Contraception

Introduction

Contraception is the prevention of pregnancy by inhibiting sperm from reaching a mature ovum or by preventing a fertilized ovum from implanting in the endometrium.

The Menstrual Cycle

• The median length of the menstrual cycle is 28 days (range 21–40 days).
• The first day of menses is day 1. Ovulation usually occurs on day 14. After ovulation, the luteal phase lasts until the beginning of the next cycle.
• The hypothalamus secretes gonadotropin-releasing hormone,which stimulates the anterior pituitary to secrete gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH).
• In the follicular phase, FSH levels increase and cause recruitment of a small group of follicles for continued growth. Between days 5 and 7, one of these becomes the dominant follicle, which later ruptures to release the oocyte. The dominant follicle develops, increasing amounts of estradiol and inhibin, providing negative feedback on the secretion of gonadotropin-releasing hormone and FSH.
• The dominant follicle continues to grow and synthesizes estradiol, progesterone, and androgen. Estradiol stops the menstrual flow from the previous cycle, thickens the endometrial lining, and produces thin, watery cervical mucus. FSH regulates aromatase enzymes that induce conversion of androgens to estrogens in the follicle.
• The pituitary releases a midcycle LH surge that stimulates the final stages of follicular maturation and ovulation.

Ovulation occurs 24 to 36 hours after the estradiol peak and 10 to 16 hours after the LH peak.

• The LH surge is the most clinically useful predictor of approaching ovulation. Conception is most successful when intercourse takes place from 2 days before ovulation to the day of ovulation.
• After ovulation, the remaining luteinized follicles become the corpus luteum, which synthesizes androgen, estrogen, and progesterone.
• If pregnancy occurs, human chorionic gonadotropin prevents regression of the corpus luteum and stimulates continued production of estrogen and progesterone. If pregnancy does not occur, the corpus luteum degenerates, progesterone declines, and menstruation occurs.

TREATMENT

• Goal of Treatment: the prevention of pregnancy following sexual intercourse.

NONPHARMACOLOGIC THERAPY

• The abstinence (rhythm) method is associated with relatively high pregnancy rates. Barrier Techniques
• Diaphragms are effective because they are barriers and because of the spermicide placed in the diaphragm before insertion. It should be inserted up to 6 hours before intercourse and must be left in place for at least 6 hours after. It should not be left in place for more than 24 hours because of the risk of toxic shock syndrome (TSS).
• The cervical cap can be inserted 6 hours prior to intercourse, and should not remain in place for longer than 48 hours to reduce the risk of TSS. A condom should also be used to protect against sexually transmitted diseases (STDs) including human immunodeficiency virus (HIV).
• Most condoms made in the United States are latex, which is impermeable to viruses, but ~5% are made from lamb intestine, which is not impermeable to viruses. Mineral oil–based vaginal drug formulations (e.g., Cleocin vaginal cream, Premarin vaginal cream, Vagistat 1, Femstat, and Monistat vaginal suppositories) can decrease the barrier strength of latex. Condoms with spermicides are not recommended, as they provide no additional protection against pregnancy or STDs and may increase vulnerability to HIV.
• The female condom (Reality) covers the labia, as well as the cervix. However, the pregnancy rate is higher than with male condoms.

PHARMACOLOGIC THERAPY

Spermicides and Spermicide Implanted Barrier Techniques

• Most spermicides contain nonoxynol-9, surfactants that destroy sperm cell walls and block entry into the cervical os. They offer no protection against STDs, and when used more than twice daily, nonoxynol-9 may increase the transmission of HIV.
• The vaginal contraceptive sponge (Today) contains nonoxynol-9 and provides protection for 24 hours. After intercourse, the sponge must be left in place for at least 6 hours before removal. It should not be left in place for more than 24 to 30 hours to reduce the risk of TSS. It is available without a prescription.

