Prospective comparative trial comparing O-RADS, IOTA ADNEX model, and RMI score for preoperative evaluation of adnexal masses for prediction of ovarian cancer.

INTRODUCTION: Preoperative assessment of ovarian tumors to distinguish between benign and malignant is important. At this time, many diagnostic models were available and the popularity of the risk of malignancy index (RMI) in Thailand is still high. The IOTA Assessment of Different NEoplasias in adneXa (ADNEX) model and the Ovarian-Adnexal Reporting and Data System (O-RADS) model were both new models with good performance. OBJECTIVES: The purpose of this study was to compare O-RADS, RMI, and ADNEX models. DESIGN: This diagnostic study was performed using data from the prospective study. METHODS: Data from 357 patients from a previous study were included and calculated using the RMI-2 formula then applied to the O-RADS system and the IOTA ADNEX model. The diagnostic significance of the results was evaluated by receiver operating characteristic (ROC) analysis and pairwise comparison between models was made. RESULTS: The area under the receiver operating characteristic curve (AUC) to distinguish an adnexal mass as a benign or malignant tumor was 0.975 (95% CI, 0.953-0.988) for the IOTA ADNEX model; 0.974 (95% CI, 0.960-0.988) for O-RADS; 0.909 for RMI-2 (95% CI, 0.865-0.952). There were no differences in pairwise AUC comparisons between the IOTA ADNEX and O-RADS models, and both were better than those of RMI-2. CONCLUSIONS: The IOTA ADEX and O-RADS models are excellent tools for distinguishing the adnexal mass in the preoperative assessment and were better than RMI-2. The use of one of these models is recommended.

Prevalence of ovarian mass and diagnostic performance of ultrasonography pattern recognition among women at the Gynaecologic Ultrasonography Unit at University Hospital in Thailand.

The aim of this retrospective study was to determine the prevalence of ovarian masses and calculate the diagnostic performance of the pattern recognition approach in ovarian pathology. A total of 1001 patients diagnosed with ovarian mass were included, of which 92.6% were diagnosed with ovarian pathology and the presence of a pathological result, while 7.4% of cases were diagnosed with functional ovarian cyst. The prevalence of ovarian malignancy was 15%. A specific ultrasound diagnosis was suggested in 62.9% of all cases, while sonographers did not explicitly provide a diagnosis in remaining cases. A subjective assessment showed 80.3% sensitivity (95% confidence interval (CI) 68.7-89.1) and 97.6% specificity (95% CI 96-98.6) in differentiating between benign and malignant ovarian masses. The sensitivity and specificity for the diagnosis of endometriotic cyst were 77.03% and 90.63% and 63.19% and 94.3% for mature cystic teratoma, respectively. In conclusion, assessment showed good performance in differentiating between benign and malignant ovarian mass and it was possible to diagnose several specific ovarian tumours. Impact StatementWhat is already known on this subject? Pattern recognition is an acceptable method for classifying ovarian mass, which exhibits specific morphological features on grey-scale ultrasonography, and can be used to predict nature and histological type.What do the results of this study add? Even in the hands of an expert examiner, there were a number of cases in which the diagnoses could not be specifically stated. Pattern recognition correctly classified 90.3% of ovarian masses as either benign or malignant and correctly provided specific histologic diagnoses after exclusion of unspecified diagnosis in 80.6% of all cases. The diagnostic performance of this approach was high in differentiating between benign and malignant ovarian mass and in diagnosing some specific ovarian pathologies.What are the implications of these findings for clinical practice and/or further research? A subjective assessment is simple and easy to use in clinical practice and has shown promising results in classifying benign and malignant ovarian mass. Moreover, it can also be used to make some specific diagnoses. However, specialised and experienced gynaecological ultrasound examiners are required to provide the most accurate diagnosis. Therefore, criteria to describe ultrasound features and convincing operators to make a definite diagnosis as often as possible should be encouraged. A prospective study to verify diagnostic performance of pattern recognition or comparing with other ultrasonographic diagnostic tools should be considered.

