Norethindrone, in small doses (minipills), is used for the prevention of conception in women who elect to use oral contraceptives as a method of contraception. Progestin-only oral contraceptives are generally reserved for women who do not tolerate estrogens or in whom estrogens are contraindicated, since progestin-only oral contraceptives are less effective than estrogen-progestin combinations and require a high level of patient compliance. When taken according to the prescribed regimen, progestin-only oral contraceptives provide almost completely effective contraception. The efficacy of oral contraceptives mainly depends on compliance with the prescribed regimen. Progestin-only oral contraceptives must be taken daily, without interruption, to be effective.
Progestin-only oral contraceptives are reported to be somewhat less effective than estrogen-progestin combinations. The pregnancy rate in women using progestin-only oral contraceptives is generally reported to be about 3 pregnancies per 100 woman-years of use. For information on the pregnancy rates reported with other methods of contraception, including estrogen-progestin combinations, . Pregnancy rates are derived from various studies conducted by different investigators in different population groups and, therefore, cannot be compared precisely.
In women receiving norethindrone, the pregnancy rate, especially during the first 6 months of use, is reportedly greater in women who had not previously received oral contraceptives than in those who had been immediately switched from an estrogen-progestin combination. The reported difference in pregnancy rates probably resulted from failure to comply with the prescribed regimen. Therefore, it is especially important that women who are prescribed progestin-only oral contraceptives as initial oral contraception be advised to strictly adhere to the prescribed regimen.
For the use of norethindrone or norethindrone acetate in combination with estrogens as an oral contraceptive, . For the use of the drugs in the treatment of secondary amenorrhea, endometriosis, or abnormal uterine bleeding,
Levonorgestrel-releasing intrauterine system is used for prevention of conception in women who elect to use this method of contraception. The manufacturer states that the system is recommended for use in women who have had one or more children; are in a stable, mutually monogamous relationship; have no history of pelvic inflammatory disease (PID); and have no history of ectopic pregnancy or any condition that would predispose to ectopic pregnancy. Each system may be used for up to 5 years; thereafter, the system should be removed and may be replaced with a new system if continued contraception is desired. The pregnancy rate in women using the levonorgestrel-releasing intrauterine system is reported as up to 0.2 pregnancies per 100 women during the first year of use; the cumulative 5-year pregnancy rate is reported to be approximately 0.7 pregnancies per 100 women.
Etonogestrel for subcutaneous implantation (Implanon) is used for prevention of conception in women who elect to use this method of contraception. The system consists of a single rod containing etonogestrel that is implanted subcutaneously in the upper arm to provide contraception for up to 3 years.
Postcoital (Emergency) Contraception
Levonorgestrel is used as an emergency contraceptive (EC) to prevent pregnancy following unprotected intercourse or known or suspected contraceptive failure. To achieve optimal efficacy, the postcoital contraceptive regimen should be initiated as soon as possible within 72 hours of unprotected intercourse. Studies show that emergency contraception is moderately effective when the regimen is administered up to 120 hours after unprotected intercourse. Postcoital contraceptive efficacy diminishes as the time period between intercourse and initiation of contraception increases.
An emergency contraceptive regimen employing a progestin alone (levonorgestrel) appears to be more effective and better tolerated than a common estrogen-progestin emergency contraceptive (''Yuzpe'') regimen when the regimens are initiated within 72 hours of unprotected intercourse; therefore, the progestin-only regimen generally is preferred when readily available. In a double-blind, randomized multicenter study in women who reported unprotected intercourse within 72 hours of receiving emergency contraception, a single-dose of levonorgestrel 1.5 mg was as effective in preventing pregnancy as levonorgestrel 0.75 mg every 12 hours for 2 doses. In a double-blind, randomized, multicenter study in women who reported only one act of unprotected intercourse within 72 hours of receiving emergency contraception, the expected pregnancy (failure) rate of 8% (with no contraception) was reduced to approximately 1% with a progestin-only regimen (levonorgestrel 0.75 mg every 12 hours for 2 doses). In another prospective, randomized study in women who reported a single act of intercourse within 48 hours of receiving emergency contraception, failure rates with the 2-dose levonorgestrel regimen and Yuzpe regimens (levonorgestrel 0.5 mg and 0.1 mg ethinyl estradiol every 12 hours for 2 doses) were similar (2.6 versus 2.4%, respectively). The efficacy of treatment in both studies was greatest when the contraceptive was given during the first 24 hours after unprotected intercourse; efficacy declined during subsequent 24-hour periods. The 2-dose levonorgestrel regimen was better tolerated than the Yuzpe regimen. In these 2 studies, nausea occurred in 23.1 versus 50.5% and in 16.1 versus 46.5% of women receiving the 2-dose levonorgestrel regimen versus the Yuzpe regimen, respectively, while vomiting occurred in 5.6 versus 18.8% and in 2.7 versus 22.4% of women with the 2-dose levonorgestrel regimen or Yuzpe regimen, respectively.
Since unprotected intercourse that occurs outside the fertile period is unlikely to result in conception, not all women given emergency postcoital contraception are at genuine risk for pregnancy. Therefore, a more accurate indication of the efficacy of postcoital contraceptive regimens would be based on the timing of unprotected intercourse and the probability that pregnancy would occur without treatment. Analysis of data from the multicenter, progestin-only (levonorgestrel) study involving approximately 2000 women suggest that when efficacy of postcoital contraception is based on the observed versus expected number of pregnancies, the levonorgestrel-only regimen would prevent 85% of pregnancies; pooled analysis of observed-versus-expected pregnancy data from other studies employing the Yuzpe regimen suggest that such therapy is approximately 74% effective in preventing pregnancy. However, postcoital (emergency) contraceptive regimens are not as effective as most other forms of long-term contraception.
Since postcoital contraceptive efficacy diminishes as the time period between intercourse and administration of the regimen increases, available data suggest that as with combination estrogen-progestin regimens, progestin-only postcoital contraception should ideally begin within 72 hours of unprotected intercourse. Emergency contraception is moderately effective when the regimen is administered up to 120 hours after unprotected intercourse. The effectiveness of postcoital contraception administered after more than 120 hours has not been established.
The American College of Obstetricians and Gynecologists (ACOG), other experts, and some states (e.g., Alaska, California, Hawaii, Maine, New Mexico, Washington) have advocated increased access to emergency postcoital contraception (e.g., nonprescription access via pharmacies, advance provision by clinicians) as a means of decreasing unintended pregnancy and abortion rates. There is some evidence that increased access to emergency postcoital contraception may not compromise conventional contraceptive use or sexual behavior, potentially allaying some concerns that have prompted others to advocate for restricted access. The FDA has approved the single-dose levonorgestrel regimen (Plan B One-Step) for nonprescription (over-the-counter [OTC]) status for women of childbearing potential regardless of age. Another FDA-approved product (Next Choice One Dose) is commercially available as a single-dose levonorgestrel regimen for OTC status in women 17 years of age or older or as a prescription-only preparation in women younger than 17 years of age. A 2-dose levonorgestrel preparation is also commercially available as a prescription-only preparation for women younger than 17 years of age.
For information on the use of combination estrogen-progestin contraceptives for postcoital contraception, .