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Testosterone supplementation and bone parameters: a systematic review and meta-analysis study

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Abstract

Background

The role of testosterone (T) replacement therapy (TRT) in subjects with late onset hypogonadism is still the object of an intense debate.

Methods

All observational studies and placebo-controlled or -uncontrolled randomized trials (RCTs) comparing the effect of TRT on different bone parameters were considered.

Results

Out of 349 articles, 36 were considered, including 3103 individuals with a mean trial duration of 66.6 weeks. TRT improves areal bone mineral density (aBMD) at the spine and femoral neck levels in observational studies, whereas placebo-controlled RTCs showed a positive effect of TRT only at lumber spine and when trials included only hypogonadal patients at baseline (total testosterone < 12 nM). The effects on aBMD were more evident in subjects with lower T levels at baseline and increased as a function of trial duration and a higher prevalence of diabetic subjects. Either T or estradiol increase at endpoint contributed to aBMD improvement. TRT was associated with a significant reduction of bone resorption markers in observational but not in controlled studies.

Conclusion

TRT is able to inhibit bone resorption and increase bone mass, particularly at the lumbar spine level and when the duration is long enough to allow the anabolic effect of T and estrogens on bone metabolism to take place.

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Author information

Authors and Affiliations

  1. Endocrinology Unit, Medical Department, Azienda Usl, Maggiore-Bellaria Hospital, Bologna, Italy

    G. Corona

  2. Unit of Endocrinology, Diabetology and Medical Andrology, IRCSS, Humanitas Research Hospital, Rozzano, Milan, Italy

    W. Vena, A. Pizzocaro & G. Mazziotti

  3. Santa Maria Hospital, GVM Care & Research, Bari, Italy

    V. A. Giagulli

  4. Unit of Internal Medicine and Endocrinology, Madonna Delle Grazie Hospital, Velletri, Rome, Italy

    D. Francomano

  5. Andrology, Women’s Endocrinology and Gender Incongruence Unit, Mario Serio Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

    G. Rastrelli & L. Vignozzi

  6. Department of Biomedical Sciences, Humanitas University, Milan, Italy

    G. Mazziotti

  7. Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy

    A. Aversa

  8. Department of Experimental Medicine, Sapienza University of Rome-Policlinico Umberto I Hospital, Rome, Italy

    A. M. Isidori

  9. Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Unità di Andrologia e Medicina della Riproduzione e della Sessualità Maschile e Femminile, Università Federico II di Napoli, Naples, Italy

    R. Pivonello

  10. UNESCO Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy

    R. Pivonello

  11. Department of Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy

    E. Mannucci

  12. Endocrinology Unit, Mario Serio Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    M. Maggi

  13. Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy

    A. Ferlin

Authors
  1. G. Corona
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  2. W. Vena
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  3. A. Pizzocaro
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  4. V. A. Giagulli
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  5. D. Francomano
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  6. G. Rastrelli
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  7. G. Mazziotti
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  8. A. Aversa
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  9. A. M. Isidori
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  10. R. Pivonello
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  11. L. Vignozzi
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  12. E. Mannucci
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  13. M. Maggi
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  14. A. Ferlin
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Corresponding author

Correspondence to M. Maggi.

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Corona, G., Vena, W., Pizzocaro, A. et al. Testosterone supplementation and bone parameters: a systematic review and meta-analysis study. J Endocrinol Invest 45, 911–926 (2022). https://doi.org/10.1007/s40618-021-01702-5

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  • DOI: https://doi.org/10.1007/s40618-021-01702-5

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