Uterine leiomyomata: a retrospective study of correlations with hypertension and diabetes mellitus from the Japan Nurses' Health Study.

We performed a scrutiny survey of self-reported uterine leiomyomata (UL) to investigate the associations of parental history with hypertension and personal history of hypertension in the UL cases in Japanese women. Questionnaires that included items on the sites of UL determined by imaging techniques and surgical procedure were mailed to 2015 women with a self-reported UL at a baseline survey of the Japan Nurses' Health Study (n = 15,019). We found that women with a past history and a maternal history of hypertension had an increase in their risk of UL. A maternal history of hypertension was significantly associated with an increase in the risk of UL in women without a past history of hypertension but not in the women with a past history of hypertension. A past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. Women of reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL. Impact Statement What is already known on this subject? A positive association of uterine leiomyomata (UL) with a past history of hypertension has been found but the association of a parental history of hypertension with UL has not yet been clarified. What do the results of this study add? Maternal hypertension, as well as a personal history of hypertension, was associated with an increased risk of UL and a past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. What are the implications of these findings for clinical practice and/or further research? Women of a reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL.

Effect of individualised dietary education at medical check-ups on maternal and fetal outcomes in pregnant Japanese women.

BACKGROUND AND OBJECTIVES: An increased prevalence of low maternal weight and insufficient pregnancy weight gain may be responsible for an increase in low birthweight infants in Japan. We aimed to examine the effects of individualised dietary education at medical check-ups on maternal/fetal outcomes in Japanese women. METHODS AND STUDY DESIGN: Four hundred and six underweight and normal weight singleton pregnant women, who attended check-ups at an obstetric facility until ≥30 weeks gestation and delivered at 36-41 weeks gestation, were selected for analyses. Weight gain was assessed at each check-up based on the official "Dietary Guidelines for Pregnant and Lactating Women". Individual dietary advice was provided by dieticians to those with insufficient or excess weight gain status around 28 weeks gestation. The medical records from uncomplicated singleton deliveries (36-41 weeks gestation) at the same facility from 2008-2010 were used (n=792) to examine the effect of dietary education on maternal/fetal outcomes. RESULTS: Pre-pregnancy underweight was present in >24% of women in both the intervention and non-intervention groups. Adequate weight gain occurred more frequently in the intervention group (p<0.01). There were no significant differences in mean birthweight or the proportion of low birthweight infants. However, the proportion of extremely small for gestational age infants (birthweight <3rd percentile) was lower in the intervention group (p=0.011). There were no differences in the frequency of caesarean delivery, pregnancy induced hypertension, or infant Apgar scores <7. CONCLUSIONS: Dietary education during pregnancy check-ups promotes adequate maternal weight gain and helps prevent extreme fetal growth restraint.

Higher intake of cryptoxanthin is related to low body mass index and body fat in Japanese middle-aged women.

OBJECTIVES: The prevalence of cardiovascular diseases increases with age, especially in postmenopausal women. In this study, we investigated the dietary patterns associated with body mass and body fat in Japanese middle-aged women. STUDY DESIGN: Cross-sectional. MAIN OUTCOME MEASURES: This study used baseline data collected in a previous study in 88 women aged 40-60 years. Participants were assessed for age, menopausal status, lifestyle factors, body composition, and dietary habits using a brief-type self-administered diet history questionnaire, which provides information on the amounts of nearly 100 nutritional factors consumed during the previous month. Classifying body mass index (BMI) as low (≤22kg/m2) or high (>22kg/m2) and percentage body fat as low (≤25%) or high (>25%), we sought to identify the nutritional factors associated with BMI and percentage body fat. RESULTS: Consumption differences between high/low BMI and high/low body fat percentage groups were not significant for any nutritional factors except cryptoxanthin. Multiple logistic regression analysis adjusting for age, menopausal status, working, exercise, and smoking revealed that higher cryptoxanthin intake was associated with low BMI (adjusted odds ratio, 1.22 per 100µg/day increase of cryptoxanthin intake; 95% confidence interval, 1.01-1.52) and low body fat percentage (adjusted odds ratio, 1.36 per 100µg/day increase of cryptoxanthin intake; 95% confidence interval, 1.13-1.70). CONCLUSIONS: Higher intake of cryptoxanthin was shown to be related to low body mass and body fat in Japanese middle-aged women.

Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and Reproduction.

The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene in the Y chromosome have not been completely elucidated, partly owing to difficulties in gene targeting analysis of the Y chromosome. Zfy was first proposed to be a sex determination factor, but its function in spermatogenesis has been recently elucidated. Nevertheless, Zfy gene targeting analysis has not been performed thus far. Here, we adopted the highly efficient CRISPR/Cas9 system to generate individual Zfy1 or Zfy2 knockout (KO) mice and Zfy1 and Zfy2 double knockout (Zfy1/2-DKO) mice. While individual Zfy1 or Zfy2-KO mice did not show any significant phenotypic alterations in fertility, Zfy1/2-DKO mice were infertile and displayed abnormal sperm morphology, fertilization failure, and early embryonic development failure. Mass spectrometric screening, followed by confirmation with western blot analysis, showed that PLCZ1, PLCD4, PRSS21, and HTT protein expression were significantly deceased in spermatozoa of Zfy1/2-DKO mice compared with those of wild-type mice. These results are consistent with the phenotypic changes seen in the double-mutant mice. Collectively, our strategy and findings revealed that Zfy1 and Zfy2 have redundant functions in spermatogenesis, facilitating a better understanding of fertilization failure and early embryonic development failure.

Obstetrical management of patients with extra-anatomic vascular bypass grafts due to Takayasu arteritis.

Little is known about the obstetrical management of patients with Takayasu arteritis (TA) who have undergone extra-anatomic vascular bypass (EAVB). We describe two cases of EAVB. Case 1 underwent EAVB due to renovascular hypertension associated with stenosis of the abdominal aorta, and Case 2 due to amaurosis fugax episodes associated with stenosis of the brachiocephalic and left common carotid arteries. Pregnancy outcomes were favorable for both cases, though the original symptoms recurred during the third trimester in each case, possibly due to increased blood flow to the pregnant uterus. Neither bypass occlusion nor anastomotic aneurysm formation was observed. Pregnancy outcomes of patients with EAVB due to TA are favorable, although pregnancies of patients with TA who have cardiovascular complications are associated with an increased risk of maternal and fetal morbidity. The obstetrical management of these patients, however, should include monitoring for complications related to the EAVB.

Vanishing intravenous leiomyomatosis after hysterectomy: Assessment of the need to perform complete resection.

Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor that may extend into extrauterine veins. A high IVL recurrence rate has been reported after hysterectomy. A 44-year-old woman underwent total hysterectomy as a result of uterine leiomyoma, and IVL within the left uterine vein was incidentally found during the surgery. A residual tumor within the right ovarian vein was detected on contrast-enhanced computed tomography (CT) two days postoperatively. The tumor was diagnosed as IVL because it showed contrast enhancement on preoperative magnetic resonance imaging by retrospective re-interpretation. However, the tumor completely disappeared on contrast-enhanced CT without any medical treatment five months postoperatively. This is the first report of spontaneous regression of IVL. Postsurgical imaging was important to determine the residual extrauterine extension of IVL when it was incidentally found during gynecologic surgery. A hysterectomy alone may be adequate in selected cases, but long-term follow-up imaging is strongly recommended in all cases.

SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomas.

AIMS: To investigate how SNAIL and SLUG were involved in the nature of high-grade endometrial carcinomas (grade 3 endometrioid carcinoma, serous carcinoma and clear cell carcinoma), we analysed the correlation of their expression status with clinicopathological characteristics and evaluated their prognostic significance. METHODS AND RESULTS: We performed immunohistochemical staining in 52 high-grade endometrial carcinomas. Expression status of SNAIL and SLUG was classified into a high expression (positive in more than 50% of the tumour cells) and a low expression. Thirteen cases (25%) showed a high expression of SLUG, whereas all 52 cases showed a low expression of SNAIL. High expression of SLUG was correlated significantly with tumour recurrence (P = 0.0203) and aberrant p53 expression (P = 0.000559). Overall survival was worse in patients with high SLUG expression at all stages (P = 0.0327) and in those who underwent adjuvant therapy (P = 0.00963). Among the patients with complete tumour resection, high SLUG expression was associated with worse recurrence-free survival (RFS) in the patients at all stages (P = 0.00264), at stages III/IV (P = 0.0146), and who underwent adjuvant therapy (P = 0.000743). SLUG expression was identified as an independent factor of RFS by multivariate analysis (hazard ratio 5.938, 95% confidence interval 1.251-28.18, P = 0.025). CONCLUSIONS: SLUG expression could be correlated with TP53 mutational status and could be involved in therapeutic resistance resulting in tumour recurrence. A high expression level of SLUG can be an indicator of recurrence and a therapeutic target for long-term remission in high-grade endometrial carcinomas.

Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome.

The conventional Δ5 and Δ4 steroidogenic pathways mediate androgen production in females. While multiple non-conventional pathways to dihydrotestosterone (DHT) have recently been postulated in humans, the functional significance of these pathways remains to be elucidated. The aim of this study was to clarify the origin of androgens in healthy women and in patients with polycystic ovary syndrome (PCOS), a multifactorial disorder characterized by androgen overproduction. We measured 13 steroids in blood samples of 31 eumenorrheic females and 28 PCOS patients using liquid chromatography-tandem mass spectrometry and chemiluminescent enzyme immunoassay. We found that 17-hydroxy (17-OH) progesterone (17-OHP), androstenedione (Δ4A), testosterone, androstanedione, androsterone, and androstanediol levels were higher in the patient group than in the eumenorrheic group, while levels of other steroids were comparable between the two groups. In the eumenorrheic group, DHT levels were correlated with testosterone, androstanedione, and androstanediol. Quantitative correlations were also observed among 17-OH allopregnanolone, androsterone, androstanediol, and DHT, and among Δ4A, androstanedione, androsterone, and androstanediol. In the patient group, DHT levels were correlated with testosterone levels, but not with androstanedione or androstanediol levels. Δ4A and testosterone paralleled 17-OHP. Androstanedione, androsterone, androstanediol, and 17-OH allopregnanolone were quantitatively correlated. In both groups, multivariable linear regression analyses suggested relationships between androsterone and androstanedione, as well as between androsterone and 17-OH allopregnanolone. These results indicate that multiple androgen biosynthesis pathways are operating in eumenorrheic females and PCOS patients. In PCOS patients, excessive androgens are produced primarily via the conventional pathways, while two alternative pathways; i.e., an androstanedione-mediated pathway and a so-called backdoor pathway, likely serve as sources of a weak androgen and potential precursors of DHT.

Ovarian infertility is associated with cardiovascular disease risk factors in later life: A Japanese cross-sectional study.

OBJECTIVES: This study aimed to clarify the association between ovarian infertility and cardiovascular disease risk factors in later life in Japanese women. STUDY DESIGN: The Japan Nurses' Health Study (JNHS) is a cohort study of Japanese women's health. Data from the JNHS baseline survey (n = 49,927) between 2001 and 2007 were used in a cross-sectional, retrospective analysis. A total of 44,601 women were classified into three categories: ovarian infertility group (n=1167), other infertility group (n = 4619), and no infertility group (n = 38,815). Logistic regression analysis compared with the no infertility group was performed. MAIN OUTCOME MEASURES: Age-adjusted odds ratios (ORs) and multivariable-adjusted ORs for hypertension, hypercholesterolemia, and diabetes mellitus (DM). RESULTS: The prevalence of obese women (BMI ≥ 25) who were < 45 years old in the ovarian infertility group was significantly higher compared with that in the other groups. Women in the ovarian infertility group were at risk for hypertension at ≥ 45 years old (age-adjusted OR: 1.65%, confidence interval [CI]: 1.23-2.21); for hypercholesterolemia at < 45 and ≥ 45 years old (age-adjusted OR: 1.42, 95% CI: 1.06-1.88 at < 45 years; age-adjusted OR: 1.39, 95% CI: 1.06-1.81 at ≥ 45 years); and for DM at < 45 years old (age-adjusted OR: 2.92, 95% CI: 1.57-5.46). CONCLUSIONS: Japanese women with ovarian infertility (most women have polycystic ovary syndrome) are at high risk of hypertension from 45 years of age, hypercholesterolemia at all ages, and diabetes mellitus (DM) before 45 years old.

