Khaleque N Khan1, Akira Fujishita2, Hideki Muto3, Hiroshi Masumoto3, Kanae Ogawa4, Akemi Koshiba4, Taisuke Mori4, Kyoko Itoh5, Satoshi Teramukai6, Katsuya Matsuda7, Masahiro Nakashima7, Jo Kitawaki4. 1. Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, 602-8566 Kyoto, Japan. Electronic address: nemokhan@koto.kpu-m.ac.jp. 2. Department of Gynecology, Saiseikai Nagasaki Hospital, 2-5-1, Katafuchi, 850-0000 Nagasaki, Japan. 3. Biomedical Research Support Center, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852-8523 Nagasaki, Japan. 4. Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, 602-8566 Kyoto, Japan. 5. Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, 602-8566 Kyoto, Japan. 6. Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, 602-8566 Kyoto, Japan. 7. Department of Molecular and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852-8523 Nagasaki, Japan.
Abstract
OBJECTIVE: We examined the hypothesis that antibiotic treatment with or without gonadotropin releasing hormone agonist (GnRHa) may decrease intrauterine infection with consequent decrease in tissue inflammation, cell proliferation and angiogenesis in human endometriosis. STUDY DESIGN: This is a prospective non-randomized observational study. Endometrial/endometriotic samples were collected during surgery from 53 women with endometriosis and 47 control women who were treated with levofloxacin (LVFX, 500 mg, once per os) or GnRHa (1.88 mg/IM for 3 months) before surgery. Endometrial samples were analyzed by broad-range polymerase-chain reaction (PCR) amplification of bacteria targeting V5-V6 region of 16S rRNA gene. Immunohistochemical analysis was performed using antibodies against CD138 (Syndecan-1, a marker of plasma cells), CD68 (marker of macrophages), Ki-67 (cell proliferation marker), and CD31 (vascular cells marker). RESULTS: 16S rDNA metagenome assay indicated that treatment with either of LVFX or GnRHa + LVFX significantly decreased some components of major bacterial genera comparing to untreated group. In women with endometriosis, treatment with either of LVFX or GnRHa + LVFX significantly decreased Gardnerella, Prevotella, Acidibactor, Atopobium, Megasphaera, and Bradyrhizobium (p < 0.05 for each) comparing to untreated group. Cochran-Mantel-Haenszel test indicated that occurrence rate of chronic endometritis was significantly decreased after GnRHa + LVFX treatment comparing to GnRHa treatment group (p = 0.041). These findings were coincided with significantly decreased CD68-stained macrophage infiltration, Ki-67- stained cell proliferation and CD31-stained micro-vessel density in endometria and endometriotic lesions with histology proven improvement in the morphological appearance of ovarian endometrioma. CONCLUSIONS: These findings suggest that clinical administration of a broad-spectrum antibiotic with or without GnRHa may be effective in improving uterine infection with decrease of tissue inflammation, cell proliferation, and angiogenesis in human endometriosis.
OBJECTIVE: We examined the hypothesis that antibiotic treatment with or without gonadotropin releasing hormone agonist (GnRHa) may decrease intrauterine infection with consequent decrease in tissue inflammation, cell proliferation and angiogenesis in human endometriosis. STUDY DESIGN: This is a prospective non-randomized observational study. Endometrial/endometriotic samples were collected during surgery from 53 women with endometriosis and 47 control women who were treated with levofloxacin (LVFX, 500 mg, once per os) or GnRHa (1.88 mg/IM for 3 months) before surgery. Endometrial samples were analyzed by broad-range polymerase-chain reaction (PCR) amplification of bacteria targeting V5-V6 region of 16S rRNA gene. Immunohistochemical analysis was performed using antibodies against CD138 (Syndecan-1, a marker of plasma cells), CD68 (marker of macrophages), Ki-67 (cell proliferation marker), and CD31 (vascular cells marker). RESULTS: 16S rDNA metagenome assay indicated that treatment with either of LVFX or GnRHa + LVFX significantly decreased some components of major bacterial genera comparing to untreated group. In women with endometriosis, treatment with either of LVFX or GnRHa + LVFX significantly decreased Gardnerella, Prevotella, Acidibactor, Atopobium, Megasphaera, and Bradyrhizobium (p < 0.05 for each) comparing to untreated group. Cochran-Mantel-Haenszel test indicated that occurrence rate of chronic endometritis was significantly decreased after GnRHa + LVFX treatment comparing to GnRHa treatment group (p = 0.041). These findings were coincided with significantly decreased CD68-stained macrophage infiltration, Ki-67- stained cell proliferation and CD31-stained micro-vessel density in endometria and endometriotic lesions with histology proven improvement in the morphological appearance of ovarian endometrioma. CONCLUSIONS: These findings suggest that clinical administration of a broad-spectrum antibiotic with or without GnRHa may be effective in improving uterine infection with decrease of tissue inflammation, cell proliferation, and angiogenesis in human endometriosis.