Thai Interest Group for Endometriosis (TIGE) consensus statement on endometriosis-associated pain.

This consensus statement has been developed by the Thai Interest Group for Endometriosis (TIGE) for use by Thai clinicians in the diagnosis and management of endometriosis. TIGE is a group of clinical and academic gynaecologists with a particular interest in endometriosis. Endometriosis is an oestrogen-dependent inflammatory disease which causes chronic symptoms such as dysmenorrhoea, chronic pelvic pain, dyspareunia and subfertility, and it is common in reproductive-age women. There is limited overall data on its prevalence in different clinical settings in Thailand, but it is clear that the disease causes significant problems for patients in terms of their working lives, fertility, and quality of life, as well as placing a great burden on national healthcare resources. Decisions about selecting the appropriate treatment for women with endometriosis depend on many factors including the age of the patient, the extent and severity of disease, concomitant conditions, economic status, patient preference, access to medication, and fertility need. Several hormonal treatments are available but no consensus has been reached about the best option for long-term prevention of recurrence. Bearing in mind differences in environment, genetics, and access to the healthcare system, this treatment guideline has been tailored to the particular circumstances of Thai women.

Gastrointestinal injuries during gynaecologic operations at a university teaching hospital in Thailand: a 10-year review.

The objective of this study was to investigate the incidence of gastrointestinal injuries during gynaecologic operations, the management of such injuries and associated risk factors. This case-control study (1:4) examined patients who received gynaecologic operations from 2007 to 2016 in Ramathibodi Hospital. The study cases comprised patients who had gastrointestinal injuries, while the control cases comprised patients who had gynaecologic surgeries in the same period with matching the types of procedures. The 10-year incidence was 0.38% (104 cases of gastrointestinal injuries among a total of 27,520 cases). The most common injury site was the small bowel (43.3%). There were 102 cases (98%) of gastrointestinal injuries which were diagnosed intraoperatively and which were immediately repaired with successful outcomes. Logistic regression indicated that a pelvic adhesion, previous pelvic surgery and previous abdominal surgery were predictive risk factors associated with the injuries (odds ratios: 9.45, 3.20 and 11.84, respectively). An immediate consultation with a surgeon and surgical repair of the injury resulted in excellent outcomes. Impact statement What is already known about this subject? Gastrointestinal injury is a rare, but fatal complication of gynaecologic operations. The previous small study identified some risk factors such as surgical approach and pelvic surgery associated with the injury. What do the results of this study contribute? Our study identified the associated risk factors for gastrointestinal injury, including previous abdominal injury, pelvic adhesion and previous pelvic surgery. A previous abdominal surgery was the most associated risk factor. Patients with the history of abdominal surgery had an almost 4-fold higher odds ratio than the ones with previous pelvic surgery. Other factors, including endometriosis, ovarian cancer and subsequent oncological procedures, and surgical staging were less related to the gastrointestinal injury. What are the implications of these findings for clinical practice and/or further research? The knowledge is useful for pre-operative evaluation and preparation. Bowel preparation and consultation with surgeon are necessary for patients with these risk factors prior to their surgeries. Moreover, an immediate intra-operative surgical correction of the injury results in excellent outcomes.

Differential expressions of estrogen and progesterone receptors in endometria and cyst walls of ovarian endometrioma from women with endometriosis and their responses to depo-medroxyprogesterone acetate treatment.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) is an injectable progestin contraceptive that provides a highly effective reduction of pelvic pain in women with endometriosis. Despite its wide use to treat pain associated with endometriosis, its precise mechanisms of action remain unclear. The aims of this study were to investigate the differential expressions of estrogen receptors (ERs), and progesterone receptors (PRs) in endometria and ovarian endometrioma cyst walls of women with endometriosis with and without DMPA treatment. METHODS: Endometria and cyst walls of endometrioma were obtained from 25 to 45 year-old women who suffered from endometriosis and had ovarian endometrioma with the size ≥3 cm. The expression levels of ERs and PRs and the numbers of ER- and PR-positive cells before and after treatment with DMPA were evaluated by Western blot, real-time PCR, and immunohistochemistry. RESULTS: The levels of ERα and ERß expression, their corresponding mRNAs, and numbers of ERα- and ERß-immunoreactive cells in stroma and glands of endometria of the DMPA group were significantly decreased when compared with those of the untreated groups (p < 0.05). In contrast, the levels of PRA/B expression and numbers of PRA/B positive cells in stroma and number of PRB positive cells in stroma and endometrial glands were significantly increased in endometria of the DMPA group when compared with those of the untreated groups. However, in cyst wall the expression levels of these proteins, their corresponding mRNAs, and immonoractive cells were low compared to those in endometria, and DMPA-treatment did not cause any significant changes in these parameters. CONCLUSION: These data indicated that DMPA could upregulate the expressions of PRA/B and down-regulate ERα and ERß in endometria but not in cyst walls from women with endometriosis.

