Mean Plasma Concentration, Metabolic Clearance and Basal Plasma Production Rates of Testosterone in Normal Young Men and Women Using a Constant Infusion Procedure: Effect of Time of Day and Plasma Concentration on the Metabolic Clearance Rate of Testosterone

Abstract

Plasma specimens were obtained from 2 normal men and 2 normal women at 90-min intervals (16 specimens) during a 24-hr period, pooled and analyzed for testosterone using a double isotope derivative method. The data were compared to those obtained in individual plasma specimens taken at approximately 4-hr intervals. The plasma testosterone level found in the pool of the 16 specimens in each subject was considered a close approximation of the daily mean. The plasma testosterone levels of the pool in the men were 22.0 and 21.8% lower than the respective values seen at 9 am. Thus, the use of a morning plasma level of testosterone for the calculation of a mean daily plasma production rate of the steroid in men would introduce a significant error. Since the mean of the 9 am, 5 pm and 10 pm specimens was considerably closer to the daily mean (pool), it has been used as a reasonable compromise to the true mean. In contrast to the males, the female subjects failed to show any significant diurnal variation in plasma levels of testosterone. The similarity of the values for the pooled and morning specimens indicated that the latter figure was valid as a daily mean plasma concentration of the androgen in the female subjects. The metabolic clearance rate of testosterone (constant infusion procedure) did not vary significantly at various times of the day when studied under basal conditions. This indicated that the observed diurnal variation in the plasma concentration was due to a true decrease in the production rate of the androgen rather than to an alteration in the metabolic clearance rate of the steroid. The plasma concentration of testosterone was found to significantly affect the metabolic clearance rate of the steroid. A decrease in the plasma concentration of the hormones following bilateral orchiectomy was associated with an appreciable fall in the metabolic clearance of the steroid (1156 to 566 1/day). Administration of 20 mg testosterone propionate (equivalent to 16.8 mg free testosterone) to a bilaterally adrenalectomized castrated woman resulted in an increase in circulating testosterone from 0.02 to 2.0 μg/100 ml of plasma within a 12-hr period. The subsequent single daily injection of a similar dose of the steroid was sufficient to maintain the plasma level of testosterone at the latter value. The increase in the plasma levels of testosterone was associated with an increase in the metabolic clearance rate of the steroid (414 to 831 1/day). The validity of the constant infusion procedure was demonstrated by the similarity of the estimated testosterone production rate (17.5 mg) and the daily administered dose of free testosterone (16.8 mg). In the bilaterally adrenalectomized castrated women, in 2 normal female subjects and in a woman with treated hypothyroidism, the MCR's were measured before and after 2 successive weekly intramuscular injections of 200 mg testosterone enanthate. Following this regimen the MCR's increased from 2 to 4 times the control level. In a study of the MCR's of testosterone (constant infusion procedure) in normal men and women, a significant sex difference was found in the plasma clearance of the steroid, the male values being approximately twice the female values. The basal plasma production rates of testosterone in normal men and women were 7.08±2.11 (sd) and 0.35±0.13 (sd) mg/day, respectively.