Testosterone's short-term positive effect on luteinizing-hormone secretory-burst mass and its negative effect on secretory-burst frequency are attenuated in middle-aged men.
BACKGROUND
Testosterone (T) production declines and LH pulses become smaller and more frequent in middle-aged men. The mechanisms underlying these changes are not known.


BACKGROUND
Small frequent LH pulses in middle-aged men could reflect impaired feedback by systemic T.


OBJECTIVE
Middle age disrupts negative feedback by T on selected facets of LH secretion.


METHODS
Healthy men were studied at an academic medical center.


METHODS
The protocol comprised blockade of gonadal steroidogenesis and graded transdermal addback of T doses of 0, 2.5, 5, or 7.5 mg/d designed to span the castrate to physiological range of T concentrations in each of 23 healthy men ages 19-71 yr (interquartile range, 28-53 yr). We quantified 12-h basal and pulsatile LH secretion (92 time series) using a mathematically justified deconvolution method.


RESULTS
Stepwise T supplementation from the hypogonadal through the eugonadal range repressed mean (12-h) LH concentrations (P = 0.001). By regression analysis, age attenuated the capabilities of increasing T concentrations to 1) increase LH secretory-burst mass (P < 0.0001); and 2) decrease LH secretory-burst frequency (P = 0.025). Age did not alter T's feedback on basal LH secretion, interpulse regularity, the waveform of LH secretory bursts, or the slow half-life of LH.


CONCLUSIONS
Middle age impairs both the positive and negative actions of systemic T on pulsatile LH secretion in healthy men, thus potentially explaining earlier inconsistencies in feedback studies based upon single-sample mean LH concentrations. Longitudinal studies will be required to elucidate the precise age dependence of inferred dual feedback failure.
Liu
Peter Y
PY
Endocrine Research Unit, Mayo Medical School, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905, USA.
Takahashi
Paul Y
PY
Roebuck
Pamela D
PD
Bailey
Joy N
JN
Keenan
Daniel M
DM
Veldhuis
Johannes D
JD
D000279:Administration, Cutaneous; D000328:Adult; D000367:Age Factors; D000368:Aged; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D006801:Humans; D016014:Linear Models; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D013739:Testosterone; D007986:Luteinizing Hormone