The effectiveness of desogestrel for endometrial protection in women with abnormal uterine bleeding-ovulatory dysfunction: a non-inferiority randomized controlled trial.

Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference - 9.1-24.4%, non-inferiority limit of - 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).

Adult female acne: Clinical characteristics and factors significantly associated with polycystic ovary syndrome.

BACKGROUND: Adult female acne (AFA) may be different from adolescent acne, and may be a sign of polycystic ovary syndrome (PCOS). The objective of the study was to investigate the clinical characteristics of AFA, and the factors significantly associated with PCOS in AFA. METHODS: AFA patients aged 25 years or older were enrolled. History taking and dermatologic examinations were performed by dermatologists. PCOS was diagnosed by gynaecologists. Perimenopausal acne (aged 45 years or older) and the Dermatology Life Quality Index (DLQI) were also evaluated. RESULTS: Among 208 patients, mean age was 31.8 ± 7.1 years and 47.1%, 26.9%, and 26% had persistent, late-onset, and recurrent acne, respectively. The common aggravating factors included pre-menstruation (72.6%) and stress (53.8%). Recurrent acne was significantly aggravated by cosmetic products. Higher body mass index (BMI) was positively correlated with acne severity. Acne lesions were predominately located on both cheeks (87.0%) and at the perioral area (81.7%). PCOS was identified in 48.1%. Younger age (≥25 to <33 years), premenstrual flare, and irregular menstruation, but not hirsutism or androgenetic alopecia, were associated with PCOS in univariate and multivariate analysis. Perimenopausal acne was identified in 6.7%. The total mean DLQI score was 8.0 ± 5.4 (range from 0 to 23). CONCLUSIONS: Persistent acne with moderate severity was common in AFA patients and higher BMI was associated with acne severity. PCOS should be screened in AFA patients with younger age, premenstrual flare, and irregular menstruation.

Preoperative Evaluation of the ADNEX Model for the Prediction of the Ovarian Cancer Risk of Adnexal Masses at Siriraj Hospital.

INTRODUCTION: Distinguishing benign adnexal masses from malignant tumors plays an important role in preoperative planning and improving patients' survival rates. The International Ovarian Tumor Analysis (IOTA) group developed a model termed the Assessment of Different NEoplasias in the adneXa (ADNEX). OBJECTIVE: Our objective was to evaluate the performance of the ADNEX model in distinguishing between benign and malignant tumors at a cutoff value of 10%. METHODS: This was a prospective diagnostic study. 357 patients with an adnexal mass who were scheduled for surgery at Siriraj Hospital were included from May 1, 2018, to May 30, 2019. All patients were undergoing ultrasonography, and serum CA125 was measured. Data were calculated by the ADNEX model via an IOTA ADNEX calculator. RESULTS: Of the 357 patients, 296 had benign tumors and 61 had malignant tumors. The area under the receiver operating characteristic curve for using the ADNEX model was 0.975 (95% confidence interval, 0.953-0.988). At a 10% cutoff, the sensitivity was 98.4% and specificity was 87.2%. The best cutoff value was at 16.6% in our population. CONCLUSIONS: The performance of the ADNEX model in differentiating benign and malignant tumors was excellent.

Prevalence of type 2 diabetes mellitus compared between lean and overweight/obese patients with polycystic ovarian syndrome: a 5-year follow-up study.

PURPOSE: To investigate the prevalence of type 2 diabetes mellitus (T2DM) at the 5-year follow-up after polycystic ovarian syndrome (PCOS) diagnosis compared between lean and overweight/obese groups. METHODS: This retrospective cohort study included 400 prediabetes PCOS women who attended our clinic. Participants were divided into either the lean group (body mass index [BMI]: < 23 kg/m2) or the overweight/obese group (BMI: ≥ 23 kg/m2). Patient demographic, clinical characteristics, metabolic profiles, and laboratory values were collected and compared between groups at baseline and during follow-up for 5 years. RESULTS: At the end of the follow-up, overweight/obese group had a higher risk for developing T2DM than lean group (11.5% vs. 0.5%, p < 0.001). Lean group had a lower incidence of hypertension (3% vs. 38.5%, p < 0.001) and dyslipidemia (35% vs. 53.5%, p < 0.001) than overweight/obese group. The factors found to be independently associated with increased risk for developing T2DM were BMI ≥ 23 kg/m2 (odds ratio [OR]: 1.075, p = 0.047), non-use of oral combined contraceptive pills (OR: 0.312, p = 0.028), and impaired fasting glucose at baseline (OR: 38.167, p < 0.001). CONCLUSIONS: Overweight/obese PCOS patients were found to be at significantly higher risk for developing T2DM than lean PCOS patients. Higher BMI, IFG at baseline, and non-use of oral contraceptive pills found to be independent predictors of T2DM in PCOS.

