ergoline and Uterine-Diseases

Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50  μg/kg per day oral Cb2, or 50 or 200  μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.

Topics: Animals; Blood Vessels; Cabergoline; Cell Count; Cell Proliferation; Claviceps; Disease Models, Animal; Dopamine Agonists; Endometriosis; Endometrium; Ergolines; Female; Humans; Mice; Neovascularization, Pathologic; Receptors, Dopamine D2; Uterine Diseases; Vascular Endothelial Growth Factor Receptor-2

Cystic endometrial hyperplasia-pyometra (CEH-P) complex is a progesterone-dependent disease that requires medical treatment in bitches intended for breeding. To test the efficacy and safety of a combined protocol and to assess the effect of age, stage of cycle, previous steroid hormone administration and parity on treatment, 29 bitches diagnosed with CEH-P complex were treated daily with cabergoline 5 microg/kg PO and cloprostenol 1 microg/kg SC for 7-14 days, along with supportive antibiotic and hydration therapies. Before treatment, and on Days 3, 7 and 14, all bitches were evaluated clinically and uterine horn diameter measured during trans-abdominal ultrasonography. Twenty-four of 29 bitches were cured by either Day 7 or 14. Nine bitches had mild digestive side effects. Clinical signs related to pyometra began to improve markedly as early as Day 2 of treatment. Uterine diameters decreased (P < 0.05) by Day 3 of treatment, and continued to gradually decrease, reaching normal size by Day 14. Relapses occurred in 6 of 29 cases. Pregnancy was achieved in one of the two young bitches bred after treatment. No significant relationships were found between success rate and age, stage of the estrous cycle, previous hormone administration or parity. Although no variables affecting treatment results could be identified, this combination of compounds was found to be an efficient and safe for treatment of CEH-P.

Topics: Animals; Cabergoline; Cloprostenol; Dog Diseases; Dogs; Dopamine Agonists; Drug Therapy, Combination; Endometrial Hyperplasia; Endometritis; Ergolines; Female; Prostaglandins, Synthetic; Ultrasonography; Uterine Diseases