Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia

Fertil Steril. 2011 Mar 1;95(3):882-8.e1. doi: 10.1016/j.fertnstert.2010.10.024. Epub 2010 Nov 5.

Abstract

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.

Design: Proof-of-concept study.

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

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

Intervention(s): 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.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): By interfering with angiogenesis, enhancing fibrinolysis, and reducing inflammation, quinagolide reduces or eliminates peritoneal endometriotic lesions in women with endometriosis.

Trial registration: ClinicalTrials.gov NCT00625950.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / administration & dosage*
  • Aminoquinolines / adverse effects
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / adverse effects
  • Endometriosis / complications*
  • Endometriosis / genetics
  • Endometriosis / surgery
  • Endometrium / pathology
  • Endometrium / physiology
  • Endometrium / surgery
  • Female
  • Gene Expression Profiling
  • Humans
  • Hyperprolactinemia / drug therapy*
  • Hyperprolactinemia / etiology*
  • Hyperprolactinemia / genetics
  • Laparoscopy
  • Patient Compliance
  • Pilot Projects
  • Polymerase Chain Reaction
  • Prospective Studies
  • Severity of Illness Index

Substances

  • Aminoquinolines
  • Dopamine Agonists
  • quinagolide

Associated data

  • ClinicalTrials.gov/NCT00625950