Progesterone Resistance, Aromatase, and Inflammation: The Important Relationships Between Hormones and Inflammation

Abstract

Endometriosis is a complex gynecologic disorder in which alterations of specific biological processes involving both the endocrine and the immune systems have been identified. Recently, a reduced endometrial responsiveness to progesterone has been suggested as a crucial element in the pathophysiology of the disease but it is unclear whether this reduced sensitivity to the steroid is involved in the disease induction or is simply a consequence of the disease condition. Indeed, endometriosis is associated with a local and systemic inflammatory process that is strongly inter-related to the steroid activity, and both the systems mutually interact in a complex loop that strongly influences the disease development and maintenance. The link between prostaglandin E2 (PGE2), aromatase activity, and local estrogen synthesis represents a paradigm of this loop. A better understanding of the pathophysiology of this interaction should enable researchers to develop targeted therapeutics that may limit this self-supporting pathologic loop.