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The Distinct Activation of Activating Transcription Factor 2 (ATF2) may Play a Crucial Role in Pathogenesis of Endometriosis
antioxidants may be beneficial in endometriosis by increasing eutopic endometrial apoptosis thereby resulting in reduced peritoneal implantation and growth. Supported by: NIH/NICHD 5PO-1 HD35276 (SP, AAM)
P-110 The Distinct Activation of Activating Transcription Factor 2 (ATF2) may Play a Crucial Role in Pathogenesis of Endometriosis. C. S. Chou, P. Y. Lee, P. H. Chen, C. R. Tzeng. Taipei Medical University Hospital, Taipei, Taiwan, Republic of China. OBJECTIVE: Endometriosis is one of the commonest chronic gynecological disorders diagnosed in women of reproductive age. The pathogenetic factors of endometriosis still remain unclear. There is increasing evidence that endometriosis is inherited as a complex genetic trait in which multiple genes conferring disease susceptibility interact with each other and the environment to produce the phenotype. Furthermore, the signaling transduction pathway and transcriptional regulation of this disease are mostly uncharacterized. In the current study, we proposed that activating transcription factor 2 (ATF2) may involve the pathogenesis and unique phenotype of endometriosis. DESIGN: Prospective study MATERIALS AND METHODS: Nuclear extracts were obtained from three endometriosis tissues and normal endometrium tissue. A set of biotinlabeled DNA binding oligonucleotides were incubated with nuclear extracts from endometriosis and normal endometrium tissues respectively and then formed DNA/Transcriptional factor complexes. The DNA/Transcriptional factor complexes were separated from the free probes by protein G beads. The beads and associated TF-probe complexes were washed four times and the probes were eluted. The eluted probes were then hybridized to the array membrane, which consisted of complementary sequences to the probes. The membranes were exposed by using Hyperfilm ECL system. EMSA was performed to verify the results from the transcriptional array. RESULTS: The DNA/Transcriptional factor interaction array identifies ATF2 and associated transcription factors in endometriosis tissues and normal endometrial tissues. ATF2 activity increases several folds in endometriosis tissues comparing to normal endometrium. CONCLUSIONS: Transcription factors (TF) are a group of proteins that regulate gene expression in cell nuclear. The transcription factor activating transcription factor 2 (ATF2) has been reported to transactivate CREcontaining genes or to interfere with transactivation by CREB. We found that ATF2 activity was closely related to the transformation of normal endometrium to endometriosis tissue. Supported by: None
P-111 Thyroid Disorders in Women With Endometriosis. S. Ferrero, B. M. Colombo, P. Anserini, V. Remorgida, N. Ragni. San Martino Hospital, University of Genoa, Genoa, Italy; University of Genoa, Department of Internal Medicine, Genoa, Italy. OBJECTIVE: It has previously been suggested that hypothyroidism is significantly more frequent in women with endometriosis than in the general population. The objective of this study is to determine the prevalence of thyroid disorders in women with and without endometriosis. DESIGN: Retrospective study. MATERIALS AND METHODS: This study included 661 consecutive women with endometriosis and 635 controls (uterine fibroids, n ⫽ 244; ovarian cyst, n ⫽ 190; infertility, n ⫽ 115; pelvic pain, n ⫽ 75; tubal sterilization, n ⫽ 6; hydrosalpinx, n ⫽ 5) who underwent laparoscopy at our Institution. Before surgery, the presence of thyroid disorders was always investigated by the anaesthesiologist; in all cases, both gynaecological and anaesthesiological records were examined. The presence and type of thyroid disorders were evaluated. Findings at laparoscopy and pathological description of specimens removed at surgery were considered for classifying the patient. In women with endometriosis, the severity of the disease was classified according to the revised American Fertility Society (rAFS) classification. Data were analyzed by using by using the t test, the MannWhitney U test, chi-square test, and Fisher’s exact test as appropriate. RESULTS: No significant difference (p ⫽ 0.058) was observed in the
