[The endogenous testosterone secretion rate returned to baseline at approximately week 23 in all three dose groups.]
Study Highlights
WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
Long-term excessive dosing of anabolic steroids can lead to serious health risks. One of the most significant physiologic changes induced by the use of testosterone esters is a dose-dependent impairment of normal testicular androgen secretion and spermatogenesis.
WHAT QUESTION DID THIS STUDY ADDRESS?
This study characterizes and quantifies changes in testosterone and luteinizing hormone concentration, and spermatogenesis following long-term testosterone cypionate administration.
WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
The study developed a PK-PD model based on a randomized three-arm (100mg, 250mg, 500 mg/week) clinical trial which quantified the relationship between testosterone exposure after exogenous administration and suppression of LH and spermatogenesis. Model results showed that the suppression of endogenous testosterone secretion, LH synthesis and spermatogenesis was more severe and of greater duration in 250mg and 500mg dose groups.
HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?
This PK/PD model provides a framework to quantify and predict the change in LH and spermatogenesis after exogenous testosterone administration. The average concentration of total testosterone in the past 18 weeks was found to have the strongest association with suppression of spermatogenesis.
Bi Y, Perry PJ, Ellerby M, Murry DJ. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Depot Testosterone Cypionate in Healthy Male Subjects. CPT: Pharmacometrics & Systems Pharmacology. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Depot Testosterone Cypionate in Healthy Male Subjects
A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate. Thirty-one healthy males were randomized into a dose group of 100, 250 or 500mg/wk and received 14 weekly injections of TC.
A PK-PD model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration.
A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution.
Weight, albumin and their changes from baseline were identified as significant covariates for testosterone. The estimated potency of total testosterone with respect to suppression of LH synthesis was 9.33 ng/ml.
Simulation based on the indirect response model suggests the suppression of endogenous testosterone secretion, LH synthesis and spermatogenesis was more severe and of greater duration in 250mg and 500mg dose groups.
Study Highlights
WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
Long-term excessive dosing of anabolic steroids can lead to serious health risks. One of the most significant physiologic changes induced by the use of testosterone esters is a dose-dependent impairment of normal testicular androgen secretion and spermatogenesis.
WHAT QUESTION DID THIS STUDY ADDRESS?
This study characterizes and quantifies changes in testosterone and luteinizing hormone concentration, and spermatogenesis following long-term testosterone cypionate administration.
WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
The study developed a PK-PD model based on a randomized three-arm (100mg, 250mg, 500 mg/week) clinical trial which quantified the relationship between testosterone exposure after exogenous administration and suppression of LH and spermatogenesis. Model results showed that the suppression of endogenous testosterone secretion, LH synthesis and spermatogenesis was more severe and of greater duration in 250mg and 500mg dose groups.
HOW MIGHT THIS CHANGE DRUG DISCOVERY, DEVELOPMENT, AND/OR THERAPEUTICS?
This PK/PD model provides a framework to quantify and predict the change in LH and spermatogenesis after exogenous testosterone administration. The average concentration of total testosterone in the past 18 weeks was found to have the strongest association with suppression of spermatogenesis.
Bi Y, Perry PJ, Ellerby M, Murry DJ. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Depot Testosterone Cypionate in Healthy Male Subjects. CPT: Pharmacometrics & Systems Pharmacology. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Depot Testosterone Cypionate in Healthy Male Subjects
A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate. Thirty-one healthy males were randomized into a dose group of 100, 250 or 500mg/wk and received 14 weekly injections of TC.
A PK-PD model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration.
A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution.
Weight, albumin and their changes from baseline were identified as significant covariates for testosterone. The estimated potency of total testosterone with respect to suppression of LH synthesis was 9.33 ng/ml.
Simulation based on the indirect response model suggests the suppression of endogenous testosterone secretion, LH synthesis and spermatogenesis was more severe and of greater duration in 250mg and 500mg dose groups.
