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023 Concentration of adiponectin in peritoneal fluid is decreased in women with endometriosis
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European Journal o f Obstetrics & Gynecology and Reproductive Biology 123 (2005) S 1 ~ 6 6
consequences, providing the best diagnostic benefit and the utilization of the adequate therapy, keeping the appropriate functions of the organism and for prevention of all those factors that may cause sterility and to program the treatment. Considering the ethiopathogenesis of this enigmatic disease (increase of aromatase, induced by growth factors and cytokines, endometrial progesterone resistance increase, hipoapoptosis, increase of TNF, granulocites and angiogenesis), the treatment with hyperapoptic, hypoangiogenic and immunomodulatory drugs was started in 2002. Desogestrel: hyperapoptotic: broader empathy of receptors to progesterone, low empathy of estrogenic and androgenic receptors, reduction of the serum concentration of LH and FSH, suppression of follicular development, absence of luteinization, lower endometrial proliferation, avoiding the secretory transformation: double effect: contraceptive and hyperapoptic protection: immune histochemic localization of the DNA fragmentation by deoxy nucleotidyl transferase. Arginine: Immunomodulators: reduces granulocytes and TNF, inhibits fagocytosis, dioxins generation and proteolytic enzymes, which means that it increases the immunologic response. Celicoxib: hypoangiogenic. Age: between 14 and 31 years old. Echography: 70 cysts not exceeding 20 ram, 10 with cysts bigger than 20 ram, 100 without echographic pathology. Microlaparoscopy: following the principal basis of microsurgery: 107 endometriosis at different stages, 12 pelvic varicocele, 25 adhesions, 36 without pathology. Comments: The no utilization of levonorgestrel was due to the alteration of the hydro carbonate metabolism. Results: The experience carried out proved that the use of these three drugs produced an objective pain relief and prevention from recurrence, that was confirmed by symptoms, CA 125, ecography and second look until today. Conclusions: With this, we believe in pursuing a common goal that is the enhancement of quality of life of women with endometriosis, protecting their future fertility, and that may be used for every young woman suffering from this disease around the world.
prescribed NSAIDs and five of the 19 patients took no NSAIDs, and these data suggested a degree of pain relief with LTR-A (p=0.0002). Four of 10 infertility patients treated with LTR-A became pregnant at 3 4 months after surgery and have already given birth. No case discontinued to treat, because of the side effect. Conclusions: Our findings revealed that LTR-A has significant therapeutic value for treatment of human endometriosis. Anti-LT therapy must have a significant therapeutic effect, relieves some clinical symptoms, inhibits mast cell activation, decreases stromal proliferation and adhesion formation, and improving infertility for endometriosis. We believe that the anti-LT therapy is a promising new treatment modality for human endometriosis.
References [1] Fertil Steril 2002; 78: 782-786. [2] Am J Reprod Immunol 2005; 53: 120-125. [3] Fertil Steril 2004; 81: 819-823.
I~'-~ A new look at menstruation: the anatomy of shedding and regeneration R. Garry, J. Crewe. University of WesternAustralia, Perth, Australia The surface layers of the endometrium are shed in an irregular manner during menstruation and the endometrial epithelium subsequently regenerates within 48 72 hours. It has been widely accepted that this repair originates from epithelial cells produced at the distal ends of the residual glandular stumps. This regeneration however occurs at a time of minimal estrogen mitogenic stimulation and without obvious mitotic activity. We wish to present new hysteroscopic, scanning electron microscopic and immunohistochemical images of menstruation. From a detailed analysis of these images we hypothesise that endometrial epithelial repair does not occur primarily from residual gland stumps but from stem cells located in the stroma. We also hypothesise that endometrial glandular and stromal cells are also regenerated by means of differentiation from stems cells of mesodermal origin.
