Many women choose Depo-Provera for birth control because it is easy to use and very
effective. However, a significant number of Depo-Provera users experience irregular bleeding
during the first 90 days. Many users discontinue after their first injection due to
irregular bleeding. This study will evaluate the effect of using an estrogen vaginal ring
during the first 90 days of Depo-Provera use to see if it is acceptable to women and whether
it decreases irregular bleeding during the first 90 days of use and increases continuation
to a second injection.
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
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).
To summarize, prior studies have not identified an acceptable or effective prophylactic
intervention to prevent or minimize irregular bleeding or improve continuation rates in DMPA
users. The first cycle of DMPA is a critical time for such an intervention. Our study will
evaluate estrogen supplementation with an estrogen vaginal ring during the first 90 days of
DMPA use versus no estrogen supplementation and report on acceptability, bleeding patterns,
and continuation rates. Femring®, an estradiol vaginal ring currently used for treatment of
postmenopausal symptoms, provides 100 mcg of estradiol per day with one ring designed for 90
days of consecutive use. This dose provides systemic levels sufficient to suppress vasomotor
symptoms in postmenopausal women (Speroff). The vaginal ring would require minimal user
involvement when placed at the time of DMPA initiation. If acceptable and effective, this
intervention could prevent or minimize irregular bleeding and improve continuation rates of
this highly effective contraceptive method.
- Women age 18 or older who are initiating Depo-Provera for contraception
- English or Spanish-speaking
- Have a negative urine pregnancy test
- Contraindications to either Depo-Provera or Femring (estrogen vaginal ring)
- Have used Depo-Provera or Mirena in the prior 6 months
- Have had an induced abortion, spontaneous abortion, or birth in prior 8 weeks