Progestins are classified according to their structure in C19 and C21 progestagens. The C19 ones are derived from testosterone, the C21 ones from progesterone. C21 progestagens include cyproterone acetate, dydrogesterone, medroxyprogesterone acetate, chlormadinone acetate, megestrol and promegestone. Of these, dydrogesterone is structurally most similar to progesterone. C19 progestagens include norethisterone, (levo)norgestrel, lynestrenol, desogestrel, norgestimate, gestodene and tibolone.

Different progestins have different combinations of androgen (testosterone-like) and progesterone activity. If the activity of 1 mg of norethindrone is taken as the baseline, 1 mg of the other progestins have activities as follows:

Norethindrone was synthetized for the first time in 1951 by the Mexican chemist Luis E. Miramontes. This substance became the basis for the contraceptive pill.

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Plan-B Contraception Decreases Risk of Pregnancy - levonorgestrel emergency contraceptive
From American Family Physician, 6/1/00 by Barbara Apgar

A contraceptive "pill pack" that contains two 0.75-mg tablets of levonorgestrel has been labeled by the U.S. Food and Drug Administration (FDA) for emergency contraception use. It is marketed under the brand name Plan B and is the second product to be labeled by the FDA for this indication. The Preven Emergency Contraceptive Kit contains four tablets of 50 mg of ethinyl estradiol and 0.25 mg of levonorgestrel, and a pregnancy test. The Medical Letter on Drugs and Therapeutics reviewed the safety and efficacy of Plan B.

It is unclear exactly how high doses of estrogen and progestins prevent pregnancy after sexual intercourse. It is postulated that these hormones inhibit or delay ovulation. Some studies have shown endometrial changes, suggesting that these changes could also interfere with implantation of a fertilized egg, while other studies have shown no such effects. Other possible mechanisms include interference with fertilization or with tubal transport of the embryo. The probability of pregnancy after unprotected intercourse more than two days after ovulation approaches zero.

A randomized controlled trial compared levonorgestrel in a dosage of 0.75 mg alone with a combination of ethinyl estradiol in a dosage of 100 mg and levonorgestrel in a dosage of 0.5 mg. Both were taken twice, 12 hours apart, within 72 hours after intercourse. Pregnancy occurred in 11 of 976 women (1.1 percent) taking levonorgestrel alone and in 31 of 979 women (3.2 percent) taking ethinyl estradiol and levonorgestrel. The sooner the drug is taken after intercourse, the more effective the treatment. Delaying the first dosage by 12 hours increases the risk of pregnancy by almost 50 percent.

Nausea and vomiting occur more frequently with the estrogen-progestin combination than with levonorgestrel alone. Mastalgia can occur with either regimen. No fetal malformation caused by unsuccessful use of high-dose oral contraceptives for emergency contraception has been reported.

One 0.75-mg levonorgestrel tablet should be taken as soon as possible after intercourse but at least within 72 hours, and the other tablet 12 hours later. If vomiting occurs within one hour of taking either dose, it should be repeated. That would require purchase of another package. One Plan B pill pack costs about $21 compared with $20 for the Preven kit.

The consultants conclude that Plan B emergency contraception, if taken as soon as possible after unprotected intercourse, can decrease the risk of pregnancy. It appears to be more effective and better tolerated than the estrogen-progestin combinations.

BARBARA APGAR, M.D., M.S.

Medical Letter Consultants. Plan B: a progestin-only emergency contraceptive. Med Lett Drugs Ther January 24, 2000;42(1070):10.

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