Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia.
OBJECTIVE
To assess whether dopamine receptor 2 agonists reduced the size of peritoneal lesions in women with endometriosis and elucidate whether affectation of vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2)-dependent angiogenesis was mediating the observed effects.


METHODS
Proof-of-concept study.


METHODS
University hospital and a university-affiliated private IVF research center.


METHODS
Hyperprolactinemic patients (n = 9) with endometriosis requiring a first surgical intervention (L1) and benefiting from a second-look laparoscopy (L2) were evaluated.


METHODS
During L1, four to six peritoneal red lesions were identified. One-half of the lesions were removed and the remaining one-half were labeled with silk knot sutures. After L1, quinagolide was administered in a titrated manner (25-75 μg/d) for 18-20 weeks. During L2, the remaining lesions were surgically excised.


METHODS
Both L1 and L2 were video recorded to compare the effects of quinagolide treatment on lesion size. Lesions removed at L1 and L2 were compared by means of: 1) histologic analysis; 2) immunohistochemical quantitative analysis of angiogenesis; and 3) quantitative fluorescence polymerase chain reaction array analysis of 84 chemokines and pro-/antiangiogenic molecules.


RESULTS
Quinagolide induced a 69.5% reduction in the size of the lesions, with 35% vanishing completely. Histologic analysis showed tissue degeneration, which was supported by down-regulation of VEGF/VEGFR2, three proangiogenic cytokines (CCL2, RUNX1, and AGGF1) and plasminogen activator inhibitor (PAI) 1, a potent inhibitor of fibrinolysis in the L2 lesions.


CONCLUSIONS
By interfering with angiogenesis, enhancing fibrinolysis, and reducing inflammation, quinagolide reduces or eliminates peritoneal endometriotic lesions in women with endometriosis.
Instituto Universitario Instituto Valenciano de Infertilidad, Valencia University School of Medicine and Fundación Investigación Clínico Valencia, Valencia, Spain.
Raul
R
Gómez
Antonio
A
Abad
Francisco
F
Delgado
Silvia
S
Tamarit
Carlos
C
Simón
Antonio
A
Pellicer
D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D004715:Endometriosis / Q000150:complications* / Q000235:genetics / Q000601:surgery; D004717:Endometrium / Q000473:pathology / Q000502:physiology / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006966:Hyperprolactinemia / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D010535:Laparoscopy; D010349:Patient Compliance; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012720:Severity of Illness Index
D000634:Aminoquinolines; D018491:Dopamine Agonists; C046650:quinagolide