Accuracy of anti-Müllerian hormone and total follicles count to diagnose polycystic ovary syndrome in reproductive women.

OBJECTIVE: Recently, there was a new recommendation of ultrasonographic criteria to diagnosis polycystic ovary syndrome (PCOS). In addition, serum anti-Müllerian hormone (AMH) was proposed as a surrogate marker for diagnosis of PCOS, but AMH cut-off level for diagnosis of PCOS is unclear. This study aimed to investigate the accuracy of serum AMH and evaluate new ultrasonographic criteria, follicle number per ovary (FNPO) threshold ≥ 25 follicles and ovarian volume (OV) > 10 mL, for diagnosis of PCOS. MATERIALS AND METHODS: A cross-sectional study was conducted. Fifty-five PCOS women and sixty-three normal ovulatory, non-hyperandrogenic women were recruited. Transvaginal or transrectal ultrasonography was performed in all participants to evaluate follicle number and OV. Serum AMH was evaluated in both study groups. RESULTS: The mean age of the participants was 25.1 ± 5.3 years old in PCOS group and 29.7 ± 7.2 years old in control group. Mean AMH, FNPO and OV in PCOS women were significantly higher than those in non-PCOS women. The area under the receiver-operating characteristic (ROC) curve of AMH was 0.903. The threshold of AMH at 4.7 ng/mL offered the best compromise between 80% sensitivity and 77.8% specificity. The appropriated threshold values for FNPO, follicle number per cross-section (FNPS) and OV were 15 follicles, 7 follicles and 6.5 mL, respectively. Serum AMH level was significantly positively correlated with FNPO, FNPS and OV in both PCOS and control groups. In PCOS women, serum AMH showed strongly correlation with FNPO (r = 0.53, p < 0.001) and weakly correlation with total testosterone (r = 0.283, p = 0.036). CONCLUSION: Serum AMH had a good diagnostic performance for diagnosis of PCOS presenting with oligo/anovulation and hyperandrogenism. AMH threshold at 4.7 ng/mL was the best compromise level for diagnosis of PCOS. FNPO ≥15, FNPS ≥7 and OV ≥ 6.5 mL were reliable threshold for detecting polycystic ovaries in women with frank manifestation of PCOS.

Endometrial neoplasia in reproductive-aged Thai women with polycystic ovary syndrome.

OBJECTIVE: To determine the risk of endometrial neoplasia in relation to endometrial thickness and to evaluate factors influencing endometrial thickness in reproductive-aged Thai women with polycystic ovary syndrome (PCOS). METHODS: The present cross-sectional study was done at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, between October 1, 2010, and January 31, 2013. We recruited women (aged ≥18 years) with PCOS diagnosed according to the revised 2003 Rotterdam criteria. Data were collected for physical examinations, pelvic ultrasonography, hormonal profiles, and carbohydrate metabolic profiles. Endometrial tissue was obtained using a disposable endometrial-suctioning device. RESULTS: The final analysis included 122 women. Six (4.9%) patients had endometrial neoplasia. All six women had an endometrial thickness of 7 mm or more, representing a risk of 8.7% (6/69) in this group. The endometrial thickness was significantly but weakly associated with body mass index (r=0.227, P=0.012), 2-hour blood glucose (r=0.323, P=0.001), fasting glucose to insulin ratio (r=0.185, P=0.042), homeostatic model assessment of insulin resistance (r=0.183, P=0.044), and free testosterone (r=0.236, P=0.009). No categorical risk factors for an endometrial thickness of 7 mm or more were identified. CONCLUSION: Thai women with PCOS and a thick endometrium (≥7 mm) had an 8.7% risk of endometrial neoplasia. Invasive endometrial surveillance for the prevention of endometrial cancer is recommended in these women.

Endometrial androgen signaling and decidualization regulate trophoblast expansion and invasion in co-culture: A time-lapse study.