Cancer-related fatigue and physical activity among premenopausal cervical and endometrial cancer survivors in Japan.

PURPOSE: To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. METHODS: A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. RESULTS: The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had severe fatigue. The participants had higher physical activity levels compared with the findings in previous studies, and reported an average of 40 min/day of moderate to vigorous activity. Moderate to vigorous levels of physical activity were derived from essential social activities rather than leisure time exercise. There were no significant differences in physical activity levels between the lower and higher CRF groups. CONCLUSION: Our study results suggested that the higher level of physical activity in daily living itself had no relationship with decreasing CRF among premenopausal cervical and endometrial cancer survivors. It would be better to focus on cognitive and psychological factors before introducing physical activity programs and be careful of the characteristics of the participants' physical activity among this population in daily basis.

Disease history and risk of comorbidity in women's life course: a comprehensive analysis of the Japan Nurses' Health Study baseline survey.

OBJECTIVE: To classify diseases based on age at peak incidence to identify risk factors for later disease in women's life course. DESIGN: A cross-sectional baseline survey of participants in the Japan Nurses' Health Study. SETTING: A nationwide prospective cohort study on the health of Japanese nurses. The baseline survey was conducted between 2001 and 2007 (n=49,927). MAIN OUTCOME MEASURES: Age at peak incidence for 20 diseases from a survey of Japanese women was estimated using the Kaplan-Meier method with the Kernel smoothing technique. The incidence rate and peak incidence for diseases whose peak incidence occurred before the age of 45 years or before the perimenopausal period were selected as early-onset diseases. The OR and 95% CI were estimated to examine the risk of comorbidity between early-onset and other diseases. RESULTS: Four early-onset diseases (endometriosis, anaemia, migraine headache and uterine myoma) were significantly correlated with one another. Late-onset diseases significantly associated (OR>2) with early-onset diseases included comorbid endometriosis with ovarian cancer (3.65 (2.16 to 6.19)), endometrial cancer (2.40 (1.14 to 5.04)) and cerebral infarction (2.10 (1.15 to 3.85)); comorbid anaemia with gastric cancer (3.69 (2.68 to 5.08)); comorbid migraine with transient ischaemic attack (3.06 (2.29 to 4.09)), osteoporosis (2.11 (1.71 to 2.62)), cerebral infarction (2.04 (1.26 to 3.30)) and angina pectoris (2.00 (1.49 to 2.67)); and comorbid uterine myoma with colorectal cancer (2.31 (1.48 to 3.61)). CONCLUSIONS: While there were significant associations between four early-onset diseases, women with a history of one or more of the early-onset diseases had a higher risk of other diseases later in their life course. Understanding the history of early-onset diseases in women may help reduce the subsequent risk of chronic diseases in later life.

Risk profiles for endometriosis in Japanese women: results from a repeated survey of self-reports.

BACKGROUND: The prevalence and risk factors for endometriosis may differ according to diagnosis methodologies, such as study populations and diagnostic accuracy. We examined risk profiles in imaging-diagnosed endometriosis with and without surgical confirmation in a large population of Japanese women, as well as the differences in risk profiles of endometriosis based on history of infertility. METHODS: Questionnaires that included items on sites of endometriosis determined by imaging techniques and surgical procedure were mailed to 1025 women who self-reported endometriosis in a baseline survey of the Japan Nurses' Health Study (n = 15 019). RESULTS: Two hundred and ten women had surgically confirmed endometriosis (Group A), 120 had imaging-diagnosed endometriosis without a surgical procedure (Group B), and 264 had adenomyosis (Group C). A short menstrual cycle at 18-22 years of age and cigarette smoking at 30 years of age were associated with significantly increased risk of endometriosis (Group A plus Group B), while older age was associated with risk of adenomyosis (Group C). In women with a history of infertility, a short menstrual cycle was associated with a significantly increased risk of endometriosis in both Group A and Group B, but risk profiles of endometriosis were different between Group A and Group B in women without a history of infertility. CONCLUSIONS: Women with surgically confirmed endometriosis and those with imaging-diagnosed endometriosis without surgery have basically common risk profiles, but these risk profiles are different from those with adenomyosis. The presence of a history of infertility should be taken into consideration for evaluation of risk profiles.

