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Aim: To present evidence‐ and consensus‐based recommendations for the diagnosis abnormal uterine bleeding. Methods: A literature search for the diagnosis of abnormal uterine bleeding was systematically conducted in PubMed from its inception to May 2024 to identify meta‐analyses, reviews, randomized controlled trials, and clinical trials, followed by an additional systematic search using keywords. Based on this evidence, an expert panel developed background, clinical, and future research questions. Results: Based on a systematic search and the collected evidence, we developed five background questions, three clinical questions, and one future research question, with recommendations and/or statements. Evidence and recommendations are provided for clinical questions. Additionally, we developed a flowchart for diagnosis showing the steps of the examinations to be performed. Conclusion: The flowchart and nine recommendations/statements specify an efficient diagnostic procedure to differentiate abnormal causative diseases of uterine bleeding optimized for actual Japanese situations. [ABSTRACT FROM AUTHOR]

Aim: To clarify the diagnostic process of the causative disease of abnormal uterine bleeding (AUB) in Japan according to the International Federation of Gynecology and Obstetrics AUB diagnostic system. Methods: Patients diagnosed with AUB were included in a nationwide survey of AUB conducted during any 2‐week period between December 2019 and January 2020. The second survey included information on patient background, AUB symptoms, examinations for diagnosing AUB, the order in which they were performed, and the causative diseases of AUB. Results: Correspondence analysis showed an association between hormonal testing, hysterosalpingography, and magnetic resonance imaging (MRI) in patients with amenorrhea, and heavy menstrual bleeding was strongly correlated with various examinations, such as coagulation tests, pelvic MRI, and endometrial cytology or biopsy. The results also indicated that each AUB causative disease can be diagnosed based on a specific examination profile. Conclusion: We clarified the process of diagnosing the causative disease of AUB in our country and determined that it was mainly diagnosed by imaging and pathological examination in cases of structural disease. The high rate of AUB‐E and the low rate of AUB‐C are possibly associated with specific examination trends in Japan. The results of this study will be useful for the development of a standard protocol for AUB diagnosis in our country. [ABSTRACT FROM AUTHOR]

Aim: Abnormal uterine bleeding, as proposed in 2007, is defined as unexpected uterine bleeding in women of reproductive age; the cause of the bleeding is categorized using the PALM‐COEIN system. Identifying the diagnostic and treatment modalities for each cause might be intriguing. To summarize the options for abnormal uterine bleeding assessment, we employed text‐mining analysis for each of its causes. Methods: We analyzed abstracts based on PALM‐COEIN from PubMed and Web of Science in March 2022. The literature was divided into categories; topics about the disorders were retrieved, and covalent network analysis was conducted to find information for evaluating abnormal uterine bleeding. Results: Diagnostic approaches for PALM included histological and image analysis, including computerized tomography, magnetic resonance imaging, sonography, and hysteroscopy. The therapeutic approaches varied according to the cause. Diagnostic approaches for COEIN were mostly medical history interviews and blood sampling, and the therapeutic approaches for COEIN were ablation, hysteroscopy, and hormonal treatment. The PALM‐COEIN classification co‐occurrence search revealed each cause's diagnostic procedures, symptoms, and treatment procedures. Conclusion: Our text‐mining methodology revealed comprehensive insights, important study themes, and clinical trends for abnormal uterine bleeding. A tailored approach to medical realities is required for treating abnormal uterine bleeding properly. [ABSTRACT FROM AUTHOR]

Purpose: To test the theory that invaginated ovarian surface epithelium and endometrial implants on the ovary form ovarian endometriomas. Methods: Adhesion sites of ovarian endometrioma on the peritoneum and consecutive ovarian endometrioma cyst wall, called non‐adhesion sites, were histologically examined. DNA methylomes of the adhesion sites, non‐adhesion sites, and blueberry spots were compared with those of ovary, endometrium, and peritoneum. Results: The non‐adhesion sites showed an ovarian surface epithelium‐like structure near the adhesion site, which continued to a columnar epithelium‐like structure. Calretinin staining was strong in the ovarian surface epithelium‐like structure but weak in the columnar epithelium‐like structure. Estrogen receptors were absent in the ovarian surface epithelium‐like structure, but present in the columnar epithelium‐like structure. The adhesion sites had endometrial gland‐like structures that expressed estrogen receptors. Analyses of DNA methylomes classified the non‐adhesion sites and ovaries into the same group, suggesting that ovarian endometriomas originate from the ovarian surface epithelium. The adhesion sites, blueberry spots and peritoneum were classified in the same group, suggesting that the adhesion sites and blueberry spots originate from the peritoneum. Conclusions: The present results support the invagination theory. Ovarian endometriomas consist of invaginated ovarian surface epithelium with celomic metaplasia and endometrium implants on the peritoneum. [ABSTRACT FROM AUTHOR]

