Levonorgestrel and ethinyl estradiol birth control pills

LISA MCCARTHY, PharmD, AND HARVINDER BRAR, BScPharm, Leslie Dan Faculty of Phamacy, University of Toronto, Toronto, Ontario, Canada

Am Fam Physician. 2008;77(2):222-225

Author disclosure: Nothing to disclose.

Each tablet of Lybrel is composed of 90 mcg of levonorgestrel and 20 mcg of ethinyl estradiol. It is labeled for use as a continuous-cycle oral contraceptive. There is no physiologic reason for cyclic use of monophasic oral contraceptives, and research has demonstrated the safety and effectiveness of other estrogen/progestin combinations.1

SAFETY

Levonorgestrel and ethinyl estradiol are used in several other combination products that have demonstrated long-term safety. Safety of the continuous use of combined hormonal contraceptives has not been followed beyond two years. However, if there are greater safety risks associated with long-term use of extended or continuous-cycle combined hormonal contraceptives than with cyclic contraceptives, they are likely minimal.2

Cautions and contraindications of Lybrel are similar to those of other combined oral contraceptives. It is contraindicated for patients with a history of thromboembolic disorder, undiagnosed vaginal bleeding, active liver disease, or uncontrolled hypertension.3 There also is an increased risk of thrombosis; smoking increases this risk, particularly in women older than 35 years.3 In a 12-month phase 3 study, two cases of deep venous thrombosis and one case of pulmonary embolism were reported in 2,134 patients taking Lybrel.4

As with other oral contraceptives, Lybrel does not protect against sexually transmitted infections,3 and use during pregnancy is contraindicated because the product will be ineffective. Exposure to other combined oral contraceptives has not been shown to increase the risk of fetal malformations.5,6 Use during lactation is not recommended for the first six weeks postpartum; after this time, it is considered safe, but it may affect the quantity of breast milk because of the ethinyl estradiol component.7,8

On cessation of Lybrel, 38.5 percent of women experienced return to menses or pregnancy within 30 days, and 99 percent experienced this within 90 days.9

TOLERABILITY

Studies have found that extended or continuous-cycle combined hormonal oral contraceptive regimens have fewer bleeding days than cyclic regimens; however, there is no difference in the number of spotting days.1,10,11 Patients should be advised that they will likely experience unpredictable bleeding (spotting or more), which will gradually decrease with time. In the largest study to date, after 12 months of continuous use, 60 percent of patients were amenorrheic and 79 percent reported an absence of bleeding (i.e., did not require the use of feminine hygiene products) but may have still experienced spotting. Seventeen percent of patients discontinued therapy because of adverse effects, with one half attributing discontinuation to unexpected uterine bleeding.4

It can be determined from the limited published data that tolerability of Lybrel is similar to that of other combined oral contraceptives. The most common adverse effects include headache, dysmenorrhea, abdominal pain, and back pain.4 Continuous-cycle combined oral contraceptives have also been associated with decreased rates of headache, genital itch, bloating, and menstrual pain compared with cyclic regimens; however, some studies have shown no difference.1

EFFECTIVENESS

The effectiveness of Lybrel is likely similar to that of other continuous-cycle combined oral contraceptives, which are as effective as cyclic regimens in preventing pregnancy.1,10–12 Based on North American data, 2.38 per 100 typical women taking Lybrel for one year will become unintentionally pregnant, which is a rate similar to that of other combined oral contraceptives.3,13 Perfect users will have a lower rate of pregnancy (about 1.60 pregnancies per 100 women per year).4 As with all medications, it is reasonable to expect that effectiveness outside a structured clinical trial setting will be less than that observed in studies. Continuous-cycle combined oral contraception is also useful for decreasing dysmenorrhea in patients with endometriosis.14,15

PRICE

Lybrel costs approximately $54 per month. Alesse and Desogen, which are combined oral contraceptives that can be taken continuously, cost approximately $38 and $44 per month, respectively.

SIMPLICITY

Lybrel is taken at the same time each day, continuously without a seven-day break.3 Most women will continue to experience menstrual bleeding for the first several months; however, it may be less predictable than it is with other cyclic combined oral contraceptive regimens. Women should expect menstrual bleeding at any time and need to be counseled about this possibility.

Bottom Line

Lybrel appears to be as safe and effective as other combined oral contraceptives; however, at this time, there is little published data about this specific product. Other combined monophasic oral contraceptives, some of which cost less than Lybrel, can be used continuously and have been shown to produce similar results. Patients who choose to take contraceptives continuously should be advised that they may experience spotting or irregular menses at any time.