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01-09-2019 | Testosterone | Original Article

Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene

Authors: Lina E. Aguirre, Georgia Colleluori, David Robbins, Richard Dorin, Vallabh O. Shah, Rui Chen, Irum Zeb Jan, Clifford Qualls, Dennis T. Villareal, Reina Armamento-Villareal

Published in: Endocrine | Issue 3/2019

Abstract

Purpose

To evaluate the influence of single nucleotide polymorphisms (SNPs) of CYP19A1 on the response and susceptibility to side effects from testosterone therapy. This is a prospective, single-arm study of men with low-morning serum testosterone (<10.68 nmol/l) administered testosterone cypionate 200 mg intramuscularly every 2 weeks for 18 months.

Methods

We measured areal bone mineral density (aBMD) and body composition by dual energy X-ray absorptiometry, tibial volumetric BMD and geometry by peripheral quantitative computer tomography, bone turnover markers by enzyme-linked immunosorbent assay, testosterone, and estradiol by liquid-chromatography/mass-spectroscopy, genotyping by microarray, CYP19A1 expression by quantitative polymerase chain reaction, hematocrit and prostate-specific antigen (PSA).

Results

We enrolled 105 men (40–74-years-old). SNPs rs1062033 and rs700518 were associated with significant differences in outcomes at 18 months. The GG genotype in rs1062033 had significant increase in whole body aBMD, but had significant decrease in tibial bone size compared to the CG and CC genotypes. Body composition analysis showed that the CC genotype of rs1062033, and the AA genotype of rs700518, had significant increase in total lean and appendicular lean mass compared to CG and GG, and AG and GG, respectively. The GG genotype of rs700518 had significant increase in PSA (GG = 105.8 ± 23.3% vs. AG + AA = 53.4 ± 11.3%, p = 0.046) while hematocrit changes were comparable among genotypes. CYP19A1 expression was highest in GG genotype in both SNPs.

Conclusions

For the first time, we demonstrated that CYP19A1 SNPs influence response to testosterone therapy in hypogonadal men, highlighting the importance of genetic profiling in therapeutics even for common clinical conditions.

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Title: Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene
Authors: Lina E. Aguirre
Georgia Colleluori
David Robbins
Richard Dorin
Vallabh O. Shah
Rui Chen
Irum Zeb Jan
Clifford Qualls
Dennis T. Villareal
Reina Armamento-Villareal
Publication date: 01-09-2019
Publisher: Springer US
Keywords: Testosterone
Estradiol
Published in: Endocrine / Issue 3/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-019-02008-6

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Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene

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