Combined Hormonal Contraceptives Key Points

• When used correctly and consistently, CHCs are very effective in preventing pregnancy.

• CHCs offer many noncontraceptive health benefits, such as increased cycle regularity, decreased risk of endometrial and ovarian cancers, and decreased PMS/PMDD.

• CHCs have not been shown to cause significant weight gain.

• The contraceptive patch and vaginal contraceptive ring can increase perfect-use compliance by decreasing dosing frequency.

• Ethinyl estradiol levels are higher in women using the contraceptive patch than in those using OCs or the ring, but there is no evidence of increased risk of venous thromboembolism.

• The patch may have decreased efficacy in women weighing more than 90 kg.

Mechanism of Action

Combined (or combination) hormonal contraceptives (CHCs) contain both an estrogen (ethinyl estradiol) and one of many progestins, which act in concert to suppress ovulation. This is achieved through negative feedback on the hypothalamic-pituitary system, leading to decreased gonad-otropin-releasing hormone (GnRH) pulsatility, decreased pituitary responsiveness to GnRH stimulation, suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production, and inhibition of the midcycle LH surge (Nelson et al., 2007). In addition, the progestin component causes thickening of the cervical mucus, which can inhibit sperm access to the upper genital tract.

Oral Contraceptives

Combined oral contraceptives (COCs, OCs), often referred to as "the pill," are the most common form of reversible contraception used in the United States (Chandra et al., 2005). Many formulations exist, with varying amounts of ethinyl estradiol and differing progestins. Newer formulations with 4-day pillfree intervals (vs. traditional 7 days), can offer increased relief from hormonal side effects (Sulak et al., 2000) and increased suppression of ovarian activity (Spona et al., 1996).

Advantages

The CHCs are very effective in preventing pregnancy when used correctly and consistently. OCs help to regulate menses, decrease menstrual flow and dysmenorrhea, and eliminate mittelschmerz. Certain formulations can be used to treat premenstrual dysphoric disorder (PMDD) (Lopez et al., 2009). Rapid return to fertility follows discontinuation of OCs. No

Box 26-1 Contraindications to Estrogen Use

• Smoker (>15 cigarettes/day) >35 years old

• Active liver disease

• History of breast cancer

• Breast feeding (<6 weeks postpartum)

• Migraine with aura

• Uncontrolled hypertension

• History of clotting disorder

• Known thrombogenic mutations

• SLE with positive or unknown antiphospholipid antibodies

• Diabetes with vascular disease/retinopathy/neuropathy/nephropathy

• Major surgery with prolonged immobilization

• Multiple risk factors for CV disease/stroke

• DVT/PE (history of, acute, or established on anticoagulant therapy)

• Complicated valvular heart disease

• History of COC-related cholestasis or current gallbladder disease evidence exists for significant weight gain in women taking CHCs. OCs may help reduce acne and may be used as emergency contraception with alternate dosing. Use of CHCs decreases benign breast disease, risk of ovarian and endo-metrial cancers, and risk of death from colorectal cancer (Zieman et al., 2007).

Disadvantages

Women must remember every day to follow the regimen for OCs to be effective. CHCs may cause spotting, breast tenderness, nausea, or headaches, especially in the first few months of use, as well as decreased libido. OCs offer no protection against STIs and cannot be used by women with contraindications to estrogen use (Box 26-1).

Contraceptive Patch

The contraceptive patch (OrthoEvra) is a 4.5-cm2 adhesive patch placed on the upper arm, abdomen, back, or buttocks that provides 20 ^.g of ethinyl estradiol and 150 ^.g of norelgestromin daily. The patch is changed every 7 days for 3 weeks, with a patch-free week during which a woman is expected to menstruate. Steady-state hormone levels are achieved after 3 days, and there is enough hormone for up to 10 days' use (Abrams et al., 2002).

Advantages

Weekly dosing may offer increased compliance with correct use compared with COC use (Lopez et al., 2008). Sustained therapeutic hormone levels past the recommended 7 days for each patch give women leeway if they forget to change the patch on time. Other advantages are similar to those for COCs, although data on cancer and other noncontraceptive health benefits are not yet available.

Disadvantages

Overall, the contraceptive patch is similar to COCs, although the rate of side effects may be higher (Lopez et al., 2008). Localized skin reactions may occur. Decreased efficacy is noted in women weighing more than 90 kg (198 lb) (Nanda, 2007). Ethinyl estradiol concentrations are higher in women using the contraceptive patch than in those using either COCs or the vaginal ring (van den Heuvel et al., 2005), raising concern for an increased risk of venous thromboembolism (VTE) or other cardiovascular events. However, the risk of nonfatal VTE for the contraceptive patch is actually similar to that for COCs with 35 ^g of ethinyl estradiol (odds ratio 0.9; 95% CI 0.5-1.6) (Jick et al., 2006; Level A). Also, the risk of VTE with pregnancy remains much higher than with CHC use.

Vaginal Contraceptive Ring

NuvaRing is a flexible, colorless ring 4 mm thick and 5.4 cm in diameter. It is placed into the vagina and provides 15 ^.g of ethinyl estradiol and 120 ^.g of etonorgestrel daily. Each ring is left in place for 3 weeks, followed by a ring-free week during which a woman is expected to menstruate. Ovulation suppression begins within 3 days of use and continues for up to 35 days while the ring is in place (Nanda, 2007).

Advantages

Monthly dosing with the vaginal ring may increase compliance with correct use compared with COCs (Nanda, 2007). Sustained therapeutic hormone levels past the 21-day recommendation for each ring give women leeway if they forget to change the ring on time. The ring may be removed for up to 3 hours for intercourse, although this is not recommended because most women and their partners are not bothered by its presence. Other advantages are similar to those for COCs, although again, data on cancer and other noncontraceptive health benefits are not yet available.

Disadvantages

Overall, drawbacks to vaginal ring use are similar to COC use. Although rates of breast discomfort, nausea, and vomiting may be decreased, rates of vaginitis and leukorrhea may increase compared with COCs (Lopez et al., 2008).

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