A case report of Tubo-ovarian abscess caused by Burkholderia pseudomallei.

BACKGROUND: Melioidosis, the disease caused by Burkholderia pseudomallei is endemic in the Northeastern part of Thailand, South-East Asia, and Northern Australia. The pelvic involvement of disease is rare even in an endemic area. Therefore, we describe in this report the clinical presentation, management, and outcome of the patient with primary tubo-ovarian abscess due to melioidosis. CASE PRESENTATION: A 31-year-old Thai cassava farmer woman presented with fever and abdominal pain at left lower quadrant for one month. She also had pain, swelling, and redness of the genitalia without any ulcer. She had odorless whitish vaginal discharge. The pelvic examination revealed excitation pain on the left side of her cervix. Transvaginal ultrasonography revealed a large left tubo-ovarian abscess size 9.4 × 4.8 cm located at anterior of the uterus. Urgent exploratory laparotomy revealed left hydrosalpinx with a large amount of pus. The pus culture grew Burkholderia pseudomallei. The computer tomography of the abdomen revealed multiple hepatosplenic abscesses. The patient underwent left salpingo-oophorectomy and pus drainage. The pathological examination of excised left adnexa revealed chronic and acute suppurative inflammation with necrotic tissue. She was given intravenous ceftazidime for one month, and her clinical symptom improved. She was diagnosed with type 2 diabetes mellitus at this visit and treated with insulin injection. She continued to take oral co-trimoxazole for 20 weeks. The final diagnosis was disseminated melioidosis with left tubo-ovarian abscess and hepatosplenic abscesses in a newly diagnosed morbidly obese diabetic patient. CONCLUSION: Burkholderia pseudomallei should be considered as the causative organism of gynecologic infection among patient with risk factor resided in an endemic area who do not respond to standard antibiotics. The pus culture from the site of infection is the only diagnostic method of pelvic melioidosis, appropriate antibiotics, and adequate surgical drainage were the components of the successful outcome.

Prevalence of polycystic ovary syndrome in Thai University adolescents.

Polycystic ovarian syndrome (PCOS) is a common and complex condition characterized by endocrine features and influenced by genetic and environmental factors. In Southeast Asia and Thailand, the prevalence of PCOS is unknown. The aim of this study was to estimate the prevalence of and determine factors associated with PCOS in Thai adolescents. We administered a validated questionnaire to 600 university female participants aged 17-19 years from Mahidol University in Bangkok. Of these, 548 (91.33%) responded and agreed to participate. Two-hundred and seventy-nine girls (50.91%) were identified as likely having PCOS and defined as 'probable cases'. Of those 279 participants, 248 (88.88%) were evaluated further for PCOS using the Rotterdam criteria. A complete history was taken, and a physical examination including trans-abdominal ultrasound was performed. Blood chemistry tests were performed to exclude similar conditions and to investigate potential co-morbidities. The prevalence of PCOS in Thai adolescents was found to be 5.29%. After multivariate analyses, moderate acne was the strongest risk factor for PCOS. The odd ratios (95% confidence interval) for the presence of mild acne, moderate acne, and oligo- or amenorrhea in participants with PCOS were 2.83 (1.01-7.90; p = .47), 31.69 (10.07-99.67; p < .001), and 5.89 (2.42-14.37; p < .001), respectively.

Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial.

BACKGROUND: Simvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis. METHODS: A prospective, randomized, controlled study was conducted at the Reproductive Endocrinology Unit of the Department of Obstetrics and Gynecology at the Faculty of Medicine Ramathibodi Hospital. Forty women (mean age: 18-45 years) scheduled for laparoscopic surgery who had been diagnosed with endometriosis were recruited and randomly assigned to either a treatment group (20 mg/d of orally administered simvastatin for 2 weeks before surgery) or an untreated control group. Serum was collected before and after treatment and protein levels of MCP-1 were determined. MCP-1 and CD68 transcript levels were also quantified using real-time PCR on endometriotic cyst tissues. RESULTS: MCP-1 gene expression on endometriotic cyst was not significantly different between the simvastatin-treated and untreated groups (P = 0.99). CD68 expression was higher in the treatment group compared to the control group, but this was not statistically significant (P = 0.055). Serum MCP-1 levels following simvastatin treatment were higher than in samples obtained before treatment (297.89 ± 70.77 and 255.51 ± 63.79 pg/ml, respectively) (P = 0.01). CONCLUSIONS: Treatment with 20 mg/d of simvastatin for 2 weeks did not reduce the expression of either the chemokine MCP-1 gene or macrophage-specific genes. Cumulatively, this suggests that simvastatin is not ideal for treating endometriosis because a higher dose of simvastatin (40-100 mg/d) would be needed to achieve the target outcome, which would significantly increase the risk of myopathy in patients. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20130627003 Registered: June 27, 2013.

The Optimal Cut-Points for Weight and Non-Weight Quantitative Ultrasound of the Calcaneus to Screen Osteoporosis in Postmenopausal Women.

OBJECTIVE: To determine the optimal cut-off point of quantitative ultrasound (QUS) of the calcaneus, and optimized position for QUS of the calcaneus, between non-weight (sitting) and weight (standing) position, to screen osteoporosis in postmenopausal women. MATERIAL AND METHOD: A cross-sectional study of postmenopausal women aged 65 years or older who came for bone mineral density (BMD) evaluation at the menopause unit, Department of Obstetrics and Gynecology, Ramathibodi Hospital between April 2013 and October 2015. Bone tissue was measured by using QUS of the calcaneus in the standard sitting (non-weight position) and in standing (weight position) consecutively of non-dominant calcaneus to compared with BMD that measured by dual energy X-ray absorptiometry (DXA) of lumbar spine and hip within the same visit of QUS measurement. The area under Receiver Operating Characteristic (ROC) curve and optimal of diagnostic properties to diagnosed osteoporosis were analyzed by sensitivity, specificity, positive and negative likelihood ratio (LR +/-). RESULTS: One hundred sixty one postmenopausal women were enrolled, median age was 70 (65, 94) years old, median time since menopause was 22 (10, 55) years. Ten point five percent of subjects had history of osteoporotic fracture at wrist. The prevalence of osteoporosis was 23% at lumbar spine and 30% at femoral neck respectively. Area under ROC curve for diagnosed osteoporosis was 0.73 in the non-weight QUS of the calcaneus and correlated well with using DXA at neck of femur (gold standard). However the weight or standing position did not improve the diagnostic power of QUS of the calcaneus. The optimal cut-point value of QUS of the calcaneus to screen osteoporosis at stiffness index was determined by T-score of ≤ -2.6 with 81.42%, 45.83%, 1.5, and 0.41 for the sensitivity, specificity, LR +/- respectively. CONCLUSION: QUS of the calcaneus was acceptable and promising to be alternative tool for screening osteoporosis in postmenopausal woman age older than 65 years by the optimal cut-point of stiffness index T-score at ≤ -2.6 measured in standard position or non-weight method.

DMPA Suppresses Cell Proliferation and Enhances Cell Apoptosis of Eutopic Endometrium in Women with Endometriosis: A Randomized Controlled Study.

