The quality of life and work productivity are affected by the presence of nausea/vomiting in patients taking iron preparations for heavy menstrual bleeding or anemia: a population-based cross-sectional survey in Japan.

BACKGROUND: Patients with iron deficiency anemia are treated with iron preparations, but gastrointestinal symptoms such as nausea and vomiting occur frequently. These symptoms may negatively affect the quality of life and work productivity in patients with iron deficiency anemia. This study assessed the impact of nausea and vomiting on the quality of life and work productivity of patients taking iron preparations for heavy menstrual bleeding or anemia. METHODS: An online survey was conducted among patients taking iron preparations for heavy menstrual bleeding or anemia. Demographic data and information about medication use and the health condition were collected. The patients were asked to answer the 5-level EQ-5D version, and work productivity and activity impairment questionnaires. The outcomes were reported by patients in the presences of nausea, vomiting, and nausea or vomiting. The association with the 5-level EQ-5D version utility score for the severity and frequency of the symptoms were also assessed. RESULTS: A total of 385 patients were enrolled, and 96 were patients with nausea or vomiting, of which 94 were with nausea and 27 were with vomiting. The 5-level EQ-5D version utility scores for the patients with nausea, vomiting, and nausea or vomiting were significantly lower than those of the patients without these symptoms (p < 0.001 for each). The 5-level EQ-5D version utility score was correlated with the severity of nausea and the frequency of vomiting per day (p < 0.001 for each). As for the work productivity and activity impairment, the presenteeism, the overall work impairment, and the activity impairment of the patients with nausea, vomiting, and nausea or vomiting were significantly higher than those without these symptoms (p < 0.001 for each). The absenteeism was slightly higher trend was observed, but not significant. CONCLUSION: Patients taking iron preparations who have nausea or vomiting experience a significant burden in terms of poorer quality of life and higher work productivity impairment. TRIAL REGISTRATION: UMIN000045700 ( http://www.umin.ac.jp/ctr/ ). Registered on October 11, 2021.

Efficacy and safety of a novel pain management device, AT-04, for endometriosis-related pain: study protocol for a phase III randomized controlled trial.

BACKGROUND: Endometriosis-related pain encompassing dysmenorrhea, dyspareunia, and chronic pelvic pain, reduces the quality of life in premenopausal women. Although treatment options for endometriosis alleviate this pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. The Angel Touch device (AT-04) is a portable magnetic fields irradiation device that incorporates a combination of mixed alternative magnetic fields at 2 kHz and 83.3 MHz. A phase III trial confirmed the efficacy and safety of AT-02, a prototype of AT-04, for pain relief in patients with fibromyalgia. METHODS: This is a phase III, multicenter, prospective, randomized, sham device-controlled, double-blind, parallel study. The participants will be premenopausal women aged > 18 years who have endometriosis-related pain with at least moderate severity. Considering dropouts, 50 participants have been deemed appropriate. Eligible women will be centrally registered, and the data center will randomly allocate them in a 1:1 ratio to the intervention and control groups. Women in the intervention group will receive electromagnetic wave irradiation generated by AT-04 and those who in the control group will wear a sham device for 16 weeks, and both groups will wear AT-04 for another 4 weeks. The primary outcome measure is the change in the Numeric Rating Scale score at 16 weeks compared with the baseline. Secondary outcome measures are efficacy for pelvic pain including dysmenorrhea and non-menstrual pain, and chronic pelvic pain not related to menstruation, dysmenorrhea, and dyspareunia, and improvement of quality of life during the study period. Safety will be evaluated by device defects and the frequency of adverse events. The study protocol has been approved by the Clinical Study Review Board of Chiba University Hospital, Chiba, Japan, and will be conducted in accordance with the principles of the Declaration of Helsinki and the Japanese Clinical Trials Act and relevant notifications. DISCUSSION: This study aims to develop a novel method of managing endometriosis-related pain. The AT-04 is an ultralow-invasive device that can be used without inhibiting ovulation, suggesting potential benefits to women of reproductive-age. Trial registration number Japan Registry of Clinical Trials (jRCTs032230278).

