Aspirin inhibition of naloxone-induced luteinizing hormone secretion in man

It is well known that endogenous opioid peptides exert a tonic inhibitory control on GnRH release, leading to the inhibition of LH secretion, whereas eicosanoids, particularly prostaglandin E2(PGE2), stimulate GnRH output. Furthermore, in vitro studies suggest the existence of an interaction between these two regulatory systems in animals. The present work was designed to evaluate the acute effect of the prostaglandin blocker aspirin on plasma LH response to the opiate antagonist naloxone or GnRH in normal volunteers in a placebo-controlled, single-blind study. To exclude a hypothetical action of aspirin directly at the testis level, plasma testosterone concentrations were monitored during basal sampling after acetylsalicylic acid ingestion, whereas the efficacy of the drug as a prostaglandin blocker was tested by the determination of seminal PGE2 levels. Aspirin pretreatment significantly lowered seminal PGE2 levels (from 86 +/- 5 before to 11 +/- 2 micrograms/mL [corrected] after drug administration; P < 0.001) without affecting testosterone concentrations. Moreover, the drug induced a significant reduction of LH response to naloxone, assessed as the mean integrated area under the curve, from 1666.5 +/- 116 to 1197.5 +/- 98 mUI/mL per min (P < 0.05), whereas it did not influence GnRH-induced LH release. We conclude that the effective cycloxygenase blockade inhibits the stimulatory activity of naloxone on LH release, suggesting that the inhibitory tone of opioids on GnRH secretion may be caused by the block of hypothalamic prostaglandin biosynthesis with consequent inhibition of PGE2-induced GnRH secretion.