Effects of a synthetic gonadotrophin-releasing hormone agonist, leuprolide, on rut-associated events in male red deer

This study examined the effectiveness of leuprolide, a gonadotrophin-releasing hormone agonist, in suppressing rut-associated events in farmed male red deer. In mid-January (~6 weeks before the rut period in the southern hemisphere) adult red deer (Cervus elaphus scoticus) stags that had been allocated to three groups (n = 10 per group) received leuprolide, administered subcutaneously in a 90-day release formulation, at zero (control), low (22.5 mg) or high (45 mg) doses. Following treatment with leuprolide there was evidence of suppression of mean plasma luteinising hormone concentration that was significant (P < 0.05) at 9 weeks. Mean plasma testosterone concentration of all three groups rose following treatment, then declined prematurely in the low- and high-dose leuprolide-treated groups, so that it was significantly (P < 0.05) suppressed (0.66 ± 0.29 and 2.0 ± 0.88 ng mL–1, low and high dose respectively) in early April when the peak value (9.0 ± 1.94 ng mL–1) was recorded from control stags. A reduction in mean liveweight occurred in all three groups through February–April and this did not differ among treatments. However, a corresponding reduction in mean body condition score was greater in the control stags (P < 0.05). There was little effect of leuprolide treatment on aggressive behaviours, but it lowered roaring frequency in the latter period of the rut. The results indicate that this gonadotrophin-releasing hormone agonist has potential for application in the deer farming industry to suppress undesirable effects of the rut.

Inflammatory myopathy and severe rhabdomyolysis induced by leuprolide acetate therapy for prostate cancer: a case report

Introduction Leuprolide acetate is a synthetic analog of gonadotropin-releasing hormone used for the treatment of prostate cancer. Its side effects are hot flashes, nausea, and fatigue. We report a case of a patient with proximal inflammatory myopathy accompanied by severe rhabdomyolysis and renal failure following the second application of leuprolide acetate. Drug withdrawal and steroid therapy resulted in remission within six weeks of the diagnosis. To the best of our knowledge, our case report describes the second case of leuprolide acetate-induced inflammatory myopathy and the first case of severe leuprolide acetate-induced rhabdomyolysis and renal failure in the literature. Case presentation A 64-year-old Swiss Caucasian man was admitted to the hospital because of progressive proximal muscle weakness, dyspnea, and oliguria. He had been treated twice with leuprolide acetate in monthly doses. We performed a muscle biopsy, which excluded other causes of myopathy. The patient's renal failure and rhabdomyolysis were treated with rehydration and steroid therapy. Conclusion The aim of our case report is to highlight the rare but severe side effects associated with leuprolide acetate therapy used to treat patients with inflammatory myopathy: severe rhabdomyolysis and renal failure.

Organogel à base d'un dérivé de la L-alanine pour la libération prolongée de leuprolide : étude pharmacocinétique et pharmacodynamique chez le rat

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Organogel à base d'un dérivé de la L-alanine pour la libération prolongée de leuprolide : étude pharmacocinétique et pharmacodynamique chez le rat

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Adjuvant Effect of Leuprolide on Stroke: A Case report

Objectives: To contribute to current knowledge on the vascular risk of oestrogens. Materials and methods: A 44-year-old woman received a 11.25 mg Leuprolide exteneded release injection to control bleeding from a 7 cm uterine fibroid tumour; 45 days later, she had a stroke due to right frontal lobe ischaemia. Thrombolysis induced complete remission. Three years previously, while taking a birth control pill, the patient had suffered from a stroke that involved her left temporal lobe. She was heterozygous for Factor V R2 H1299R locus and homozygous for the 4G/4G mutation of the PAI-1 gene. Even though her homocysteine level was normal, the patient was homozygous for the MTHFR C677T mutation and although she had never had severe bleeding, she was also homozygous for Factor XIII V34L. Results and conclusion: This patient’s prothrombotic condition could have been enhanced by leuprolide since its stimulatory effect on oestrogen production would still have been minimally present at the time of cerebral thrombosis.

Modulation of cognition-specific cortical activity by gonadal steroids: A positron-emission tomography study in women

There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4–5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.

Testicular germ cell tumors exhibit evidence of hormone dependence

The aim of this investigation was to test the hypothesis that testicular germ cell tumors (TGCTs) are hormone-dependent cancers. Human TGCT cells were implanted in the left testis of male severe combined immunodeficient mice receiving either no treatment or hormone manipulation treatment [blockade of gonadotropin-releasing hormone secretion and/or signaling using leuprolide or leuprolide plus exogenous testosterone]. Real-time RT-PCR analysis was used to determine the expression profiles of hormone pathway-associated genes. Tumor burden was significantly smaller in mice receiving both leuprolide and testosterone. Real-time RTPCR analysis of follicle-stimulating hormone (FSH) receptor, luteinizing hormone (LH) receptor and P450 aromatase revealed changes in expression in normal testis tissue related to presence of xenograft tumors and manipulation of hormone levels but a complete absence of expression of these genes in tumor cells themselves. This was confirmed in human specimens of TGCT. Reduced TGCT growth in vivo was associated with significant downregulation of LH receptor and P450 aromatase expression in normal testes. In conclusion, manipulation of hormone levels influenced the growth of TGCT in vivo, while the presence of xenografted tumors influenced the expression of hormone-related genes in otherwise untreated animals. Human TGCTs, both in the animal model and in clinical specimens, appear not to express receptors for FSH or LH. Similarly, expression of the P450 aromatase gene is absent in TGCTs. Impaired estrogen synthesis and/or signaling may be at least partly responsible for inhibition of TGCT growth in the animal model. (c) 2005 Wiley-Liss, Inc.