Hormonal contraceptives – emergency contraception

Estrogens

Various estrogens and estrogen + progestogen combinations have been used in post-coital contraception. Courses of high-dose oral diethylstilbestrol, ethinylestradiol, conjugated estrogens, or combinations of estrogen and progestogen for 4–6 days are all effective. Estrogens are postovulatory rather than post-coital contraceptives, and so it is necessary to know the exact time of unprotected intercourse in relation to a woman’s menstrual cycle [ ]. Depending on the frequency and timing of intercourse, a 5-day course of post-coital estrogen, introduced within 72 hours, reduces the pregnancy rate to 0.03–0.3%.

Diethylstilbestrol has been widely used as a post-coital contraceptive. However, it is no longer in use in many countries for this purpose, because of the possible adverse effect on the development of a surviving fetus (see separate monograph).

Ethinylestradiol has been used in the past as a post-coital contraceptive, in a daily dose of 5 mg/day for 5 days. This method has a high incidence of adverse reactions, nausea, vomiting, and breast tenderness being the most frequent [ ]; the first menstrual cycle after treatment is likely to be abnormal.

Progestogens

Clinical trials of desogestrel implants showed that they were effective, but with bleeding irregularities and ovarian cysts as the primary adverse reactions [ ].

The “morning after” method of suppressing pregnancy is usually less well tolerated than normal hormonal contraception, and variants on the dosage schedule continue to be studied in an attempt to improve tolerability without undermining the reliability of the method.

Two regimens for emergency contraception started within 72 hours of unprotected coitus have been studied: (a) the progestogen levonorgestrel in two separate doses each of 0.75 mg; (b) the Yuzpe regimen of combined oral contraceptives—ethinylestradiol 100 micrograms + levonorgestrel 0.5 mg repeated 12 hours later [ ]. The relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% CI = 0.18, 0.70). Nausea and vomiting were significantly less frequent with the levonorgestrel regimen. Adverse reactions to both regimens were nausea, vomiting, dizziness, fatigue, headache, breast tenderness, and low abdominal pain. However, all of these adverse reactions were less frequent with levonorgestrel.

Estrogen + progestogen combinations

In recent years it has become common to use a combination of estrogen and progestogen for post-coital contraception. For example, a tablet containing ethinylestradiol 100 micrograms and levonorgestrel 0.5 mg (or norgestrel 1 mg) taken twice with an interval of 12 hours has been used [ ]. This treatment must begin within 72 hours of unprotected intercourse. The approach seems to be as effective as ethinylestradiol alone, while producing somewhat less nausea and vomiting [ ]. Apart from this the adverse reactions most commonly experienced are as with estrogen alone. Overall failure rates are about 2–3%, with perhaps twice this failure rate when taken at mid-cycle. However, bearing in mind the rate of pregnancy after unprotected intercourse, the protective effect is not impressive, the chance of pregnancy being probably only halved.

It is probably impossible to define an ideal dose for this purpose. Essentially, the aim is to provide a sufficient hormonal jolt to derange nidation and the development of the zygote, and this might be attained in various ways; the most acceptable dosage schemes will be those that are best tolerated. Because oral contraceptives are generally more readily available than specially formulated products, they have sometimes been used for this purpose in deliberate overdose. Even low-dose oral contraceptives, if taken in sufficient quantities, will prove effective post-coital contraception [ ]; progestogen-only tablets are also effective in a single dose, for example levonorgestrel 0.6 mg taken within 12 hours, but irregular bleeding, nausea, and dizziness are common adverse reactions [ ].

The Prevent Emergency Contraceptive Kit (Gynetics) contains tablets for post-coital emergency contraception, packaged with a urinary pregnancy test. The application is based on a regimen that consists of two tablets containing ethinylestradiol and levonorgestrel to be taken within 72 hours of unprotected intercourse and two tablets to be taken 12 hours later. This regimen is about 75% effective in preventing pregnancy. The most common adverse reactions are nausea, vomiting, menstrual irregularities, breast tenderness, headache, abdominal pain and cramps, and dizziness [ ].

Androgens

The synthetic androgen danazol has also been evaluated for post-coital use, but with inconsistent results [ ]; doses of twice 400 mg or twice 600 mg seem to be reliable, while a single dose of 600 mg seems to be insufficient. A 10% incidence of vomiting, headache, and breast tenderness has been reported and a lower incidence (1–2%) of vomiting [ ].