In Clinical Trial, Women Using Once-a-Month Injectable Contraceptive Avoid Pregnancy and Approve of Method
A new monthly injectable contraceptive is highly effective, safe and well accepted among women, according to two studies based on a U.S. clinical trial comparing the injectable with an oral contraceptive. A study of the efficacy and safety of the Lunelle Monthly Contraceptive Injection reports that during the first year after participants chose their method, no pregnancies occurred among women using the injectable, while oral contraceptive users had two pregnancies.1 Side effects among women in the injectable group were generally minor and were similar to those documented in other studies of women taking combined hormonal contraceptives, including weight gain, irregular or prolonged bleeding, and acne. An assessment of women's satisfaction with their method reveals that more than 80% of those using the injectable considered their experience with it somewhat or very favorable, and more than 90% said that they were likely to recommend the injectable to a friend.2
Both studies are based on data collected from 1,103 women who sought contraceptives at 42 clinical sites in the United States between April and August 1998. Women were eligible to participate in the trial if they were aged 18-49, were not pregnant, had not had an abortion within the past five days and had not given birth within the past four weeks. All of the women had used contraceptives (hormonal or nonhormonal) prior to enrollment. Women were excluded if they had contraindications to hormonal contraceptive use; were older than 35 and smoked or had chronic hypertension or diabetes; had a history of alcoholism or drug abuse; or had received another injectable contraceptive within the past six months.
The investigators offered each participant the choice of receiving either the monthly injectable (which contains 25 mg of medroxyprogesterone acetate and 5 mg of estradiol cypionate) or a commonly prescribed triphasic oral contraceptive. Participants (of whom 782 chose the injectable and 321 the pill) agreed to use their method for at least 60 weeks and to return monthly to receive their next injection or packet of pills.
Efficacy and Safety
In both the injectable and the oral contraceptive groups, the women's average age was 27-28 years; the groups also were similar with respect to weight, body mass index and previous menstrual patterns. Injectable users were less likely than women who chose the pill to be white (68% vs. 74%) and to have used a hormonal contraceptive in the past (44% vs. 65%); they were more likely ever to have been pregnant (64% vs. 45%). Fifty-five percent of women in the injectable group completed the trial, as did 68% of those in the oral contraceptive group.
One-year contraceptive efficacy was assessed on the basis of 8,008 woman-cycles of use for the injectable and 3,434 woman-cycles for the triphasic oral contraceptive. During that year, no pregnancies occurred in the injectable group, and one occurred in the oral contraceptive group. (Another pregnancy occurred during the 15th cycle in the oral contraceptive group.)
The women used monthly diary cards to report the number of days on which they experienced bleeding or spotting. Users of both methods experienced regular menstrual cycles after the first month, and reported fewer days of bleeding or spotting as the duration of use increased. For the first six months, pill users reported more frequent bleeding than women in the injectable group; throughout the year, however, injectable users had more irregular bleeding than women taking the pill.
Over the course of the study, 89% of women in the injectable group experienced some adverse effect of method use, including infection, headache, breast tenderness, weight gain, irregular or prolonged bleeding, and acne. Eighty-four percent of pill users experienced similar effects. Only 20% of injectable users and 8% of pill users dropped out of the study because of these side effects. The only serious medical problems that investigators linked to the contraceptive method being used were two instances of gallbladder disease, which required laparoscopic surgery. Both were in the injectable group, and these women continued to participate in the study after surgery.
The acceptability study was based on the women's responses to three questionnaires: one assessing their contraceptive history and attitudes toward the method they chose for the study, one addressing specific aspects of using the method they selected and one exploring their feelings about their psychological well-being. The questionnaires were administered at the beginning of the trial and 20, 40 and 60 weeks later. Approximately 85% of the women completed the initial and final questionnaires. To assess the influence of recent pill use, the investigators divided the oral contraceptive group into those who had been using the pill for at least 60 days before they entered the study (209 women) and new users (112).
Women in the injectable group were less likely than those in the oral contraceptive group (prior and new users combined) to report that use of the method was not at all bothersome (80% vs. 92%). They also were less likely to find it very comfortable to take their method (55% vs. 75-79%); the investigators state that this discrepancy is to be expected when comparing use of an oral with an injectable method.
Of women using the injectable, 86% said that the method did not interfere with social activities (interactions with friends and family that were not work- or school-related); similar proportions of pill users (90-94%) gave this response. Somewhat greater differences emerged with respect to daily activities (such as attending work or school, or doing housework): Eighty percent of injectable users reported interference, compared with 92-95% of pill users.
About half of injectable users (47%) reported that their sexual relationship was always satisfactory; the proportion was similar among new pill users (44%), but was higher among prior users of oral contraceptives (62%). Fewer than one-fifth (17%) of the injectable group reported a dampening or loss of libido, as opposed to nearly one-fourth (23%) of new users and one in 10 (11%) prior users of oral contraceptives.
When asked whether it was difficult to return for the monthly office visits, the women in all three groups gave similar responses: Eighty-seven percent of the injectable group said it was not difficult to return monthly; 80% of new and 86% of prior users of oral contraceptives agreed that it was not.
Roughly equal proportions in all three groups (83-86%) rated their overall experience with the method as somewhat to very favorable. Likewise, more than 90% in each group said they probably or definitely would recommend the method to a friend.
In all three groups, the women's assessment of their psychological well-being decreased over time. However, the changes did not differ substantially for injectable users and new pill users; furthermore, results of regression analyses indicated that the changes were similar for the injectable group and the pill group overall.
The investigators note that the results may be limited by selection bias: First, participants chose their contraceptive method and were not randomly assigned. Second, two-thirds of women in the oral contraceptive group had been using the method for some time and therefore are not strictly comparable to women using a new method. Nevertheless, the researchers conclude that the monthly injectable "may be well accepted by those women who desire the convenience of an effective but noncoital, nondaily-use method that maintains regular cycles and causes minimal lifestyle alterations."--M. Reiss
1. Kaunitz AM et al., Comparative safety, efficacy, and cycle control of LunelleTM monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) and Ortho-Novum®7/7/7 oral contraceptive (norethindrone/ethinyl estradiol triphasic), Contraception, 1999, 60(4):179-187.
2. Shulman LP et al., Patient acceptability and satisfaction with LunelleTM monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension), Contraception, 1999, 60(4): 215-222.