INTRODUCTION: To elucidate whether trophoblast expansion and invasion are modulated by androgen signaling in an in vitro co-culture model system with decidualizing endometrial stromal cells (ESCs). METHODS: We employed an in vitro co-culture model of early embryo implantation, consisting of human ESCs (EtsT499 cells) and spheroids generated by extravillous trophoblast (EVT) derived HTR8/Svneo. The ESCs were decidualized with 8-bromo-cAMP (8-br-cAMP) in the presence or absence of dihydrotestosterone (DHT) at various concentrations for 5 days before co-culture with EVT spheroids. Trophoblast expansion was monitored by fluorescent time-lapse imaging microscopy. ESCs motility was visualized by using CellTracker™ Orange CMRA fluorescent probe. Apoptosis of ESCs was detected by CellEvent™ Caspase-3/7® green detection reagent. Invasion assays were performed to quantify EVT invasion through a chemotaxis cell membrane. RESULTS: Expansion of EVT spheroids was significantly enhanced by decidualized compared to undifferentiated ESCs. This process was further stimulated if ESCs were first decidualized in the presence of DHT. In contrast to decidualized ESCs, undifferentiated cells actively migrated away from expanding EVT spheroids. Invasiveness of EVT toward decidualized ESCs was significantly attenuated in comparison to undifferentiated ESCs. DHT had no effect on EVT invasion. However, an inhibitor of intercellular gap junction communication significantly enhanced EVT invasion towards decidualized ESCs. CONCLUSIONS: These results indicate distinct roles for androgen signaling and gap junction formation in decidual cells in regulating trophoblast expansion and invasion.

Correlation of clinical and biochemical hyperandrogenism in Thai women with polycystic ovary syndrome.

AIM: The aim of this study was to determine the correlation of clinical hyperandrogenism and biochemical hyperandrogenism (hyperandrogenemia) in Thai women with polycystic ovary syndrome (PCOS). METHODS: This cross-sectional study was conducted at Siriraj Hospital, Thailand. Subjects were 145 women with PCOS who were diagnosed in accordance with the revised Rotterdam 2003 criteria and registered during January to July 2008. Clinical hyperandrogenism was assessed using the modified Ferriman-Gallwey score for hirsutism, the American Academy of Dermatology criteria for severity of acne, and the Ludwig scale for androgenic alopecia and virilization. Biochemical hyperandrogenism was determined from serum concentration of total testosterone (TT), dehydroepiandrosterone sulfate and free testosterone (FT). RESULTS: The participants had a mean age of 25.5 ± 6.5 years and a body mass index of 26.2 ± 6.9 kg/m(2) . The most common presenting symptom was oligomenorrhea or amenorrhea. The most common expression of clinical hyperandrogenism was acne (56.6%). Most of the participants (84.8%) had high serum-FT. There was a statistically significant correlation between clinical and biochemical hyperandrogenism in the following pairs: hirsutism and FT (r = 0.3, P < 0.001); hirsutism and TT (r = 0.26, P < 0.001); and acne and TT (r = 0.26, P = 0.002). The others had little or no correlations. CONCLUSION: Clinical hyperandrogenism is not a good predictor for biochemical hyperandrogenism in Thai women with PCOS. A modified Ferriman-Gallwey score cut-off point of 8 has low sensitivity but high specificity for hyperandrogenemia; therefore, it is useful for the diagnosis but not useful for the exclusion of hyperandrogenemia in Thai women with PCOS.

Measures of body adiposity and visceral adiposity index as predictors of metabolic syndrome among Thai women with PCOS.

AIM: To evaluate the relationship between measures of body adiposity and visceral adiposity index (VAI) and risk of metabolic syndrome (MS) and to identify the optimal cut-off points of each measurement in Thai polycystic ovary syndrome (PCOS). METHODS: A cross-sectional study was completed physical examination, fasting plasma glucose, lipid profiles of 399 PCOS and 42 age-matched normal controls. Body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and VAI were calculated. Associations between different measures and MS were evaluated and the receiver-operating characteristic (ROC) curve was performed to determine appropriate cut-off points for identifying MS. RESULTS: Percentage of MS in PCOS was 24.6%, whereas none MS in controls. Previously recommended cut-off values for body adiposity and VAI were significantly associated with MS. ROC curve analysis of the only PCOS showed newly obtained optimal cut-off points for BMI and VAI of ≥28 kg/m(2) (AUC = 0.90) and >5.6 (AUC = 0.94), respectively. Values found to be more accurate than the original ones. VAI was the best predictor, followed by BMI and WHtR. CONCLUSION: All body adiposity and VAI parameters can predict the risk of MS. Optimal values for Thai PCOS were ≥28 kg/m(2) for BMI, ≥0.85 for WHR, ≥0.5 for WHtR and >5.6 for VAI.