Dkk-3 induces apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer cells.

OBJECTIVE: Dkk-3 is a Wnt signaling inhibitor that is frequently inactivated in human cancers. Dkk-3 possesses an antiproliferative activity and induces apoptosis in tumor cells, suggesting that it functions as a tumor suppressor. In this study, we investigated the molecular function of Dkk-3 in human ovarian cancer cells. METHODS: We assessed the levels of Dkk-3 protein expression in human mucinous and clear cell ovarian cancer cells, and compared cell viabilities between cell lines that expressed Dkk-3 and those that did not, as well as between cells that expressed Dkk-3 and those whose expression of Dkk-3 was reduced by small interfering RNA. We also evaluated the characteristic fragmentation of DNA to detect apoptosis in Dkk-3-deficient cells. To further investigate the molecular mechanisms of apoptosis, we assessed the expression of molecules involved in apoptosis signaling pathways in Dkk-3-deficient cells. RESULTS: The expression of the Dkk-3 protein was observed in most of the ovarian cancer cell lines tested. Dkk-3-deficient cells showed faster growth than Dkk-3-replete cells. The characteristic fragmentation of DNA was not observed in Dkk-3-deficient cells, which showed decreased levels of expression in caspase-3, activated caspase-9, Bax, p53, activated caspase-8, and Fas/CD95, as well as an increase in Bcl-2 expression. CONCLUSIONS: Although Dkk-3 expression was observed in most of human ovarian cancer cell lines, Dkk-3 has a tumor-suppressive function and a proapoptotic effect, inducing apoptosis through mitochondrial and Fas death receptor pathways in human mucinous ovarian cancer MCAS cells.

NF-κB inducing kinase, a central signaling component of the non-canonical pathway of NF-κB, contributes to ovarian cancer progression.

Ovarian cancer is one of the leading causes of female death and the development of novel therapeutic approaches is urgently required. Nuclear factor-κB (NF-κB) is constitutively activated in several types of cancer including ovarian cancer and is known to support the survival of cancer cells. However, molecular mechanisms of persistent activation of NF-κB in ovarian cancer remain largely unknown. We report here that, in addition to the previously reported canonical activation, NF-κB is activated through the noncanonical pathway in ovarian cancer cells. RNA interference-mediated silencing of NF-κB inducing kinase (NIK), a central regulator of the noncanonical pathway, reduced the NF-κB2/p52 DNA binding activity and NF-κB-dependent reporter gene expression as well as NF-κB target gene expression. Notably, anchorage-dependent and -independent cell growth was impaired in NIK-depleted cells. Depletion of NIK also suppressed tumor formation in the nude mouse xenograft assay. These results indicate that NIK plays a key role in constitutive NF-κB activation and the progression of ovarian cancer cells and suggest that NIK represents an attractive therapeutic target for ovarian cancer.

Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: This study aims to assess the effects of proanthocyanidin-a class of polyphenol antioxidants extracted from grape seeds-on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women. METHODS: We conducted a randomized, double-blind, placebo-controlled study in 96 women aged 40 to 60 years who had at least one menopausal symptom. The study participants were randomized to receive grape seed extract tablets containing either low-dose (100 mg/d) or high-dose (200 mg/d) proanthocyanidin, or placebo, for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Health-Related Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, and Athens Insomnia Scale before and after 4 and 8 weeks of treatment. Body composition and cardiovascular parameters were also measured. RESULTS: A total of 91 women (95%) completed the study. Background characteristics, including age, menopause status, subjective symptom scores, body composition, and cardiovascular parameters, were similar among the groups. The following significant changes were observed during the course of the study: (1) physical symptom score, hot flash score, and (2) Athens Insomnia Scale score decreased in the high-dose group after 8 weeks of treatment; (3) Hospital Anxiety and Depression Scale Anxiety score and (4) systolic and diastolic blood pressure decreased in the low-dose and high-dose groups after 4 weeks; and, (5) lastly, muscle mass increased in the low-dose and high-dose groups after 8 weeks of treatment. CONCLUSIONS: Grape seed proanthocyanidin extract is effective in improving the physical and psychological symptoms of menopause while increasing muscle mass and reducing blood pressure in middle-aged women.

Update in polycystic ovary syndrome: new criteria of diagnosis and treatment in Japan.

