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Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization

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Abstract

Purpose

Phosphodiesterase type-5 inhibitor administration in diabetic men with erectile dysfunction (ED) is associated with reduced waist circumference. We evaluated potential effects of daily tadalafil administration on body composition and investigated its possible mechanism(s) of action in C2C12 skeletal muscle cells in vitro.

Methods

Forty-three men on stable caloric intake (mean age 48.5 ± 7; BMI 25.5 ± 0.9 kg/m2) complaining mild ED and/or low urinary tract symptoms (LUTS) were randomly assigned to receive tadalafil (TAD) 5 mg/daily (once-a-day=OAD-TAD; n = 23) or 20 mg on-demand (on-demand=OD-TAD; n = 20) for 2 months. Primary outcomes were variations of body composition measured by Dual-energy X-ray absorptiometry; secondary outcomes were ED/LUTS questionnaire scores along with hormone (testosterone, estradiol, insulin) and endothelial function (Endopat2000) variations.

Results

OAD-TAD increased abdominal lean mass (p < 0.01) that returned to baseline after 2 months withdrawal. LUTS scores improved (p<0.01) in OD-TAD while ED scores improved (p < 0.01) in both groups. We found significant improvements in endothelial function (p < 0.05) that directly correlated with serum insulin (p < 0.01; r = 0.3641) and inversely correlated with estradiol levels (p < 0.01; r = 0.3655) even when corrected for potential confounders. Exposure of C2C12 cells upon increasing tadalafil concentrations (10−7 to 10−6 M) increased total androgen receptor mRNA and protein expression as well as myogenin protein expression after 24 and 72 h (2.8 ± 0.4-fold and 1.4 ± 0.02-fold vs. control, respectively, p < 0.05).

Conclusions

Daily tadalafil improved lean mass content in non-obese men probably via enhanced insulin secretion, estradiol reduction, and improvement of endothelial function in vivo. The in vitro increased myogenin and androgen receptor protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor.

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Acknowledgements

The authors thank Dr. Andrea D’Anselmo for revising the English language.

Funding

This study was funded by MIUR Grants (grant number 2015XCR88M_008 to Prof. Antonio Aversa and 052013 to Prof. Silvia Migliaccio) and Ministry of Health Grant (grant number 00829 to Prof. Andrea Lenzi).

Author information

Authors and Affiliations

  1. Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy

    Antonio Aversa

  2. IRCCS SDN, Napoli, Italy

    Simona Fittipaldi

  3. Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, “Sapienza” University of Rome, Rome, Italy

    Davide Francomano, Emanuela A. Greco & Andrea Lenzi

  4. Department of Movement, Human and Health Sciences, Section of Health Sciences, “Foro Italico” University of Rome, Rome, Italy

    Viviana M. Bimonte, Clara Crescioli, Luigi Di Luigi & Silvia Migliaccio

  5. LiSa Laboratory, Policlinico Catania, University of Catania, Catania, Italy

    Emanuela A. Greco

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  1. Antonio Aversa
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Correspondence to Antonio Aversa.

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The authors declare that they have no competing interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (NCT Identifier: NCT02554045).

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Informed consent was obtained from all individual participants included in the study.

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This article does not contain any studies with animals performed by any of the authors.

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Aversa, A., Fittipaldi, S., Francomano, D. et al. Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization. Endocrine 56, 639–648 (2017). https://doi.org/10.1007/s12020-016-1208-y

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