Effects of continuous versus cyclical oral contraception: a randomized controlled trial

Abstract

Context: Continuous oral contraception may better suppress the ovary and endometrium, lending itself to the treatment of other medical conditions.

Objective: Our objective was to determine the effects of continuous vs. cyclical oral contraception.

Design: This was a randomized double-blind trial.

Setting: This trial was performed at an academic medical center in Pennsylvania.

Patients: A total of 62 healthy women with regular menses were included in the study.

Intervention: Cyclical oral contraception (21-d active/7-d placebo given for six consecutive 28-d cycles) vs. continuous (168-d active pill) therapy using a monophasic pill (20 microg ethinyl estradiol and 1 mg norethindrone acetate) was examined.

Main outcome measures: The primary outcome was vaginal bleeding, and secondary outcomes included hormonal, pelvic ultrasound, quality of life, and safety measures.

Results: There was no statistically significant difference in the number of total bleeding days between groups, but moderate/heavy bleeding was significantly greater with the cyclical regimen [mean 11.0 d (sd 8.5) vs. continuous 5.2 d (sd 6.8); P = 0.005], with both groups decreasing over time. Endogenous serum and urinary estrogens measured over six cycles were significantly lower (P = 0.02 and 0.04, respectively) in the continuous group than the cyclical group. Women in the continuous group also had a smaller ovarian volume and lead follicle size over the course of the trial by serial ultrasound examinations. The Moos Menstrual Distress Questionnaire showed that women on continuous therapy had less associated menstrual pain (P = 0.01) and favorable improvements in behavior (P = 0.04) during the premenstrual period.

Conclusions: Continuous oral contraception does not result in a reduction of bleeding days over a 168-d period of observation but provides greater suppression of the ovary and endometrium. These effects are associated with improved patient symptomatology.

Figures

Figure 1

Flow chart of subjects in the study.

Figure 2

Model-based effect of time (cycle) on bleeding by treatment group. A, Number of days of any bleeding per subject. B, Number of days of moderate/heavy bleeding per subject. Lines are the model-based regression estimates, and circles and triangles are the mean values at that visit per group. The asterisk at the x-axis indicates P < 0.05 between groups at that visit.

Figure 3

Relationship between cycle day of vaginal bleeding, treatment group, and endogenous urinary sex steroids. Top, Percentage of patients with any bleeding by pill cycle day. All subjects averaged over the six cycles (model-based estimates to adjust for six cycles per subject). Mean (se) urinary estrogen (E1G) (middle) and progestin (PdG) (bottom) metabolites by treatment group. Subset (n = 20) averaged over the six cycles (model-based estimates to adjust for six cycles per subject).

Figure 4

Model-based change from baseline in serum sex steroids, gonadotropins, and ultrasound parameters by treatment cycle and treatment group. Lines are the model-based regression estimates, and circles and triangles are the mean values at that visit per group. The asterisk at the x-axis indicates P < 0.05 between groups at that visit.