A study of the effect of various factors on the metabolic clearance rate of testosterone (MCRT) is presented. Change from the supine to the erect position resulted in a sharp fall in the MCRT in one subject, with little or no significant change in 3 additional subjects. In one of the latter group, however, there subsequently occurred a significant increase in the MCRT upon changing from the erect to the supine position. Acute increases in the plasma concentration of testosterone in normal menstruating women and in a bilaterally adrenalectomized castrated woman were not associated with any appreciable change in the MCRT until a plasma level of testosterone exceeding 1.2 μg/100 ml was reached. In a normal and a hypogonadal male, an acute increase in the circulating level of testosterone produced a moderate increase in the MCRT. The increase, however, was considerably smaller than that found after chronic administration of the steroid. The decrease in the plasma concentration of testosterone following intramuscular injection of testosterone propionate was not accompanied by a proportionate fall in the MCRT. This suggests that, in addition to the possible role of testosterone binding, induction of testosterone catabolizing enzymes is involved in regulating the plasma clearance of the steroid. Sequential measurements of the MCRT in the same subjects (5 normal men and 1 normal woman) at various intervals were within 10% of the base line values. Moreover, the mean percentage change for the entire group was –1.6%. This demonstrates the temporal constancy of the clearance measurement. There was no significant difference in the MCRT measured in plasma and whole blood in male or female subjects. This suggests that the red blood cells did not take up any appreciable quantities of the labeled hormone during the period of the experiment. The measurement of the MCRT in an additional group of normal men and women again demonstrates the sex difference in the plasma clearance of the steroid, the values in men being approximately twice those found in women. The sex-related difference persisted when the MCRT was corrected for body surface area (m2). However, when the MCRT/m2 was divided by the log of the plasma production rate of testosterone, this difference disappeared. This suggests that the MCRT is a direct function of the production rate of the steroid. The basal plasma production rates of testosterone in these subjects were 5.78±1.42 (sd) mg/day in the men and 0.29±0.07 (sd) mg/day in the women. Combining these values with our previous reported data gives over-all means for 18 normal men and 14 normal women of 6.23 ± 1.73 (sd) and 0.32 ±0.10 (sd) mg/day, respectively.
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Southren et al. (1968) studied this question.