FERTILITY & STERILITY威
mean (⫾ SD) age between women with endometriosis (34.5 ⫾ 6.0 years) and controls (34.7 ⫾ 8.8 years). No significant difference was observed in the prevalence of thyroid disorders between women with endometriosis (38/661, 5.7%, 95%CI, 4.1-7.8) and controls (53/635, 8.3%, 95%CI, 6.310.8) (p ⫽ 0.067; 3.347 2). Women with mild (rAFS stage I-II) and severe (rAFS stage III-IV) endometriosis had similar prevalence of thyroid disorders (p ⫽ 0.659). The prevalence of thyroid disorders was also similar in infertile women with (7.1%, 11/155) and without endometriosis (7.0%, 8/115). Hypothyroidism was significantly less frequent in women with endometriosis (18/661, 2.7%, 95%CI, 1.6-4.3) than in controls (38/635, 6.0%, 95%CI, 4.3-8.1) (p ⫽ 0.004; 8.331, 2). No significant difference was observed in the causes of hypothyroidism between women with and without endometriosis (thyroiditis, previous surgical removal of a portion or all of the thyroid gland, previous medical therapies) (p ⫽ 0.226). Among hypothyroid subjects, two controls and a woman with endometriosis had previously been surgically treated for thyroid cancer (p ⫽ 0.540). No case of secondary hypothyroidism was observed in our study population. At the time of surgery, women with and without endometriosis had similar prevalence of thyroid nodules (p ⫽ 0.921). Hyperthyroidism prevalence was similar among women with and without endometriosis (p ⫽ 0.587). CONCLUSIONS: Thyroid disorders have a similar frequency in women with and without endometriosis. Future investigations should be aimed to confirm whether hypothyroidism prevalence is reduced in women with endometriosis. Supported by: None. P-112 Depot Medroxyprogesterone Acetate Subcutaneous Injection 104 mg/ 0.65 mL (DMPA-SC 104) is Associated With Fewer Hypoestrogenic Symptoms in Patients With Endometriosis Than Leuprolide Acetate. S. A. Carson, J. K. Jain. Baylor College of Medicine, Houston, TX; Keck School of Medicine, University of Southern California, Los Angeles, CA. OBJECTIVE: To evaluate changes in Kupperman Index scores during treatment with DMPA-SC 104 or intramuscular leuprolide acetate for endometriosis-associated pain. DESIGN: Randomized, 18-month, evaluator-blinded, comparator-controlled trial conducted in the United States and Canada. MATERIALS AND METHODS: This study included premenopausal women aged 18 to 49 years with visually diagnosed endometriosis and persistent pain symptoms. Subjects were randomized to 6 months of treatment with DMPA-SC 104 or leuprolide acetate 11.25 mg every 3 months, and were then followed for an additional 12 months post-treatment. Efficacy endpoints included patient response to treatment in 5 endometriosis-associated pain signs/symptoms (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and induration) at the end of therapy (month 6) using the modified Biberoglu and Behrman scale, where scores ranged from 0 to 3 (0 ⫽ no discomfort; 3 ⫽ severe pain). Safety endpoints included bone mineral density (BMD) changes and changes in the Kupperman Index, a composite measure of hypoestrogenic symptoms. RESULTS: The intent-to-treat population consisted of 136 patients in the DMPA-SC 104 group and 138 patients in the leuprolide group. As reported elsewhere, treatment with DMPA-SC 104 was statistically equivalent (P⬍.02; observed case analysis) to treatment with leuprolide at month 6 in reducing 4 of 5 endometriosis-associated signs/symptoms; and patients receiving DMPA-SC 104 had significantly (P⬍.005) smaller median percent changes from baseline in total hip and lumbar spine BMD at months 6 and 18, compared with patients receiving leuprolide. For hypoestrogenic