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).

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.

Effect of estradiol vaginal gel on vaginal atrophy in postmenopausal women: A randomized double-blind controlled trial.

AIM: To evaluate the efficacy and safety of 25 µg of estradiol gel on postmenopausal vaginal tissue. METHODS: This randomized double-blind controlled trial included postmenopausal women with vaginal atrophy who attended our menopause clinic during July 2017-January 2018. Women were randomly assigned to the estradiol gel group or control group (K-Y® Jelly). Treatment consisted of 2 mL of product applied intravaginally daily for 2 weeks, and two doses per week for the next 6 weeks. The most bothersome symptom (MBS), vaginal health index (VHI), vaginal pH, vaginal maturation index, vaginal maturation value (VMV), female sexual function index (FSFI), serum estradiol level and endometrial thickness were evaluated at baseline, 4 and 8 weeks. RESULTS: Seventy-five of 80 women completed the trial. After 8 weeks of treatment, VMV, VHI, vaginal pH and FSFI improved significantly in the estradiol group, with no observed change in the control group. The MBS was decreased in both groups with no significant difference between groups. Serum estradiol level and endometrial thickness were not significantly different between groups at baseline or at week 8. CONCLUSION: Estradiol vaginal gel demonstrated an ability to reverse vaginal atrophy with a high safety profile and low systemic absorption of estradiol.

Postoperative desogestrel for pelvic endometriosis-related pain: a randomized controlled trial.

OBJECTIVE: To determine the effectiveness of desogestrel for relieving endometriosis-related pain. METHODS: A double-blinded randomized placebo-controlled trial was conducted in 40 patients who had endometriosis with moderate-to-severe dysmenorrhea or chronic pelvic pain undergoing laparoscopic conservative surgery. After surgery, patients were randomized to desogestrel or placebo group. Outcomes included changes in visual analog scale (VAS) of dysmenorrhea, pelvic pain and dyspareunia, patient satisfaction, and adverse effects. RESULTS: Forty patients were randomized to desogestrel group (n = 20) and placebo group (n = 20). At month 6, the desogestrel group had significantly lower median VAS of overall pelvic pain, dysmenorrhea and noncyclic pelvic pain. Comparing with the placebo group, the desogestrel group had greater reduction in VAS of overall pain, dysmenorrhea and pelvic pain, but comparable reduction in VAS of dyspareunia. No patient in the desogestrel group but 4 patients in the placebo group still had moderate-to-severe pelvic pain at 6 months postoperatively. The proportion of patients who rated the treatment as very satisfied was higher in the desogestrel group than in the placebo group. There was no serious adverse event during the study period. CONCLUSIONS: Desogestrel is effective and acceptable for postoperative therapy for patients with moderate-to-severe pain related to endometriosis.

Prevalence of endometriosis in women undergoing surgery for benign gynecologic diseases.