Aim: To investigate the status of abnormal uterine bleeding (AUB) in Japan using the International Federation of Gynecology and Obstetrics (FIGO) classification (AUB system 1 and 2; PALM‐COEIN) and to clarify the relationship between AUB symptoms and the diseases causing AUB. Methods: In a nationwide study, we enrolled first‐time patients who visited target facilities during two consecutive weeks from December 1, 2019 to January 31, 2020. The FIGO classification was used to investigate patients with symptoms and causative diseases of AUB. Based on the proportion of patients in the nationwide study, 373 cases were included in the detailed survey. Survey items included symptoms of AUB according to AUB system 1, examination details, and causative diseases according to the PALM‐COEIN classification. Results: Within the study period, we encountered 61 740 first‐time patients, of which 8081 (13.1%) were diagnosed with AUB. Among them, 39.9% had abnormal menstrual cycles and 56.9% had abnormal menstrual bleeding. In the survey, PALM had the highest percentage of AUB‐L and COEIN had the highest percentage of AUB‐O. Correspondence analysis showed that COEIN was strongly associated with abnormal menstrual cycles and PALM with abnormal menstrual bleeding. Conclusion: We conducted the first nationwide survey of AUB in Japan. The FIGO classification was a useful tool for the diagnosis of AUB, with a strong correlation between symptoms of AUB by AUB system 1 and the causative disease of AUB by PALM‐COEIN. Conversely, a high percentage of AUB‐N and AUB‐E suggests that AUB system 1 and PALM‐COEIN are ambiguous as diagnostic tools. [ABSTRACT FROM AUTHOR]

Although changes in bone mineral density (BMD) are important indexes in osteoporosis treatment, no markers are available to predict them. Given the importance of assessing the therapeutic windows of antiresorptives, we explored potential biomarkers of bone remodeling in patients receiving treatment for osteopenia. Postmenopausal women with osteopenia (defined as a lumbar BMD T‐score <−1.0 standard deviation (SD) below that of a reference population but >−2.5 SD) were administered estradiol 1 mg/d and bazedoxifene 20 mg/d. After 3 months of treatment, we evaluated their ratio of serum bone‐specific tartrate‐resistant acid phosphatase to bone‐specific alkaline phosphatase (TRACP‐5b/BAP), which is widely used for evaluating bone turnover in postmenopausal patients with osteoporosis in Japan because their minimum significant changes are smaller than other bone turnover markers such as carboxy‐terminal collagen cross‐links (CTX) or N‐terminal propeptide of type I procollagen (P1NP) and thus, accurately reflect bone turnover. After 1 year of treatment, we assessed changes in lumbar BMD. The cut‐off TRACP‐5b/BAP scores for a ≤−2% decrease and ≥2% increase in lumbar spine BMD were 38.4 and 29.0, respectively. The TRACP‐5b/BAP scores were associated with significantly greater areas under the curve than the other evaluated parameters. These results suggest that the TRACP‐5b/BAP score after 3 months of osteopenia treatment can predict changes in lumbar BMD after 1 year of treatment. Moreover, a receiver operating characteristic curve analysis of TRACP‐5b/BAP scores after 3 months of antiresorptive therapy and percent changes in BMD at 1 year revealed that the TRACP‐5b/BAP score, as an index of the balance between bone resorption and formation markers, has the potential to serve as a modulator of the anabolic window reflective of bone remodeling. This study's findings also suggested a role for TRACP‐5b/BAP score as a predictor of a non‐response to antiresorptive therapy, thus offering health economic implications for osteoporosis treatment. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Aims: Dydrogesterone is a retro‐progesterone preparation widely used for over a half century. We sought to evaluate the efficacy and safety of dydrogesterone in Japanese women with dysmenorrhea. Methods: This study was conducted as an open‐label, single‐arm, multicenter study. One dydrogesterone 5‐mg tablet (Duphaston) was administered orally twice daily for 21 days from the 5th to 25th day of each menstrual cycle. A total of 44 (safety analysis) and 31 patients (efficacy analysis) were enrolled. Total dysmenorrhea score, dysmenorrhea subscale scores, dysmenorrhea visual analog scale, severity of menstruation‐related lower abdominal pain, low back pain, headache, and nausea/vomiting, basal body temperature, and serum estradiol and progesterone levels were evaluated. Results: Baseline of the total dysmenorrhea score was 4.61, which went down over time following the administration of dydrogesterone, and the decrease was statistically significant at and after 2nd cycle of menstruation. Mean change from baseline at the final evaluation point was −1.84 (P < 0.001). Severity of menstruation‐related lower abdominal pain, low back pain, headache, and nausea/vomiting, in the evaluated menstruation cycles tended to decrease over time. Basal body temperature showed a biphasic pattern in 70% at baseline, 50% in 2nd menstruation cycle, and 61% in 5th menstruation cycle, and at least half of the patients may have had ovulation during the treatment. Incidence of adverse drug reactions was 31.8%, and the most common adverse event was metrorrhagia. Conclusion: Dydrogesterone is efficacious, safe, and clinically beneficial in patients with dysmenorrhea, thereby indicating that dydrogesterone can be considered as a treatment option for patients with dysmenorrhea. [ABSTRACT FROM AUTHOR]

