title: The impact of mild Leydig cell dysfunction following cytotoxic chemotherapy on bone mineral density (BMD) and body composition.
abstract: BACKGROUND
  Overt testosterone deficiency is associated with a reduction in BMD and alteration in body composition. However, there are few data concerning the impact of mild hypogonadism on these parameters.
  
  
  METHODS
  We have identified a cohort of 36 men aged < 55 years with mild Leydig cell impairment, defined by a raised LH level (LH >/= 8 IU/l) in the presence of a testosterone level in the lower half of the normal range or frankly subnormal (< 20 nmol/l), following treatment with procarbazine-containing chemotherapy regimens or high-dose chemotherapy for haematological malignancy. These men underwent measurements of BMD (measured by dual-energy X-ray absorptiometry (DXA), single energy X-ray absorptiometry (SXA) and quantitative CT (QCT)), body composition (DXA), markers of bone turnover, serum lipids and serum IGF-1. To allow for changes that may be directly attributable to the underlying disease or its treatment, results were compared with those obtained in 14 men who had received the same chemotherapy for the same diseases but had normal LH and testosterone levels (controls).
  
  
  RESULTS
  When data from all 50 men were considered together there were significant reductions in BMD of the lumbar spine both by DXA (Z = - 0.34, P = 0.01) and QCT (Z = - 1.5, P < 0. 0001), at the femoral neck (Z = - 0.52, P < 0.0001) and distal forearm (Z = - 0.21, P = 0.05). Mean femoral neck BMD was significantly lower in patients compared with controls (Z = - 0.68 vs. Z = - 0.11, P = 0.05) and there was a nonsignificant trend towards lower lumbar spine BMD measured by QCT (Z = - 1.64 vs. Z = - 1.10; P = 0.09). In addition, serum testosterone level and testosterone:LH ratio significantly correlated with femoral neck BMD (r = 0.28, P = 0.05 and r = 0.37, P = 0.008, respectively). There were no significant differences in lean body mass, fat mass and percentage fat between the patients and controls. There was, however, a difference in the distribution of body fat with a propensity for the patients to accrue truncal fat, and the serum testosterone level significantly inversely correlated with percentage of truncal fat (r = - 0.29, P = 0.04). There were no significant differences in lipid levels, IGF-1 levels or markers of bone turnover between the patients and controls.
  
  
  CONCLUSIONS
  These data suggest that mild Leydig cell impairment may have significant effects on bone mineral density and may result in subtle body composition changes, although in men who have received cytotoxic chemotherapy, other factors also contribute to the observed osteopenia. Testosterone replacement may be beneficial in some of these men and this requires further evaluation.
authors.affiliation: Departments of Endocrinology, Medical Oncology, Christie Hospital NHS Trust, Withington, Manchester, University of Manchester, Manchester, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Howell
authors.forename: J A
authors.initials: JA
authors.lastname: Radford
authors.forename: J E
authors.initials: JE
authors.lastname: Adams
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D005272:Femur Neck / Q000503:physiopathology; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011344:Procarbazine / Q000009:adverse effects* / Q000627:therapeutic use; D011884:Radius / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000172:deficiency*
chemical_list: D000970:Antineoplastic Agents; D011344:Procarbazine; D013739:Testosterone; D007986:Luteinizing Hormone