Endometriosis is a chronic inflammatory disorder that negatively impacts reproductive health via endometriosis-related pain, infertility, and endometriosis-associated ovarian cancer. Although current therapeutic options for endometriosis are effective for the endometriosis-related pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. This is the first randomized controlled trial to investigate the efficacy and safety of a novel portable pain management device, AT-04, that incorporates a combination of mixed alternating magnetic fields, for endometriosis-related pain. This is a multicenter, prospective, sham device-controlled, double-blind, parallel study. Enrolled women will have undergone standard hormonal treatment for endometriosis at baseline, and this allows for assessing whether the device remains effective when used in conjunction with existing treatment methods. The study also will explore the impact of AT-04 on reducing the size of ovarian endometriotic cysts that reflect the activity of endometriosis. The study reflects the strong desire by physicians to liberate women from the unbearable pain associated with endometriosis. The sole efficacy of AT-04 in treating endometriosis-related pain is difficult to evaluate as there is a possibility that menstrual cycles may influence the assessment of pain and quality of life. However, the study findings regarding the effectiveness of AT-04 for the treatment of endometriosis-related pain may benefit women with endometriosis who have pain that is not effectively relieved by other treatments. Consequently, it may contribute to the improvement of reproductive health within society.

Impact of nausea/vomiting on EQ-5D-5L utility scores in patients taking iron preparations for heavy menstrual bleeding or anemia.

BACKGROUND: The purpose of this study was to establish an estimating equation to predict the 5-level EQ-5D version (EQ-5D-5L) utility score in patients taking iron preparations for heavy menstrual bleeding (HMB) or anemia and to evaluate whether the presence of nausea or vomiting was a significant predictor of EQ-5D-5L-based quality of life. METHODS: A cross-sectional survey was conducted to collect EQ-5D-5L utility scores and other patient reported outcomes from 385 patients taking iron preparations for HMB or anemia who were selected from the disease patient panel. Using the utility scores as objective variables, explanatory variable candidates were selected considering correlations, multicollinearity, and clinical validity. Predicting models were constructed using regression-based models (linear model, generalized linear model (GLM), Tobit model). Stepwise regression method was applied for selecting statistically significant (p < 0.05) predictors. Goodness-of-fit of models were assessed by mean absolute error and mean squared error (MSE). RESULTS: The EQ-5D-5L utility scores (mean ± standard deviation) of 96 patients with nausea/vomiting and 289 patients without nausea/vomiting were 0.67 ± 0.16 and 0.84 ± 0.14, respectively (p < 0.001). The presence of nausea/vomiting was shown to be the most significant factor reducing the utility score in the statistical models using the explanatory variable candidates selected in the study. As the results of the goodness-of-fit test, GLM with the smallest MSE was selected to establish the estimating equation. CONCLUSION: The estimating equation to predict the EQ-5D-5L utility scores in patients taking iron preparations for HMB or anemia was established. The presence of nausea/vomiting was found to be a factor significantly reducing utility scores, with a decrement of the value estimated to be -0.117. TRIAL REGISTRATION: UMIN000045700 ( http://www.umin.ac.jp/ctr/ ). Registered on October 11, 2021.

Clinical feasibility of absorbable gelatin film adhesion barrier (GM142 "TENALEAF®") in gynecological laparoscopic surgery: Safety assessment for first-in-human use and surgical video.

AIM: To evaluate the safety and operability of the GM142 (TENALEAF®, Medical Division, Gunze Limited, Tokyo, Japan) adhesion barrier applied in patients undergoing surgery for benign gynecologic disease. METHODS: This multicenter open study enrolled 34 patients from November 2018 to October 2019. RESULTS: The primary outcome was the incidence of adverse events (AE) within 12 weeks postoperatively. None of the 30 patients completing the study experienced a life-threatening AE. Thirteen patients (43.3%) suffered 30 mild or moderate AE in total. No intestinal obstruction (0/30) was observed, with the sample size justified by the AdSpray® trial (8/61 patients with AE). No gelatin-specific Immunoglobulin E (IgE) antibodies were induced in the patients. The adhesion barrier could be easily inserted (even via trocar) and positioned. After malfunctions were reported in six patients, the instructions for use were updated for trocar use. CONCLUSION: This study showed the safety and clinical feasibility GM142 as an adhesion barrier.

Hysteroscopy-guided laparoscopic resection of a cesarean scar defect in 5 steps: the usefulness of nonperfusion hysteroscopy.

