Age in men does not determine gonadotropin-releasing hormone's dose-dependent stimulation of luteinizing hormone secretion under an exogenous testosterone clamp.
BACKGROUND
Aging is associated with a decline in incremental LH pulse amplitude, which could be due to decreased GnRH secretion or impaired GnRH action.


OBJECTIVE
Inconsistent published studies of GnRH action in older men may be due to disparate sex-steroid milieus.


METHODS
This study was conducted at a clinical translational-research unit.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Iranmanesh
Ali
A
Endocrine Section, Department of Medicine, Salem Veterans Affairs Medical Center, Salem, Virginia 24153, USA.
Mulligan
Thomas
T
Veldhuis
Johannes D
JD
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013268:Stimulation, Chemical; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood; D055815:Young Adult
D043373:Follicle Stimulating Hormone, Human; D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone