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Alcohol consumption is internationally recognized as one of the compelling risk factors for breast cancer, but it does not necessarily correlate with the prognosis of breast cancer patients. Alcohol consumption in breast cancer patients was addressed in the 2022 Breast Cancer Clinical Practice Guidelines. A systematic review and meta-analysis of epidemiological studies on alcohol consumption and breast cancer recurrence, breast cancer-related mortality, all-cause mortality, and cardiovascular disease mortality in breast cancer patients was performed. The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant publications reporting cohort or case–control studies published until March 2021. A total of 33 studies (32 cohort studies and 1 case–control study) met the eligibility criteria; 4638 cases of recurrence, 12,209 cases of breast cancer-specific mortality, and 21,945 cases of all-cause mortality were observed. With regard to breast cancer recurrence, 7 studies assessed pre-diagnosis alcohol consumption (relative risk (RR) 1.02, 95% confidence interval (95% CI) 0.77–1.37, p = 0.88) and 3 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.85–1.10, p = 0.57), and no significant increase or decrease in risk was observed. With regard to breast cancer-related mortality, 19 studies assessed pre-diagnosis alcohol consumption (RR 1.02, 95% CI 0.93–1.11, p = 0.69), 9 studies assessed post-diagnosis alcohol consumption (RR 0.96, 95% CI 0.77–1.19, p = 0.70), and no significant increase or decrease in risk was observed. With regard to all-cause mortality, 18 studies assessed pre-diagnosis alcohol consumption (RR 0.90, 95% CI 0.82–0.99, p = 0.02), 8 studies assessed post-diagnosis alcohol consumption (RR 0.88, 95% CI 0.74–1.02, p = 0.08), and pre-diagnosis alcohol consumption was associated with a significantly decreased risk. With regard to cardiovascular disease mortality and alcohol consumption, 2 studies assessed it, and the RRwas 0.47 (95% CI 0.28–0.79, p = 0.005), showing that alcohol consumption was associated with a significantly decreased risk. The limitations of this study are that drinking status was mainly based on a questionnaire survey, which is somewhat inaccurate and has many confounding factors, and the cut-off value for the maximum alcohol intake in many studies was low, and it is possible that the actual intake was only an appropriate amount. In many countries, a standard drinking amount is set, and wise decisions are required.

Takumi Kurabayashi,1 Yuki Ideno,2 Kazue Nagai,3 Naho Maruoka,3 Kiyoshi Takamatsu,4 Toshiyuki Yasui,5 Kunihiko Hayashi3 1Department of Obstetrics and Gynecology, Niigata City General Hospital, Niigata, Japan; 2Gunma University Center for Mathematics and Data Science, Maebashi, Gunma, Japan; 3Department of International/Community Health Laboratory Sciences, Graduate School of Health Sciences, Gunma University, Maebashi, Gunma, Japan; 4Department of Obstetrics and Gynecology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; 5Department of Reproductive and Menopausal Medicine, Institute of Biomedical Science, Tokushima University Graduate School, Tokushima, JapanCorrespondence: Takumi KurabayashiDepartment of Obstetrics & Gynecology, Niigata City General Hospital, 463-7, Shumoku, Chuo-ku, Niigata City, Niigata Prefecture, 950-1197, JapanTel +81-25-281-5151Fax +81-25-281-5169Email takumi@hosp.niigata.niigata.jpPurpose: Although the validity of self-reported osteoporosis is often questioned, validation studies are lacking. This study was performed to investigate how well self-reported diagnoses of osteoporosis agreed with validated clinical information in young and middle-aged women in the Japan Nurses’ Health Study (JNHS), a nationwide prospective cohort study of nursing professionals.Patients and Methods: Data were reviewed for 15,717 subjects from the combined cohorts of the JNHS and a preceding pilot study (Gunma Nurses’ Health Study). The subjects’ mean age at the baseline (BL) survey was 41.6 ± 8.3 years, and the mean follow-up period was 11.5 ± 4.4 years. Participating nurses were mailed a follow-up questionnaire every 2 years. Respondents who self-reported a positive osteoporosis diagnosis during the study period were sent an additional confirmation questionnaire to corroborate the details.Results: The number (proportion) of women with osteoporosis was 884 (5.6%) [primary osteoporosis, 812 (5.2%); secondary osteoporosis, 72 (0.5%)]. The cumulative incidence of osteoporosis at the age of 40, 50, 60, 70, and 80 years was estimated to be 0.1% (95% confidence interval, 0.1– 0.2), 1.1% (0.9– 1.3), 7.7% (7.0– 8.4), 23.6% (21.6– 25.7), and 54.2% (40.2– 68.1), respectively. For BL and regular follow-up + expert review versus BL and regular follow-up + confirmation questionnaire + expert review, the positive predictive value (PPV) was 61.3% versus 85.6% and the negative predictive value (NPV) was 98.9% versus 98.2%, respectively.Conclusion: Self-reporting was associated with a high NPV for the incidence of osteoporosis. Although the PPV was slightly lower, additional corroborations by confirmation questionnaire might improve the PPV.Keywords: validation, self-reported diagnosis, osteoporosis, prospective cohort study, Japan Nurses’ Health Study

Objective: The aim of this study was to find out whether ThinPrep Integrated Imager (Hologic Inc.) screening is non-inferior to manual screening in the detection of cervical lesion. Study Design: For a total of 4,011 ThinPrep Pap test specimens stained by ThinPrep staining, manual screening (Manual arm) and ThinPrep Integrated Imager screening (Imager arm) were performed so as not to be screened by the same cytotechnologist, and the sensitivity and specificity in the detection of cervical lesion were compared using McNemar’s test. Results: The sensitivity to detect CIN1 or more squamous cell abnormalities or glandular abnormalities was 91.67% (= 374/408, 95% confidence interval [CI]: 88.44–94.08%) for the Manual arm and 92.40% (= 377/408, 95% CI: 89.28–94.70%) for the Imager arm, and the specificity was 88.87% (= 3,113/3,503, 95% CI: 87.77–89.88%) for the Manual arm and 89.55% (= 3,137/3,503, 95% CI: 88.48–90.54%) for the Imager arm. The differences in sensitivity and in specificity, respectively, were 0.74% (95% CI: −3.14–4.61%, McNemar’s test, p = 0.8041) and 0.69% (95% CI: −0.13–1.50%, McNemar’s test, p = 0.1125). About the equality of sensitivity and specificity between the 2 methods, 95% CIs of the difference between sensitivity and specificity are in the clinical equivalence range of ±5%, so the Imager arm is non-inferior to the Manual arm. Conclusion: The Imager arm was confirmed to have an equivalent and non-inferior capacity in the detection of cervical lesions compared with the Manual arm, suggesting that its practical application in cervical cytology tests is highly possible.

Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery.We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks).Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group. Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Objective We aimed to investigate whether hypertensive disorders of pregnancy are associated with problematic hot flashes in Japanese women. Methods In this study, we included participants in the Japan Nurses' Health Study who were women aged 41 to 55 years at baseline, parous, and complete a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology. Results At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of hypertensive disorders of pregnancy. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of hypertensive disorders of pregnancy of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with hypertensive disorders of pregnancy as compared with those without these disorders. Conclusions In this prospective study, we found that women with a history of hypertensive disorders of pregnancy have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of hypertensive disorders of pregnancy.

Background Many women experience various symptoms during the period of menopausal transition, including complaints of reduced cognitive functioning. However, these complaints are not necessarily recognized as core menopausal symptoms. In this study, we sought to characterize subjective complaints of reduced cognitive functioning by analyzing cross-sectional data from the Japan Nurses’ Health Study (JNHS). Methods The JNHS 4-year follow-up questionnaire containing a 21-item climacteric symptom checklist, which included a question about “poor memory or forgetfulness”, was mailed between 2005 and 2011 to all JNHS participants, regardless of their age at the time of the survey. We estimated the prevalence of slight and severe complaints in 5-year age-groups. We used principal component analysis to explore the underlying factors among the 21 symptoms during the menopausal transition period in women aged 45–54 years at the time of the survey. We also examined risk factors for complaints using multivariable modified Poisson regression analysis. Results In total, 12,507 women responded to the 4-year survey. The mean age at the time of the 4-year survey was 46.5 years (range 27–82). “Poor memory or forgetfulness” showed a peak prevalence of 81.7% (severe 27.9%; slight 53.8%) at 50–54 years, and gradually decreased after 55 years. Principal component analysis indicated that “poor memory or forgetfulness” belonged to somatic symptoms and was close to psychological symptoms in women aged 45–54 years. In women aged 45–54 years, the complaint was also significantly associated with hot flashes and sweats. Multivariable modified Poisson regression analysis showed that menopausal status (uncertain and postmenopausal), less sleep (sleep of Conclusions We found that prevalence of “poor memory or forgetfulness” was highest during the menopausal transition period and among perimenopausal women. This subjective complaint was associated with somatic, psychological complaints and VMS. It may be useful for women with cognitive problems in the transition period to consider management of comorbid menopausal symptoms.

The World Conference of the International Society of Psychosomatic Obstetrics and Gynecology held in The Hague, Netherlands in October 2019 ran a dedicated session debating the global research prio...

Background Perimenopausal women experience a wide variety of systemic symptoms: hot flashes, sweating, mental health concerns and various oral sensory complaints (OSC). OSC in perimenopausal women include xerostomia, taste disturbance and burning mouth. However, the factors associated with these OSC have not been identified. The purpose of this investigation was to elucidate the factors associated with OSC in perimenopausal women. Methods The study cohort comprised 43 perimenopausal women aged 45–55 years. Data on medical history, medications, menstrual status, menopausal symptoms, quality of life, xerostomia, taste disturbance and burning mouth were collected. Volumes of unstimulated and stimulated saliva were measured. Tongue coating was evaluated according to a tongue coating index. Univariate analysis was performed to identify factors significantly associated with having xerostomia, taste disturbance, burning mouth and more than two OSC (2OSC). Next, the factors strongly associated with these symptoms were examined by logistic regression analysis. Results The number of menopausal symptoms was significantly higher, and volume of unstimulated saliva was significantly lower in participants with xerostomia, taste disturbance, burning mouth or 2OSC than in those without these characteristics. Agents targeting the central nervous system were more frequently taken by participants with burning mouth and 2OSC than by those without these characteristics. According to logistic regression analysis, the number of menopausal symptoms was an explanatory variable for xerostomia, taste disturbance, burning mouth and 2OSC. Conclusions Our findings suggested that OSC associated with the number of menopausal symptoms. Management of menopausal symptoms may decrease OSC, leading to improved quality of life of perimenopausal women.

OBJECTIVES Various oral symptoms, including xerostomia and burning mouth syndrome, may occur in menopausal women. These symptoms reduce quality of life (QOL). However, the actual condition of xerostomia after menopause is not clear. The purpose of this study was to reveal the factors associated with xerostomia in perimenopausal women. METHODS Participants included 118 outpatients (mean age, 49.9 ± 3.2 years; range, 45-55 years) at a department of gynecology in Japan. Information was collected concerning age, medical history, medications, menstrual status, and history of treatment for climacteric symptoms. Oral symptoms, including xerostomia were evaluated with a 3-point scale. The climacteric symptom checklist for Japanese women and 36-Item Short-Form Health were used to evaluate climacteric symptoms and QOL, respectively. In addition, the volume of unstimulated saliva, oral moisture, salivary α-amylase, chromogranin A, and 17-β estradiol were measured. RESULTS Higher age, the total number of medications, psychotropic drug, hormone replacement therapy, treatment for climacteric symptoms, sticky mouth, burning sensation of tongue, dryness of nose and 14 of the 21 climacteric symptoms significantly affected xerostomia. In addition, treatment for climacteric symptoms, fall asleep but often awake at night, headaches and dryness of nose were significantly associated with xerostomia. In conclusion, xerostomia is closely associated to factors such as treatment for climacteric symptoms and certain menopausal symptoms, and it may be related to QOL in perimenopausal women.

Objective. Kampo medicine, a traditional Japanese medicine, is widely used in Japan, especially in the field of menopause medicine. However, few studies have shown evidence-based effects. This study aimed to confirm the effects of kamishoyosan on menopausal symptoms with a randomized, placebo-controlled, double-blind clinical trial. Methods. Subjects were randomly allocated to groups that received either kamishoyosan (n = 101) or a placebo resembling kamishoyosan (n = 104). The primary outcomes were the change in the number of hot flashes, depression scores, improvements of anxiety, quality of life (QOL), and menopausal symptoms before and 4 and 8 weeks after initiation of treatment with the study drug. The secondary outcome was drug safety. Results. After 8 weeks, the number of hot flashes decreased after treatment in both groups, but there was no significant difference between the two groups. The changes in SDS scores showed the same results. Moreover, no significant differences were observed between the two groups in assessments with the STAI, SF-36, and JSOG menopausal index. No serious adverse effect was reported. Conclusions. This first placebo-controlled double-blind randomized trial with kamishoyosan demonstrated that it was safe and had some effects on climacteric symptoms, but not significant compared with placebo. Some problems, such as placebo effects, in the study of Kampo therapy for menopausal symptoms, were revealed. This trial is registered with the trial registration number. UMIN 000006042.

