Context: Complex changes in GnRH secretion occur with aging in women, but little is known about the effect of aging on the pituitary per se.

Objectives: To determine if pituitary responsiveness to GnRH is attenuated with aging.

Design and Setting: A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness in Clinical Research Center studies at an academic medical center.

Subjects: Subjects were healthy postmenopausal women (PMW) aged 48–57 yr (n = 10) or 70–77 yr (n= 9).

Interventions: A suppressive dose of the NAL-GLU GnRH antagonist (150 mcg/kg sc) was administered followed by GnRH doses of 25, 75, 250 or 750 ng/kg iv every 4 hr.

Results: The LH response to GnRH was attenuated with aging (p=0.05) with an interaction between age and dose (p=0.01) such that the LH amplitude was less in older PMW at the higher doses (250 ng/kg: 50±9 vs 29±4.9 IU/L, for young and old PMW, respectively; p=0.02 and 750 ng/kg: 97.7±11 vs 70.2±9.3 IU/L; p=0.002), but not the lower doses of GnRH. The FSH response to GnRH was also attenuated with aging in PMW (p=0.005).

Conclusions: In studies that isolated the pituitary from endogenous GnRH stimulation, aging attenuated the LH and FSH responses to exogenous GnRH in postmenopausal women. These studies indicate that the pituitary plays a role in the decline in gonadotropin levels with aging, further supporting the potential contribution of age-associated changes in both hypothalamic and pituitary function to reproductive senescence.