Lecture 26: Contraceptives Flashcards
COMBINED ORAL CONTRACEPTIVES
- Contain a combination of an estrogen and a progestin.
- The estrogen is either ethinyl estradiol or mestranol
- Mestranol is a prodrug that is converted to ethinyl estradiol.
Progestins drugs
- Norethindrone
- Norgestrel
- Levonorgestrel
- Desogestrel
- Norgestimate
- Drospirenone
Androgenic activity of combined oral contraceptives
- Levonorgestrel and norgestrel: highest.
- Norethindrone: lower.
- Third-generation progestins, such as desogestrel and norgestimate: even lower.
- Drospirenone: antiandrogenic.
TYPES OF COMBINED ORAL CONTRACEPTIVES
- The combined oral contraceptives most commonly used today are called “low-dose”.
- They contain 35 μg of ethinyl estradiol or less.
- The low hormone content has decreased adverse effects and risks.
- But they are more likely to result in contraceptive failure if doses are missed.
- Most of the formulations available have 21 hormonally active pills followed by 7 placebo pills to allow for withdrawal bleeding (facilitates consistent daily pill intake.)
- Extended-cycle formulations increase the number of hormone-containing pills to 84 days, followed by a 7-day placebo phase -> results in four menstrual cycles per year.
- Continuous combination regimens provide hormone-containing pills for 21 days, then very- low-dose estrogen and progestin for an additional 4-7 days.
OCP: MOA
- prevents ovulation.
- They suppress LH and FSH release and
- ovulation does not occur.
- Additionally, the progestin thickens cervical mucus thus preventing sperm penetration, and induces changes in the endometrium that impair implantation.
BENEFITS OF COMBINED ORAL CONTRACEPTIVES
- Reduction in the risk of endometrial cancer
- Reduction in the risk of ovarian cancer
- Improved regulation of menstruation
- Relief of benign breast disease
- Prevention of ovarian cysts
- Reduction in the risk of symptomatic pelvic inflammatory disease
- Improvement in acne control
OCP: Adverse
- Concerns about cardiovascular toxicity initially limited the long-term use of these drugs.
- The decrease in estrogen and progestin content has led to a reduction in adverse effects.
- Many adverse effects (eg nausea, bloating, breakthrough bleeding) improve spontaneously by the third cycle.
- Therefore, patient education and early reevaluation are necessary to identify and manage adverse effects in an effort to improve compliance.
- Many adverse effects can be avoided by adjusting the estrogen and/or progestin content of the oral contraceptive.
- Breakthrough bleeding
- Most common adverse effect of oral contraceptives.
- It is more of a problem with lower doses of estrogen because estrogen stabilizes the endometrium.
Headache: Usually mild and transient.
- However, migraine may be associated with cerebrovascular accidents.
- Women who develop migraines should stop taking the contraceptive.
Insulin Resistance
- Progestins may cause insulin resistance by competing with insulin for its receptor.
- Current oral contraceptives have a low progestin content and rarely cause hyperglycemia.
Hirsutism
- Acne, oily skin and hirsutism are adverse effects of androgenic progestins.
- The patient should be switched to a product with less androgenicity.
Melasma: Due to estrogen stimulation of melanocyte production.
Amenorrhea
Dyslipidemia: Most low-dose oral contraceptives have no impact on HDL, LDL, triglycerides or total cholesterol.
Cardiovascular disorders: includes thromboembolism, thrombophlebitis, hypertension, MI, cerebral and coronary thrombosis; most common among women who smoke and who are older than 35 years.
- Estrogens increase production of factor VII, factor X and fibrinogen, therefore increasing the risk of thromboembolic events.
- The risk is increased by obesity, smoking, hypertension and diabetes.
Depression
OCP Interactions
LIVER ENZYME INDUCTION
- Rifampin induces hepatic P450 enzymes and
- increases metabolism of estrogen.
- Use of a backup nonhormonal contraceptive method during the course of rifampin therapy is recommended.
- Carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate, vigabatrin and St John’s Wort are P450 inducers.
- They are known to increase metabolism of oral contraceptives.
ANTIBACTERIALS
- Ethinyl estradiol is conjugated in the liver, excreted in the bile, hydrolyzed by intestinal bacteria, and reabsorbed as active drug.
- Certain broad-spectrum antibiotics, by reducing the population of intestinal bacteria, may interrupt the enterohepatic circulation of the estrogen.
- This may decrease estrogen levels.
- Various antibiotics have been reported to decrease contraceptive efficacy.
- However, the only antibiotic for which there is evidence that it substantially lowers steroid levels is rifampin.
- Women using combined oral contraceptives should be informed about the small risk of interactions with antibiotics.
Absolute contradindications
Pregnancy
• Thrombophlebitis or thromboembolic disorders
• Stroke or coronary artery disease
• Cancer of the breast
• Undiagnosed abnormal vaginal bleeding
• Estrogen-dependent cancer
• Benign or malignant tumor of the liver
• Uncontrolled hypertension
• Diabetes mellitus with vascular disease
• Age over 35 and smoking >15 cigarettes daily
• Thrombophilia
• Migraine with aura
• Active hepatitis
• Surgery or orthopedic injury with prolonged immobilization
CONTRAINDICATIONS: RELATIVE
Migraine without aura
• Hypertension
• Heart or kidney disease
• Diabetes mellitus
• Gallbladder disease
• Cholestasis during pregnancy
• Sickle cell disease (S/S or S/C type) • Lactation
PROGESTIN-ONLY PILLS
- Not widely used in the US.
- Contain norethindrone or norgestrel.
- Slightly less effective than combined oral contraceptives.
- No risk of thromboembolic events.
- Other benefits: decreased dysmenorrhea, decreased menstrual blood loss and decreased premenstrual syndrome symptoms.
- Unscheduled bleeding and spotting are common.
NON-ORAL HORMONAL CONTRACEPTIVES
- THE PATCH: Transdermal patch that contains both ethinyl estradiol and a progestin.
- THE RING:
Transvaginal delivery system that delivers ethinyl estradiol and a progestin.
- THE PROGESTIN INJECTION: Depo-Provera® Contains depot medroxyprogesterone acetate (DMPA); Given IM every 3 months; Extremely effective
- Adverse: **Causes significant loss of bone mineral density. **
- THE PROGESTIN IMPLANT
- THE INTRAUTERINE SYSTEMS
PLAN B® & NEXT CHOICE®
- Both Plan B® and Next Choice® contain twotablets of levonorgestrel.
- The first tablet is taken within 72 hours of unprotected intercourse and the second 12 hours later.
- Adverse effects include nausea and vomiting.
- Available without a prescription for consumers ≥ 17.
ELLA®
- Ella® contains ulipristal acetate.
- Ulipristal acetate is a selective progesterone receptor modulator (SPRM).
- It acts as a progesterone antagonist to inhibit or delay ovulation.
- A single tablet is taken within 5 days after intercourse.
- Adverse effects are similar to those of levonorgestrel.
- Available only by prescription.
