The Clinical Effect of Leydig Cell Dysfunction

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A significant proportion of men have evidence of impairment of Leydig cell function after high-dose chemotherapy, procarbazine-containing chemotherapy, or radiation involving the testis. The biochemical abnormalities are usually mild and consist of a raised LH level associated with a low/normal testosterone level. A deleterious effect of overt testosterone deficiency and a clear benefit of androgen replacement in such patients on bone density, body composition, and quality of life, has been well demonstrated. However, there are few data concerning the effect of milder forms of testosterone deficiency.

Howell et al. (22) investigated a cohort of men treated with MVPP, ChlVPP/EVA hybrid, or high-dose chemotherapy for several malignancies. They identified a cohort of 35 men with biochemical evidence of mild Leydig cell insufficiency, as defined by a raised LH level and a testosterone level in the lower half of the normal range or, frankly, subnormal. They demonstrated significantly reduced bone mineral density at the hip in these men compared with a similarly treated cohort with normal hormone levels and found some evidence of altered body composition, reduced sexual activity, and mood alterations (42,43). The men were then enrolled into a 12-mo randomized, single-blind placebo-controlled testosterone replacement trial (44). However, during the 12-mo study period, there were no significant improvements in bone density, body composition, sexual function, energy levels, or mood in the testosterone-treated group compared with the controls.

Thus, it seems likely that the mild biochemical abnormalities (raised LH and low/normal testosterone) observed in many men after cytotoxic chemotherapy are of limited clinical importance in the majority of patients and that androgen replacement cannot be routinely recommended for such patients. However, it remains possible that a minority of men with more marked biochemical abnormalities may benefit from androgen therapy.

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