OBJECTIVE: To determine the prevalence of endometriosis among other benign gynecologic diseases and to identify the characteristics of patients at increased risk of concomitant diagnosis before surgery MATERIAL AND METHOD: A descriptive cross-sectional study of331 women with benign gynecologic diseases who underwent surgery in the Department of Obstetrics and Gynecology, Faculty ofMedicine Siriraj Hospital, Mahidol University, Bangkok, Thailand were included The subjects were interviewed for demographic data, obstetrics, and medical history. Data from medical records were reviewed and collected Operative notes and pathological reports were reviewedfor the diagnosis of endometriosis. The outcome measurement is the prevalence of endometriosis that was diagnosed by the surgeon from operative finding or pathological report and the characteristics of the patients at increased risk of concomitant diagnosis before surgery. RESULTS: Of the 331 women with benign gynecologic diseases, 101 had coexistent endometriosis. Prevalence ofendometriosis in benign gynecologic diseases was 30.5%. Of the 285 women with benign gynecologic diseases that did not have concomitant diagnosis of endometriosis before surgery, endometriosis was found in 55 patients postoperatively. Prevalence of endometriosis in this group was 19.3%. The three most common diseases in women undergoing surgery were uterine leiomyoma, adenomyosis, and benign ovarian cysts, respectively. The coexistence ofendometriosis with uterine leiomyoma, adenomyosis, and benign ovarian cysts were 28%, 43.5%, and 50%, respectively. Women with preexisting endometriosis were significantly younger than those with postoperative diagnosed endometriosis. CONCLUSION: The prevalence of coexistence of endometriosis and benign gynecologic diseases, especially uterine leiomyoma, adenomyosis, and benign ovarian cyst, was high. The diagnosis of concomitant diseases was made intra-operatively and postoperatively in more than half of the cases. Physicians should be concerned about the coexistence of both conditions and put this finding into the preoperative counseling data and definite surgery should be informed in advanced stage of endometriosis.

Hyperprolactinemia: a 12-year retrospective study at gynecologic endocrinology unit, Siriraj Hospital.

BACKGROUND: Hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis. To date, no available data about hyperprolactinemia in Thai women has been published OBJECTIVE: To determine clinical and laboratory findings of Thai female patients with different etiology of hyperprolactinemia, as well as the response of treatment, recurrence, and pregnancy after treatment. MATERIAL AND METHOD: Medical records of 139 female patients with the diagnosis of hyperprolactinemia in Gynecologic Endocrinology Unit, Siriraj Hospital between January 1, 1999 and December 30, 2011 were retrospectively reviewed after the study protocol was approved by Siriraj Institutional Review Board. The data was analyzed to determine patient demographic data, presenting symptoms, duration of symptoms, initial serum prolactin levels, causes, imaging studies, treatment, treatment outcomes, and adverse events. RESULTS: Ninety-seven female patients with hyperprolactinemia were included in the study. Mean age at diagnosis was 31.8 +/- 7.7 years. Amenorrhea was the most common presenting symptom (49.5%) followed by galactorrhea (44.3%). Median initial serum prolactin level was 117 ng/mL (25.1-1,624 ng/mL). Pituitary adenoma is the most common cause (40.2%) followed by idiopathic hyperprolactinemia (37.1%). Microadenomas were found in 74.3% of pituitary adenoma. The median size of the tumor was 9 mm. Medical treatment was given to 79 (88.8%) patients. Bromocriptine was given to 66 patients. Mean of maximum dose of bromocriptine was 5.8 mg. Median duration of treatment was 35.8 months. Adverse events were reported in 24.2% of patients, dizziness was the most common adverse event. Median time to normalize serum prolactin level was 3.8 months. In 29 patients who desired pregnancy, eight patients got pregnant. Median time to pregnancy was 25.9 months. Patients with macroadenoma had significantly higher prolactin level than those with microadenoma (p = 0.024). Patients with galactorrhea had the shortest duration of symptom (p = 0. 010). There were no statistically significant difference in symptoms, duration of symptoms, and initial prolactin level between patients with and without pituitary adenoma. Patients with pituitary adenoma needed higher doses (p = 0.009) and longer duration of treatment (p = 0.007) than those without a tumor Normalization of prolactin level and recurrence rate was not different between the two groups (p = 0.056 and 0.374). Log rank test showed that the time to normalize and survival time of recurrence were not significantly different between patients with and without a tumor (p = 0.136 and 0.146, respectively). CONCLUSION: Amenorrhea was the most common presenting symptom in Thai hyperprolactinemic females, who attended Siriraj gynecologic endocrinology unit, followed by galactorrhea. Pituitary adenoma is the most common cause followed by idiopathic hyperprolactinemia. Patients with pituitary adenoma needed higher doses and longer duration of treatment than those without a tumor

Intraperitoneal sub-diaphragmatic instillation of bupivacaine plus morphine for reducing postoperative shoulder pain after gynecologic endoscopy.

