Metabolic Clearance Rate and Conversion Ratios of [3H]2-Hydroxyestrone in Normal Men*

Abstract

The metabolism of 2-hydroxyestrone (2-OHE1) was studied in eight normal men with pulse injections of [6,7-3H]2-OHE1 (four subjects) and [6,7-3H]2-OHE1/[4-14C]E1 (four subjects). After the pulses, blood samples were withdrawn at increasing time intervals for 1440 min (24 h) and analyzed for total radioactivity and for radioactivity as 2-OHE1, 2-methoxyestrone (2-MeOE1), 2-hydroxyestrone 3-methyl ether (2-OHE1 3Me), 2-hydroxyestradiol (2-OHE2), 2-methoxyestradiol (2-MeOE2), and 2-hydroxyestradiol 3-methyl ether (2-OHE2 3Me).In addition, all urine was collected for 120 h and analyzed for conjugated metabolites of the above steroids. There was a rapid disappearance of 2-OHE1 from the blood, such that by 100–240 min, none was measurable. The mean (±SE) MCR of 2-OHE1 was 89,600 ± 15,700 liters/day. Most of the 3H radioactivity present in the blood at the initial sampling times was associated with 2-MeOEi, and the mean conversion ratio for 2-OHE1 to 2-MeOE1 [CR 2-OHE1, 2-MeOE1 = ratio of radioactivity (integrated over 1,440 min) as 2-MeOE1 to that as 2-OHE1] was 47.7 ± 9.9.3H was also recovered as 2-OHE1 3Me, 2-OHE2, 2-MeOE2) and 2-OHE2 3Me. The CRs for these compounds were 0.62 ± 0.13, 1.02 ± 0.03, 2.58 ± 0.24, and 0.54, respectively. In the urine, the major radioactive metabolites identified were 2-MeOE1 and 2-OHE1 in almost equal amounts, with the former as both glucuronide and sulfate, and the latter primarily as glucuronide. All of the other 2-oxygenated compounds found in the blood and the 2-oxygenated compounds in the estriol series were also identified, but in far lower amounts. After the administration of [4-14C]E1, we were not able to measure radioactivity in any of the 2-oxygenated compounds in the blood. However, 14C was identified in all of the 2-oxygenated compounds isolated from the urine, and the 3H to 14C ratios were greater for 2-MeOE1 and 2-MeOE2 than for all of the other oxygenated compounds. We conclude that 2-OHE1 is cleared very rapidly from the blood, in part by metabolism to 2-MeOE1. The excretion of substantial amounts of conjugates of [3H]2-OHE1 into the urine indicates that [3H]2-OHE1 is transferred directly from the blood into other tissues and conjugated there, and/or there is further metabolism of the rapidly formed [3H]2-Me0E1. (J Clin EndocrinolMetab54: 374,1982)