I~ I-~A
new therapy for human endometriosis: the therapeutic value of leukotriene receptor antagonist for endometriosis patients
M.S. Sugamata 1 , T.I. Ihara 1 , I.U. Uchiide2, M.M. Miura 1 . ]Tochigi Institute
of Clinical Pathology, Tochigi, Japan," 2Japan Red Cross Hospital Omori, Tokyo, Japan Background/Objective: We have reported that hypersensitivity reaction is observed in lesion of endometriosis patients [1,2] and leukotriene receptor antagonist (LTR-A), which is one of anti-allergic drugs, has a significant therapeutic effect in experimental rat endometriosis [3]. In this study, to evaluate that effect on anti-leukotriene (LT) therapy on human endometriosis, we examined endometriosis patients both with and without LTR-A treatment. Design: Clinical and pathological evaluation of treatment study. Patients/Methods: 25 cases (including 10 infertility cases, mean age; 32.7±7.80) of endometriosis taken LTR-A (Montelukast sodium; 10rag/day. The mean treatment period; 66.7 days [rain: 14 days; max: 90 days]) were examined laparoscopically and evaluated formation of fibrous adhesion by r-AFS score. As comparative control, 20 endometriosis patients (including 10 infertility cases, mean age; 30.4±6.98) with no treatment at all were also examined and evaluated. The mean number and SD of r-AFS score were calculated, and comparison of the score mean in between LTR-A and no treatment cases was made using Mann Whitney U test, and the correlation between the score and the LTR-A treatment period was also made using Spearman rank correlation coefficient. The tissues collected from these patients by laparoscopic surgery were examined morphologically. With regard to the evaluation of pain control by LTR-A treatment, the quantity of prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) for 19 patients, who complained of a dysmenorrhea and had taken NSAIDs customarily, on LTR-A (the mean period for LTR-A treatment: 73.6 days [rain: 56 days, max: 90 days]) was investigated, and evaluated using Nonparametric one sample sign test. All examinations were performed in the patients after informed consent in accordance with the Helsinki declaration. Results: In LTR-A treatment cases, a significant decrease of r-AFS score was observed laparoscopically when compared with no treatment cases (p < 0.0001), furthermore, a significant correlation between the r-AFS score and LTR-A treatment period was found (p < 0.0001). And the severe adhesions of pelvic organs were relived and detached easily in laparoscopic surgery. Morphologically, the LTR-A treatment cases showed numerous apoptotic fibroblasts and collagen fibers became filamentous, thin and partially condensed or disappeared in the lesions. Moreover, eight of the 19 patients had a decrease in ingestion of
Concentration of adiponectin in peritoneal fluid is decreased in women with endometriosis
Y. Takemura, Y. Osuga, M. Harada, T. Hirata, K. Koga, O. Yoshino, "L Hirota, C. Morimoto, T. Yano, xL Taketani. University of Tokyo, Tokyo, Japan Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by the growth of endometrial tissue in the peritoneal cavity. Adiponectin is a novel adipocytokine of extreme importance for the metabolism. Recent studies have indicated that adiponectin suppresses inflammation, angiogenesis, and fibrosis, which are central pathogenic factors for endometriosis. To investigate possible implication of adiponectin in endometriosis, concentrations of adiponectin in peritoneal fluid (PF) of women with endometriosis (stage I/iI, n = 22; stage Ill/IV, n = 32) and without endometriosis (n = 26) were measured using specific enzyme-linked immunosorbent assay. The degree of endometriosis was evaluated according to the revised American Society for Reproductive Medicine (rASRM) classification. Adiponectin concentrations in PF of women with endometriosis (median, 2.06ug/ml; IQR, 1.70 2.39) were significantly lower than those of women without endometriosis (2.36ug/ml, 1.95 2.72, P=0.04). With respect to the stages of the disease, the concentrations of adiponectin in women with stage Ill/iV endometriosis (1.79ug/ml, 1.61 2.23) were significantly lower than in those without endometriosis (P = 0.002) and with stage I/II endometriosis (2.25ug/ml, 2.02 2.83, P=0.003 vs. stage IIl/W). Body mass indices were comparable among the groups. Furthermore, there were significant inverse relationships of PF adiponectin levels with rASRM total scores (r = 0.361, P=0.001), endometriosis scores (r= 0.320, P=0.004) and adhesion scores (r= 0.268, P=0.02) in combined population without endometriosis and with endometriosis. Concentrations of adiponectin in PF of women with posterior cul-de-sac obliteration (n=21, 1.79 ug/ml, 1.60 2.17) were significantly lower than those of women without posterior cul-de-sac obliteration (n=59, 2.21 ug/ml, 1.89 2.71, P =0.003). These findings imply that adiponectin may be an anti-endometriotic factor, possibly due to its anti-inflammatory, anti-angiogenic, and anti-fibrotic properties.