No association between CYP17 -34T/C polymorphism and insulin resistance in Thai polycystic ovary syndrome.

AIM: To investigate the association of CYP 17 -34T/C polymorphism with insulin resistance (IR) in Thai polycystic ovary syndrome (PCOS). METHODS: A cross-sectional study was performed on 210 Thai women diagnosed with PCOS. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze CYP17 polymorphism at -34T/C. Student's t-test was used to compare the mean of normally distributed variables between A1/A1 and A2/X. Chi-squared or Fisher's exact tests and OR were used to analyze the association at P < 0.05. RESULTS: Out of 210 cases, PCR-RFLP was successful in 199. Mean patient age was 24.4 ± 4.7 years, with body mass index 25.2 ± 6.3 kg/m(2) . There were 65 and 134 women in the A1/A1 genotype group and A2/X genotype group, respectively. The A2/X genotype group was statistically significantly younger and had a strong trend toward overweight/obesity compared with the A1/A1 genotype group. The prevalence of IR according to different methods varied from 15.4% to 70.8% and was not different between the two groups. On subgroup analysis, in the overweight/obese PCOS group, the A2/X genotype was not associated with any indices of IR. CONCLUSION: No significant association between CYP17-34T/C polymorphism and IR was found in Thai PCOS women, although the A2/X genotype group was statistically significantly younger than the A1/A1 genotype group.

Ratio of ovarian stroma and total ovarian area by ultrasound in prediction of hyperandrogenemia in reproductive-aged Thai women with polycystic ovary syndrome: a diagnostic test.

AIM: To evaluate the performance of ovarian stromal area to total ovarian area (S/A) ratio for the prediction of biochemical hyperandrogenism in Thai women with polycystic ovary syndrome (PCOS). METHODS: A cross-sectional study was performed in 222 reproductive-aged Thai women with PCOS attending the Gynecologic Endocrinology Unit (GEU), Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital from May 2007 to January 2009. The patients were interviewed for medical history and examined for anthropometry and clinical hyperandrogenism. Venous blood samples were obtained for androgen profiles. An ovarian ultrasonogram was obtained via transvaginal or transrectal ultrasonography. RESULTS: The prevalences of clinical and biochemical hyperandrogenism were 48.6% and 81.1%, respectively. The S/A ratio at a cut-off point of 0.33 had modest predictability for hyperandrogenism, namely, 0.537 area under the receiver-operator curve, 36.6% sensitivity, 72.1% specificity, 83.8% positive predictive value (PPV) and 20.9% negative predictive value (NPV). The combination of clinical hyperandrogenism and S/A ratio improved the predictability for biochemical hyperandrogenism, with sensitivity, specificity, PPV and NPV of 72.1%, 58.1%, 87.8% and 33.3%, respectively. CONCLUSION: The S/A ratio alone is not a good predictor for biochemical hyperandrogenism in Thai PCOS women attending GEU for menstrual dysfunction. The combination of S/A ratio and clinical hyperandrogenism has better performance than the S/A ratio alone to predict biochemical hyperandrogenism.

Challenging Regimen for Long-Term Conservative Treatment of Endometrial Adenocarcinoma in Young Women: A Case Report and Review of the Literature.

A 20-year-old obese Thai woman with polycystic ovary syndrome and clinical stage I well-differentiated endometrial carcinoma denied surgical staging. Chest X-ray and magnetic resonance imaging of the whole abdomen suggested neither distance metastasis nor local invasion of the cancer. After 3 months of systemic progestin therapy with megestrol acetate (MA) 480 mg/day, the endometrial carcinoma persisted. The treatment was changed to a combination of levonorgestrel intrauterine system (LNG-IUS) and MA with a stepping-up from 160 to 480 mg/day. Complete remission was achieved at treatment month 9. Prevention of recurrence was provided using LNG-IUS plus MA 160 mg/day. Endometrial surveillance using trimonthly transvaginal ultrasonography and endometrial biopsy suggested no recurrence for at least 24 months after remission.

