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Aging Attenuates the Pituitary Response to Gonadotropin-Releasing Hormone

Reproductive Endocrine Unit (N.D.S., S.S.S., S.N.H., K.E.M., J.E.H.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; and the Division of Endocrinology (N.D.S), Children’s Hospital, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Janet E. Hall, M.D., Reproductive Endocrine Unit, BHX-5, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: jehall{at}partners.org

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.

Objective: The aim of the study was to determine whether 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 µg/kg sc) was administered and was followed by GnRH doses of 25, 75, 250, or 750 ng/kg iv every 4 h.

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/liter, for young and old PMW, respectively, P = 0.02; and 750 ng/kg, 97.7 ± 11 vs. 70.2 ± 9.3 IU/liter, 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 PMW. 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.