I'~
GnRH II as a possible cytostatic regulator in the development of endometriosis
C. Morimoto, "L Osuga, T. Yano, "L Takemura, M. Harada, T. Hirata, Y. Hirota, O. Yoshino, K. Koga, ~L Taketani. University of Tokyo, Tokyo, Japan Background: GnRH II is the second form of GnRH, which is widely distributed in peripheral tissues of the female reproductive tract as well as in the central
European Journal o f Obstetrics & Gynecology and Reproductive Biology 123 (2005) S 1 ~ 6 6
consequences, providing the best diagnostic benefit and the utilization of the adequate therapy, keeping the appropriate functions of the organism and for prevention of all those factors that may cause sterility and to program the treatment. Considering the ethiopathogenesis of this enigmatic disease (increase of aromatase, induced by growth factors and cytokines, endometrial progesterone resistance increase, hipoapoptosis, increase of TNF, granulocites and angiogenesis), the treatment with hyperapoptic, hypoangiogenic and immunomodulatory drugs was started in 2002. Desogestrel: hyperapoptotic: broader empathy of receptors to progesterone, low empathy of estrogenic and androgenic receptors, reduction of the serum concentration of LH and FSH, suppression of follicular development, absence of luteinization, lower endometrial proliferation, avoiding the secretory transformation: double effect: contraceptive and hyperapoptic protection: immune histochemic localization of the DNA fragmentation by deoxy nucleotidyl transferase. Arginine: Immunomodulators: reduces granulocytes and TNF, inhibits fagocytosis, dioxins generation and proteolytic enzymes, which means that it increases the immunologic response. Celicoxib: hypoangiogenic. Age: between 14 and 31 years old. Echography: 70 cysts not exceeding 20 ram, 10 with cysts bigger than 20 ram, 100 without echographic pathology. Microlaparoscopy: following the principal basis of microsurgery: 107 endometriosis at different stages, 12 pelvic varicocele, 25 adhesions, 36 without pathology. Comments: The no utilization of levonorgestrel was due to the alteration of the hydro carbonate metabolism. Results: The experience carried out proved that the use of these three drugs produced an objective pain relief and prevention from recurrence, that was confirmed by symptoms, CA 125, ecography and second look until today. Conclusions: With this, we believe in pursuing a common goal that is the enhancement of quality of life of women with endometriosis, protecting their future fertility, and that may be used for every young woman suffering from this disease around the world.
prescribed NSAIDs and five of the 19 patients took no NSAIDs, and these data suggested a degree of pain relief with LTR-A (p=0.0002). Four of 10 infertility patients treated with LTR-A became pregnant at 3 4 months after surgery and have already given birth. No case discontinued to treat, because of the side effect. Conclusions: Our findings revealed that LTR-A has significant therapeutic value for treatment of human endometriosis. Anti-LT therapy must have a significant therapeutic effect, relieves some clinical symptoms, inhibits mast cell activation, decreases stromal proliferation and adhesion formation, and improving infertility for endometriosis. We believe that the anti-LT therapy is a promising new treatment modality for human endometriosis.
References [1] Fertil Steril 2002; 78: 782-786. [2] Am J Reprod Immunol 2005; 53: 120-125. [3] Fertil Steril 2004; 81: 819-823.
I~'-~ A new look at menstruation: the anatomy of shedding and regeneration R. Garry, J. Crewe. University of WesternAustralia, Perth, Australia The surface layers of the endometrium are shed in an irregular manner during menstruation and the endometrial epithelium subsequently regenerates within 48 72 hours. It has been widely accepted that this repair originates from epithelial cells produced at the distal ends of the residual glandular stumps. This regeneration however occurs at a time of minimal estrogen mitogenic stimulation and without obvious mitotic activity. We wish to present new hysteroscopic, scanning electron microscopic and immunohistochemical images of menstruation. From a detailed analysis of these images we hypothesise that endometrial epithelial repair does not occur primarily from residual gland stumps but from stem cells located in the stroma. We also hypothesise that endometrial glandular and stromal cells are also regenerated by means of differentiation from stems cells of mesodermal origin.
