Five-year, multicenter study of a triphasic, low-dose, combination oral contraceptive.

A total of 4,342 women received a triphasic oral contraceptive combination containing levonorgestrel and ethinyl estradiol (Triphasil in the United States, Trinordiol in Europe) over a 5-year period, for a total of 70,282 cycles. Medication was begun on day 1 in the first cycle, with no backup contraception, and consisted of levonorgestrel (LNg) 50 micrograms + ethinyl estradiol (EE2) 30 micrograms for 6 days, LNg 75 micrograms + EE2 40 micrograms for 5 days, and LNg 125 micrograms + EE2 30 micrograms for 10 days. Twelve pregnancies occurred during the study, resulting in a Pearl Index of 0.22. Medication was missed in an overall total of 5,067 cycles (7.2%), and 9 of the 12 pregnancies were attributed by the investigators to misuse of the drug, resulting in a corrected Pearl Index of 0.06. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of adverse experiences was low (generally less than 1% of total cycles). The results indicate that this triphasic combination, given in pharmacologic doses that are patterned after normal cycles, is a predictable, efficacious, well-tolerated, and accepted means of oral contraception.

A low-dose triphasic oral contraceptive.

Controlled clinical investigations of a three-phase, low-dose oral contraceptive combination of levonorgestrel and ethinyl estradiol were conducted at 17 sites in the United States and 60 sites in the United Kingdom. A day 1 start in cycle one with no backup contraception was used. A total of 3546 female volunteers participated in 35,036 cycles. Medication was missed in 2688 (7.7%) cycles. Nine pregnancies were reported for an uncorrected use-effectiveness rate of 0.33 per 100 woman-years. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of side effects was very low. No clinically significant variations in blood pressure means or weight means were observed. Carbohydrate and lipid metabolism studies were limited to 6 months and showed minimal alterations. Subject compliance with the preparation was excellent. It is concluded that this triphasic oral contraceptive with its varying ratios of levonorgestrel and ethinyl estradiol is an effective, predictable, and well-tolerated combination oral contraceptive.

Eight years of fertility control with norgestrel-ethinyl estradiol (Ovral): an updated clinical review.

Data on a combination norgestrel-ethinyl estradiol oral contraceptive (Ovral) were obtained from eight large family planning clinics. The safety and efficacy of the drug were evaluated for 6,806 mature, sexually active women who received a total of 127,872 cycles of the medication; this represents 9,836 woman-years of usage. No pregnancy attributable to medication failure occurred, but 19 women who omitted two or more consecutive tablets became pregnant. This produced an overall use-effectiveness pregnancy rate of 0.19/100 woman-years. Cycle control was excellent, and intermenstrual bleeding was rare. Adverse effects were minimal; laboratory values seldom deviated from pretreatment levels. Fertility returned promptly upon withdrawal of the contraceptive, and no infant abnormalities were attributed to its use.

PIP: A clinical review of the oral contraceptive Ovral (.5 mg norgestrel, .05 mg ethinyl estradiol), representing 6806 users over 9836 woman-years of use, is presented. 19 pregnancies occurred (.19 per 100 woman-years), though none were attributable to failure of the drug. Menstrual periods were regular and predictable in at least 80% of the patients. The incidence of intermenstrual bleeding was low (2.5% of the cycles). 306 patients (4.5%) discontinued medication for medical reason s, the most prevalent of which were headache, nausea and vomiting, weight gain, and nervousness. Breast masses developed in 19 women, carcinoma in situ of the cervix in 16 patients, and thrombophlebitis in 9 women. Hepatic and thyroid functions were slightly altered, though there was no evidence of abnormal adrenal function or neuro-ophthalmologic effects related to the medication. Fertility promp tly returned after cessation of treatment in most cases, and no infant a bnormalities were attributable to the drug. The contraceptive effect of Ovral is suggested to be due primarily to gonadotropin suppression with subsequent inhibition of ovulation.