Pilot Study of Femring Estrogen Supplementation During Depo-Provera Initiation

Many women choose depot medroxyprogesterone acetate (DMPA) for contraception because it is long-acting, highly effective, and requires minimal user involvement. One of the most common side effects of DMPA use during the first 90 day cycle is irregular bleeding. There are few studies that report mean number of bleeding days among DMPA users. A large World Health Organization (WHO) trial including ten international centers and menstrual data on 748 women using DMPA including 372 woman-years of follow-up reported 23.6 mean days of spotting and bleeding during the first cycle with a standard deviation of 18.9 days (WHO). Another study sponsored by WHO (n=575) reported that 25% of subjects had bleeding/spotting episodes during the first cycle of DMPA that exceeded 13 days. The number of bleeding/spotting days and number of bleeding/spotting episodes decreased over successive reference periods (Said 1987).

Discontinuation rates are high after the first injection and related to irregular bleeding. Rates of discontinuation after the first injection range from 15-60% but were around 30% in most studies (Harel, Paul, Polaneczy, Lim, Hubacher, Sangi, Rickert). Several studies noted that the largest percentage of discontinuation during the first year of DMPA use occurs after the first injection (Rickert, Hubacher, Lim). Irregular bleeding is uniformly cited as one of the most common reasons for discontinuation, accounting for 17-60% of all reasons given (Harel, Paul, Polaneczy, Lim, Sangi). An intervention to prevent or minimize irregular bleeding during the first 90 days of DMPA use could potentially minimize or prevent this bothersome side effect and thus improve continuation.

Few studies have examined the effect of prophylactic or therapeutic estrogen supplementation on irregular bleeding in DMPA users. A randomized trial (n=132) of cyclic transdermal estradiol 0.1 mg/day (Climara) for 3 months versus placebo in women initiating DMPA immediately post-abortion showed no difference in continuation rates at 12 months; however, the authors of this study reported a high rate of non-compliance with the study protocol and lacked an adequate sample size to detect a difference (Goldberg). This is the only study to report on prophylactic estrogen supplementation in DMPA users.

Two studies evaluated therapeutic estrogen supplementation in DMPA users. In 1996, WHO published results of a trial in which women using DMPA and experiencing a bleeding episode greater than 7 days during the first or second injection interval were offered treatment. Subjects (n=278) were randomized to a 14 day course of 50 mcg ethinyl estradiol, 2.5 mg oestrone sulphate, or placebo. The authors found that subjects treated with ethinyl estradiol had shorter median time to cessation of bleeding and fewer bleeding/spotting days (Said 1996). An observational study (n=131) of adolescents reporting vaginal bleeding on DMPA who were treated with monophasic oral contraceptive pills identified improvement of bleeding patterns and a high rate of continuation in those receiving treatment (Rager).

Estrogen supplementation appears to be more effective than placebo in stopping and decreasing bleeding in Norplant users. Women who presented with a spontaneous complaint of prolonged or irregular bleeding were randomly assigned to receive 20 days of treatment with a combined oral contraceptive, 50 mcg ethinyl estradiol, or placebo. Both combined oral contraceptive pills and estradiol were significantly more effective than placebo in stopping bleeding and decreasing the mean number of bleeding days during treatment (Alvarez).