OBJECTIVE: To demonstrate a 5-step approach to accurately identify the extent of resection of a cesarean scar defect (CSD) and perform excision and repair of the lesion. DESIGN: Technical video introducing laparoscopic scar repair using nonperfusion hysteroscopy for patients with a CSD. SETTING: Tertiary referral facility for gynecology. PATIENT(S): A 33-year-old woman who underwent intrauterine insemination for secondary infertility 3 times but did not conceive complained of repeated irregular bleeding caused by a CSD during infertility treatment. INTERVENTION(S): This video presents a systematic 5-step approach to laparoscopic repair of a CSD. Step 1: the lesion was coagulated and marked using a hysteroscope. Step 2: the lesion was thinned by cutting it using the hysteroscope. Step 3: after laparoscopic dissection of the bladder from the lower uterine segment and turning off the laparoscope's light source, the thinned lesion could be identified using light from the hysteroscope. Step 4: an incision was made at the lit-up point from the abdominal cavity side using an ultrasonic coagulation incision device to access the uterus. Step 5: once the uterine lumen was reached, reflux from the hysteroscope was stopped. Intraperitoneal insufflation gas then flowed into the uterus through the uterine wall perforation, and the lesion could be observed without the use of a reflux fluid. This technique is called nonperfusion hysteroscopy. By observing the marked lesion using nonperfusion hysteroscopy, it could be resected laparoscopically along the appropriate incision line. MAIN OUTCOME MEASURE(S): Advantage of performing 5 successive surgical steps to completely resect a CSD using laparoscopic repair and resolve the patient's symptoms. RESULT(S): Laparoscopic repair using nonperfusion hysteroscopy allowed recognition of the upper and lower edges of the lesion from the abdominal cavity side. CONCLUSION(S): The combined use of nonperfusion hysteroscopy allows observation of the uterine lumen without the use of a reflux fluid because pneumoperitoneum gas fills the uterine lumen. Intraoperative monitoring using a hysteroscope and laparoscope allows visualization of the lesion site from both sides while resection is being performed. This 5-step procedure permits precise identification of the lesion area, complete removal of lesions, and prevention of excessive resection that may reduce uterine function and increase perinatal risk.

Real-world outcomes of the levonorgestrel-releasing intrauterine system for heavy menstrual bleeding or dysmenorrhea in Japanese patients: A prospective observational study (J-MIRAI).

OBJECTIVES: We collected real-world data on the safety and clinical outcomes of the levonorgestrel-releasing intrauterine system (LNG-IUS) for heavy menstrual bleeding and dysmenorrhea. STUDY DESIGN: This was a prospective, multicenter, single-cohort, open-label, post-authorization 12-month follow-up study of Japanese patients initiating the LNG-IUS for heavy menstrual bleeding and/or dysmenorrhea. The primary endpoint was the safety profile based on adverse events and adverse drug reactions (ADRs), including expulsions and abnormal bleeding, within 12 months of LNG-IUS insertion. Secondary endpoints included changes from baseline in menstrual blood loss based on bleeding days and dysmenorrhea graded on a visual analog scale (VAS). RESULTS: Of the 595 patients included, many had underlying conditions such as adenomyosis (39.5%), uterine leiomyoma (30.8%), or endometriosis (12.9%). The incidences of ADRs and serious ADRs were 59.7% and 0.3%, respectively. Frequently reported ADRs were metrorrhagia (48.9%), procedural pain (14.1%), and ovarian cyst (6.2%). The cumulative incidence of expulsions at 12 months was 8.7%. Risk factors for expulsion were obesity (body mass index ≥25 kg/m2), adenomyosis, and uterine cavity length ≥8 cm. The median [interquartile range] VAS score for dysmenorrhea improved from 46.5 [13.0-68.0] at insertion to 1.0 [0.0-13.0] at 12 months, and improvements were also observed in chronic pelvic pain and painful defecation. CONCLUSIONS: The LNG-IUS safely and effectively reduced dysmenorrhea, chronic pelvic pain, and painful defecation. Risk factors for expulsion suggest that patients with underlying organic disease should be monitored carefully when using the LNG-IUS. IMPLICATIONS: The LNG-IUS is an effective treatment for secondary dysmenorrhea with organic disease, and for the reduction of chronic pelvic pain; however, physicians should be aware of the increased risk of expulsion in patients with organic conditions.

Bleeding patterns of women with heavy menstrual bleeding or dysmenorrhoea using the levonorgestrel-releasing intrauterine system: results from a real-world observational study in Japan (J-MIRAI).

