Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis.

A Pizzocaro, W Vena, R Condorelli, A Radicioni, G Rastrelli, D Pasquali, R Selice, A Ferlin, C Foresta, E A Jannini, M Maggi, A Lenzi, R Pivonello, A M Isidori, A Garolla, S Francavilla, G Corona

Journal: Journal of endocrinological investigation 2021;43(12):1675-1687

PMID: 32567016

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Abstract

PURPOSE

Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls.

METHODS

We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search.

RESULTS

Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls.

CONCLUSION

TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.

Address: Unit of Endocrinology, Diabetology and Medical Andrology, IRCSS, Humanitas Research Hospital, Rozzano, Milan, Italy.; Unit of Andrology and Endocrinology, University Teaching Hospital "Policlinico-Vittorio Emanuele", Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.; Department of Experimental Medicine, Sapienza University of Rome - Policlinico Umberto I Hospital, Rome, Italy.; Careggi Hospital, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.; Department of Advanced Medical and Surgical Science, University of Campania "Luigi Vanvitelli", Naples, Italy.; Centre for Klinefelter Syndrome, Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Via Gustavo Modena 9, 35121, Padua, Italy.; Endocrine and Metabolic Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; 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.; Staff of UNESCO Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy.; Unit of Medical Andrology, Departments of Life, Health and Environmental Sciences, San Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.; Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Bologna, Italy. [email protected].

DOI: 10.1007/s40618-020-01299-1

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MeSH Terms: Adult, Body Composition, Body Mass Index, Bone Density, Humans, Hypogonadism, Klinefelter Syndrome, Male, Middle Aged, Testosterone