*Significant within-group difference; Wilcoxon signed rank test, significance defined at Pⱕ.05 † Significant difference between groups; KruskalWallis test, significance defined at Pⱕ.05
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P-110 The Distinct Activation of Activating Transcription Factor 2 (ATF2) may Play a Crucial Role in Pathogenesis of Endometriosis. C. S. Chou, P. Y. Lee, P. H. Chen, C. R. Tzeng. Taipei Medical University Hospital, Taipei, Taiwan, Republic of China. OBJECTIVE: Endometriosis is one of the commonest chronic gynecological disorders diagnosed in women of reproductive age. The pathogenetic factors of endometriosis still remain unclear. There is increasing evidence that endometriosis is inherited as a complex genetic trait in which multiple genes conferring disease susceptibility interact with each other and the environment to produce the phenotype. Furthermore, the signaling transduction pathway and transcriptional regulation of this disease are mostly uncharacterized. In the current study, we proposed that activating transcription factor 2 (ATF2) may involve the pathogenesis and unique phenotype of endometriosis. DESIGN: Prospective study MATERIALS AND METHODS: Nuclear extracts were obtained from three endometriosis tissues and normal endometrium tissue. A set of biotinlabeled DNA binding oligonucleotides were incubated with nuclear extracts from endometriosis and normal endometrium tissues respectively and then formed DNA/Transcriptional factor complexes. The DNA/Transcriptional factor complexes were separated from the free probes by protein G beads. The beads and associated TF-probe complexes were washed four times and the probes were eluted. The eluted probes were then hybridized to the array membrane, which consisted of complementary sequences to the probes. The membranes were exposed by using Hyperfilm ECL system. EMSA was performed to verify the results from the transcriptional array. RESULTS: The DNA/Transcriptional factor interaction array identifies ATF2 and associated transcription factors in endometriosis tissues and normal endometrial tissues. ATF2 activity increases several folds in endometriosis tissues comparing to normal endometrium. CONCLUSIONS: Transcription factors (TF) are a group of proteins that regulate gene expression in cell nuclear. The transcription factor activating transcription factor 2 (ATF2) has been reported to transactivate CREcontaining genes or to interfere with transactivation by CREB. We found that ATF2 activity was closely related to the transformation of normal endometrium to endometriosis tissue. Supported by: None
P-111 Thyroid Disorders in Women With Endometriosis. S. Ferrero, B. M. Colombo, P. Anserini, V. Remorgida, N. Ragni. San Martino Hospital, University of Genoa, Genoa, Italy; University of Genoa, Department of Internal Medicine, Genoa, Italy. OBJECTIVE: It has previously been suggested that hypothyroidism is significantly more frequent in women with endometriosis than in the general population. The objective of this study is to determine the prevalence of thyroid disorders in women with and without endometriosis. DESIGN: Retrospective study. MATERIALS AND METHODS: This study included 661 consecutive women with endometriosis and 635 controls (uterine fibroids, n ⫽ 244; ovarian cyst, n ⫽ 190; infertility, n ⫽ 115; pelvic pain, n ⫽ 75; tubal sterilization, n ⫽ 6; hydrosalpinx, n ⫽ 5) who underwent laparoscopy at our Institution. Before surgery, the presence of thyroid disorders was always investigated by the anaesthesiologist; in all cases, both gynaecological and anaesthesiological records were examined. The presence and type of thyroid disorders were evaluated. Findings at laparoscopy and pathological description of specimens removed at surgery were considered for classifying the patient. In women with endometriosis, the severity of the disease was classified according to the revised American Fertility Society (rAFS) classification. Data were analyzed by using by using the t test, the MannWhitney U test, chi-square test, and Fisher’s exact test as appropriate. RESULTS: No significant difference (p ⫽ 0.058) was observed in the