Prevalence of metabolic syndrome in reproductive-aged polycystic ovary syndrome Thai women.

OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) in reproductive-aged polycystic ovary syndrome (PCOS) Thai women. MATERIAL AND METHOD: A Cross sectional study was done at the Gynecologic Endocrinology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital of 250 PCOS Thai women who were diagnosed using Revised Rotterdam 2003 criteria, and who did not take medications affecting sex hormones or lipid metabolism, and attended the Gynecologic Endocrinology Unit between May 2007 and January 2009. Patents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood sample of each patient was drawn after 12-hour fasting. Prevalence of MS determined using the definitions of National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), International Diabetes Federation (IDF), and National Heart Lung and Blood Institutes/American Heart Association (NHLBI/AHA). RESULTS: Mean +/- SD of age, body mass index (BMI), and waist circumference (WC) were 25.4 +/- 5.8 years, 26.2 +/- 7.6 kg/M2, and 82.3 +/- 16.3 cm, respectively. Prevalence of MS by the definitions of NCEP ATP III, IDF and NHLBI/AHA was 18.0%, 21.2%, and 21.2%, respectively. Of non-MS women, > 40% already had one to two criteria of IDF definition. Among MS women, 100% had central obesity, 50.9% had high blood pressure, 28.3% had impaired fasting blood glucose, 62.3% had hypertriglyceridemia, and 92.5% had high-density lipoprotein cholesterol < 50 mg/dL. The prevalence of MS increased from 10.3% in women aged < 20 years to 50.0% in those aged > or = 40 years (p of trend = 0.003), and from 0.0% in women with BMI < 23 kg/M2 to 54.5% in those with BMI > or = 30 kg/M2 (p of trend < 0.001). CONCLUSION: The prevalence of MS in reproductive-aged PCOS Thai women was 18.0% by NCEP ATP III and 21.2% by IDF and NHLBI/AHA. The prevalence varies only little with definitions of diagnostic criteria. The prevalence increases with age and body mass index. Slightly more than 40% of the non-MS PCOS Thai women already had one to two criteria of MS.

Characteristics of 250 reproductive-aged polycystic ovary syndrome Thai women at Siriraj Hospital.

OBJECTIVE: To determine the clinical characteristics of reproductive-aged polycystic ovary syndrome (PCOS) Thai women. STUDY DESIGN: Cross sectional study SETTINGS: Gynecologic Endocrinology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital. SUBJECTS: 250 PCOS Thai women who registered at the Siriraj PCOSprojectfrom May 2007 to January 2009. PCOS were diagnosed using Revised Rotterdam 2003 criteria. Women who were taking medications affecting sex hormones or lipid metabolism within 3 months before registration were excluded from the present study. MATERIAL AND METHOD: Patients were interviewed and examined for weight, height, waist circumference, blood pressure, presence of acanthosis nigricans, and signs of hyperandrogenism. Ovarian ultrasonography was examined using vaginal probe inserting into the vagina or rectum. Venous blood sample of each patient was drawn during 8.00-10.00 o'clock after 12-hour fasting. MAIN OUTCOME MEASURES: Clinical characteristics and laboratoryprofiles in PCOS Thai women. RESULTS: Of all participants, 62% were 20-29.9 years old, 30% had high blood pressure, 57% were overweight to obese, 49% had central obesity, and 27% had acanthosis nigricans. Clinical hyperandrogenism was found in 15.6% of the patients. Approximately 7% of PCOS women had impaired fasting glucose and one third had dyslipidemia. Prevalence of the PCOS criteria presenting in the population were oligomenorrhea and/or amenorrhea (98.4%), hyperandrogenism (49 2%), and ultrasonographic polycystic ovary (97.2%). Of all participants, 44% had three components of diagnostic criteria. Among those who had two components, presence of abnormal menstrual cycle plus polycystic ovary was the most common finding. CONCLUSION: Menstrual problem was the most common presenting symptom among the presented participants. Hyperandrogenism/ -emia adds only a little value on making PCOS diagnosis. Most of the PCOS Thai women have menstrual problem. In these patients, ovarian ultrasonography has high value to diagnose PCOS; addition of androgen blood test can diagnose only 3% more PCOS cases. Although the presented PCOS Thai women are stillyoung, approximately 50% already have some parameters of health risk. It is suggested to provide preventive measures for these patients to prevent long term medical problems.