BACKGROUND: Gynecologic endoscopic surgery is a minimally invasive surgical technique for treatment of various gynecologic diseases. When compared to conventional laparotomy, this procedure has advantages in many aspects such as reduced postoperative pain, short hospital stay, and decreased morbidity associated with laparotomy. However 15 to 30% of the patients experienced moderate or severe postoperative shoulder pain. Methods to minimize postoperative shoulder pain after gynecologic endoscopy are essential to maximize the quality of life of the patients. OBJECTIVE: To evaluate the benefit of intraperitoneal instillation of bupivacaine plus morphine for reducing postoperative shoulder pain incidence after gynecologic endoscopy. MATERIAL AND METHOD: A randomized clinical trial was conducted in 158 patients undergoing laparoscopic procedures. The patients were randomly assigned to receive either 0.5% bupivacaine hydrochloride 20 mL mixed with morphine 3 mg (study group) or normal saline (control group) instillation to subdiaphragmatic area before finishing the procedure. Shoulder pain was evaluated at immediate post-operative time, and at 12 and 24 hours from the termination of surgery. The data of requested analgesic drugs after surgery was also recorded. RESULTS: Baseline characteristics were comparable between the two groups. Diagnosis, laparoscopic procedures, and duration of operation were also comparable. There were comparable proportions of patients reporting shoulder pain at 12 and 24 hours between the study and control group (30.4% and 30.4% at 12 hours, and 11.3% and 21.5% at 24 hours, respectively). Median pain scores at 12 and 24 hours were comparable between the study and control group (3 and 2 at 12 hours, and 4 and 4 at 24 hours, respectively). Requirement of analgesics was slightly greater among control than study group, but without statistical significance (17.7% and 24.1% respectively). CONCLUSION: Intraperitoneal instillation of bupivacaine plus morphine had no efficiency for reducing postoperative shoulder pain incidence after gynecologic endoscopy.

Postoperative levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: a randomized controlled trial.

OBJECTIVES: To estimate the effectiveness of a postoperative levonorgestrel-releasing intrauterine system for relieving pelvic pain in patients with endometriosis. METHODS: A double-blind randomized controlled trial was conducted in 55 patients with endometriosis and moderate-to-severe dysmenorrhea (visual analog scale, greater than 50 mm) undergoing laparoscopic conservative surgery. After surgery, patients were randomized to a levonorgestrel-releasing intrauterine system (n=28) or expectant management (n=27) group. Primary outcome was the change of dysmenorrhea visual analog scale. Secondary outcomes included changes of pelvic pain and dyspareunia visual analog scale, Short Form-36 score, and adverse effects. RESULTS: The two groups were comparable in age, body mass index, parity, and baseline pain scores. At 12 months, the levonorgestrel-releasing intrauterine system group had a significantly lower median value of dysmenorrhea and noncyclic pelvic pain score. Compared with the control group, the levonorgestrel-releasing intrauterine system group had greater reduction in dysmenorrhea visual analog scale (-81.0 compared with -50.0 mm, P=.006) and pelvic pain visual analog scale (-48.5 compared with -22.0 mm, P=.038) but a comparable reduction in dyspareunia visual analog scale (-15.0 compared with -19.0 mm, P=.831). Two patients in levonorgestrel-releasing intrauterine system group (7.4%) and nine in the expectant management group (39.1%) had recurrent dysmenorrhea within 1 year postoperatively (P=.014). Number-needed-to-treat to prevent one case with recurrent dysmenorrhea within the first year was three cases. The Short Form-36 scores improved in the levonorgestrel-releasing intrauterine system group but did not change in the expectant management group. There was no serious adverse event during the study period. CONCLUSION: The levonorgestrel-releasing intrauterine system is effective and well accepted for long-term therapy after conservative surgery for patients with moderate to severe pain related to endometriosis. It can improve the patient's quality of life, including physical and mental health.