Laparoscopic myomectomy may become a cause to increase intraoperative hemorrhage. The purpose of this investigation was to study the relationship between clinical features, MR imaging findings and intraoperative hemorrhage during laparoscopic myomectomy. This study included 126 patients clinically and pathologically diagnosed as uterine leiomyoma between 2010 and 2015. These findings were statistically compared between significant intraoperative hemorrhage group (greater than 300 ml) and nonsignificant intraoperative hemorrhage group (less than 300 ml). Correlation between the maximum diameter of resected leiomyomas and the maximum diameter leiomyomas on MR imaging were also evaluated. Significant hemorrhage group showed larger maximum diameter of resected leiomyoma (p = 0.01), larger maximum diameter of leiomyoma on MR imaging (p = 0.01) and have cellular leiomyomas on MR imaging more frequently (p = 0.03) than nonsignificant intraoperative hemorrhage group. The maximum diameter of resected leiomyomas significantly correlated with that of leiomyomas on MR imaging (Spearman’s rho = 0.797, p

Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.

To improve women's quality of life, the activity of the Women's Health Care Committee over a year up to July 2017 focused upon: (i) breast management; (ii) the influence of gynecological disease therapy on physical condition; (iii) non-surgical management of pelvic organ prolapse; (iv) survey of infectious diseases in obstetrics and gynecology in Japan; (v) health care for female athletes; (vi) a training program for women's health care advisors; (vii) revising the Japanese guidelines on hormone replacement therapy; and (viii) revising the 2016 Japanese guidelines for the proper use of emergency contraceptives. The detailed activity of the eight subcommittees is described herein. This report is based on the Japanese version of our annual report (Acta Obst Gynaec Jpn 2017;69(6):1480-1491), to publicize the activities of our committee.

Hereditary breast and ovarian cancer syndrome (HBOC) is a hereditary tumor that can be definitively diagnosed by detection of germline mutation of the BRCA1 or BRCA2 gene. The HBOC Public Awareness and Management Sub-committee of the Tumor Committee, Japan Society of Obstetrics and Gynecology carried out a fact-finding survey on the status of treatment of HBOC in Japan. The directors of medical specialty teaching facilities were notified of the questionnaire by post, with the request for one respondent per facility. The response period was from 8 July 2014 to 31 March 2015. Of the 678 facilities that were asked to compete the questionnaire, 341 (50.3%) responded. The responses are shown in the respective tables. For questions with free responses, similar answers have been grouped together, and the written answers have been freely translated. Based on these results, the Japan Society of Obstetrics and Gynecology considers that the 14 conditions, including consultations by specialist staff, must be met before risk-reducing salpingo-oophorectomy is carried out.

Aim We hypothesized that feeling mucosal dryness in one body region and the skin may be associated with dryness in other regions and that there are common background factors for dryness. In an earlier web-based survey, we reported prevalence figures of dry eyes, nose, mouth, skin, and vagina. In the present study, additional analyses were made to investigate the factors associated with dryness in each region, and simultaneous dryness in multiple regions. Methods A web-based questionnaire was completed by 310 Japanese women. The questions included dryness of the eyes, nose, mouth, vagina, and skin. Menopausal and other symptoms were also addressed. Multiple logistic regression modeling was performed to identify factors associated with dryness in each region and in multiple dry regions. Results Dry eyes were associated with dryness in the nose and with headache; dry nose was associated with dryness in the vagina and eyes; dry mouth was associated with sticky mouth symptom and dryness of the nose; dry skin was associated with use of xerogenic medications and vaginal discharge; and dryness of the vagina was associated with vaginal itchiness and dry nose. Vaginal discharge (odds ratio, 9.64; 95% confidence interval, 3.15–29.51) and sticky mouth (odds ratio, 6.35; 95% confidence interval, 1.29–31.29) were further associated with dryness in multiple regions. Conclusion The present results confirmed our study hypothesis by showing that dryness in one region was clearly associated with that in another or in multiple regions. The result implies the need for holistic diagnosis and counseling for patients with dryness complaints.

Prognostic clinicopathological factors for type 1 endometrial cancer are unknown and the purpose of the current study was to determine the independent prognostic variables for type 1 endometrial cancer. We performed a retrospective study of 168 patients with type 1 endometrial cancer primarily treated with comprehensive staging surgery. The median follow-up time was 68 (12–100) months. Independent risk factors for disease-free survival (DFS) and overall survival (OS) were determined using multivariate Cox regression models. Sub-group analysis of stage I was also performed. We also assessed the patterns of failure among patients with recurrences and investigated the associations with the prognostic variables determined by multivariate analysis. Twenty patients (11.9%) had recurrence and 13 patients (7.7%) died of the disease overall. Multivariate analysis revealed that grade 2 (G2) histology (p = 0.008) and positive peritoneal cytology (p = 0.001) predicted the recurrent event in type 1 endometrial cancer. G2 histology (p = 0.007) and positive peritoneal cytology (p = 0.003) were also found to be independent risk factors for tumor-related deaths. Among stage I patients, G2 histology and positive peritoneal cytology were also independent prognostic variables for DFS and OS. Patients with G2 histology and/or positive peritoneal cytology were more likely to have recurrence at distant sites. G2 histology and positive peritoneal cytology were independent prognostic factors for DFS and OS in type 1 endometrial cancer.

We analyzed seminal plasma of 88 normozoospermic, 40 oligozoospermic and 32 azoospermic donors. During this study, we focus to record the protamine concentration in the seminal plasma of azoospermic donors. The seminal protamine concentrations were found to be 19.6–62.8 IU/ml in normozoospermic donors; 25.4–100.8 IU/ml in oligozoospermic donors; and, most notably, 23.7–219.4 IU/ml in azoospermic donors. These results indicate that, based on seminal plasma protamine concentrations, even azoospermic donors were able to produce as much sperm as normo- and/or oligozoospermic donors. Using statistical analyses, significant differences were found between azoospermic and normozoospermic donors (p = 0.0018). Protamine content was found to be a direct marker for the presence of sperm. The data from this study provided evidence for a new therapeutic approach for testicular varicose veins, which are found in obstructive or non-obstructive azoospermia. High seminal protamine concentrations indicated the future possibility of acquiring childbearing sperm for insemination sperm injection (ICSI) and testicular sperm extraction (TESE), even with azoospermic donors. Given these results, we also suggest a new cut-off value for acquisition of childbearing sperm in selection for ICSI.

Intracytoplasmic sperm injection (ICSI), in which a single sperm is injected into the oocyte, is the most common single-cell therapy. Some of the swimming sperm will already have undergone early stage DNA fragmentation, so verification of DNA integrity is essential in single-nucleus analyses. We have developed a novel single-cell pulsed-field gel electrophoresis (SCPFGE) method to detect the early stage of fragmentation. Although the comet assay is recognized as the primary tool for detecting DNA fragmentation, SCPFGE revealed that it is insufficiently sensitive to detect the genetic effect of the sperm on embryogenesis and subsequent fetal development. Our novel examinations have revealed previously unknown or unseen aberrations and enriched our understanding of intersperm heterogeneity. They also suggest further stringent requirements for the injections. A pitfall of single-cell therapy is that ICSI is rather ineffective in cases of severe male infertility resulting from dysfunctional spermatogenesis.

Objective. The KOSMOS study, a multicenter, randomized, double-blind, placebo-controlled trial, investigated the effects and safety of kamishoyosan (TJ-24), a traditional Japanese medicine, in the treatment of climacteric disorder. Methods. Japanese women with climacteric disorder were administered a placebo during a 4-week run-in period, after which they were classified as placebo responders (R group) if their score on the modified Questionnaire for the Assessment of Climacteric Symptoms in Japanese Women (m-QACS) with excitability and irritability as the primary outcome improved by ≥ 3 points and as placebo nonresponders (NR group) otherwise. Members of the NR group were randomly allocated to receive either TJ-24 or placebo. After 12 weeks, their m-QACS scores, anxiety and depression, sleep, and overall quality of life (QOL) were compared. Results. The TJ-24 and placebo arms in the NR group included 20 patients each. The change in the m-QACS scores of members of the NR group for excitability and irritability at 12 weeks versus baseline was –3.1 ± 1.7 in the TJ-24 arm, a significant decrease, but compared with –2.7 ± 2.2 in the placebo arm, no significant difference was between two arms. However, the proportion of participants whose score improved by ≥3 points was significantly higher in the TJ-24 arm. In the subgroup analysis of premenopausal women, the changes in the score for excitability and irritability were significantly larger in the TJ-24 arm. The incidence of adverse drug reactions or adverse events did not differ between the two arms, and no serious events were reported. Conclusion. Although no significant difference was identified for the primary outcome, a significantly higher proportion of patients who received TJ-24 displayed improvement. Its high level of safety and effects on excitability and irritability in premenopausal women suggest that TJ-24 may be a useful treatment.

