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

• Published in: Journal of endocrinological investigation Vol. 43; no. 12; pp. 1675 - 1687
• Main Authors: Pizzocaro, A., Vena, W., Condorelli, R., Radicioni, A., Rastrelli, G., Pasquali, D., Selice, R., Ferlin, A., Foresta, C., Jannini, E. A., Maggi, M., Lenzi, A., Pivonello, R., Isidori, A. M., Garolla, A., Francavilla, S., Corona, G.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-12-2020; Springer Nature B.V
• Subjects: Age; Blood glucose; Body composition; Body mass index; Bone composition; Bone density; Bone mass; Bone mineral density; Bone turnover; Cardiovascular diseases; Cholesterol; Clinical trials; Endocrinology; High density lipoprotein; Homeostasis; Hypogonadism; Internal Medicine; Klinefelter's syndrome; Low density lipoprotein; Medicine; Medicine & Public Health; Meta-analysis; Metabolic Diseases; Metabolism; Review; Testosterone; Testosterone; Bone mineral density; Klinefelter’s syndrome; Body composition
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-020-01299-1

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.