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.

Health check-up program for pre/postmenopausal women at Siriraj Menopause Clinic.

OBJECTIVE: To determine the general health status of pre/postmenopausal women attending the menopause clinic. STUDY DESIGN: Retrospective descriptive study. SETTING: Siriraj Menopause Clinic, Gynecologic Endocrinology Unit, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University. STUDY POPULATION: Pre/postmenopausal women (i) presumed to have no medical disease (no disease group) or (ii) with unknown status of medical disease (no record group) and undergoing health check-up program at the time of registration without prior hormone therapy. MATERIAL AND METHOD: Medical records of new patients registering at the menopause clinic from January 1999 to December 2005 were reviewed. RESULTS: Among 1,020 patients undergoing health check-up program, there were 366 patients in the no disease group. They had abnormal health parameters listing by frequency of prevalence including hypercholesterolemia (62.3%), suboptimal blood pressure (49.3%), overweight to obese (30.2%), suboptimal fasting blood sugar (2 7.9%), hypertriglyceridemia (21.3%), abnormal liver function tests (5.4-6.9%), and abnormal kidney function tests (0.5%). The prevalence of dyslipidemia was statistically higher in the no record group compared to the no disease group; such abnormal parameters included hypercholesterolemia (> or =200 ml/dL), high blood level of low density lipoprotein cholesterol (LDL-C > or = 130 mg/dL), and high ratio between LDL-C and high density lipoprotein cholesterol (LDL-C/HDL-C ratio >3). Osteoporosis was found in 6.6% of the patients. Abnormal mammographic findings that needed close follow-up or breast biopsy were found in 13.5%. Twelve patients had breast biopsy and none had breast cancer. CONCLUSION: Abnormal health parameters are common in pre/postmenopausal women presumed to have no medical disease. The similar or even worse findings are also found in those whose status of medical diseases was unknown. Therefore, a routine health screening program, especially for metabolic diseases, should be offered to pre/postmenopausal women regardless of their medical history.

Serum follicle stimulating hormone and estradiol in peri/postmenopausal women attending Siriraj Menopause Clinic: a retrospective study.

OBJECTIVES: To determine serum levels of Follicle Stimulating Hormone (FSH) and Estradiol (E) in peri/postmenopausal women attending the menopause clinic. STUDY DESIGN: Retrospective descriptive study. SETTING: Siriraj Menopause Clinic, Gynecologic Endocrinology Unit, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital. STUDY POPULATION: Peri/postmenopausal women attending Siriraj Menopause Clinic from January 1994 to December 2003. MATERIAL AND METHOD: Medical records of women who had a blood test for FSH and/or E2 prior to hormonal therapy were reviewed. RESULTS: During a 10 year period, there were 116 eligible patients who could be classified into perimenopausal (31 cases), natural postmenopausal (43 cases), and surgical postmenopausal (32 cases) groups. Age at registration of perimenopausal (47.87 +/- 4.38 yr) and surgical postmenopausal (48.06 +/- 6.49 yr) groups were younger than that of the natural postmenopausal group (55.74 +/- 6.80 yr). The perimenopausal group, who still had regular menstruation, was the youngest. The average FSH level of 60.46 +/- 33.15 mIU/mL was not different among groups. The estradiol level of perimenopausal (79.05 +/- 83.62 pg/mL) and surgical postmenopausal (63.05 +/- 136.39 pg/mL) groups were significantly higher than that of natural postmenopausal (25.05 +/- 37.663 pg/mL) group (p = 0.001). Serum level of FSH or E2 was not correlated with age or years since menopause. There was significant but minimal negative correlation between serum levels of FSH and E2. CONCLUSION: Serum FSH and/or E2 levels are not accurate enough by themselves to rule in or rule out perimenopause. The authors suggested that clinicians should diagnose perimenopause based on menstrual history and age, without relying on laboratory testing.