FERTILITY & STERILITY威
mean (⫾ SD) age between women with endometriosis (34.5 ⫾ 6.0 years) and controls (34.7 ⫾ 8.8 years). No significant difference was observed in the prevalence of thyroid disorders between women with endometriosis (38/661, 5.7%, 95%CI, 4.1-7.8) and controls (53/635, 8.3%, 95%CI, 6.310.8) (p ⫽ 0.067; 3.347 2). Women with mild (rAFS stage I-II) and severe (rAFS stage III-IV) endometriosis had similar prevalence of thyroid disorders (p ⫽ 0.659). The prevalence of thyroid disorders was also similar in infertile women with (7.1%, 11/155) and without endometriosis (7.0%, 8/115). Hypothyroidism was significantly less frequent in women with endometriosis (18/661, 2.7%, 95%CI, 1.6-4.3) than in controls (38/635, 6.0%, 95%CI, 4.3-8.1) (p ⫽ 0.004; 8.331, 2). No significant difference was observed in the causes of hypothyroidism between women with and without endometriosis (thyroiditis, previous surgical removal of a portion or all of the thyroid gland, previous medical therapies) (p ⫽ 0.226). Among hypothyroid subjects, two controls and a woman with endometriosis had previously been surgically treated for thyroid cancer (p ⫽ 0.540). No case of secondary hypothyroidism was observed in our study population. At the time of surgery, women with and without endometriosis had similar prevalence of thyroid nodules (p ⫽ 0.921). Hyperthyroidism prevalence was similar among women with and without endometriosis (p ⫽ 0.587). CONCLUSIONS: Thyroid disorders have a similar frequency in women with and without endometriosis. Future investigations should be aimed to confirm whether hypothyroidism prevalence is reduced in women with endometriosis. Supported by: None. P-112 Depot Medroxyprogesterone Acetate Subcutaneous Injection 104 mg/ 0.65 mL (DMPA-SC 104) is Associated With Fewer Hypoestrogenic Symptoms in Patients With Endometriosis Than Leuprolide Acetate. S. A. Carson, J. K. Jain. Baylor College of Medicine, Houston, TX; Keck School of Medicine, University of Southern California, Los Angeles, CA. OBJECTIVE: To evaluate changes in Kupperman Index scores during treatment with DMPA-SC 104 or intramuscular leuprolide acetate for endometriosis-associated pain. DESIGN: Randomized, 18-month, evaluator-blinded, comparator-controlled trial conducted in the United States and Canada. MATERIALS AND METHODS: This study included premenopausal women aged 18 to 49 years with visually diagnosed endometriosis and persistent pain symptoms. Subjects were randomized to 6 months of treatment with DMPA-SC 104 or leuprolide acetate 11.25 mg every 3 months, and were then followed for an additional 12 months post-treatment. Efficacy endpoints included patient response to treatment in 5 endometriosis-associated pain signs/symptoms (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and induration) at the end of therapy (month 6) using the modified Biberoglu and Behrman scale, where scores ranged from 0 to 3 (0 ⫽ no discomfort; 3 ⫽ severe pain). Safety endpoints included bone mineral density (BMD) changes and changes in the Kupperman Index, a composite measure of hypoestrogenic symptoms. RESULTS: The intent-to-treat population consisted of 136 patients in the DMPA-SC 104 group and 138 patients in the leuprolide group. As reported elsewhere, treatment with DMPA-SC 104 was statistically equivalent (P⬍.02; observed case analysis) to treatment with leuprolide at month 6 in reducing 4 of 5 endometriosis-associated signs/symptoms; and patients receiving DMPA-SC 104 had significantly (P⬍.005) smaller median percent changes from baseline in total hip and lumbar spine BMD at months 6 and 18, compared with patients receiving leuprolide. For hypoestrogenic
*Significant within-group difference; Wilcoxon signed rank test, significance defined at Pⱕ.05 † Significant difference between groups; KruskalWallis test, significance defined at Pⱕ.05
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