Protective Effects of Medroxyprogesterone Acetate on Testicular Cytotoxicity of Doxorubicin in Rats

Jeong, Young Chick; Chai, Soo Eung

Abstract

As the number of long-term survivors is increasing with recent advances of anticancer chemotherapeutics, the late toxic effects of anticancer agents are assuming increased importance. Many young men who have been successfully treated with antineoplastic agents develop azoospermia which persist long after cessation of treatment. Post-pubertal sexual development and spermatogenesis are often unaffected in males who have received chemotherapy before puberty. On the basis of this observation and from animal studies it has been suggested that chemotherapy-induced damage to spermatogenesis can be avoided or at least reduced by the induction of a "resting state" of the testes. This can be achieved by analogues of LH-RH or medroxyprogesterone acetate. The aim of present study was to evaluate protective effect from doxorubicin-induced testicular damage with medroxyprogesterone acetate in rats. 1. Comparing with control group, body weight was not changed in medroxyprogesterone acetate treated group. The rats which received doxorubicin displayed significant weight loss. Body weight was decreased more significantly in group III (doxorubicin only administration) than in group IV (medroxyprogesterone acetate and doxorubicin administrational(p <0.001) 2. Testicular weight was markedly decreased by medroxyprogesterone acetate injection but the weight was increased gradually after cessation of administration. In group III and group IV, testicular weights were also decreased markedly, but there was no difference between two groups(p <0.5 ). 3. Sperm head count was reduced with medroxyprogesterone acetate administration but the count was increased gradually after cessation of administration. In group III and group IV sperm head counts were also decreased but more significantly reduced in group III.( <0.005). 4. Repopulation index was diminished with medroxyprogesterone acetate administration up to medical castration level but repopulation index was returned to nearly normal after cessation of administration. In group III and group IV, repopulation indices were also diminished but more significantly diminished in group III.( p <0.005) With above results we can suggest that temporary interruption of the pituitary gonadal axis with medroxyprogesterone acetate may ameliorate the gonadal toxicity of doxorubicin therapy.