Transcriptional inhibition of the estrogen response element by antiestrogenic piperidinediones correlates with intercalation into DNA measured by energy calculations.

The energy of interaction of antiestrogenic ligands bound to DNA derived from molecular modeling was compared to the capacity of the ligands to directly inhibit the transcriptional activity of an estrogen responsive gene. 3-Phenylacetylamino-2,6-piperidinedione (A10) and related compounds were intercalated into a partially unwound DNA site in a canonical estrogen response element (ERE). The piperidinedione/ERE complexes were subjected to energy minimization and the strength of interaction of the ligands with the DNA was measured. The ability of the ligands to inhibit transactivation was assessed using a reporter gene constructed with the ERE of the vitellogenin gene promoter (ERE(v)-tk-Luc) transiently transfected into the human estrogen receptor-positive MCF-7 breast cancer cell line. The results demonstrate a direct correlation between the calculated energetic fit of the compounds in the ERE and inhibition of ERE(v) transactivation. The order of potency of the compounds to suppress estrogen-dependent reporter gene activity was identical to that previously shown for inhibiting the growth of MCF-7 cells. To our knowledge, these results provide the first direct experimental evidence that the predicted fit of a class of compounds into a defined DNA binding site correlates with the ability of the compounds to modulate specific gene functions regulated at that site.

Up-regulation of gap junctional intercellular communication and connexin43 expression by retinoic acid in human endometrial stromal cells.

CONTEXT: Gap junctions, made up of connexins (Cxs), play fundamental roles in coordinating a number of cellular processes through their ability to directly regulate cell-cell communication. Cx43 is the most widely expressed Cx in the endometrium and is known to be important in a variety of physiological and pathological processes in this tissue. OBJECTIVE: In this study, we investigated the ability of the retinoid, all-trans-retinoic acid (RA), to regulate Cx43 expression in human endometrial stromal cells. DESIGN: Primary endometrial stromal cells obtained from patients undegoing surgery for infertility workup were treated in vitro with RA and control compounds for different time periods, up to 48 h. Cx43 mRNA and protein levels, protein phosphorylation, and gap junctional intercellular communication (GJIC) were analyzed. RESULTS: Treatment of the cells with RA showed a dose-dependent increase in Cx43 expression at both the mRNA and protein levels. In addition, RA induced a relative decrease in the phosphorylated species of Cx43 while causing a corresponding increase in the nonphosphorylated form. Concomitant with these changes, RA-treated cells demonstrated up to a 250% enhancement of GJIC as assessed by dye transfer experiments. Augmentation of GJIC and alterations of Cx43 expression were observed over the same range of RA concentrations. Treatment of cells with the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate increased the phosphorylated species of Cx43 and correspondingly inhibited GJIC. CONCLUSIONS: Phosphorylation of Cx43 is inversely related to GJIC in endometrial stromal cells. Retinoids increase GJIC in endomentrial stromal cells through upregulation of Cx43 expression while inducing a decrease in the phosphorylated species of the protein. The data suggest a novel mechanism by which retinoids can influence endometrial cell biology.

Clinical and pathological responses of progestin therapy for non-atypical endometrial hyperplasia: a prospective study.

