ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP65 | DOI: 10.1530/endoabs.63.GP65

Testosterone replacement therapy outcomes in subjects with Klinefelter syndrome: preliminary results from a meta-analysis study

Walter Vena1, Alessandro Pizzocaro1, Fiore Pelliccione2, Rosario Pivonello3, Antonio Radicioni4, Riccardo Selice5, Giulia Rastrelli6, Daniela Pasquali7, Aldo Eugenio Calogero8, Alberto Ferlin9, Sandro Francavilla10, Andrea Garolla5 & Giovanni Corona11


1Endocrinology Unit, Humanitas Research Hospital, Rozzano (Milan), Italy; 2Diabetology and Metabolic Disease Unit, F. Renzetti Hospital, Lanciano (Chieti), Italy; 3Clinical Medicine and Surgery Department, University or Naples Federico II, Naples, Italy; 4Section of Medical Pathophysiology, Center of Rare Diseases, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; 5Department of Medicine, Andrology and Reproductive Medicine Unit, University of Padova, Padua, Italy; 6Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 7Department of Cardiothoracic and Respiratory Sciences, Endocrine Unit, Second University of Naples, Naples, Italy; 8Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy, Catania, Italy; 9Department of Clinical and Experimental Medicine, University of Brescia, Brescia, Italy; 10Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy; 11Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Bologna, Italy.


Background: In patients with Klinefelter syndrome (KS) morbidity and mortality seem to be higher than general population, this depending on a wide number of possible comorbidities. Impaired metabolic profile, increased risk of venous thrombosis and the consequent increase of cardiovascular diseases might play a key role in this condition as well as reduced bone mineral density and higher fracture risk. Nowadays testosterone replacement therapy (TRT) is the first-choice treatment for this condition, but no evidence so far has been able to define its positive role in this population related to metabolic, cardiovascular and bone-related outcomes.

Objective: The aim of this study is to meta-analyze currently available data reporting about metabolic, cardiovascular and bone metabolism parameters before and after TRT in KS subjects.

Methods: An extensive Medline search was performed, including the following words: ‘klinefelter’ [All Fields] AND ‘testosterone’ [All Fields]. The search was restricted to English-language articles and studies including humans published up to December 31th, 2017. All trials reporting TRT metabolic outcomes in hypogonadal KS in comparison to healthy controls or untreated hypogonadal KS without any arbitrary restriction were included.

Results: Out of 525, 20 trials were included, enrolling 1060 KS patients and 806 age-matched controls with a mean age of 30.8±4.9 years. Among the studies included, 15 reported information on body composition and/or on metabolic profile whereas only 4 and 2, included outcomes on bone and cardiovascular parameters, respectively. Meta-analysis of the data showed a significant increase of body-mass index (BMI) (mean difference 1.17 kg/m2), body fat mass (mean difference 1.27 SD), waist circumference (mean difference 11.61 cm) and plasma fasting glucose (mean difference 0.26 mmol/L), total cholesterol (mean difference 0.22 mmol/L) and LDL cholesterol (mean difference 0.59 mmol/L) in untreated KS patients compared to age-matched controls (P< 0.01, CI 95%). A significant improvement was observed for body fat mass (P<0.01, CI 95%), LDL cholesterol (P=0.02) and waist circumference (P=0.03) but not for plasma fasting glucose (P=0.09), comparing treated vs untreated KS patients. Finally, comparison of treated KS to age-matched control showed an improvement of BMI, total cholesterol and LDL cholesterol, but persistence of significant difference between two groups (P<0.05). Similar results were observed when bone and cardiovascular outcomes were considered.

Conclusions: Our preliminary results suggest that TRT can only partially improve metabolic profile as well as body composition. Reduction of CV risk in treated KS patients should be confirmed through specific RCT.