Background: Although Depo-medroxyprogesterone acetate (DMPA), an injectable contraceptive progestin, is very effective for pain relief and prevention of recurrence in women with endometriosis, there is no report on the mechanism of this medication about cell proliferation and apoptosis. Objective: To investigate the effects of DMPA on cell proliferation and apoptosis in the eutopic endometrium of women with endometriosis. Material and Method: A randomized controlled study was conducted in 28 women with endometriosis. The DMPA-treated group included 14 women who were scheduled to undergo laparoscopic surgery after 150 mg of DMPA injections. The control group included 14 women who were scheduled to undergo the surgery without DMPA injection. The endometrial tissue was obtained from each woman by endometrial aspiration before surgery. The ELISA formats of PCNA and the quantitative colorimetric analysis of TUNEL were used for estimating cell proliferation and apoptosis of the eutopic endometrium. Results: There were no differences in the women characteristics between the two groups. The relative level of cell proliferation was significantly less in the DMPA than the control groups (1.08±0.57 vs. 1.73±0.50, p = 0.014). Whereas the relative level of cell apoptosis was greater in the DMPA group than that in the control group (1.12±0.36 vs. 0.82±0.39, p = 0.034). Conclusion: Three months of 150 mg DMPA treatment could suppress cell proliferation and enhance cell apoptosis of the eutopic endometrium of women with endometriosis.

Effects of Multispecies Probiotic Supplementation on Serum Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Probiotics have been found to have beneficial effects on bone metabolism. In this randomized, double-blind, placebo-controlled trial, the effects of multispecies probiotic supplementation on bone turnover markers were evaluated after 12 weeks. Forty postmenopausal women with osteopenia were included and randomly divided into two groups. The intervention group received multispecies probiotics, while the control group received identical placebo sachets daily. The baseline characteristics of both groups were similar. Still, the median serum bone resorption marker C-terminal telopeptide of type I collagen (CTX) was slightly higher in the multispecies probiotic group than in the placebo group (0.35 (0.12, 0.53) vs. 0.16 (0.06, 0.75); p-value = 0.004). After 12 weeks, the mean difference in serum CTX at baseline versus 12 weeks was significantly different between the multispecies probiotic and placebo groups (-0.06 (-0.29, 0.05) vs. 0.04 (-0.45, 0.67); p-value < 0.001). The multispecies probiotic group showed a significant decrease in serum CTX at 12 weeks compared with baseline (p-value 0.026). However, the placebo group showed no significant change in serum CTX (p-value 0.18). In conclusion, multispecies probiotics may have a preventive effect on bone through their antiresorptive effect in osteopenic postmenopausal women.

Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Postmenopausal Women: A Prospective, Double-Blinded Randomized Controlled Trial.

Chronic insomnia disorder is one of the most common problems in postmenopausal women, exacerbated by underdiagnosis and improper treatment. This double-blinded, randomized, placebo-controlled trial was conducted to evaluate the potential of vitamin E to treat chronic insomnia as an alternative to sedative drugs and hormonal therapy. The study enrolled 160 postmenopausal women with chronic insomnia disorder, divided randomly into two groups. The vitamin E group received 400 units of mixed tocopherol daily, while the placebo group received an identical oral capsule. The primary outcome of this study was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), a self-evaluated and standardized questionnaire. The secondary outcome was the percentage of participants using sedative drugs. There were no significant differences in baseline characteristics between the study groups. However, the median PSQI score at baseline was slightly higher in the vitamin E group compared with the placebo (13 (6, 20) vs. 11 (6, 20); p-value 0.019). After one month of intervention, the PSQI score was significantly lower (indicating better sleep quality) in the vitamin E group compared with the placebo (6 (1, 18) vs. 9 (1, 19); p-value 0.012). Moreover, the improvement score was significantly higher in the vitamin E group compared with the placebo (5 (-6, 14) vs. 1 (-5,13); p-value < 0.001). In addition, there was a significant reduction in the percentage of patients using sedative drugs in the vitamin E group (15%; p-value 0.009), while this reduction was not statistically significant in the placebo group (7.5%; p-value 0.077). This study demonstrates vitamin E's potential as an excellent alternative treatment for chronic insomnia disorder that improves sleep quality and reduces sedative drug use.