PURPOSE: To collect real-world safety and clinical outcome data on the levonorgestrel-releasing intrauterine system (LNG-IUS) for functional/organic heavy menstrual bleeding (HMB) and dysmenorrhoea in Japanese women (J-MIRAI). MATERIALS AND METHODS: In this prospective, multicentre, single-cohort, open-label, post-authorisation study, we assessed menstrual blood loss after LNG-IUS insertion by changes from baseline in pictorial blood loss assessment chart (PBAC) scores. Scores for the menorrhagia multi-attribute scale (MMAS) were collected for 12 months to assess quality of life. RESULTS: We included 47 patients with complete PBAC score and patient diary data. The median PBAC score before LNG-IUS insertion was 159.0, which decreased significantly to 6.0 at 12 months post-insertion; for patients with adenomyosis (n = 20), PBAC score decreased from 174.5 pre-insertion to 19.5 at 12 months. The number of patient-reported bleeding days was correlated with PBAC score ≥5. The proportion of women with prolonged bleeding decreased from 85.7% to 34.6% by the study's end. Some women reported no bleeding after the first 90-day reference period. The mean MMAS overall score significantly increased from 50.50 before insertion to 88.67 at 12 months. CONCLUSIONS: Japanese women with functional/organic HMB experienced substantial reductions in bleeding symptoms and improvements in quality of life after 12-month use of the LNG-IUS.

A case of two ovarian tissue transplantations that led to a biochemical pregnancy in Japan.

Ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT) are fertility preservation options for prepubertal girls or those in whom cancer treatment cannot be delayed. They are important to increasing number of cancer survivors, but there are very few reports on this topic in Japan. This is the first report of a biochemical pregnancy after OTT in Japan. An 18-year-old woman, diagnosed with Ewing sarcoma of the seventh thoracic vertebra, underwent tumor resection. OTC was performed before postoperative chemotherapy. After 7 years, she decided to undergo OTT following the diagnosis of chemotherapy-induced premature ovarian insufficiency. On postoperative day 104, ovarian stimulation was started, yielding one embryo after 3 days. Embryo transfer was performed during a hormone replacement cycle. At 6 weeks and 1 day, the human chorionic gonadotropin level was 81.5 mIU/mL; however, no gestational sac was observed on ultrasonography, indicating a biochemical pregnancy. Our data will be useful for the further development of fertility preservation options in Japan in the future.

Comparison of efficacy and safety between intravenous ferric carboxymaltose and saccharated ferric oxide in Japanese patients with iron-deficiency anemia due to hypermenorrhea: a multi-center, randomized, open-label noninferiority study.

The intravenous formulation for supplementing iron currently available in Japan requires frequent administration. In contrast, ferric carboxymaltose (FCM) can improve iron-deficiency anemia (IDA) with only a small number of administrations; however, its efficacy and safety have not been established in Japanese patients. In this randomized, open-label study, we verified the noninferiority of FCM to saccharated ferric oxide (SFO) in Japanese patients with IDA due to hypermenorrhea, with the mean change from baseline to the highest observed hemoglobin level as the primary endpoint. Two hundred and thirty-eight eligible subjects (119 in FCM group, 119 in SFO group) were administered the investigational medicinal product and included in the analysis. The adjusted mean change from baseline to the highest observed hemoglobin level (95% CI) was 3.90 g/dL (3.77, 4.04) in the FCM group and 4.05 g/dL (3.92, 4.19) in the SFO group, and the difference between the groups (95% CI) was - 0.15 g/dL (- 0.35, 0.04). The noninferiority of FCM was verified. Incidence of adverse events was < 60% in both groups, and no significant difference was observed between the treatment groups. These results indicate that FCM can be a new, well-tolerated, and rapid treatment option for Japanese patients with IDA.

Cost-effectiveness of the recommended medical intervention for the treatment of dysmenorrhea and endometriosis in Japan.

