Short-term buserelin administration induces apoptosis and morphological changes in adult rat testes

Abstract Purpose: To investigate the effect of buserelin on gonadal structure and function in adult male rats. Methods: Twenty-four adult Wistar male rats were divided into three groups: two treated groups and controls. The first and second treated groups received 300 (low dose) and 500 (high dose) µg/kg buserelin, respectively, and the control group received normal saline. All groups were treated subcutaneously for five days. Results: The seminiferous tubular epithelial thickness was significant decreased in the treated groups compared with those in the control. There was a significant increase in apoptotic cell death in high dose treated group compared with low dose treated and control groups. No significant difference in serum testosterone level was observed after one month in the three groups. Conclusion: Buserelin induces apoptotic cell death and decreased diameter and epithelium thickness of seminiferous tubules in the adult rat testes.

Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue

INTRODUCTION: Infertility is the primary concern for boys with uni- or bilateral undescended testes. An early and seemingly successful orchiopexy does not improve fertility in a substantial number of cryptorchid males. We confirmed that LH-RH analogue (LH-RHa) treatment induces an increase in and maturation of the germ cells; however, it was uncertain if treatment would improve the chance of fertility later in life. MATERIALS AND METHODS: Thirty unilateral cryptorchid boys, with an average age of 3 years at the time of surgery, were included in the study. Testicular biopsy showed that they had impaired testicular maturation and were therefore at high risk for infertility. Fifteen of the 30 unilateral cryptorchid boys were treated with 10 µg LH-RHa (Buserelin) nasal spray, administered on alternate days for a period of 6 months, following orchiopexy. The control group consisted of 15 cryptorchid boys who had been treated by Schoemakers type of orchiopexy, alone. After puberty, the ejaculates of both groups were analyzed. RESULTS: All males in the untreated group were severely oligospermic, with 20 percent being azoospermic. In contrast, 86 percent of the treated ex-cryptorchid males had a sperm concentration within the normal range; this was significantly different from the sperm concentration found in the untreated group (p = 0.000008). CONCLUSION: For the first time, we demonstrate that infertility in cryptorchidism can be successfully corrected when suitably treated with a LH-RHa. Sperm parameters normalized following therapy in the majority of cryptorchid males who, untreated, would have remained infertile. This innovative hormonal treatment will have a profound effect on the current recommended surgical treatment of boys with undescended testes.

Buserelin acetate implants in the treatment of pain in endometriosis.

OBJECTIVE: To examine the treatment of pain in endometriosis by buserelin acetate implants. DESIGN: Fourteen patients with laparoscopically confirmed pelvic endometriosis were included in the study. All presented with severe dysmenorrhea with or without deep dyspareunia and pelvic pain. Buserelin acetate 6.6 mg. Implants were injected subcutaneously in the lateral region of the anterior abdominal wall, 3 doses every 8 weeks in group 1 (n=7) and 2 doses every 12 weeks in group 2 (n=7). Bone mineral density (BMD) was measured at the lumbar spine by dual energy X-ray absorptiometry (DEXA) before initiation of treatment and 1 year after. Symptoms, pelvic examination, ultrasonogram and serum estradiol were recorded every 4 weeks until two regular menses were established. RESULTS: All the painful symptoms were relieved and eventually disappeared in every patient within 4-6 weeks. Mean duration of amenorrhea in group 1 (408.4+/-47.7 days) was significantly longer than group 2 (331.3+/-22.4 days), p < 0.01. Mean duration of first observed side effects was 2.7+/-1.6 weeks. Hot flushes were the most common side effects. Serum estradiol levels were below 15 pg/ml in all patients and there were no significant differences between the two groups during amenorrhea. There was significant bone loss in both groups, 6.49+/-4.90 per cent in group 1 and 7.71+/-5.67 per cent in group 2. However, there were no significant differences between the two groups for lumbar BMD before and after treatment. CONCLUSION: Buserelin acetate implants are effective in the treatment of pain in endometriosis. These implants should have an important clinical application when chronic treatment is indicated. Further study is needed to design how this preparation should be used to minimize the adverse effects.

Supressäo hipofisária com altas doses do agonista do hormônio liberador de gonatrofinas / Pituitary suppresion with high dosage of gonadotropin releasing hormone agonist

Neste trabalho, quatro mulheres voluntárias, ovulatórias foram submetidas a administraçäo diária do agonista do hormônio liberador de gonadotrofinas (aGnRH). O aGnRH (Buserelin) foi administrado intranasal na dose de 900 ug/dia durante 12 dias dividio em 3 doses de 300 ug, iniciando-se as 8:00hs. Amostras sanguíneas foram colhidas diariamente, imediatamente antes da primeria dose do Buserelin (8:00hs), sendo que nos dias 1, 4, 8 e 12 foram colhidos 3 amostras adicionais 60, 120 e 180 minutos após a primeira amostra. Avaliaram-se os níveis plasmáticos do hormônio luteinizante (LH), hormônio folículo estimulante (FSH e estradiol (E2). A administraçäo do aGnRH resultou inicialmente numa grande liberaçäo do LH (média de 60 mUI/ml) e do FSH (média de 20 mUI/ml) no 2§ dia, com queda progressiva a partir do 3§ dia, com estabilizaçäo a partir do 7§ dia, em valores em torno de 10 mUI/ml para ambos hormônios. A desensibilizaçäo hipofisária já foi observada a partir do quarto dia do ciclo, visto que houve um aumento do LH, após a administraçäo do aGnRH, nas amostras colhidas aos 180 minutos de apenas 79,3 por cento no quarto dia, contra 1.642 por cento nas amostras do primeiro dia. Para o FSH o incremento do 1§ dia foi de 162 por cento contra 25 por cento do 4§ dia. Os níveis de E2 apresentaram queda de seus valores a partir do 7§ dia, sendo que mostraram-se abaixo de 60pg/ml no 12§ dia, apesar dos níveis de LH e FSH se situarem em torno de 10mUI/ml. Os resultados sugerem que embora mantenha níveis razoáveis circulantes de LH e FSH mesmo no 12§ dia, a partir do 4§ dia, a hipófise já seria refratária ao GnRH endógeno e que os níveis plasmáticos de LH e FSH näo deveriam ser considerados como parâmetros para avaliaçäo do tempo necessário para a supressäo hipofisária quando do uso do aGnRH