I~ I-~A
new therapy for human endometriosis: the therapeutic value of leukotriene receptor antagonist for endometriosis patients
M.S. Sugamata 1 , T.I. Ihara 1 , I.U. Uchiide2, M.M. Miura 1 . ]Tochigi Institute
of Clinical Pathology, Tochigi, Japan," 2Japan Red Cross Hospital Omori, Tokyo, Japan Background/Objective: We have reported that hypersensitivity reaction is observed in lesion of endometriosis patients [1,2] and leukotriene receptor antagonist (LTR-A), which is one of anti-allergic drugs, has a significant therapeutic effect in experimental rat endometriosis [3]. In this study, to evaluate that effect on anti-leukotriene (LT) therapy on human endometriosis, we examined endometriosis patients both with and without LTR-A treatment. Design: Clinical and pathological evaluation of treatment study. Patients/Methods: 25 cases (including 10 infertility cases, mean age; 32.7±7.80) of endometriosis taken LTR-A (Montelukast sodium; 10rag/day. The mean treatment period; 66.7 days [rain: 14 days; max: 90 days]) were examined laparoscopically and evaluated formation of fibrous adhesion by r-AFS score. As comparative control, 20 endometriosis patients (including 10 infertility cases, mean age; 30.4±6.98) with no treatment at all were also examined and evaluated. The mean number and SD of r-AFS score were calculated, and comparison of the score mean in between LTR-A and no treatment cases was made using Mann Whitney U test, and the correlation between the score and the LTR-A treatment period was also made using Spearman rank correlation coefficient. The tissues collected from these patients by laparoscopic surgery were examined morphologically. With regard to the evaluation of pain control by LTR-A treatment, the quantity of prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) for 19 patients, who complained of a dysmenorrhea and had taken NSAIDs customarily, on LTR-A (the mean period for LTR-A treatment: 73.6 days [rain: 56 days, max: 90 days]) was investigated, and evaluated using Nonparametric one sample sign test. All examinations were performed in the patients after informed consent in accordance with the Helsinki declaration. Results: In LTR-A treatment cases, a significant decrease of r-AFS score was observed laparoscopically when compared with no treatment cases (p < 0.0001), furthermore, a significant correlation between the r-AFS score and LTR-A treatment period was found (p < 0.0001). And the severe adhesions of pelvic organs were relived and detached easily in laparoscopic surgery. Morphologically, the LTR-A treatment cases showed numerous apoptotic fibroblasts and collagen fibers became filamentous, thin and partially condensed or disappeared in the lesions. Moreover, eight of the 19 patients had a decrease in ingestion of
Concentration of adiponectin in peritoneal fluid is decreased in women with endometriosis
Y. Takemura, Y. Osuga, M. Harada, T. Hirata, K. Koga, O. Yoshino, "L Hirota, C. Morimoto, T. Yano, xL Taketani. University of Tokyo, Tokyo, Japan Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by the growth of endometrial tissue in the peritoneal cavity. Adiponectin is a novel adipocytokine of extreme importance for the metabolism. Recent studies have indicated that adiponectin suppresses inflammation, angiogenesis, and fibrosis, which are central pathogenic factors for endometriosis. To investigate possible implication of adiponectin in endometriosis, concentrations of adiponectin in peritoneal fluid (PF) of women with endometriosis (stage I/iI, n = 22; stage Ill/IV, n = 32) and without endometriosis (n = 26) were measured using specific enzyme-linked immunosorbent assay. The degree of endometriosis was evaluated according to the revised American Society for Reproductive Medicine (rASRM) classification. Adiponectin concentrations in PF of women with endometriosis (median, 2.06ug/ml; IQR, 1.70 2.39) were significantly lower than those of women without endometriosis (2.36ug/ml, 1.95 2.72, P=0.04). With respect to the stages of the disease, the concentrations of adiponectin in women with stage Ill/iV endometriosis (1.79ug/ml, 1.61 2.23) were significantly lower than in those without endometriosis (P = 0.002) and with stage I/II endometriosis (2.25ug/ml, 2.02 2.83, P=0.003 vs. stage IIl/W). Body mass indices were comparable among the groups. Furthermore, there were significant inverse relationships of PF adiponectin levels with rASRM total scores (r = 0.361, P=0.001), endometriosis scores (r= 0.320, P=0.004) and adhesion scores (r= 0.268, P=0.02) in combined population without endometriosis and with endometriosis. Concentrations of adiponectin in PF of women with posterior cul-de-sac obliteration (n=21, 1.79 ug/ml, 1.60 2.17) were significantly lower than those of women without posterior cul-de-sac obliteration (n=59, 2.21 ug/ml, 1.89 2.71, P =0.003). These findings imply that adiponectin may be an anti-endometriotic factor, possibly due to its anti-inflammatory, anti-angiogenic, and anti-fibrotic properties.
I'~
GnRH II as a possible cytostatic regulator in the development of endometriosis
C. Morimoto, "L Osuga, T. Yano, "L Takemura, M. Harada, T. Hirata, Y. Hirota, O. Yoshino, K. Koga, ~L Taketani. University of Tokyo, Tokyo, Japan Background: GnRH II is the second form of GnRH, which is widely distributed in peripheral tissues of the female reproductive tract as well as in the central