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Age in men does not determine gonadotropin-releasing hormone's dose-dependent stimulation of luteinizing hormone secretion under an exogenous testosterone clamp.


ABSTRACT:

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.

SUBMITTER: Iranmanesh A 

PROVIDER: S-EPMC2902075 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

Age in men does not determine gonadotropin-releasing hormone's dose-dependent stimulation of luteinizing hormone secretion under an exogenous testosterone clamp.

Iranmanesh Ali A   Mulligan Thomas T   Veldhuis Johannes D JD  

The Journal of clinical endocrinology and metabolism 20100331 6


<h4>Background</h4>Aging is associated with a decline in incremental LH pulse amplitude, which could be due to decreased GnRH secretion or impaired GnRH action.<h4>Hypothesis</h4>Inconsistent published studies of GnRH action in older men may be due to disparate sex-steroid milieus.<h4>Facility</h4>This study was conducted at a clinical translational-research unit.<h4>Subjects</h4>We studied 16 healthy men (8 young men and 8 older men).<h4>Methods</h4>An overnight transdermal testosterone (T) cla  ...[more]

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