GENERAL CONSIDERATIONS FOR ORAL CONTRACEPTIVES

• With perfect use, their efficacy is more than 99%, but with typical use, up to 8% of women may experience unintended pregnancy.
• Monophasic OCs contain a constant amount of estrogen and progestin for 21 days, followed by 7 days of placebo. Biphasic and triphasic pills contain variable amounts of estrogen and progestin for 21 days and are followed by a 7-day placebo phase.
• Extended-cycle pills and continuous combination regimens may offer some side effect and convenience benefits. One particular extended-cycle OC increases the number of hormone-containing pills from 21 to 84 days, followed by a 7-day placebo phase, resulting in four menstrual cycles per year. Another product provides hormone-containing pills daily throughout the year. Continuous combination regimens provide OCs for 21 days, then very-low-dose estrogen and progestin for an additional 4 to 7 days.
• Third-generation OCs contain newer progestins (eg, desogestrel, drospirenone, gestodene, and norgestimate). These potent progestins have no estrogenic effects and are less androgenic than levonorgestrel, and thus are thought to have fewer side effects (eg, less likelihood or severity of acne). Drospirenone may also cause less weight gain compared with levonorgestrel.
• The progestin-only “minipills” tend to be less effective than combination OCs, and they are associated with irregular and unpredictable menstrual bleeding. They must be taken every day of the menstrual cycle at approximately the same time of day to maintain contraceptive efficacy. They are associated with more ectopic pregnancies than other hormonal contraceptives
• In the “quick start” method for initiating OCs, the woman takes the first pill on the day of her office visit (after a negative urine pregnancy test). In the first-day start method, women take the first pill on the first day of the next menstrual cycle. The Sunday start method was used for many years, whereby the first pill was taken on the first Sunday after starting the menstrual cycle

CHOICE OF AN ORAL CONTRACEPTIVE

• In women without coexisting medical conditions, an OC containing 35 mcg or less of EE and less than 0.5 mg of norethindrone is recommended.
• Adolescents, underweight women

DRUG INTERACTIONS

• Tell women to use an alternative method of contraception if there is a possibility of a drug interaction compromising OC efficacy.
• Rifampin reduces the efficacy of OCs. Advise women to use an additional nonhormonal contraceptive agent during the course of rifampin therapy.
• Tell women about the small risk of interaction with other antibiotics, and that additional nonhormonal contraceptives can be considered if desired. If there is breakthrough bleeding in women taking concomitant antibiotics and OCs, an alternate method of contraception should be used during the time of concomitant use.
• Phenobarbital, carbamazepine, and phenytoin potentially reduce the efficacy of OCs, and many anticonvulsants are known teratogens. Intrauterine devices (IUDs), injectable medroxyprogesterone, or nonhormonal options may be considered for women taking these drugs.

EMERGENCY CONTRACEPTION (EC)

• Oral EC will not disrupt the fertilized egg after implantation has occurred.
• A progestin-only formulation containing levonorgestrel (available in Plan B OneStep and Next Choice) is approved for EC in the United States.
• Plan B One-Step is one tablet containing 1.5 mg levonorgestrel which is taken within 72 hours of unprotected intercourse. It is available for women and girls of all ages in the United States without a prescription. Next Choice is two tablets, each containing 0.75 mg levonorgestrel. The first tablet is taken within 72 hours of unprotected intercourse (the sooner, the more effective); the second dose is taken 12 hours later.
• Evidence suggests that the levonorgestrel containing products can be moderately effective up to 120 hours after unprotected intercourse.
• Ulpristal is a selective progesterone receptor modulator available by prescription as a single dose of 30 mg taken within 120 hours of unprotected intercourse. It is considered noninferior to levonorgestrel containing ECs.
• Use of higher doses of CHCs can be used for EC, but they may not be as effective, and they may cause more side effects.
• Nausea and vomiting occur significantly less often with progestin-only and progesterone receptor modulator EC.
• Backup barrier methods should be used after EC for at least 7 days.