CHARACTERIZATION OF PROGESTERONE RESISTANCE IN A PROSPECTIVE COHORT OF SURGICALLY CONFIRMED PATIENTS WITH OR WITHOUT ENDOMETRIOSIS

Retrospective studies of endometriosis have suggested that progesterone resistance may contribute to invasive disease, and that progesterone receptor status was strongly associated with response to progestin-based therapies. However, the association between progesterone resistance and invasive endometriotic lesions has not been well characterized in a prospective cohort of surgically confirmed disease. The objective of this study was to determine the association of clinically defined progesterone resistance in a well characterized cohort of endometriosis patients scored using the rASRM classification of endometriosis. The study was an IRB approved, prospective, observational study of females undergoing laparoscopic surgery for endometriosis (cases) or other gynecological conditions (controls). We defined progesterone resistance as a medical treatment failure with the patient deciding to move to a GnRH agonists/antagonist or to surgery rather than remain on oral contraceptives. Concomitant medication use was confirmed by a participant interview to identify a clinically apparent phenotype of progesterone resistance. The r-ASRM classification was used to score lesions at surgery and the diagnosis was confirmed by histopathology. Lesions were also categorized as superficial peritoneal lesions, typically red, black or white; or deep lesions, typically infiltrating or nodular. Results were compared using descriptive statistics and non-parametric tests. Of the 90 study participants, 24 had no endometriosis. Of the 66 cases with endometriosis, 24 had Stage I disease, 9 had Stage II, 7 had Stage III, and 23 had Stage IV endometriosis. The prevalence of progesterone resistance in controls was 20.8%. The percentage of progesterone resistance significantly decreased with increased endometriosis severity of staging using the rASRM classification system in cases from 58.3% (Stage I), to 55.5% (Stage II), 30% (Stage III), and 21.7 % (Stage IV)( p<0.01). Of the 66 study participants with endometriosis, 16 had superficial endometriosis lesions and 50 had deeply infiltrative or nodular endometriosis. When participants with ovarian endometriomas were compared to deeply infiltrating or nodular peritoneal lesions, the study subjects with deeply infiltrating peritoneal or nodular lesions had a 47.8% prevalence of progesterone resistant disease compared to subjects with ovarian endometriomas (25.92%). Contrary to expectation, clinically apparent progesterone resistance decreased with higher rASRM disease severity score. Patients with deeply infiltrating peritoneal and nodular lesions were found to have a higher percent of progesterone resistant disease than patients with ovarian endometriomas.