BACKGROUND AND OBJECTIVE: This study aims to assess the cost-effectiveness of early physician consultation and guideline-based intervention to prevent endometriosis and/or disease progression using oral contraceptive (OC) and progestin compared to follow-up of self-care for dysmenorrhea in Japan. METHODS: A yearly-transmitted Markov model of five major health states with four sub-medical states was constructed. Transition probabilities among health and medical states were derived from Japanese epidemiological patient surveys and converted to appropriate parameters for inputting into the model. The dysmenorrhea and endometriosis-associated direct costs included inpatient, outpatient visit, surgery, and medication (OC agents, over-the-counter drugs), etc. The utility measure for patients with phase I-IV endometriosis comprised a visual analogue scale. We estimated the cost per quality-adjusted life year (QALY) at a time horizon of 23 years. An annual discount rate at 3% for both cost and outcome was considered. RESULTS: The base case outcomes indicated that the intervention would be more cost-effective than self-care, as the incremental cost-effectiveness ratio (ICER) yielded 115,000 JPY per QALY gained from the healthcare payers' perspective and the societal monetary value (SMV) was approximately positive 3,130,000 JPY, favoring the intervention in the cost-benefit estimate. A tornado diagram depicting the stochastic sensitivity analysis of the ICER and SMV from both the healthcare payers' and societal perspectives confirmed the robustness of the base case. A probabilistic analysis resulting from 10,000-time Monte Carlo simulations demonstrated efficiency at willingness-to-pay thresholds in more than 90% of the iterations. CONCLUSIONS: The present analysis demonstrated that early physician consultation and guideline-based intervention would be more cost-effective than self-care in preventing endometriosis and/or disease progression for patients with dysmenorrhea in Japan.

Identification of TRIM22 as a progesterone-responsive gene in Ishikawa endometrial cancer cells.

Progesterone plays important roles in implantation and maintains pregnancy. It antagonizes estrogen-mediated cell proliferation and promotes differentiation in the uterus. The action of progesterone is mediated by specific receptors, namely, the progesterone receptors (PRs). We generated two Ishikawa cell clones stably expressing PR isoform A (PR-A) and identified progesterone-responsive genes using cDNA microarray analysis. Fifteen genes were identified as progesterone-responsive gene candidates by microarray analysis and their progesterone-responsiveness was shown by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis. Out of these 15 genes, we focused on TRIM22. A database search revealed a progesterone response element (PRE) located from the -25 to -11 bp region upstream of TRIM22 exon 1. This PRE had a 1-bp mismatch in the consensus PRE sequence. A chromatin immunoprecipitation assay revealed that the interaction of PR with the TRIM22 PRE region increased in a hormone-dependent manner. The progesterone-dependent enhancer activity of TRIM22 PRE was demonstrated using a luciferase assay. Based on these results, we propose that TRIM22 is a direct target gene of PR and that it can mediate progesterone actions in uterine cells.

Does the presence of coexisting diseases modulate the effectiveness of a low-dose estrogen/progestin, ethinylestradiol/drospirenone combination tablet in dysmenorrhea? Reanalysis of two randomized studies in Japanese women.

BACKGROUND: The purpose of this study was to investigate the effectiveness of a combination of ethinylestradiol (EE) and 0.02 mg/drospirenone (DRSP) 3 mg in Japanese women with dysmenorrhea and in particular to determine whether or not the presence of specific coexisting organic diseases (eg, endometriosis, uterine fibroids, uterine adenomyosis) has an impact on treatment. METHODS AND RESULTS: Four hundred and ten patients with dysmenorrhea aged 20 years or older (315 without coexisting organic disease, 28 with endometriosis, 37 with uterine fibroids, and 46 with uterine adenomyosis [some patients had multiple coexisting organic diseases]) were enrolled and treated with EE/DRSP in either a 16-week comparator study or a 52-week long-term safety study. Evaluations included changes in total dysmenorrhea score, visual analog scale for dysmenorrhea, severity of symptoms, hormone levels, endometrial thickness, and safety outcomes. In both studies, the total dysmenorrhea score was significantly (P<0.001) decreased from baseline during treatment with EE/DRSP. Time-dependent changes in visual analog score for dysmenorrhea and alleviation of symptoms, such as lower abdominal pain, low back pain (lumbago), headache, and nausea/vomiting, were similar in all patient groups with and without any specific coexisting organic diseases. These improvements with EE/DRSP were observed for both short-term (16 weeks) and long-term (52 weeks) use. These effects were associated with suppressed increases in serum estradiol and progesterone levels and decreased endometrial thickness. The safety profile of EE/DRSP was similar in all patients, irrespective of the presence of coexisting organic diseases. CONCLUSION: EE/DRSP may be prescribed for patients with dysmenorrhea irrespective of the presence of any specific coexisting organic diseases.

