Gynecology clinic-based studies have consistently demonstrated that induced
hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced
hypogonadism nor
estradiol replacement influenced cognitive performance. Thus, the effects of induced
hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of
hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman's symptomatic experience during menopause. In this study, we examined the effects of induced
hypogonadism and ovarian
steroid replacement on cognitive performance in healthy premenopausal women. Ovarian suppression was induced with a
GnRH agonist (
Lupron) and then physiologic levels of
estradiol and
progesterone were reintroduced in 23 women. Cognitive tests were administered during each
hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. With the exception of an improved performance on mental rotation during
estradiol, we observed no significant effects of
estradiol or
progesterone on measures of attention, concentration, or memory compared with
hypogonadism. In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression
therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short-term changes in gonadal
steroids have a limited effect on cognition in young, healthy women. Differences in the clinical characteristics of the women receiving
GnRH agonists could predict a risk for ovarian
steroid-related changes in cognitive performance during induced, and possibly, natural menopause.