Vaginal microbiome of women with adenomyosis: A case-control study.

Immune dysregulation can involve invasion and survival of endometrial glands inside the myometrium of the adenomyosis. There is limited available data concerning alterations of the bacterial microbiome in the reproductive tract of adenomyosis women. The present cross-sectional age-matched study aims to compare vaginal microbiota between women with and without adenomyosis. We recruited women with adenomyosis (N = 40) and age-matched women without adenomyosis (N = 40) from the Departments of Obstetrics and Gynaecology, Ramathibodi Hospital Mahidol University, from August 2020 to January 2021. Vaginal swab samples were collected from the participants. DNA isolation and bacterial 16s rDNA gene sequencing and data analyses were then performed. Comparison of the diversity of vaginal microbiota, microbiota composition, and the operational taxonomic unit (OTU) between adenomyosis and non-adenomyosis (control) groups were undertaken. Data from 40 and 38 women with and without adenomyosis, respectively, were analyzed. Alpha-diversity analysis (Chao1 index) at the species level showed higher vaginal microbial richness in the adenomyosis group when compared with the control group (p = 0.006). The linear discriminant analysis effect size technique (LeFSe) indicated an elevated abundance of several vaginal microbial taxa in the adenomyosis group, including Alloscardovia, Oscillospirales, Ruminoccoccaceae, UCG_002, Oscillospiraceae, Enhydrobacter, Megamonas, Moraxellaceae, Subdoligranulum, Selenomonadaceae, and Faecalibacterium. On the other hand, an increase in the abundance of Megaspehera, Fastidiosipila, Hungateiclostridiaceae, and Clostridia was identified in the control group. Vaginal community state type (CST)-III and -IV were dominated in adenomyosis, while only CST-IV was dominated in the non-adenomyosis group. Lactobacillus was the most abundant vaginal microbial in both groups. In this study, the differences in vaginal microbiome profile were noted between adenomyosis and non-adenomyosis group. The increasing of microbial richness was associated with adenomyosis. Nevertheless, further investigations were required to elucidate the mechanisms and apply them for clinical implications.

A Comparison of Shear Wave Elastography between Normal Myometrium, Uterine Fibroids, and Adenomyosis: A Cross-Sectional Study.

BACKGROUND: The differential diagnosis between uterine fibroid and adenomyosis is sometimes difficult; a precise diagnosis is required in women with infertility because of the different choice of treatments. Ultrasound elastography (UE) is a novel technique to evaluate the elasticity or the stiffness of the tissue of interest. The present study aims to compare UE shear wave velocity (SWV) among normal uterine myometrium, uterine fibroid, and adenomyosis, and assess the accuracy of shear wave elastography in the diagnosis of adenomyosis. MATERIALS AND METHODS: This cross-sectional study recruited 25 subjects for each group (control, adenomyosis, and fibroid) from April 2019 to April 2020. Transvaginal UE using an Aplio 500 (Toshiba Medical Systems, Japan) with ultrasound mapping for point of tissue biopsy was performed for all subjects. The diagnosis was confirmed by histology. Masson's trichrome staining for collagen was performed and quantified. RESULTS: The mean ± standard deviation (SD) for SWV was 3.44 ± 0.95 m/seconds (control group), 4.63 ± 1.45 m/ seconds (adenomyosis group), and 4.53 ± 1.07 m/seconds (fibroid group). The mean SWV differed when comparing normal myometrium and adenomyosis after adjustments for age and endometrial pathology (P=0.019). The cut-off point of SWV at 3.465 m/seconds could differentiate adenomyosis from the normal uterus with an 80% sensitivity, 80% specificity, and an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.68-0.93) (P<0.001). No significant difference in SWV between the adenomyosis and fibroid groups was detected. CONCLUSION: Shear wave elastography could be an alternative tool to distinguish between normal myometrium and adenomyosis; however, it could not differentiate adenomyosis from uterine fibroid or uterine fibroid from normal myometrium.

Macrophages and Natural Killer Cells Characteristics in Variously Colored Endometriotic Lesions: A Cross-Sectional Analytic Study.

