Disposition and metabolic profile of the weak androgen Dehydroepiandrosterone (DHEA) following administration as part of a nutritional supplement to exercised horses

Abstract

In order to ensure the welfare of performance horses and riders as well as the integrity of the sport, the use of both therapeutic and illegal agents in horse racing is tightly regulated. While Dehydroepiandrosterone (DHEA) is not specifically banned from administration to racehorses in the United States and no screening limit or threshold concentration exists, the metabolic conversion of DHEA to testosterone make its presence in nutritional supplements a regulatory concern. The recommended regulatory threshold for total testosterone in urine is 55 and 20 ng/mL for mares and geldings, respectively. In plasma, screening and confirmation limits for free testosterone (mares and geldings), of no greater than 0.1 and 0.025 ng/mL, respectively are recommended. DHEA was administered orally, as part of a nutritional supplement, to 8 exercised female thoroughbred horses and plasma and urine samples collected at pre-determined times post administration. Using liquid chromatography-mass spectrometry (LC-MS), plasma and urine samples were analyzed for DHEA, DHEA-sulfate, testosterone, testosterone-sulfate, pregnenolone, androstenedione, and androstenediol. DHEA was rapidly absorbed with maximal plasma concentrations reaching 52.0 ± 43.8 ng/mL and 32.1 ± 12.9 ng/mL for DHEA and DHEA sulfate, respectively. Free testosterone was not detected in plasma or urine samples at any time. Maximum sulfate conjugated testosterone plasma concentrations were 0.98 ± 1.09 ng/mL. Plasma testosterone-sulfate concentrations did not fall below 0.1 ng/mL and urine testosterone-sulfate below 55 ng/mL until 24-36 h post DHEA administration. Urine testosterone sulfate concentrations remained slightly above baseline levels at 48 h for most of the horses studied.

Keywords: DHEA; horse; metabolism; testosterone.