Abstract
The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.
Highlights
Testes show a higher incidence of chemotherapy-induced damage (Rivkees & Crawford, 1988; Wang et al, 1980)
The aim of this study was to investigate the effects of the treatment with microcapsules of the agonist D-Trp-6-luteinising hormone-releasing hormone (LH-RH) on the prevention of ovarian damage induced by cyclophosphamide
Three months after discontinuation of treatment, the rats receiving cyclophosphamide alone, had lower body weights than the controls (P
Summary
Testes show a higher incidence of chemotherapy-induced damage (Rivkees & Crawford, 1988; Wang et al, 1980). Several studies on gonadal protection against the damage induced by cytotoxic drugs have been performed in males of different species (Glode et al, 1982; Karashima et al, 1988; Lewis et al, 1985; Nseyo et al, 1985), but the information about females is limited. The evaluation was performed immediately after the cessation of cyclophosphamide administration, and women submitted to chemotherapeutic drugs may progress after several months or several years from a condition of fertility and normal menses to sterility and premature menopause (Chapman et al, 1979). Much additional information is needed to establish whether LH-RH agonists can prevent the delayed manifestations of gonadotoxicity and protect the ovary from injury inflicted by cytotoxic drugs. The ovarian recovery was evaluated after a long-term follow-up
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