Background: Dysregulation of the immune response contribute to a significant role in endometriosis. This research examined macrophages and natural killer (NK) cells numbers in endometriotic lesions and their association with the different lesion colors: red, black, and white. To investigate the amount of the CD68 and CD56 in eutopic endometrium and different type of the endometriotic lesions. Materials and Methods: A cross-sectional analytic study was conducted. Women suspected endometriosis requiring laparoscopic surgery between July 2016 and January 2017 were recruited. Their lesions were classified as red, black, or white and these lesions were excised by standard laparoscopic surgery. Twenty-four endometriotic lesions from each color group were obtained from 45 women who met the inclusion criteria. One type of lesion was collected from 25 women. Two different lesion types and three-color lesion types were collected from the same women in 13 and 7 subjects, respectively. Immunohistochemistry staining with anti-human mouse cluster of differentiation (CD) 68 monoclonal antibody for macrophages and mouse anti-human CD56 monoclonal antibody for NK cells were performed. Results: The number of CD68 macrophages in red lesions was higher than in black and white lesions [median (25th-75th percentile); 10 (5-19.4), 0 (0-6.9), 0 (0-2.5) cells per mm2, respectively, adjusted P=0.001 for red vs. black lesions and red vs. white lesions, and adjusted P=1.000 for black and white lesions]. The number of CD56 NK cells was not significantly different among red, black, and white lesions [median (25th-75th percentile; 5 (2-16.5), 3.8 (0-14.4), 1.3 (0-6.9) respectively, adjusted P=1.000 for red vs. black lesions and black vs. white lesions, and adjusted P=0.617 for red vs. white lesions]. Conclusion: The dynamic changes in the immune cells in ectopic endometrium were specific to the macrophages but not to the NK cells, as demonstrated by the highest number of CD68 macrophages in the red lesion, the earliest established ectopic endometrium. NK cells in endometriosis may have a role in the uterus.

Clinical Diagnosis and Early Medical Management for Endometriosis: Consensus from Asian Expert Group.

This work provides consensus guidance regarding clinical diagnosis and early medical management of endometriosis within Asia. Clinicians with expertise in endometriosis critically evaluated available evidence on clinical diagnosis and early medical management and their applicability to current clinical practices. Clinical diagnosis should focus on symptom recognition, which can be presumed to be endometriosis without laparoscopic confirmation. Transvaginal sonography can be appropriate for diagnosing pelvic endometriosis in select patients. For early empiric treatment, management of women with clinical presentation suggestive of endometriosis should be individualized and consider presentation and therapeutic need. Medical treatment is recommended to reduce endometriosis-associated pelvic pain for patients with no immediate pregnancy desires. Hormonal treatment can be considered for pelvic pain with a clinical endometriosis diagnosis; progestins are a first-line management option for early medical treatment, with oral progestin-based therapies generally a better option compared with combined oral contraceptives because of their safety profile. Dienogest can be used long-term if needed and a larger evidence base supports dienogest use compared with gonadotropin-releasing hormone agonists (GnRHa) as first-line medical therapy. GnRHa may be considered for first-line therapy in some specific situations or as short-term therapy before dienogest and non-steroidal anti-inflammatory drugs as add-on therapy for endometriosis-associated pelvic pain.

Randomized controlled trial of different doses of metformin for ovulation induction in infertile women with polycystic ovary syndrome.

AIM: To compare the efficacy of 1000 mg and 1700 mg of metformin on ovulation induction in polycystic ovary syndrome (PCOS) women. MATERIAL AND METHODS: A randomized controlled trial was conducted at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand of 60 PCOS women diagnosed by Rotterdam criteria. Group A (30 women) and B (30 women) received 1000 mg and 1700 mg/day of metformin, respectively. Clomiphen citrate 50-150 mg per day for 5 days was added, if no dominant follicle developed. The main outcome measures were ovulation and pregnancy rates, fasting insulin (FI), testosterone (T), androstenedione (ADD) and DHEAS before and 4 weeks after metformin. RESULTS: The ovulation rate did not differ between the groups (84.8% vs 87.7% between groups A and B, P=NS). Most of the women developed one follicle (91% in group A and 88.2% in group B, P=NS). The pregnancy rate in group A (46.4% per woman and 12.4% per ovulatory cycle) did not differ from that in group B (51.9% per woman and 13.2% per ovulatory cycle, P=NS). With regard to dosages, the ovulation rate in PCOS women without insulin resistance (IR) was significantly higher than those with IR. FI, T and ADD were significantly decreased after 4 weeks of metformin in both groups. CONCLUSION: 1000 mg of metformin had as high efficacy as 1700 mg on induction of ovulation and pregnancy in PCOS women.

