Objective: To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues.
Methods: In 32 women with endometriomas (17 untreated and 15 treated with GnRH analogue) and 21 with ovarian cystadenomas, we examined the expression of secretory leukocyte protease inhibitor messenger RNA (mRNA) by Northern blot analysis; protein distribution was measured immunohistochemically. Concentrations of secretory leukocyte protease inhibitor in peritoneal fluid were measured by enzyme-linked immunosorbent assay. Expression of secretory leukocyte protease inhibitor in endometrioma explants in vitro was also studied with and without the GnRH analogue treatment.
Results: Secretory leukocyte protease inhibitor mRNA expression was identified only in untreated endometriomas. In the GnRH agonist-treated endometriomas, the semiquantitative H-score for secretory leukocyte protease inhibitor immunostaining was significantly lower than that for untreated endometriomas (P < .001). The peritoneal fluid of the GnRH agonist-treated women also contained significantly lower concentrations of secretory leukocyte protease inhibitor (median 76 ng/mL, interquartile range 51–131 ng/mL; P < .001) than untreated women (124 ng/mL, 70–186 ng/mL). Secretory leukocyte protease inhibitor in endometrioma explants in vitro was significantly inhibited by the GnRH analogue (P < .05).
Conclusion: Expression of secretory leukocyte protease inhibitor in tissue and peritoneal fluid of women with ovarian endometriomas was decreased by GnRH agonist treatment.
Endometriosis is relatively common, mostly affecting the extrauterine pelvic cavity. Transcripts of secretory leukocyte protease inhibitor have been localized in the epithelium with ovarian, peritoneal, and rectovaginal endometriosis by in situ hybridization.1 Our immuno-histochemical studies found that secretory leukocyte protease inhibitor localized in epithelial cells of ovarian endometriomas.1.
A molecule sized 12 kDa, secretory leukocyte protease inhibitor inhibits elastase, cathepsin G, trypsin, chymotrypsin, and mast cell chymase.2–4 It is contained in human cervical, nasal, and bronchial mucus under pathophysiologic conditions5,6 and helps protect mucosas from injury associated with inflammation.3 Recent findings suggested that secretory leukocyte protease inhibitor production by cervical tissues is regulated by ovarian hormones.7
Although data concerning the relation between endometriomas and secretory leukocyte protease inhibitor are limited, our previous findings suggested that secretory leukocyte protease inhibitor may have a great influence on the pathogenesis of ovarian endometriomas,1 which grow progressively and invasively in an estrogen-dependent manner.8 In most affected women, induction of hypoestrogenism using a GnRH agonist results generally in temporary involution, but not complete regression, of endometriotic implants.9,10 It also has been reported that more than half of ovarian endometriomas are decreased in size by treatment with drainage and GnRH agonist.11 The induced hypogonadal state causes regression, which allows for symptomatic improvement.12
The effects of GnRH agonist therapy on the production of secretory leukocyte protease inhibitor and the significance of secretory leukocyte protease inhibitor expression in endometriomas are unclear. Secretion of secretory leukocyte protease inhibitor under the influence of GnRH analogues and estradiol (E2) in vitro has yet to be elucidated. The present study was designed to measure secretory leukocyte protease inhibitor production by ovarian endometriomas in women with or without GnRH agonist treatment.
Expression of secretory leukocyte protease inhibitor in tissue and peritoneal fluid of women with ovarian endometriomas is suppressed by GnRH agonist treatment.
Department of Obstetrics and Gynecology, Nagoya City University Medical School, Nagoya; the Department of Anatomy (2), Fukui Medical University, Fukui, Japan; and the Department of Pathology, Baylor College of Medicine, Houston, Texas.
Address reprint requests to: Nobuhiro Suzumori, MD, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: email@example.com
Received July 5, 2000. Received in revised form December 6, 2000. Accepted December 7, 2000.