A randomized, double-blind, placebo-controlled comparison of the impact of low-dose and triphasic oral contraceptives on follicular development

Abstract

Objective: This investigation tests the hypothesis that triphasic oral contraceptives are associated with the development of large, persistent ovarian cysts.

Study design: Weekly vaginal ultrasonography was used in a randomized, double-blind, placebo-controlled, parallel-group, single-center study that compared the incidence, risk, size, and time to resolution of ovarian follicles in healthy women who took Estrostep or Loestrin oral contraceptives (manufactured by Parke-Davis) or a placebo during three consecutive menstrual cycles.

Results: Sixty-three percent of placebo-treated subjects developed follicles greater than 18 mm, compared with 39% and 23% in the Estrostep and Loestrin groups. The risks for each group of developing a large follicle during a single cycle were not different. No dominant follicle persisted for greater than 2 weeks for any subject.

Conclusion: These results demonstrate that follicular development continues during treatment with oral contraceptives. In addition, the findings fail to support the hypothesis that triphasic oral contraceptives result in persistent ovarian cysts.

PIP: Health practitioners randomly enrolled 48 18-35 year old healthy women into either the group receiving a low dose oral contraceptive (Loestrin, 30 mcg of ethinyl estradiol and 1.5 mg of norethindrone acetate) or the group receiving a triphasic oral contraceptive (Estrostep, 20, 30, and 35 mcg of ethinyl estradiol and 1.5 mg of norethindrone acetate) and followed them for a 4-week control period. They were able to follow only 42-45 women during active treatment. This double blind, placebo controlled study took place at the Baylor College of Medicine in Houston, Texas. Its purpose was to determine whether Estrostep was causally related to development of ovarian cysts. 63% of the women in the placebo group had a follicle 18 mm sometime during treatment compared with 43% of those treated with Estrostep and 25% of those treated with Loestrin. No group was more prone to developing follicular cysts than the other 2 groups. Mean size of these follicles were 21, 21.5, and 23.8 mm for the control, Loestrin, and Estrostep groups, respectively, and were not significantly different. The mean largest follicle sizes were also not significantly different. None of the women experienced a follicle 18 mm for 2 weeks. The results indicated that follicular development persists during oral contraceptive treatment. They also do not support the hypothesis that triphasic oral contraceptives cause continual ovarian cysts.