Clinical characteristics of patients in Japan with ovarian cancer presumably arising from ovarian endometrioma.

OBJECTIVE: To investigate the clinical features of patients in Japan with malignant transformation of ovarian endometrioma. PATIENTS: Thirty-three patients diagnosed with ovarian cancer presumably arising from endometrioma were recruited retrospectively. These patients had been followed for at least 2 years after the ovarian endometrioma diagnosis, then continued to be followed after they had been found to have malignant transformation. RESULTS: The average age of the patients was 47.7 ± 9.3 years; 75.7% were premenopausal at the time of diagnosis of ovarian cancer. Among the 33 patients, ovarian cancer developed in the ipsilateral ovary of 6 patients with endometrioma after cystectomy. Twenty-eight patients were diagnosed with stage I ovarian cancer, and major histotypes were clear cell in 23 cases and endometrioid in 8. Before surgery for cancer, mural nodules within the endometriomas were detected in 32 patients, and 1 patient had a small 3-mm nodule. In 30 patients, the diameter of the tumor doubled in size 6 months prior to the diagnosis of malignant transformation. The diameter of the endometrioma and the preoperative CA125 value did not significantly correlate. CONCLUSIONS: To detect malignant transformation of ovarian endometrioma early and precisely, the clinician should determine the existence of a mural nodule and assess the rapid growth of the endometrioma.

[Cross-reactivity evaluation of improved estradiol (E2) assay reagent based on chemiluminescent enzyme immunoassay].

We evaluated the performance of a newly-improved estradiol(E2) assay reagent (NEW LP-E2-N), which replaces murine monoclonal antibody in the present reagent (LP-E2-N) with sheep monoclonal antibody, since we had experienced discrepant E2 assay results between LP-E2-N and other commercially available E2 assay kits. Several examinations with the new assay reagent indicated a good performance in terms of the limit of quantity, reproducibility (within-run and between-day), dilution linearity, and influence of blood components except hemoglobin. Using analogues and/or metabolites of E2, low or no cross-reactivity has been shown in NEW LP-E2-N: 0.26% with 25 ng/mL of estrone (El), 0.14% with 100 ng/mL of estradiol-3-sulfate, 0.02% with 200 ng/mL of 17α-ethynylestradiol, and less than 0.001% with 100 ng/mL of estriol(E3), estra-17-glucuronide, and estramustine, respectively. Although discrepant results between NEW LP-E2-N and LP-E2-N were observed in 12 samples, including 9 cases under oral hormone therapy, data from these samples were similar to those using 2 commercially available E2 assay kits, Architect and Eclusys, suggesting that the NEW LP E2-N shows adequate clinical efficacy. A correlation study was performed with LP E2-N, Architect, and Eclusys using 149 serum samples obtained from patients and healthy volunteers, and the correlation results were as follows: r = 0.831, y = 0.98x + 40.6 against LP-E2-N, r = 0.991, y = 1.08x + 12.4 against Architect, r = 0.995, y = 0.80x - 3.7 against Eclusys. In conclusion, the NEW LP-E2-N reagent displayed a relatively favorable kit performance except for in the elevation of assay results with hemoglobin, as well as a low cross-reactivity with E2 analogues and/or metabolites.

Burden of menstrual symptoms in Japanese women - an analysis of medical care-seeking behavior from a survey-based study.

BACKGROUND: Menstrual symptoms are associated with various health problems in women of reproductive age, and this may impact their quality of life. Despite this, Japanese women are likely to hesitate seeking a specialist's medical help for their menstrual symptoms. PURPOSE: To study subject parameters including symptom severity, gynecological disorders, and treatments in medical care-seeking women (outpatient) and women opting for self-care (nonvisit), to identify reasons why Japanese women do not see a gynecologist, and to document the benefit of gynecologist visits by assessing the impact on women's daily lives. METHODS: Two online surveys were conducted among women aged 15-49 years. Sampling was structured to approximate the age and geographic distribution in Japan. Results of the first survey and part of the second survey on the overall current burden of menstrual symptoms are reported in a separate publication. Further outcomes from the second survey reported in this paper included data from the outpatient (n=274) and nonvisit (n=500) groups on symptom severity, gynecological disorders, medical treatment use, reasons for not seeking medical care, and the improvement of daily life. RESULTS: The outpatient group tended to have greater symptom severity compared to the nonvisit group. Uterine fibroids, dysmenorrhea, endometriosis, and premenstrual syndrome were the most commonly self-reported diagnoses, and oral contraceptives were frequently prescribed at gynecologist visits. Nonvisit group subjects felt that gynecologist consultations were unnecessary or felt resistant to them. Daily life was significantly improved after medical treatment from a gynecologist visit with associated economic savings, whilst the nonvisit group had no change after taking over-the-counter drugs to relieve their menstrual symptoms. CONCLUSION: The present study results indicate that Japanese women who were suffering from menstrual symptoms could benefit from visiting a gynecologist for easing their symptoms, hence improving their daily life.

