CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1) Gene and Pharmacogenetics of Response to Testosterone Therapy

Summary

Testosterone (T) replacement prevents bone loss and relieves symptoms associated with androgen deficiency in male patients with hypogonadism, but at the expense of an increase in prostate-related adverse events and in the hematocrit values above the normal which may lead to bad circulatory outcomes. Most of the effects of T on the male skeleton are mediated by its conversion to estradiol (E2) by the enzyme aromatase. Genetic variations in the aromatase (CYP19A1) gene result in enzymes with variable activity and variable levels of E2 and T. This project is designed to determine if genetic variations in the CYP19A1 gene will result in differences in the skeletal response and incidence of side effects from T treatment in patients with low T. A large number of male Veterans are on T. Results from this project will help identify patients who would benefit from the therapy from those at risk for side effects, and would definitely have an impact in the future care of these patients and male patients in general once genetic profiling becomes part of the standard of care.

Timeline

Start

2011-10-01

Primary completion

2016-11-07

Completion

2017-11-07

Publications

• Joad S, Ballato E, Deepika F, Gregori G, Fleires-Gutierrez AL, Colleluori G, Aguirre L, Chen R, Russo V, Fuenmayor Lopez VC, Qualls C, Villareal DT, Armamento-Villareal R. Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne). 2021 Dec 28;12:788107. doi: 10.3389/fendo.2021.788107. eCollection 2021.
• Colleluori G, Aguirre L, Napoli N, Qualls C, Villareal DT, Armamento-Villareal R. Testosterone Therapy Effects on Bone Mass and Turnover in Hypogonadal Men with Type 2 Diabetes. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3058-e3068. doi: 10.1210/clinem/dgab181.

Drugs

Indications