oral contraceptive (OC)

Introduction

Two types are available:

• combination of estrogen & progestin
  • estrogen is mestranol, estetrol or ethinyl estradiol
  • all low-dose OCs have ethinyl estradiol
  • progestin is one of six derivatives of 19-nor-testosterone
    • 2nd generation agents contain levonorgestrel
      • levonorgestrel with 20 ug estrogen associated with lower risk for pulmonary embolism, stroke, or MI, relative to 7 other combinations
    • 3rd generation agents contain desogestrel & gestodene
  • see Femlyv for orally disintegrating birth control pill
• progestin only
  • norgestrel OTC first over the counter oral contraceptvie FDA-approved (7/23)

Indications

• prevention of pregnancy#
• treatment of acne
• hyperandrogenic states & hirsutism
• premenstrual syndrome
• dysmenorrhea
• heavy menses
• endometriosis

# may be less effective in overweight women (BMI > 27)

# LoSeasonique effective in obese women as well as women with normal BMI

Contraindications

• current or past thrombophlebitis or thromboembolic disease
• cardiovascular disease
• impaired liver function
• known or suspected endocrine-dependent tumors of the breast or uterus
• pregnancy & 1st 40 days post-partum
  • generally safe with breastfeeding > 40 days post-partum
• hyperlipidemia
  • familial hypertriglyceridemia (may precipitate pancreatitis)
  • serum triglycerides > 250 mg/dL
  • low-density lipoprotein (LDL) cholesterol > 160 mg/dL
  • newer oral contraceptives have minimal effect on lipids & a lipid profile is not indicated prior to initiating an oral contraceptive
• hypertension (uncontrolled)
• migraine with aura (estrogen-containing contraceptives)*
• women > 35 years of age who smoke > 15 cigarettes daily (estrogen-containing contraceptives)*
• stop 4 weeks prior to surgery
  • 2-4 fold increased risk of post-operative thrombosis

* increased risk for stroke

Caution:

• smoking
  • if age is > 35 years & patient smokes > 15 cigarettes/day, estrogen-containing are contraindicated
    • use progestin-only contraceptive
• obesity
• varicose veins
• diabetes mellitus: use ONLY in diabetics < 35 years of age who do NOT smoke
• AVOID in women with migraine syndrome
• hypertension (avoid in women > 35 with hypertension)

Advantages

* reduced risk of epithelial ovarian cancer with oral contraceptives, esp those containing high-dose progestins (RR=0.72) {protective effect of progestins}

* reduced risk of endometrial cancer (RR=0.68)

Dosage

• therapy is best begun with onset of menses
  • OCs NOT fully effective for 1st week or more
• Sunday-start packaging
  • begin 1st pill on Sunday following onset of menses
  • if menses begins on Sunday, start 1st pill on that day
  • 1 tablet daily
  • last 7 days of 28 day package are inert tablets
• MISSED dosages
  • 1 missed tablet:
    • take one as soon as you remember, or
    • take two the next day
  • 2 missed tablets:
    • take 2 tablets as soon as remembered & continue with the next daily dose at the scheduled time
    • take 2 tablets/day for the next 2 days
    • use additional contraceptive methods for 7 days
  • 3 missed tablets:
    • start a new package on day 1 of the cycle after the last pill was taken, or
    • start 7 days after the last pill was taken
    • use additional contraceptive methods for the remainder of the cycle
• tricycle regimen
  • three 21 day packs (monophasic) consecutively
  • wait one week, then restart another cycle
  • reduces number of periods
• discontinuation of oral contraceptive
  • amenorrhea can last up to 3 months
  • longer duration should be investigated
• do NOT insert vaginally*

* Cosmopolitan magazine 2001 or 2002 site 2 studies of vaginally inserted BCP; these studies used higher dose pills than those in common use

Pharmacokinetics

• 1st pass metabolism in liver
• conjugated in liver, excreted in the bile
• deconjugated by gut bacteria -> enterohepatic circulation
• at least one week of therapy is necessary for preventing conception
• efficacy depends upon degree of compliance
• monophasic:
  • fixed doses of estrogen & progestin throughout the cycle
• biphasic
  • amount of estrogen remains the same for the 1st 21 days
  • decreased progestin:estrogen ratio in the 1st 2 weeks of the cycle allows endometrial proliferation
  • increased ratio of progestin:estrogen in the 2nd 2 weeks of the cycle allows secretory development
• triphasic
  • estrogen remains the same or varies throughout the cycle
  • progestin varies

