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- Title
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.
- Authors
Liu, Peter Y; Takahashi, Paul Y; Roebuck, Pamela D; Bailey, Joy N; Keenan, Daniel M; Veldhuis, Johannes D
- Abstract
<bold>Background: </bold>Testosterone (T) production declines and LH pulses become smaller and more frequent in middle-aged men. The mechanisms underlying these changes are not known.<bold>Rationale: </bold>Small frequent LH pulses in middle-aged men could reflect impaired feedback by systemic T.<bold>Hypothesis: </bold>Middle age disrupts negative feedback by T on selected facets of LH secretion.<bold>Subjects and Setting: </bold>Healthy men were studied at an academic medical center.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
AGE distribution; BIOAVAILABILITY; DRUG administration; DOSE-effect relationship in pharmacology; LUTEINIZING hormone; PSYCHOTHERAPY; REGRESSION analysis; RESEARCH funding; TESTOSTERONE; TIME; TRANSDERMAL medication
- Publication
Journal of Clinical Endocrinology & Metabolism, 2009, Vol 94, Issue 10, p3978
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2009-0135