Use of dopamine agonists to target angiogenesis in women with endometriosis.

Abstract

Endometriosis requires medical management during a woman's reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment. Herein, we review experimental and clinical data that investigate this concept. In experimental models of endometriosis, DAs (bromocriptine, cabergoline, quinagolide) downregulate proangiogenic and upregulate antiangiogenic pathways in inflammatory, endothelial and endometrial cells, blocking cellular proliferation and reducing lesion size. Impaired secretion of vascular endothelial growth factor (VEGF) and inactivation of its receptor type-2 are key events. VEGF inhibition also reduces nerve fiber density in lesions. In humans, quinagolide shows similar effects on lesions, and DAs reduce pain and endometrioma size. Moreover, a 20-fold downregulation of Serpin-1, the gene that encodes for plasminogen activator inhibitor 1 (PAI-1), has been observed after DAs treatment. Pentoxifylline, a PAI-1, increases pregnancy rates in women with endometriosis. Thus, the data support the use of DAs in the medical management of endometriosis to reduce lesion size and pain while maintaining ovulation. A combined approach of DAs and pentoxifylline is perhaps a smart way of targeting the disease from a completely different angle than current medical treatments.

• Authors: Nuria Pellicer, Daniela Galliano, Sonia Herraiz, Yu Z Bagger, Joan-Carles Arce, Antonio Pellicer
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 36 Issue 4 Pg. 850-858 (03 18 2021) ISSN: 1460-2350 [Electronic] England
• PMID: 33355352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Dopamine Agonists
• Vascular Endothelial Growth Factor A
• Cabergoline

Topics

• Cabergoline
• Dopamine Agonists (therapeutic use)
• Endometriosis (drug therapy)
• Endometrium
• Female
• Humans
• Pregnancy
• Vascular Endothelial Growth Factor A