In order to improve women's quality of life, over the year leading up to June 2016, the Women's Health Care Committee of the Japan Society of Obstetrics and Gynecology focused upon: (i) breast management; (ii) influence of a therapy for gynecologic disease on physical condition; (iii) nonsurgical management of pelvic organ prolapse; (iv) survey of infectious diseases in Obstetrics and Gynecology in Japan; (v) health care for female athletes; (vi) a training program for women's health-care advisers; and (vii) revising the Japanese guideline on hormone-replacement therapy. In order to publicize the activities of our committee widely, the detailed activities of the seven subcommittees are described in this report, which is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2016; 68 (6): 1404–1416).

The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.

Remarkable technological advances have been made in the field of medicine in recent years, one result of which is that a prenatal diagnosis of cleft lip and/or cleft palate (CL/P) is now possible. In this situation, it is extremely important to provide the parents with mental care from the moment they are informed. Here, we describe cases of CL/P treated at our hospital and how such a diagnosis and prenatal counseling are handled. A survey was carried out on 4 cases seen at our department between April 2013 and March 2014. Patients are referred to our department from local or our own obstetrics clinics on a prenatal diagnosis of CL/P based on findings from ultrasonography. If the case is a referral from outside, the patient will first be seen at our own obstetrics department. Our department may then be subsequently requested to provide the parents with prenatal counseling. Effort is made to reassure the parents that postnatal support will be provided, right from the start. Next, the multidisciplinary nature of the treatment process is explained. However, only the essential outline is given at first so as to avoid inducing unnecessary anxiety. A response is also given to any questions the parents may have. Our experience of giving such care leads us to believe that improvements are required in the way that explanations and assistance are provided. The number of cases in which prenatal counseling is required is expected to increase in future.

Background: Patients with malignancy (n = 130) participated in the sperm cryopreservation program.

Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.

The activity of the Women's Health Care Committee over a two year period up to June 2015 focused upon: (i) management of breast diseases in obstetrics and gynecology; (ii) investigation of lifestyle-related disease and bone mineral density after gynecologic cancer therapy; (iii) postoperative women's health care; (iv) current surgical treatment for pelvic organ prolapse among gynecologists in Japan; (v) cesarean indication for pregnant women with active/inactive genital viral lesions; (vi) health care of young female athletes concerned about menstrual cycle abnormalities, stress fractures and premenstrual syndrome/premenstrual dysphoric disorder; (vii) a training program for women's health care advisers; and (viii) a new edition of the oral contraceptive and low-dose estrogen-progestogen guideline. Detailed activities of the eight subcommittees are described in the text.

Ovaries are the primary sites of cancerous disease that is derived from endometriosis. Uterine cancer originating from endometriosis is very rare. The most frequent histological subtype of cancer derived from endometriosis is endometrioid adenocarcinoma, a subtype of clear cell carcinoma which is exceedingly rare. We report a case of a 40-year-old Japanese woman with a six year history of uterine leiomyoma. The patient was clinically and radiologically suspected to have degenerative uterine myoma with a possible malignant association and underwent a transabdominal total hysterectomy. Histopathological examination of the specimens revealed clear cell adenocarcinoma arising from the adenomyotic cyst. A literature review of clear cell adenocarcinomas arising from uterine adenomyotic cysts (cystic adenomyosis), emphasizes the clinically and radiologically important features of this very rare entity. Clear cell carcinoma association should be suspected in patients who are under follow-up for uterine myomas and present with cystic uterine changes with solid component on magnetic resonance imaging or computed tomography scans.

