenic: norgestimate, etonogestrel, and desogestrel
Antiandrogenic activity: drospirenone (spironolactone analog)
Multiple different progestins are used in HCs → different properties of the progestins are responsible for different side-effect profiles of various HCs
Normal Physiology of theMenstrual Cycle
HPO axis
Understanding hormonal regulation of ovulation and themenstrual cycleis key to understanding the mechanisms of hormonal contraceptives
HPO axis:
Hypothalamussecretes gonadotropin-releasing hormone (GnRH)
Pituitary secretes:
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Ovary secretes:
Estrogen
Progesterone
Menstrual cycle regulation is primarily by the hypothalamic-pituitary-ovarian (HPO) axis
Normal Physiology of theMenstrual Cycle
Follicular/Proliferative phase
Follicular/Proliferative phase:
GnRH pulse stimulates the release of FSH
FSH stimulates follicular development within theovaries
Developing follicles produce estrogen (estradiol)
Estrogen:
Stimulates endometrial proliferation
Inhibits FSH secretion (feedback inhibition)
Ovulation:
Triggered by a midcycle surge of LH
Normal Physiology of theMenstrual Cycle
Luteal/Secretory phase
Luteal/Secretory phase:
The ovulated follicle is now called the corpus luteum
The corpus luteum produces progesterone and a moderate amount of estrogen
Progesterone:
Stabilizes endometrium
Causes endometrium to mature into secretory endometrium, capable of sustaining apregnancy
Progesterone = “progestational hormone” → produced only after ovulation, when gestation is possible
If pregnant: corpus luteum continues producing progesterone until theplacentacan take over
If not pregnant: corpus luteum involutes → estradiol and progesterone levels fall
Normal Physiology of theMenstrual Cycle
menstrual phase
Menstrual phase:
Loss of stabilizing hormones (particularly progesterone) triggers breakdown of the endometrium → menses
Key point: Progesterone withdrawal triggers bleeding
Mechanism of Action of Hormonal Contraceptives
Estrogen
Both estrogens and progestins cause an antiovulatory effect
Used together, this effect is SYNERGISTIC
Estrogen component:
Inhibits FSH release → prevents the selection and maturation of the dominant follicle = No ovulation
Stimulates endometrial proliferation if given without progestin (↑ a patient’s risk for certain cancers) → ethinyl estradiol is NOT given alone
Mechanism of Action of Hormonal Contraceptives
Progestin
Progestin component:
Inhibits LH surge that is necessary for ovulation by decreasing the pulse frequency of the GnRH
Effects on the endometrium:
Natural progesterone is required to make the endometrium healthy forpregnancy
Androgenic nature of synthetic progestins thins the endometrial lining, making it unsuitable for implantation
All hormonal contraceptives are “progestin-dominant” → overall endometrial effect of hormonal contraceptives is endometrial atrophy
↑ Cervical mucus viscosity → inhibits sperm transport into the uterus
↓ Cilia motility in the fallopian tube
Classification of Hormonal Contraceptives
Grouped by the length of their action and route of administration
Short-acting contraceptives
Includes pills, patches, rings, and injections
Long-acting reversible contraceptives (LARCs)
Emergency contraception
Short-acting contraceptives
Combined Oral Contraceptive Pills (COCPs)
We
Classified by the number of “phases”:
Monophasic: Each pill contains fixed amounts of ethinyl estradiol and progestin
Biphasic: Variable amounts of ethinyl estradiol and a form progestin
Triphasic: Variable amounts of ethinyl estradiol and a form progestin
Low-dose ethinyl estradiol (10-35 mcg) preferred to high-dose (50 mcg)
Daily administration
Initiation on the first day of the menstrual cycle or first Sunday after the onset of the cycle
NOTE: Patients using the first Sunday start are not protected from pregnancy in the first 7 days and an additional form of birth control will be needed
Pregnancy rate
0.3% with perfect use
8% with typical use
Combined Oral Contraceptive Pills (COCPs)
Non-contraceptive benefits:
More regular, lighter, shorter menses
Improvement of dysmenorrhea symptoms (cramping)
Decreased risk of ovarian, endometrial, and colon cancers
Improvement of acne and unwanted hair growth
Functional ovarian cysts are less likely
Lower frequency of uterine myomas with taking COCPs > 4 years
Reduce the frequency of migraines associated with menstruation (NOT for use in patients with migraines with aura)
Transdermal patch
Small, square adhesive patch worn on the skin
Buttocks, chest (not the breasts), upper back or arm, or abdomen
Releases ethinyl estradiol and norelgestromin or levonorgestrel daily which is absorbed through the skin
Hormone blood levels are more constant with the patch than with OCs
Weekly administration
1 patch applied per week for 3 weeks in a row
Rotate application sites
No patch applied for 7 days…menses occurs
Less effective in women > 90 kg
Vaginal ring
Flexible, transparent, plastic ring that is placed in the upper vagina
Releases ethinyl estradiol and a progestin (etonorgestrel = NuvaRing; segesterone = Annovera) that is absorbed through the vaginal tissues
Ring types
Month-long (NuvaRing)
1 ring inserted for 3 weeks/21 days; removed for 7 days…menses occurs
Replaced each month
Year-long (Annovera)
1 ring inserted for 3 weeks/21 days; removed for 7 days…menses occurs
Replaced once a year
Methods of Administration
Cyclic administration
Cyclic administration:
Pills/patches/rings containinghormonesare typically used for 21–24 days in a row (ovulation and endometrial growth are suppressed during this time)
Hormone-free interval (HFI):
Typically 4–7 days in length
Pill packs include placebo pills
Patch/ring is withheld during this time
Withdrawal bleeding during this time
methods of administration
prolonged cyclic/ continuous administration
Prolonged cyclic administration:
Hormones taken for up to 84 days (12 weeks) followed by a 4–7-day HFI
Withdrawal bleeding typically 4 times per year
Hormone use can be extended beyond 12 weeks if tolerated by the patient
Continuous administration:
Hormones are taken continuously, with no HFI
Monophasic pills, the patch, and vaginal ring can all be administered this way
Higher risk of breakthrough bleeding owing to prolonged endometrial atrophy
Progestin-only pills (POPs)
Commonly called “mini pills”
Daily administration at the same time every day
Packs of 28 active pills
Packs of 24 active pills and 4 inactive pills
Can be inconsistent in preventing ovulation
Hormone: norethindrone or drospirenone
Pregnancy rate
0.3% with perfect use
9% with typical use
Progestin injections
Sightly more effective than progestin-only pills
“Quarterly” administration by an OB/GYN
1 injection (IM or SC) every 3 months or 13 weeks
Can be given up to 2 weeks late (15 weeks from the last injection)
Hormones: depot medroxyprogesterone acetate (DMPA)
In the 3 months after the first injection
30% have amenorrhea
30% have spotting or irregular bleeding
After 2 years, ~70% have amenorrhea
Pregnancy rate
0.2% with perfect use
6% with typical use
Takes an average of 10 months to conceive following discontinuation of the injections
Long-acting reversible contraceptives (LARCs)
Subdermal contraceptive implant
4 cm, single-rod implant inserted through a trocar subdermally in the upper arm
Releases etonogestrel at a rate of 50 mcg/day to prevent ovulation, thicken cervical mucus, and thin the uterine lining
Lasts 3 years
LARCs
Intrauterine device (IUD)
T-shaped, plastic device that is inserted into and left inside the uterus
Works to prevent fertilization by thickening cervical mucus and thinning the uterine lining
Includes:
Copper IUD (ParaGard)
Lasts 10 years
Hormonal IUD
levonorgestrel
Mirena & Liletta(52 mg of levonorgestrel): last 7 years - Mirena and 6 years - Liletta
Kyleena(19.5 mg of levonorgestrel): lasts 5 years
Skyla(13.5 mg of levonorgestrel): lasts 3 years
Emergency contraception (EC)
Contraception administered after unprotected intercourse (UPI) or if birth control fails
♀ with regular menses and a single act of intercourse → 5% risk of pregnancy
♀ with irregular menses and a single act of intercourse → 12-20% risk of pregnancy
Acts to prevent fertilization and/or implantation
Commonly used emergency contraception regimens:
Insertion of a copper IUD
Insertion of a levonorgestrel 52 mcg IUD
Oral regimens
Emergency contraception
Insertion of an IUD:
Provide ongoing contraception
Not impacted by body mass index or risk ofpregnancy(UPI midcycle, multiple episodes of UPI)
Options:
Copper IUD
More effective than oral methods
Pregnancy rate is 0.1%
Levonorgestrel 52-mg IUD
emergency contraception
Oral methods - “the morning after pill”
Less effective in individuals with BMI > 30
Less effective in individuals at higher risk ofpregnancy (when UPI occurs)
Options:
Taken as a single course as soon as possible after UPI
Ulipristal acetate 30 mg PO once (can be used up to 5 days after UPI)
Oral levonorgestrel 1.5 mg PO once (can be used up to 3 days after UPI)
Combined EC pills taken at higher doses than normal as soon as possible after UPI (often causes nausea and vomiting)
Time in the menstrual cycle that EC is administered and the patient’s BMI are major factors in the likelihood of pregnancy!
Adverse Effects of Hormonal Contraception
Risk of venous thromboembolism (VTE):
↑ risk with ethinyl estradiol > progestins and is dose dependent
Ethinyl estradiol should be avoided in people at risk for VTE
Progestin-only methods are recommended
Abnormal bleeding (unscheduled bleeding (spotting), prolonged bleeding)
More often associated with progestin-only methods
Estrogen tends to stabilize bleeding patterns
Worst with etonogestrel implant
Ovarian cysts
Associated with progestin-only methods
Ethinyl estradiol generally suppresses cyst formation
Breast symptoms:
Fibrocystic breast changes
Mastalgia (breastpain)
Decreased breast milk production during breastfeeding(ethinyl estradiol only)
Weight gain
Progestin injections
Average < 5 pounds
Due to changes in appetite rather than metabolism
Nausea/vomiting
Headaches/migraines
Decreased libido
Melasma
contraception
Unique Adverse Effects
Vaginal ring: ↑ vaginal discharge
depot medroxyprogesterone acetate (DMPA) injections:boneloss (reversible)
IUDs:
Pelvicpain
Endometritis
Uterine perforation
Device expulsion: copper IUD > hormonal IUD
If pregnancy occurs, significantly ↑ risk of that pregnancy being ectopic (though the absolute rate ofectopic pregnancyis lower in IUD users than in individuals on no contraception)
Drug interactions
Metabolism of COCPs and POPs is increased by any drugs that increase liver microsomal enzyme activity, resulting in reduced contraceptive efficacy
Anticonvulsants:
Phenytoin
Carbamazepine
Barbiturates
Topiramate
Felbamate
Oxcarbazepine
Lamotrigine (HC ↓ lamotrigine levels and affect seizure control)
Antimicrobials:
Rifampin
Rifabutin
The vast majority of antibiotics do not interact with HCs
Antiretroviral drugs
Non-nucleoside reverse transcriptase inhibitors
Protease inhibitors
