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

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

doi:10.1007/s12020-019-02008-6

Cited by 10 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is a secondary analysis using the baseline data from 2 clinical trials in veterans who volunteered to be screened for the study evaluating the effect polymorphisms in the CYP19A1 gene on the response to testosterone therapy in men with hypogonadism (NCT: 01378299) between October 2011 to November 6, 2016 ( 9 , 10 ) and part of the population of men who screened between May 2018 to October 2019 for the study on the effect of aromatase inhibitors and weight loss in obese men with hypogonadism (NCT: 03490513) ( 11 , 12 ). There were 105 men from the former and 112 from the latter study were included in this analysis.…”

Section: Methodsmentioning

confidence: 99%

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

et al. 2021

Self Cite

View full text Add to dashboard Cite

BackgroundEmerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.MethodA cross-sectional analysis of baseline data was obtained from 217 men, ages 35–65, regardless of the presence or absence of hypogonadism or T2D, who participated in 2 clinical trials. The following data were obtained: A1c by HPLC, testosterone and estradiol by LC/MS, bone turnover markers Osteocalcin [OC], C-terminal telopeptide [CTx], and sclerostin by ELISA, and BMD by DXA. Patients were grouped into 4 categories based of A1c (group I: <6%, group II: 6.0–6.4%, group III: 6.5–6.9%, and group IV: ≥7%). Threshold models were fit to the data using nonlinear regression and group comparisons among the different A1c categories performed by ANOVA.ResultsThreshold model and nonlinear regression showed an A1c cut-off of 7.0, among all choices of A1cs, yields the least sum of squared errors. A comparison of bone turnover markers revealed relatively lower OC (p = 0.002) and CTx (p = 0.0002) in group IV (A1c ≥7%), compared to the other groups. An analysis of men with T2D (n = 94) showed relatively lower OC (p=0.001) and CTx (p=0.002) in those with A1c ≥7% compared to those with <7%, respectively. The significance between groups persisted even after adjusting for medications and duration of diabetes.ConclusionAn analysis across our entire study population showed a breakpoint A1c level of 7% or greater is associated with lower bone turnover. Also in men with T2D, an A1c ≥7% is associated with low bone turnover.

show abstract

Section: Methodsmentioning

confidence: 99%

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…First, the severity of hypogonadism obviously influences the amount of circulating serum E2. Second, several associated clinical conditions may modulate aromatase expression and estrogen production 61,67‐69 . As an example, obesity may boost estrogen production even in the presence of low serum T in hypogonadal men through an increased rate of aromatization of androgens, thus preventing both relative estrogen deficiency and bone loss 68 .…”

Section: Pathophysiology Of T Deficiency and Its Metabolites In Bonementioning

confidence: 99%

“…Second, several associated clinical conditions may modulate aromatase expression and estrogen production. 61,[67][68][69] As an example, obesity may boost estrogen production even in the presence of low serum T in hypogonadal men through an increased rate of aromatization of androgens, thus preventing both relative estrogen deficiency and bone loss. 68 Third, individual genetic differences may predispose to relative estrogen deficiency on equal serum T levels.…”

Section: Late-onset Hypogonadism Relative Estrogen Deficiency Andmentioning

confidence: 99%

“…1 Both polymorphisms of the ER-alpha gene 70,71 and of the gene encoding for the aromatase enzyme 72,73 are associated with bone loss in men. Individual genetic differences influencing the expression and activity of the aromatase enzyme have been well-characterized in recent years 61,68,69,72,73 ( Figure 1). By using a genome-wide association study and Mendelian randomization analysis on a large number of men, several genetic variants of the aromatase enzyme resulted directly related to the amount of circulating E2 and BMD as the genetically determined increase of 1 pg/mL of serum E2 corresponded to a BMD increase of 0.048 standard deviation at lumbar spine.…”

Section: Late-onset Hypogonadism Relative Estrogen Deficiency Andmentioning

confidence: 99%

“…60,148 Men with LOH treated with TRT should expect that TRT may help in preventing further bone loss and increase BMD especially in men with very low serum T at baseline. 146 In order to have beneficial effects on bone, TRT should ensure serum T levels at least above 200 ng/dL 20,79 and, if accurate assays for estradiol are available, a serum E2 above 20 pg/mL 1,34,61,68,69 in order to exert a protective role on bone (Figure 1). In this perspective, serum T and serum E2 may be considered reliable targets of TRT for bone health.…”

Section: Effec Ts Of T Tre Atment On Bone In Loh Patientsmentioning

confidence: 99%

See 2 more Smart Citations

Late‐onset Hypogonadism: Bone health

Rochira

2020

Andrology

View full text Add to dashboard Cite

Background Bone health is underdiagnosed and undermanaged in men. Bone loss occurs in men with hypogonadism and in aging men. Thus, patients with a diagnosis of late‐onset hypogonadism (LOH) are at risk of osteoporosis and osteoporotic fractures. Objectives To provide an update on research data and clinical implications regarding bone health in men with LOH by reviewing literature articles on this issue. Materials and Methods A thorough search of listed publications in PubMed on bone health in older men with hypogonadism was performed, and other articles derived from these publications were further identified. Results Late‐onset Hypogonadism may be associated with reduced bone mineral density (BMD). In a pathophysiological perspective, the detrimental effects of testosterone (T) deficiency on BMD are partly ascribed to relative estrogen deficiency and both serum T and serum estradiol (E2) need to be above 200 ng/dL and 20 pg/mL to prevent bone loss. The effects of exogenous T on BMD are controversial, but most of the studies confirm that testosterone replacement therapy (TRT) increases BMD and prevents further bone loss in men with hypogonadism. No data are available on TRT and the prevention of fractures. Discussion and Conclusion In men with documented LOH, a specific clinical workup should be addressed to the diagnosis of osteoporosis in order to program subsequent follow‐up and consider specific bone active therapy. TRT should be started according to guidelines of male hypogonadism while keeping in mind that it may also have positive effects also on bone health in men with LOH.

show abstract

Estrogens and Male Osteoporosis

Rochira

Madeo

2020

Trends in Andrology and Sexual Medicine

View full text Add to dashboard Cite

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

Cited by 10 publications

References 40 publications

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

Late‐onset Hypogonadism: Bone health

Estrogens and Male Osteoporosis

Contact Info

Product

Resources

About