This survey sought to determine Japanese gynecologists' attitudes concerning administering hormone replacement therapy (HRT) for patients after surgery for endometrial cancer (EC).Eight hundred and eighty-eight members of the Japanese Gynecologic Oncology Group (JGOG) were asked to respond to an anonymous questionnaire on the JGOG website. The survey asked whether or not HRT was to be administered when surgery was performed (including a hysterectomy and bilateral oophorectomy) to treat EC before or after menopause. If HRT was not to be administered, respondents were asked the reason why. Respondents were presented with the same hypothetical patients that were featured in a previous survey in Germany, and differences in the mindsets of Japanese and German physicians were compared.Responses from 363 individuals (response rate 40.9 %) were analyzed. Seventy-eight percent of physicians considered HRT for patients undergoing surgery before menopause. The most prevalent reason of refusal to prescribe HRT was the risk of EC recurrence. Forty-eight percent of physicians considered HRT for patients undergoing surgery after menopause. The most prevalent reasons of refusal of HRT were its limited benefit and the availability of alternative therapies. Sixty-five percent of Japanese physicians responded that they would administer HRT to patients with low risk of recurrence vs. 46 % of physicians in Germany (P0.0002). Forty-nine percent of Japanese physicians approved of prescribing HRT for patients with high risk of recurrence vs. 25 % of physicians in Germany (P0.0001).Many Japanese gynecologists have a favorable attitude toward prescribing HRT after treatment of EC.

To improve women's quality of life, the activity of the Women's Health Care Committee over a year up to July 2017 focused upon: (i) breast management; (ii) the influence of gynecological disease therapy on physical condition; (iii) non-surgical management of pelvic organ prolapse; (iv) survey of infectious diseases in obstetrics and gynecology in Japan; (v) health care for female athletes; (vi) a training program for women's health care advisors; (vii) revising the Japanese guidelines on hormone replacement therapy; and (viii) revising the 2016 Japanese guidelines for the proper use of emergency contraceptives. The detailed activity of the eight subcommittees is described herein. This report is based on the Japanese version of our annual report (Acta Obst Gynaec Jpn 2017;69(6):1480-1491), to publicize the activities of our committee.

Hereditary breast and ovarian cancer syndrome (HBOC) is a hereditary tumor that can be definitively diagnosed by detection of germline mutation of the BRCA1 or BRCA2 gene. The HBOC Public Awareness and Management Sub-committee of the Tumor Committee, Japan Society of Obstetrics and Gynecology carried out a fact-finding survey on the status of treatment of HBOC in Japan. The directors of medical specialty teaching facilities were notified of the questionnaire by post, with the request for one respondent per facility. The response period was from 8 July 2014 to 31 March 2015. Of the 678 facilities that were asked to compete the questionnaire, 341 (50.3%) responded. The responses are shown in the respective tables. For questions with free responses, similar answers have been grouped together, and the written answers have been freely translated. Based on these results, the Japan Society of Obstetrics and Gynecology considers that the 14 conditions, including consultations by specialist staff, must be met before risk-reducing salpingo-oophorectomy is carried out.

We hypothesized that feeling mucosal dryness in one body region and the skin may be associated with dryness in other regions and that there are common background factors for dryness. In an earlier web-based survey, we reported prevalence figures of dry eyes, nose, mouth, skin, and vagina. In the present study, additional analyses were made to investigate the factors associated with dryness in each region, and simultaneous dryness in multiple regions.A web-based questionnaire was completed by 310 Japanese women. The questions included dryness of the eyes, nose, mouth, vagina, and skin. Menopausal and other symptoms were also addressed. Multiple logistic regression modeling was performed to identify factors associated with dryness in each region and in multiple dry regions.Dry eyes were associated with dryness in the nose and with headache; dry nose was associated with dryness in the vagina and eyes; dry mouth was associated with sticky mouth symptom and dryness of the nose; dry skin was associated with use of xerogenic medications and vaginal discharge; and dryness of the vagina was associated with vaginal itchiness and dry nose. Vaginal discharge (odds ratio, 9.64; 95% confidence interval, 3.15-29.51) and sticky mouth (odds ratio, 6.35; 95% confidence interval, 1.29-31.29) were further associated with dryness in multiple regions.The present results confirmed our study hypothesis by showing that dryness in one region was clearly associated with that in another or in multiple regions. The result implies the need for holistic diagnosis and counseling for patients with dryness complaints.