AIMS: To evaluate the clinical and pathological responses and factors predicting non-responders to various progestins currently prescribed for the treatment of non-atypical endometrial hyperplasia. METHODS: A prospective observational study was conducted in the Gynecologic Endocrinology Unit, Faculty of Medicine, Siriraj Hospital, Thailand, from 1998 to 2003. A 6-month course of progestin therapy was offered to all patients. The clinical response was evaluated from the vaginal bleeding pattern during the first 4 months of treatment. The pathological response was evaluated from the histopathology of the endometrium after completion of the 6-month therapy. RESULTS: Of 250 registered patients, the number of cases qualified for the evaluation of the clinical and pathological response were 198 and 134 cases, respectively, revealing the overall clinical and pathological response rates of 93.4% and 92.5%, respectively. Among 13 clinical non-responders, 84.6% might have associated pelvic pathology. Among 10 pathological non-responders, three had surgical treatment, and progressive disease was found in one case. Significant factors predicting clinical non-responders included a history of prior bleeding (odds ratio [OR] = 8.79, 95% confidence interval [CI] = 1.63, 47.53), the presence of associated pelvic pathology (OR = 25.52, 95% CI = 3.21, 203.01), and treatment using progestins other than medroxyprogesterone acetate. Factors predicting pathological non-responders were not statistically significant. CONCLUSIONS: The current regimens of progestin therapy for non-atypical endometrial hyperplasia have high response rates. Patients who fail to have a clinical response should be evaluated for associated pelvic pathology. Follow-up endometrial biopsy should be offered to the patients, because 7.5% have persistent or progressive lesions, necessitating aggressive treatment.

Conjugated linoleic acid blocks estrogen signaling in human breast cancer cells.

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid found in dairy products and meat from ruminants, has been widely shown to possess anticarcinogenic activity against breast cancer both in vitro and in animal models. However, little information is available concerning the mechanisms of the antitumor effects of these compounds. In this study, we investigated whether CLA has direct antiestrogenic activity in estrogen receptor positive (ER+) breast cancer cells. Treatment of the ER+ cell line, MCF-7, with 5 purified CLA isomers as well as "mixed" CLA showed a dose-dependent growth inhibition with the 9cis,11cis and 9cis,11trans being the most and least potent isomers, respectively. In assessing effects on a number of variables that play obligatory roles in the estrogen signaling pathway, we determined that CLA treatment downregulated ERalpha expression at both mRNA and protein levels and decreased binding activity of nuclear protein to a canonical estrogen response element (ERE(v)). Using a reporter gene construct (ERE(v)-tk-Luc) that was transiently transfected into MCF-7 cells, we also demonstrated inhibition of promoter activity by CLA that was directly mediated by blockage of activity through the ERE. The results indicated that the order of potency of the CLA isomers for inhibiting activation of ERE(v) was similar to that demonstrated for their antiproliferative activity on MCF-7 cells. Taken together, these findings demonstrate that CLA compounds possess potent antiestrogenic properties that may at least partly account for their antitumor activity on breast cancer cells.

Hormonal replacement therapy in surgical menopause with underlying endometriosis.

OBJECTIVE: To evaluate the effect of hormonal replacement therapy (HRT) regimens in surgical menopause patients with underlying endometriosis. DESIGN: Observational retrospective study. MATERIAL AND METHOD: 123 women with endometriosis after definite surgery (total abdominal hysterectomy with bilateral salpingo-oophorectomy) were followed in the Gynecologic Endocrinology and Menopause clinics. Patients were classified into 4 groups according to HRT regimens, i.e. control (no HRT, n=17), estrogen only (ERT, n=50), cyclic estrogen/progestin regimen (cyclic E/P, n=16), and continuous combined estrogen/progestin (ccE/P, n=24). 12 patients who received more than one regimen and 4 patients who received less than 6 months of HRT were excluded from the study. The information was obtained from the medical records. RESULTS: Mean age at surgery of all patients was 38.9 years old. Mean duration of HRT was 41.2 months. There was no difference in age at surgery or duration of follow-up in each group. There was 1 (2%) case of recurrent endometriosis and 3 (6%) cases of recurrent symptoms in the estrogen only group; none of them required additional surgical treatment. Malignant transformation was not found. CONCLUSIONS: Although the present series is small, it seems that HRT is safe for postmenopausal women with underlying endometriosis. Recurrence of endometriosis has rarely been a problem with HRT, especially in those who received the combination of estrogen and progestin regimens.