Incomplete evidence of bone density normalization following long-term reproductive hormone treatment in men with hypogonadotropic hypogonadism
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Context
The prevalence and severity of low bone mineral density (BMD) in hypogonadotropic hypogonadism (HH), as well as the ability of reproductive hormone treatment to normalize BMD have not been investigated in large multicenter studies.
Objective
We performed a systemic review and meta-analysis of several small, observational studies to investigate the effect of reproductive hormone treatment on BMD in men with HH compared with control groups where available.
Methods
We searched OVID Medline, Embase, CINAHL, SCOPUS, Web of Science, and Cochrane Library for studies reporting BMD or fractures in men with HH (congenital [CHH] or acquired). Study selection and data extraction were performed using COVIDENCE and a prespecified tool. Results were summarized using descriptive statistics. Meta-analysis compared BMD in men with HH vs healthy controls. Meta-regression assessed relationships between treatment duration and BMD Z-scores against normative population data.
Results
Of the 33 eligible studies, 24 included data specific to men with HH (n = 625). Men with HH had low lumbar spine (LS) and femoral neck BMD, improving with hormonal treatment. Meta-analysis of 5 studies found lower LS BMD in men with HH vs healthy controls (SMD −5.98; 95% CI; −11.5 to −0.47). Men with CHH may have persistently low BMD despite prolonged hormonal treatment. Higher BMD in HH was associated with younger age at treatment initiation, partial HH, and higher serum testosterone and estradiol concentrations. Fracture prevalence was high in the few studies systematically studying fractures as an outcome; in other studies, fractures were seldom reported.
Conclusion
Men with HH have low BMD that improves with reproductive hormone treatment. However, current evidence suggests that incomplete BMD normalization may be common despite long-term reproductive hormone treatment in men with HH, particularly those with CHH.
The prevalence and severity of low bone mineral density (BMD) in hypogonadotropic hypogonadism (HH), as well as the ability of reproductive hormone treatment to normalize BMD have not been investigated in large multicenter studies.
Objective
We performed a systemic review and meta-analysis of several small, observational studies to investigate the effect of reproductive hormone treatment on BMD in men with HH compared with control groups where available.
Methods
We searched OVID Medline, Embase, CINAHL, SCOPUS, Web of Science, and Cochrane Library for studies reporting BMD or fractures in men with HH (congenital [CHH] or acquired). Study selection and data extraction were performed using COVIDENCE and a prespecified tool. Results were summarized using descriptive statistics. Meta-analysis compared BMD in men with HH vs healthy controls. Meta-regression assessed relationships between treatment duration and BMD Z-scores against normative population data.
Results
Of the 33 eligible studies, 24 included data specific to men with HH (n = 625). Men with HH had low lumbar spine (LS) and femoral neck BMD, improving with hormonal treatment. Meta-analysis of 5 studies found lower LS BMD in men with HH vs healthy controls (SMD −5.98; 95% CI; −11.5 to −0.47). Men with CHH may have persistently low BMD despite prolonged hormonal treatment. Higher BMD in HH was associated with younger age at treatment initiation, partial HH, and higher serum testosterone and estradiol concentrations. Fracture prevalence was high in the few studies systematically studying fractures as an outcome; in other studies, fractures were seldom reported.
Conclusion
Men with HH have low BMD that improves with reproductive hormone treatment. However, current evidence suggests that incomplete BMD normalization may be common despite long-term reproductive hormone treatment in men with HH, particularly those with CHH.
Date Issued
2026-01-01
Date Acceptance
2025-10-01
Citation
Journal of Clinical Endocrinology and Metabolism (JCEM), 2026, 111 (1), pp.280-290
ISSN
0021-972X
Publisher
Oxford University Press
Start Page
280
End Page
290
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism (JCEM)
Volume
111
Issue
1
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for add itional terms.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41032457
PII: 8270757
Subjects
Kallmann syndrome
bone mineral density
fractures
hypogonadotropic hypogonadism
metabolic bone disease
osteoporosis
Publication Status
Published
Coverage Spatial
United States
Article Number
dgaf488
Date Publish Online
2025-10-01