The impact of mild Leydig cell dysfunction following cytotoxic chemotherapy on bone mineral density (BMD) and body composition

BACKGROUND Overt testosterone deficiency is associated with a reduction in BMD and alteration in body composition. However, there are few data concern ing the impact of mild hypogonadism on these parameters. PATIENTS AND METHOD We have identified a cohort of 36 men aged <55 years wi th mild Leydig cell impairment, defined by a raised LH level (LH greater th an or equal to 8 IU/I) in the presence of a testosterone level in the lower half of the normal range or frankly subnormal (< 20 nmol/l), following tre atment with procarbazine-containing chemotherapy regimens or high-dose chem otherapy for haematological malignancy. These men underwent measurements of BMD (measured by dual-energy X-ray absorptiometry (DXA), single energy X-r ay absorptiometry (SXA) and quantitative CT (QCT)), body composition (DXA), markers of bone turnover, serum lipids and serum IGF-1, To allow for chang es that may be directly attributable to the underlying disease or its treat ment, results were compared with those obtained in 14 men who had received the same chemotherapy for the same diseases but had normal LH and testoster one levels (controls), RESULTS When data from all 50 men were considered together there were signi ficant 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 significa ntly 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 per centage fat between the patients and controls. There was, however, a differ ence in the distribution of body fat with a propensity for the patients to accrue truncal fat, and the serum testosterone level significantly inversel y correlated with percentage of truncal fat (r= - 0.29, P = 0.04). There we re no significant differences in lipid levels, IGF-1 levels or markers of b one turnover between the patients and controls. CONCLUSIONS These data suggest that mild Leydig cell impairment may have si gnificant effects on bone mineral density and may result in subtle body com position changes, although in men who have received cytotoxic chemotherapy, other factors also contribute to the observed osteopenia. Testosterone rep lacement may be beneficial in some of these men and this requires further e valuation.