Body Composition by DXA in Patients with Klinefelter and Kallmann Syndrome: The Kama Study

Caterina Buoso; Andrea Delbarba; Matteo Riva; Giulia Artifoni; Elisa Gatta; Davide Farina; Eugenia Quiros-Roldan; Alberto Ferlin; Carlo Cappelli

doi:10.1210/clinem/dgaf565

Bone Health Hormones and Bone

Body Composition by DXA in Patients with Klinefelter and Kallmann Syndrome: The Kama Study

Buoso C, Delbarba A, Riva M, Artifoni G, Gatta E, Farina D, Quiros-Roldan E, Ferlin A, Cappelli C

Published March 17, 2026 The Journal of clinical endocrinology and metabolism

DOI 10.1210/clinem/dgaf565 PMID 41073368 PMC PMC13016807

RRM Academy Synopsis

On testosterone, Klinefelter men had less limb lean mass than Kallmann

A single-center retrospective study of 50 men on testosterone replacement found men with Klinefelter syndrome had less limb lean mass than men with Kallmann syndrome. DXA scans showed low muscle mass with excess body fat in about 21 out of 100 men with Klinefelter syndrome and 5 out of 100 with Kallmann syndrome. Bone density did not differ significantly.

Key Findings

The study included 50 men, 29 with Klinefelter syndrome and 21 with Kallmann syndrome, all receiving testosterone replacement therapy.
Appendicular lean mass index was 8.37 ± 1.15 kg/m² in Kallmann syndrome and 7.28 ± 1.20 kg/m² in Klinefelter syndrome (P < .001).
Radiologic sarcopenic obesity affected 7 men (14%): 6 of 29 with Klinefelter syndrome and 1 of 21 with Kallmann syndrome. Osteosarcopenic obesity affected 2 men (4%), both with Klinefelter syndrome.
Reduced muscle mass appeared in 12 men (24%) and reduced bone mineral density in 13 men (26%). Bone mineral density showed no significant difference between the two syndromes.
Higher follicle-stimulating hormone (FSH) was associated with lower appendicular lean mass index, before and after adjustment for confounders (P = .002 in both models).

Interpretation

A retrospective cohort study examined 50 men on testosterone therapy at one hospital. Of these, 29 men had Klinefelter syndrome and 21 had Kallmann syndrome. The authors note that testosterone therapy in every man made it hard to separate the effects of the therapy from the effects of the condition itself. They point to follicle-stimulating hormone, plus estradiol and a hormone called INSL3, as possible reasons for the lean mass gap. The findings support larger studies of body composition in these two conditions.

RRM Context

Klinefelter and Kallmann syndromes cause low testosterone in men. Both bear on male fertility. Restorative reproductive medicine evaluates both partners, so the male hormone picture belongs in the evaluation from the start.

Our editorial summary of this paper, not the article's abstract.

Abstract

Context

Klinefelter syndrome and Kallmann syndrome are 2 rare genetic disorders characterized by reduced testosterone (T) levels but differing in their gonadotrophin profiles. To date, no studies have directly compared body composition in these 2 syndromes.

Objective

This work aimed to assess the prevalence of altered body composition parameters in patients with Klinefelter and Kallmann syndromes and to compare body composition between the 2 groups. Secondary objectives included evaluating associations between body composition, bone mineral density (BMD), and serum follicle-stimulating hormone (FSH) levels.

Methods

This single-center, retrospective observational study included 50 patients, 29 with Klinefelter and 21 with Kallmann syndrome receiving T replacement therapy. Body composition was evaluated using whole-body dual-energy x-ray absorptiometry (DXA), which provided measurements of appendicular lean mass (ALM), total body fat (TBF), visceral adipose tissue (VAT), the ALM-to-height² ratio (appendicular lean mass index, ALMI), and the ALM-to-weight ratio.

Results

Radiologic sarcopenic obesity was identified in 7 patients (14%; 6/29 Klinefelter, 1/21 Kallmann), while osteosarcopenic obesity was found in 2 patients (4%), both with Klinefelter syndrome. Patients with Kallmann syndrome had significantly higher ALMI values than those with Klinefelter syndrome (8.37 ± 1.15 vs 7.28 ± 1.20 kg/m²; P < .001). Univariable analysis revealed an inverse association between FSH levels and ALMI (B = -0.026; P = .002), which remained statistically significant after adjustment for confounders (B = -0.030; P = .0022).

Conclusion

This study demonstrated a significant difference in lean mass between Klinefelter and Kallmann syndromes, supporting a potential role for FSH in modulating muscle mass independently of T levels.

Topics

Bone Health

Hormones and Bone Estrogen and Bone

Bone Health › Hormones and Bone › Estrogen and Bone

Caterina Buoso, Andrea Delbarba, Matteo Riva, Giulia Artifoni, Elisa Gatta, Davide Farina, Eugenia Quiros-Roldan, Alberto Ferlin, Carlo Cappelli

C Buoso, A Delbarba, M Riva, G Artifoni, E Gatta, D Farina, E Quiros-Roldan, A Ferlin, C Cappelli

PMID 41073368 41073368 DOI 10.1210/clinem/dgaf565 10.1210/clinem/dgaf565 Buoso et al. 2026, Buoso 2026

Body Composition by DXA in Patients with Klinefelter and Kallmann Syndrome: The Kama Study

On testosterone, Klinefelter men had less limb lean mass than Kallmann

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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