BACKGROUND: Aging is associated with a decline in incremental LH pulse amplitude, which could be due to decreased GnRH secretion or impaired GnRH action. HYPOTHESIS: Inconsistent published studies of GnRH action in older men may be due to disparate sex-steroid milieus. FACILITY: This study was conducted at a clinical translational-research unit. SUBJECTS: We studied 16 healthy men (8 young men and 8 older men). METHODS: An overnight transdermal testosterone (T) clamp was implemented before randomly ordered injections of 0, 2.5, 10, 25, 250, and 750 ng GnRH on separate days (96 study sessions). OUTCOMES: LH responses were quantified by variable-waveform deconvolution analysis. RESULTS: The T clamp maintained age-invariant mean concentrations of total, bioavailable, and free T, SHBG, LH, FSH, and prolactin. By two-way analysis of covariance, GnRH dose (P < 0.001) but not age (0.15 < or = P < or = 0.83) determined mean, peak, incremental, and pulsatile LH responses. Statistical power (median) was 95, 98, 90, and 99% to detect a 30% or greater age contrast at P < or = 0.05 in mean, peak, incremental, and pulsatile LH responses, and greater than 99% to detect a 30% or greater age contrast in bioavailable or total T concentrations. Higher GnRH doses (P < 0.001) abbreviated LH secretory bursts in both age groups. CONCLUSION: In the face of eugonadal concentrations of total, bioavailable, and free T, young and older men exhibit remarkably similar LH responses to a 300-fold dose range of exogenous GnRH. Accordingly, previously reported disparate effects of age on GnRH action may reflect in part age-discrepant sex-steroid milieus.
RCT Entities:
BACKGROUND: Aging is associated with a decline in incremental LH pulse amplitude, which could be due to decreased GnRH secretion or impaired GnRH action. HYPOTHESIS: Inconsistent published studies of GnRH action in older men may be due to disparate sex-steroid milieus. FACILITY: This study was conducted at a clinical translational-research unit. SUBJECTS: We studied 16 healthy men (8 young men and 8 older men). METHODS: An overnight transdermal testosterone (T) clamp was implemented before randomly ordered injections of 0, 2.5, 10, 25, 250, and 750 ng GnRH on separate days (96 study sessions). OUTCOMES: LH responses were quantified by variable-waveform deconvolution analysis. RESULTS: The T clamp maintained age-invariant mean concentrations of total, bioavailable, and free T, SHBG, LH, FSH, and prolactin. By two-way analysis of covariance, GnRH dose (P < 0.001) but not age (0.15 < or = P < or = 0.83) determined mean, peak, incremental, and pulsatile LH responses. Statistical power (median) was 95, 98, 90, and 99% to detect a 30% or greater age contrast at P < or = 0.05 in mean, peak, incremental, and pulsatile LH responses, and greater than 99% to detect a 30% or greater age contrast in bioavailable or total T concentrations. Higher GnRH doses (P < 0.001) abbreviated LH secretory bursts in both age groups. CONCLUSION: In the face of eugonadal concentrations of total, bioavailable, and free T, young and older men exhibit remarkably similar LH responses to a 300-fold dose range of exogenous GnRH. Accordingly, previously reported disparate effects of age on GnRH action may reflect in part age-discrepant sex-steroid milieus.
Authors: Daniel M Keenan; Ferdinand Roelfsema; Nienke Biermasz; Johannes D Veldhuis Journal: Am J Physiol Regul Integr Comp Physiol Date: 2003-05-08 Impact factor: 3.619
Authors: R Rebar; S S Yen; G VandenBerg; F Naftolin; Y Ehara; S Engblom; K J Ryan; M Amoss; R Guillemin Journal: J Clin Endocrinol Metab Date: 1973-01 Impact factor: 5.958
Authors: Ferdinand Roelfsema; Peter Y Liu; Paul Y Takahashi; Rebecca J Yang; Johannes D Veldhuis Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958