The Effect of Combined Oral Contraceptive Pills on Beclin-1 and LC3B Transcript Levels in Ovarian Endometrioma.

BACKGROUND: Autophagy is likely altered in patients with endometriosis. Ovarian steroid hormones seem to affect this changing of the autophagic process. OBJECTIVE: To study the effect of combined oral contraceptive (COC) pills on the expression of autophagic-related gene BECN1 and LC3B in the ectopic and eutopic endometria of patients with endometriosis. Material and Methods. The present quasiexperimental study recruited 36 women (18-45 years old) with endometrioma and nonendometrioma who were scheduled for surgery. Patients with endometrioma were randomly assigned to either a no-treatment group (n = 12) or a COC group (n = 12). The COC group was prescribed a daily oral pill composed of 3 mg drospirenone and 0.03 mg ethinyl estradiol for 6 weeks before surgery. The control group (n = 12) was composed of women without endometrioma. Ectopic endometriotic and endometrium tissues were collected from the no-treatment and COC groups, whereas the only endometrium was collected from the control group. These tissues were used for real-time PCR to measure the expression of the BECN1 and LC3B genes. RESULTS: The baseline demographic data were not different among the three groups. The BECN1 gene expression in endometrium tissue in the COC group was significantly less than that in the no-treatment and control groups (P = 0.011 and 0.029, respectively). No significant difference of endometriotic cyst BECN1 and LC3B gene expression was found between COC and no treatment. CONCLUSIONS: Oral COC pills for 6 weeks continuously before surgery decreased the eutopic endometrial expression (mRNA) of the BECN1 gene compared to those from healthy normal women and nontreated patients with an endometriotic cyst. The change in the expression of autophagy-related genes was more distinct in eutopic than ectopic endometria. This trial is registered with TCTR20170720002. Registered and enrolled the first patient on 20 July 2017.

Effects of Ethinyl Estradiol in Combined Oral Contraceptives on Cell Proliferation and Apoptosis in Ectopic Endometrial Tissue: A Randomized Controlled Study.

Objective: Since endometriosis is an estrogen-dependent disease; therefore, combined oral contraceptives (COCs) may not be the best choice for the treatment of endometriosis. The objective of the present study was to investigate the effects of ethinyl estradiol (EE) and desogestrel (DSG) in COCs on cell proliferation and apoptosis in ectopic endometrial tissue as compared to DSG alone. Materials and methods: Forty-five women of reproductive age with at least one endometriotic cyst were recruited into this single-blind randomized controlled trial study and randomly divided equally into three groups. EE-DSG and DSG groups received EE (0.03 mg) and DSG (0.15 mg) or DSG alone daily for 28-35 days before surgery. The control group was prescribed nothing. Endometriotic cyst tissues were collected during ovarian cystectomy for immunohistochemistry. Results: Levels of Ki-67 positive cells in the ectopic endometrial tissue of the EE-DSG group were significantly higher than the DSG group (median [IQR]; 1.4[1.2] vs 0.6 [0.7], P <0.016). There were significantly more TUNEL-positive cells in the EE-DSG group compared to the DSG group (median [IQR]; 2.8[0.7] vs 1.8[1.4], P < 0.016, respectively). Moreover, the number of TUNEL-positive cells in the EE-DSG and DSG groups were significantly higher than the control (median [IQR]; 2.8[0.7] vs 0.2[0.2] and 1.8[1.4] vs 0.2[0.2], P <0.016). The levels of cells that positively stained for Bcl2 were not different among all groups. Conclusion: Progestin alone increased cell apoptosis in ectopic endometria. However, concurrent EE in COCs enhanced proliferation and promoted a greater apoptotic effect in ectopic endometria compared to progestin alone.

Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

Perioperative Intravenous Patient-Controlled Analgesic Efficacy of Morphine with Combined Nefopam and Parecoxib versus Parecoxib in Gynecologic Surgery: A Randomized, Double-Blind Study.

BACKGROUND: Nefopam is a non-NSAIDs and opioid sparing centrally acting drug which is effective for a multimodal postoperative analgesia. The present study aimed to evaluate the analgesic efficacy of nefopam combined with parecoxib for gynecologic surgery. METHODS: This randomized double-blinded control trial recruited participants (n = 72) who underwent gynecologic surgeries and divided them into either a nefopam or control group. The study group received parecoxib 40 mg plus nefopam 20 mg, while the control group received parecoxib 40 mg plus normal saline solution intravenously during open abdominal gynecological surgery. Both groups then received either nefopam or normal saline every 6 hours postoperatively for 24 hours. Intravenous patient-controlled analgesia with morphine was given for breakthrough pain within 24 h. The participants were evaluated for morphine consumption within 24 hours and postoperative pain using a verbal numerical rating scale (VNRS) at a postanesthetic care unit, at 6-, 12-, and 24-hour postoperative periods. Adverse effects were recorded. RESULTS: Morphine consumption within 24 hours and adverse effects were not significantly different between both groups. Mean difference and 95% confident interval of morphine consumption between both groups was 1.00 (-4.56, 4.76), P=0.97. The VNRS on movement at 6 hours after surgery of the nefopam group was significantly different from that of the control group [mean (SD), 4.14 (2.11) vs. 5.14 (1.80), P=0.04]. The VNRS of the nefopam group at 12 hours after operation during resting and on movement was significantly different from that of the control group ([mean (SD), 1.47 (1.80) vs. 2.54 (2.15), P=0.03], [mean (SD), 3.22 (1.84) vs 4.17 (1.74), P=0.03]), respectively. CONCLUSIONS: The combined administration of nefopam and parecoxib during gynecologic surgery slightly reduced the VNRS at 6 and 12 hours postoperatively more than treatment with parecoxib.

Effect of combined contraceptive pill on immune cell of ovarian endometriotic tissue.

BACKGROUND: Dysregulation of immune response is associated with development of endometriosis. The study aim was to evaluate effect of combined oral contraceptive pills (COCs) consisting of ethinyl estradiol (EE) and desogestrel on the expression of macrophage, natural killer cells, and regulatory T cells of ovarian endometriotic cysts. METHODS: Endometriotic cyst wall tissues were collected from women with endometriosis who were treated (n = 22) with COCs (one table per day of EE 0.03 mg and desogestrel 0.15 mg administered for 28 to 35 days before surgery) or untreated (n = 22). The tissues were collected from endometriotic cyst wall during laparoscopic or laparotomy ovarian cystectomy. Immunohistochemistry for anti-CD68, anti-CD56, and anti-forkhead-winged helix transcription factor (FoxP3), a marker for macrophages, natural killer cells, and regulatory T cells, respectively, were investigated. RESULTS: The median (interquartile range [IQR]) number of anti-CD68 positive cells in the COC group was significantly lower than in the untreated group (12.7; 4.9-19.3) versus 45.7 (26.0-70.7), p < 0.001). Tissue infiltration of anti-CD56 positive cells in endometriotic cyst was significantly higher after the treatment when compared with tissue from untreated group (42.9, 27.4-68.9 versus 25.3 (14.1-37.3; p = 0.009). The number of regulatory T cells was also significantly increased in the COC group (6.3, 2.8-15.5) versus 0 (0-1.8; p < 0.001). CONCLUSIONS: The effects of COC, containing EE 0.30 mg with desogestrel 0.15 mg, on the immune system was demonstrated by a significant decrease in the number of macrophages and an increase in natural killer and regulatory T cells.