Expression and regulation of transient receptor potential cation channel, subfamily M, member 2 (TRPM2) in human endometrium.

To identify estrogen-responsive genes, we previously isolated estrogen receptor (ER)-binding DNA fragments from human genomic DNA using a recombinant ER protein. Six DNA fragments, each including a perfect palindromic estrogen response element (ERE), were obtained. The nucleotide sequence of one of the six fragments (E1 fragment) showed that the ERE of the E1 fragment is located in the 3'-untranslated region (UTR) of transient receptor potential cation channel, subfamily M, member 2 (TRPM2). Here, we confirmed the estrogen-dependent enhancer activity of the ERE of the E1 fragment by chloramphenicol acetyltransferase assay. TRPM2 mRNA expression was investigated in human endometrium, cultured human endometrial stromal cells (ESCs), and cultured human endometrial epithelial cells (EECs) using RT-PCR. Quantitative RT-PCR revealed that TRPM2 mRNA expression in ESCs increased after 17ß-estradiol (E2) treatment. This study demonstrated for the first time that TRPM2 is an estrogen-responsive gene expressed in human endometrial cells.

Hepatoblastoma in an infant with paternal uniparental disomy 14.

A 29-year-old primigravida developed polyhydramnios at 24 weeks of gestation, requiring six serial amnioreductions. In addition, prenatal ultrasound examinations revealed a fetus with small stomach pouch, small thorax, slightly shortened limbs, and skin edema; paternal uniparental disomy 14(upd(14)pat) phenotype was suspected. At 37 weeks, the patient delivered a 2558 g female infant with characteristic facial features, webbed neck, thoracic deformity, abdominal wall defect, skin edema, overlapping fingers, placentomegaly, and small thorax with 'coat-hanger' appearance of the ribs on chest X-ray. A phenotype consistent with upd(14)pat was confirmed by DNA analysis. Although the infant's condition was initially stable, hepatoblastoma was subsequently detected and right hepatectomy was performed on day 224. On day 382, the infant was discharged with in-home respiratory management.

The progesterone-responsive gene 14-3-3τ enhances the transcriptional activity of progesterone receptor in uterine cells.

Members of the 14-3-3 family are intracellular dimeric phosphoserine-binding proteins that can associate with and modulate the activities of many proteins. In our efforts to isolate the genes regulated by progesterone (P(4)) using suppressive subtractive hybridization, we previously found that 14-3-3τ is one of the genes upregulated by P(4). In this study, we demonstrated by quantitative RT-PCR (qRT-PCR), western blot analyses, and immunohistochemistry that 14-3-3τ mRNA and protein levels were increased in the rat uterus after P(4) treatment. Furthermore, qRT-PCR indicated that P(4) increased 14-3-3τ mRNA levels in human endometrial epithelial cells and endometrial stromal cells (ESCs). Western blot and qRT-PCR analyses revealed that in vitro decidualization using cAMP and medroxyprogesterone 17-acetate increased levels of 14-3-3τ mRNA and protein in ESCs. We have shown by qRT-PCR and western blot analyses that P(4) increased the mRNA and protein levels of 14-3-3τ in Ishikawa cells that stably express P(4) receptor-B (PR-B). Immunocytochemistry revealed that 14-3-3τ colocalizes with PR and translocates from the cytoplasm to the nucleus in response to P(4). Moreover, by luciferase reporter assay, we demonstrated that 14-3-3τ enhances the transcriptional activity of PR-B. Taken together, we propose that 14-3-3τ is a P(4)-responsive gene in uterine cells that modulates P(4) signaling.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.