Objectives: Low dose oral contraceptive pills (OCPs) that contain synthetic estrogen and progestin are often used to relieve chronic pelvic pain associated with endometriosis. We sought to evaluate the efficacy of drospirenone/ethinylestradiol (DRSP/EE) with low-dose estrogen in treating endometrioma., Study Design: A prospective clinical study in six hospitals and one clinic in Japan was conducted. Forty-nine 23- to 45-year-old patients who suffered from endometriosis-associated dysmenorrhea were included in the study. The primary endpoint was the change in size of ovarian endometrioma as measured by transvaginal ultrasonography. The secondary endpoint was the change in dysmenorrhea as evaluated by VAS (visual analog scale) scores before treatment and at 3 and 6 cycles of treatment. In addition, serum CA125, anti-mullerian hormone (AMH), interleukin (IL)-6, and IL-8 were evaluated after 6 cycles of treatment., Results: The maximum diameter and volume of the ovarian endometrioma significantly decreased after 3 and 6 cycles compared with pretreatment. VAS scores of dysmenorrhea pain were also reduced after 1, 3 and 6 cycles. A significant correlation between the reduced size of the endometrioma and the decline of VAS scores was found. The levels of serum CA125 and AMH concentration were decreased after 6 cycles. No significant changes were observed in serum IL-6 and IL-8., Conclusion: Low dose DRSP/EE therapy is a promising treatment not only to reduce the size of endometrioma but also for dysmenorrhea., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: International mortality and frequency rates for breast cancer have been associated with the wet type of human earwax. It was recently found that earwax type is determined by a single nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in ABCC11. The G allele determines the wet type of earwax as a Mendelian trait with a dominant phenotype. The present study examined the association between the frequency rate of breast cancer and the frequency of the G allele of ABCC11., Patients and Methods: Using blood samples from patients with invasive breast cancer (n = 270) and control volunteers (n = 273), the 538G>A SNP in ABCC11 was genotyped using the SmartAmp method., Results: The frequency of the G allele in breast cancer patients was higher than that in healthy controls. The odds ratio for the genotypes (G/G+G/A) to develop breast cancer was estimated to be 1.63 (p-value = 0.026), suggesting that the G allele in ABCC11 is associated with breast cancer risk., Conclusion: This study showed that Japanese women with wet earwax have a higher relative risk of developing breast cancer than those with dry earwax. The ABCC11 SNPs that determine these phenotypes should be further investigated in order to obtain insights into the mechanisms by which breast cancer develops and progresses.

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer., (Copyright 2009 Elsevier GmbH. All rights reserved.)