Monomethylarginine, asymmetric dimethylarginine and symmetric dimethylarginine were separated on a Wakopak Combi ODS with an acetonitrile–100 mm potassium phosphate buffer (pH 7.0; 1:1, v/v). Dimethylarginines were derived from o-phthalaldehyde for the fluorescence detector and from 6-ferrocenyl-1-hexanethiol for the electrochemical detector. The detection limits of the dimethylarginines in spiked plasma were 0.3–0.5 pmol by electrochemical detection and 1–2 pmol by fluorescence detection. The detection limits were improved over 30 times by electrochemical detection and 10 times by fluorescence detection compared with previous reports. In previous derivatization liquid chromatography, the reaction solutions, o-phthalaldehyde, 2-mercaptethanol and dimethylarginines were unstable and required quick derivatization at 4°C. By our proposed pre-column methods, the dimethylarginines were derivatized at room temperature and the fluorescent products were stable for 6 h. The manipulation performance was greatly advanced compared with previous LC reports. This is the first report on stable and sensitive dimethylarginines by dual detection. The selectivity was also improved by dual detection. The proposed method was applied to preliminary monitoring of dimethylargines in plasma and urine. Copyright © 2012 John Wiley & Sons, Ltd.

Epithelioid sarcoma of the vulva is an extremely rare and aggressive tumor. This tumor most commonly occurs on the labia majora in women of reproductive age. The molecular pathogenesis remains largely unknown. Only 20 cases of vulvar epithelioid sarcoma have been reported to date and more than half have had poor outcomes. We report a successfully treated case of vulvar epithelioid sarcoma in a 33-year-old woman. We performed a radical vulvectomy with flap reconstruction. Three years after surgery, the patient remains well, showing no evidence of recurrence. Early tissue diagnosis of vulvar epithelioid sarcoma is essential because this tumor can be clinically misdiagnosed as a benign lesion. Gynecologists should be aware of this rare tumor variant and carefully plan the treatment.

背景 : 卵巣明細胞腫瘍において, 境界悪性例の報告はまれであるが, 腺線維腫に合併することが知られている. 今回, われわれは術前には悪性を強く疑いえなかった borderline clear cell adenofibroma の 1 例を経験したので報告する.症例 : 72 歳, 0 経妊 0 経産. 検診において腹部腫瘤を指摘され当院を紹介受診された. 子宮頸部細胞診および子宮内膜細胞診は異常所見を認めなかった. 腫瘍マーカーは CA125 が 192 U/ml と高値を示していた. MRI 検査所見では右卵巣に充実性腫瘤を認め, T2 強調画像では低信号を示した. 手術により摘出された右卵巣腫瘍は黄白色の充実性腫瘍であり一部にスポンジ状の部分を認めた. 腫瘍割面捺印細胞診像は, 比較的きれいな背景の中に, N/C 比が増大し, クロマチンが増量した異型細胞が散在していた. 病理組織診断は, borderline clear cell adenofibroma であった.結論 : 良性の腺線維腫を想定した腫瘍割面捺印細胞診にて異型細胞を認めた. 腫瘍割面捺印細胞診は卵巣境界悪性明細胞腫瘍の診断の一助になると考えられた.

We have developed a determination method for alcohol using high-performance liquid chromatography by using a diamond electrode-electrochemical detector. At this time, 4 alcohols (methanol, ethanol, 2-propanol and 1-butanol) were separated on a Shodex® ODP2 HP-4E column with an acetonitrile-25 mM disodium hydrogen phosphate buffer (pH 11.0, 1 : 99, v/v) as the mobile phase. The electrochemical detector, equipped with a diamond electrode, was set at 2000 mV (applied voltage). The detection limits of the four alcohols were 20-25 ng/mL. The proposed liquid chromatography was fifty-times more sensitive compared to reported gas chromatography – flame ionization method, and was found to be suitable for large-volume aqueous sample solutions compared to gas chromatography. In the case of poor absorbance compounds, an easy-to-set additional detector in wide using the liquid chromatography – ultraviolet detection system. It was meaningful economical work to use an existing apparatus in the laboratory. With this method, one could determine volatile alcohols, e.g., ethanol, which could not be determined by other universal-type detectors (corona-CAD and ELSD). The proposed method was applied to the alcohol in detergents (contains ethanol and 2-propanol) and alcoholic beverages. Good relationships were obtained compared to the enzymatic method.