Incomplete bone density normalisation following long-term reproductive hormone treatment in male hypogonadotropic hypogonadism: a systematic review and meta-analysis

de Silva Nipun Lakshitha; Elizabeth Hyams; Bonnie Grant; Paras Dixit; Rajdeep Bassi; Paul Bassett; Alexander N. Comninos; Channa N. Jayasena

doi:10.1530/endoabs.117.P65

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Endocrine Abstracts (2026) 117 P65 | DOI: 10.1530/endoabs.117.P65

SFEBES2026 Poster Presentations Bone and Calcium (28 abstracts)

Incomplete bone density normalisation following long-term reproductive hormone treatment in male hypogonadotropic hypogonadism: a systematic review and meta-analysis

Nipun Lakshitha de Silva ^1,2 , Elizabeth Hyams ¹ , Bonnie Grant ¹ , Paras Dixit ¹ , Rajdeep Bassi ¹ , Paul Bassett ³ , Alexander N. Comninos ^1,4 & Channa N. Jayasena ¹

Author affiliations

¹Section of Investigative Medicine, Imperial College London, Commonwealth Building, Hammersmith Hospital, London, United Kingdom; ²Department of Clinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka; ³Statsconsultancy Ltd, Amersham, United Kingdom; ⁴Endocrine Bone Unit, Imperial College Healthcare NHS Trust, London, United Kingdom

Background: Men with hypogonadotropic hypogonadism (HH) are predisposed to reduced bone mineral density (BMD) and fracture risk. While reproductive-hormone therapy improves bone parameters, the degree of skeletal recovery and normalisation remains uncertain, and the long-term trajectory of bone health in this population is not well defined. We aimed to synthesise evidence on BMD in men with HH, compare values with healthy eugonadal men, and evaluate whether reproductive-hormone therapy achieves normalisation of BMD.

Methods: We systematically searched OVID Medline, Embase, CINAHL, Scopus, Web of Science, and the Cochrane Library from inception to July 2024 for studies reporting BMD or fracture outcomes in men with HH. Study selection and data extraction were performed using COVIDENCE and a pre-specified data extraction tool. Meta-analysis compared lumbar-spine (LS) BMD between HH and controls, and meta-regression assessed relationships of LS and femoral-neck (FN) Z-scores with treatment duration and HH subtype.

Results: Twenty-five studies meeting inclusion criteria reported 625 men with HH. LS BMD was significantly lower in HH than healthy controls (standardised mean difference −5.98; 95% CI −11.5 to −0.47; P = 0.03). Pooled mean Z-scores were −0.87 (LS) and −0.70 (FN). Meta-regression showed lower Z-scores in congenital vs acquired HH at LS (coefficient −2.28; P = 0.027) and FN (coefficient −1.31; P = 0.0049), with a non-significant trend toward higher LS Z-scores with longer treatment duration (+0.07 per year; P = 0.094). Younger age at treatment initiation, partial HH, and higher sex hormone concentrations were associated with better BMD. Among studies that reported fracture outcomes, prevalence ranged from 17–23%.

Conclusion: Reproductive-hormone therapy improves BMD in men with HH but does not fully restore skeletal health, particularly in congenital cases. Persistent bone deficits highlight the importance of early diagnosis, optimised long-term hormone replacement, and prospective studies to clarify fracture risk and define bone-recovery potential.