Objective: To determine whether low (subtherapeutic) doses of gonadotropin-releasing hormone agonists (GnRH-a) can cause ovarian hyperstimulation.
Design: The study is in two parts: a preliminary clinical trial of women and a follow-up study in laboratory primates.
Setting: Normal human volunteers were studied in an academic research environment; primates were in a conventional laboratory setting.
Patients, participants: Human volunteers were selected on the basis of apparent normal health. The monkeys were believed to be of normal reproductive status.
Interventions: Gonadotropin-releasing hormone agonists were administered at subtherapeutic doses.
Main outcome measures: After observing ovarian hyperstimulation in two of five women receiving low doses of GnRH-a, a study was specifically designed to test the hypothesis that at low (subtherapeutic) doses of GnRH-a the "flare-effect" can be sustained without achieving down regulation.
Results: The data in women and monkeys suggest that a highly individualized response to low GnRH-a doses can be manifested as ovarian hyperstimulation.
Conclusion: Four points of interpretation are offered: (1) that subtherapeutic doses of GnRH-a can cause ovarian hyperstimulation and related sequelae; (2) this may be a unique observation in that, typically, lower doses of medications have a lower incidence of negative side effects; (3) the findings suggest that GnRH-a prescribed in self-administration regimens may be more prone to such problems in noncompliant patients; and (4) the hyperstimulation response of the ovaries to low GnRH-a doses may indicate a new approach to controlled ovulation induction, although wide individualism was found.