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Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism

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Abstract

Introduction and aim

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones.

Methods

12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number).

Results

Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites.

Conclusions

Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

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Abbreviations

AR:

Androgen receptor

TRT:

Testosterone replacement therapy

BMD:

Bone mineral density

FT4:

Free T4

FT3:

Free T3

FSH:

Follicle stimulating hormone

LH:

Luteinizing hormone

Δ-:

Variations

GH:

Growth hormone

IGF-1:

Insulin-like growth factor-1

PTH:

Parathyroid hormone

CTX:

C-terminal telopeptide of collagen type I

PCR:

Polymerase chain reaction

NS:

Not significant

CI:

Confidence interval

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Acknowledgments

The Authors are very grateful to Mrs. Monica Glebocki for language editing and to Dr. Roberta Papa (Centre of Socio-economic Gerontological Research, Scientific-Technological Area, INRCA, Ancona, Italy) for statistical advice. This work was in part supported by a MIUR grant (PRIN 2009, Protocol 2009FW5SP3_002).

Conflict of interest

All authors have no conflict of interest.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Via Conca 71, 60126, Ancona, Italy

    G. Tirabassi, N. delli Muti, A. Gioia, A. Biagioli & G. Balercia

  2. Andrology Pathophysiology of Reproduction and Endocrine Diagnosis Unit, Policlinic Umberto I, University of Rome “La Sapienza”, Rome, Italy

    A. Lenzi

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  1. G. Tirabassi
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  2. N. delli Muti
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  3. A. Gioia
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  5. A. Lenzi
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  6. G. Balercia
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Correspondence to G. Balercia.

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Tirabassi, G., delli Muti, N., Gioia, A. et al. Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism. J Endocrinol Invest 37, 393–400 (2014). https://doi.org/10.1007/s40618-014-0052-2

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