Emergency contraceptives play a major role in preventing unwanted pregnancy. The use of emergency contraceptives is characterized by myths and lack of knowledge by both health professionals and users. The main objective of this paper is to summarize the clinical pharmacology of hormonal methods of emergency contraception. A literature review was done to describe in detail the mechanism of action, efficacy, pharmacokinetics, safety profile, and drug interactions of hormonal emergency contraceptive pills. This information is useful to healthcare professionals and users to fully understand how hormonal emergency contraceptive methods work.
Unintended pregnancies are widespread and may be due to different reasons. In the year 2012, there were 213 million pregnancies globally and, of these, 85 million (almost 40%) were unintended. Of the unintended pregnancies, 50% ended in abortion, 38% resulted in unplanned births and 13% led to miscarriages [
Several circumstances may warrant the use of emergency contraception. ECs can be used in the following situations: after having unprotected sexual intercourse, when a woman has incorrectly used regular contraceptives, in the event of sexual assault, or even in situations where a condom has burst, slipped, or been used incorrectly [
A thorough literature review was conducted to describe in detail the mechanism of action, efficacy, pharmacokinetics, safety profile, and drug interactions of hormonal emergency contraceptive pills. Literature review was conducted through searching PubMed, Medline, and Google Scholar. Google webpage was used as the search engine for information outside published articles. The following words were used for literature search in Google webpage: “emergency contraception”, “emergency contraception clinical pharmacology”, “levonorgestrel package insert”, and “ulipristal package insert”. From the search results, relevant websites were viewed to compile the paper. From the health databases, the following words were used as search hits: “emergency contraception”, “levonorgestrel emergency contraception”, “emergency contraception pills”, “ulipristal contraception”, “safety emergency contraception”, and “post coital contraception.” The most relevant and where applicable current articles were selected for discussion. The literature search was conducted between January 2018 and July 2018.
Emergency contraception pills (ECP) include levonorgestrel (LNG) and ulipristal acetate. Levonorgestrel is a synthetic progestin taken orally as a single dose of 1.5 mg strength. Alternatively, LNG can be taken in two doses of 0.75 mg each separated by 12 hours [
The Yuzpe method uses estrogen combined with levonorgestrel. The pills are taken in two divided doses. Each dose must contain estrogen (usually 100–120 mcg ethinylestradiol) and progestin (either 0.50–0.60 mg levonorgestrel or 1.0–1.2 mg norgestrel) [
In emergency contraception, studies have shown that levonorgestrel works by preventing or delaying ovulation and impairing luteal function [
Ulipristal acetate is thought to inhibit or delay ovulation. A clinical trial showed that it could delay ovulation for 24–48 hours even on the day of the luteinizing hormone (LH) peak. When ulipristal was given before or immediately after the LH surge, it inhibited 100% of the follicular ruptures [
Combined ECP work by inhibiting implantation of a fertilized egg [
Hormonal emergency contraception has been shown to be effective when used up to 72 hours after unprotected intercourse. However, the earlier the treatment begins, the more effective it is [
The Yuzpe regimen of emergency contraception is reported to be 97% to 98% effective in preventing pregnancy [
Levonorgestrel does not undergo “first–pass” metabolism and has 100% bioavailability [
Levonorgestrel is highly protein bound (97.5 to 99%), mainly to the sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin. Any displacement of LNG to the bound protein could potentially cause side effects, hence the need to monitor concurrent medications. Approximately 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates [
Ulipristal is rapidly absorbed after a single 30 mg dose is administered orally. Peak plasma concentration of 176 ± 89 ng/ ml occurs approximately 0.5–3hours after oral ingestion [
The side effects of hormonal emergency contraceptives are uncommon and mild and generally similar to those experienced by women using regular oral contraceptive pills. The levonorgestrel regimen is significantly better tolerated than the Yuzpe combined regimen. The double-blinded randomized trial by WHO showed that only 23.1% of women who used progestin alone experienced nausea compared with 50% of women in the Yuzpe regimen. In addition, only 5.6% of women in the progestin group reported vomiting compared with 18.8%. In both groups menstrual patterns were similar [
Ulipristal is also well tolerated and the adverse effects are mild and generally self-limiting. The side effect profile for ulipristal is similar to that of levonorgestrel emergency contraception. Data from clinical trials reported the following symptoms as more frequent: nausea, headache, abdominal pain, dizziness, back pain, and dysmenorrhea [
Other uncommon side effects associated with both the progestin and the Yuzpe regimens include headache, bloating, and uterine cramps [
Some authors have supported the view that emergency contraception is a form of abortion arguing that preovulatory administration of levonorgestrel as an emergency contraceptive has significant potential to work via abortion [
When ulipristal is administered to a pregnant woman, the risks to the fetus are unknown. When it was repeatedly administered to pregnant rats, embryo fetal loss was noted in all pregnant rats after 12 days of dosing. Repeated administration for 13 days in pregnant rabbits resulted in embryo fetal loss in 50% of the rabbits. When it was administered daily to pregnant monkeys for 4 days within the first trimester, ulipristal caused pregnancy termination in two of the five animals. There were no malformations of the surviving fetuses in these studies [
Drugs, foods, or herbs that induce the cytochrome P450 (CYP450) enzymes, including CYP3A4, that metabolize progestins, and estrogens, may decrease their plasma concentrations. This may decrease the effectiveness of progestins and estrogens. Examples may include St. John’s Wort, carbamazepine, rifampicin, phenytoin, and griseofulvin [
Since ulipristal is an antiprogestin; there are implications on starting progestin-containing hormonal contraceptives immediately after taking it. Two randomized studies found that using ulipristal and progestin containing hormonal contraceptives resulted in no significant differences in time to ovarian quiescence or cervical mucus penetrability. Both studies showed that using a progestin, containing oral contraceptive immediately after ulipristal, reduces the efficacy of ulipristal. This impairs the ability of ulipristal to delay ovulation [
Emergency contraceptives, commonly known as the “morning–after” pill, are effective in preventing unplanned pregnancy. The term “morning–after” is misleading; emergency contraceptives should be initiated sooner than the morning after, that is, immediately after unprotected intercourse. For both the levonorgestrel containing and combined emergency contraceptive pills, efficacy decreases after 72 hours; thus the sooner they are taken the better the chances of preventing unplanned pregnancy. Ulipristal, on the other hand, has no decreased efficacy and works for up to 120 hours. The progestin containing regimens are more effective and better tolerated than the estrogen—containing regimens. Emergency contraceptives should not be used as a regular form of contraception and do not protect against sexually transmitted infections, including HIV/AIDS.
The authors declare that they have no conflicts of interest.