Abstract

PIP: In October, 1993, the Fertility and Maternal Health Drugs Advisory Committee of the US Food and Drug Administration (FDA) convened to examine recent research on oral contraceptive (OC) formulation and ovarian cysts. It needed to determine whether or not various OC formulations increased the risk of follicular enlargement and then to determine whether a change in product labeling was needed. The medical officer of the FDA Center for Drug Evaluation Research provided the introductory overview of the controversy and a review of recent studies. Investigators of 3 recent FDA-requested phase IV clinical trials by manufacturers of multiphasic OCs presented their results. They found no real intrinsic difference between whether an OC formulation is multiphasic or monophasic in terms of follicular development. Yet, a major difference needed to be addressed about the potency/dose effect of the progestogen at the 30-40 mcg range of estrogen. Specifically, the newer, lower-dose OCs did not suppress follicular activity as much as the older, higher-dose OCs, resulting in the rate of ovarian cysts being closer to that of nonusers. For example, the diameter of the maximum follicular structures were around 7.5 mm in the higher-dose, monophasic OC group, compared to less than 15 mm in the lower-dose, monophasic OC group and about 13.5 mm for the nonuser group. For the multiphasic OC group, it was essentially the same as that of the nonuser group. None of the differences were statistically significant. The panel considered the normal ovarian activity level in the low-dose, monophasic OC group and the multiphasic OC group to be good. Based on these results and their discussions, panel members agreed that neither monophasic nor multiphasic OCs increase the risk of ovarian cyst development. Thus, there was no need to change product labeling.