Monitor

• pregnancy test prior to prescription of hormonal contraception if > 1 week after last menstrual period (all women)
• pelvic exam & breast exam NOT necessary prior to initiation of oral contraceptive
• lipid profile not indicated prior to initiation
• onset of menopause
  • check hormone levels on 7th day of pill-free interval
  • serum estradiol < 25 pg/mL & FSH/LH ratio of > 1 indicates menopause
  • switch to hormone replacement therapy

Adverse effects

• due to estrogens
  • increased risk of venous thromboembolism (VTE)
    • risk 9-18/100,000/year
    • increases risk 14-fold with air-travel
    • risk higher for oral contraceptives also containing progestin
      • risk higher for drospirenone than levonorgestrel (OR=2.4-3.3)
      • all combined oral contraceptives increase risk of venous thrombosis
      • the magnitidue of increase depends both on the progestin & the dose of estrogen
      • newer oral contraceptives containing desogestrel or drospirenone associated with a 4-fold risk increase; absolute risk = 0.14%; NNH=714
      • older contraceptives containing levonorgestrel* or norgestimate associated with a 2.5-fold risk increase[36]; absolute risk = 0.06%; NNH=1667
  • increased risk of arterial thromboembolism
    • increased risk of stroke (RR = 1.5-2.2) & myocardial infarction (RR = 1.3-2.3) (RR for 30-40 ug of ethinyl estradiol)
  • increased risk of coronary artery disease
    • increased risk of MI with 2nd generation agents
    • risk is minimal with 3rd generation agents*
  • no excess risk for cardiovascular disease or mortality
  • increased frequency & severity of migraine headaches
  • increased risk of hepatic adenoma
  • post-pill amenorrhea
• due to progestins
  • hair loss
  • progestin only pills do not increase risk of venous thromboembolism
  • breakthrough bleeding common with progestin-only oral contraceptives
• other
  • nausea/vomiting
  • weight gain
  • depression
  • may increase risk of cervical cancer
  • risk of breast cancer
    • increased risk of breast cancer (RR=1.10)
    • NO increase risk of breast cancer
    • may diminish risk of ovarian cancer & endometrial cancer without increasing risk for breast cancer
  • may increase risk of urinary incontinence
  • accelerates HIV progression
  • becoming pregnant while using oral contraceptives does not increase risk of birth defects
  • no increase in mortality; may confer benefit
    • no excess risk for cardiovascular disease or mortality
  • associated with new-onset depression

* levonorgestrel with 20 ug estrogen associated with lower risk for pulmonary embolism, stroke, or MI, relative to 7 other combinations

Drug interactions

• agents which decrease effectiveness of OC
  • antibiotics
    • rifampin
    • griseofulvin
    • inhibition of gut bacteria mediated deconjugation & entero-hepatic circulation of estrogen
  • antiviral agents
    • ritonavir
  • anticonvulsants
    • barbiturates
    • phenytoin
    • lamotrigine increases metabolism of OCs
  • St John's wort
• agents which increase effectiveness & toxicity of OCs
  • antidepressants
  • beta blockers
  • corticosteroids
  • theophylline
  • retroviral protease inhibitors
  • clarithromycin
  • non-nucleoside reverse transcriptase inhibitors
  • ketoconazole
  • rifampin
  • rifabutin

• drug interaction(s) of beta-adrenergic receptor antagonists with oral contraceptives
• drug interaction(s) of NSAIDs with oral contraceptive

Mechanism of action

• combination OCs inhibit ovulation by:
  • inhibition of GnRH secretion
  • inhibition of mid-cycle LH surge
• progestin only products work by:
  • altering cervical mucus
  • progestational effect on the endometrium
  • suppresses ovulation in some patients

Notes

• the American College of Obstetricians and Gynecologist recommends that oral contraceptives should be made available over the counter to improve access to contraception
• dispensing a full year supply of oral contraception improves adherence & reduces unwanted pregnancy

More general terms

• hormonal contraceptive
• pharmacologic combination

More specific terms

• biphasic oral contraceptive
• Estetrol/drospirenone (Nextstellis)
• estradiol/ethinyl estradiol/ferrous fumarate/norethindrone
• ethinyl estradiol/ethynodiol diacetate (Kelnor)
• ethinyl estradiol/norethindrone/ferrous fumarate (Larin Fe)
• monophasic oral contraceptive
• quadraphasic oral contraceptive
• triphasic oral contraceptive

Patient information

oral contraceptive patient information