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women of reproductive age. In 2006 the Japanese Society of Obstetrics and Gynecology (JSOG) proposed new, revised diagnostic criteria that in the future could also be valued internationally. Based on the new diagnostic criteria, the JSOG has also proposed the revised treatment criteria in 2008. In PCOS obese patients desiring children, weight loss and exercise is recommended. Nonobese patients, or those obese women who do not ovulate after lifestyle changes, are submitted to ovulation-induction therapy with clomiphene citrate (CC). Obese CC-resistant patients who have impaired glucose tolerance or insulin resistance are treated with a combination of metformin and CC. If these treatments options are unsuccessful, ovulation induction with exogenous gonadotropin therapy or laparoscopic ovarian drilling (LOD) is recommended. A low-dose step-up regimen is recommended with careful monitoring in order to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Alternatively, with LOD high successful pregnancy rates of around 60 % are expected with a low risk of multiple pregnancies. If ovulation induction is unsuccessful, IVF-ET treatment is indicated. In high OHSS-risk patients, systematic embryo freezing and subsequent frozen embryo transfer cycles are recommended. In nonobese, anovulatory PCOS patients not desiring children, pharmacological treatments such as Holmström, Kaufmann regimens or low-dose oral anticonceptives are used to induce regular withdrawal bleeding. These treatments are especially important for preventing endometrial hyperplasia and endometrial cancer. These new diagnostic and treatment criteria hopefully will contribute to an improved care of PCOS patients in Japan.

Independent association between age at natural menopause and hypercholesterolemia, hypertension, and diabetes mellitus: Japan nurses' health study.

AIM: Menopause is considered a cardiovascular risk factor (CRF), but age at menopause (AAM) varies considerably and could affect the risk among post-menopausal women. The aim of the study was to clarify whether AAM is associated with hypertension, diabetes mellitus (DM) and hypercholesterolemia, independent of chronological age, lifestyle and hormone replacement therapy (HRT), in a sizeable number of Japanese women. METHODS: A retrospective study was conducted using the baseline survey of the ongoing large prospective Japan Nurses' Health Study. The prevalence of hypertension, DM, and hypercholesterolemia of pre-menopausal and three post-menopausal AAM groups (early: <45 years, intermediate: 45-53 years, late: >53 years) was compared among 22,426 women aged 40-59 years. Daily lifestyle such as smoking, alcohol consumption, and physical activity were included. RESULTS: The estimated risk (odds ratio: OR) was significantly higher in post-menopausal women and linearly elevated according to the AAM groups, and the late AAM group was more likely to have hypertension, DM, or hypercholesterolemia; however, after adjustment for age, BMI (kg/m(2)), HRT and lifestyle, menopause and AAM showed a significant association with only hypercholesterolemia and the early AAM group had the highest OR (2.72 (1.93-3.82)). Menopause and AAM did not show any independent association with the risk of hypertension and DM in the fully adjusted model. CONCLUSIONS: Among the post-menopausal women, early menopause increased the risk for hypercholesterolemia independently. AAM can be a useful screening tool to identify women at high risk for adverse post-menopausal lipid profiles in the Japanese.

Hybrid transvaginal and transumbilical laparoendoscopic adnexal surgery.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is an emerging concept in the recent literature that could lead to potential benefits in clinical applications. The present study describes the initial clinical application in 15 cases of hybrid transvaginal and transumbilical NOTES and discusses the feasibility, safety, and potential benefits of the method. PATIENTS AND METHODS: We evaluated the records of 15 patients who underwent hybrid transvaginal and transumbilical laparoendoscopic adnexal surgery between January 2010 and September 2011. RESULTS: Procedures included salpingo-oophorectomy (n=7) and cystectomy (n=3) for ovarian tumors and salpingectomy (n=5) for unruptured tubal pregnancy. The mean operative time was 79 minutes (range, 49-116 minutes). Blood loss was minimal in all cases. All procedures were successfully performed, and there were no conversions to conventional multiport laparoscopy or open surgery. Gynecologic examination after 3 months showed no negative findings, and the cosmetic result was ideal with no visible scar. CONCLUSIONS: Hybrid transvaginal and transumbilical NOTES is feasible and safe in select patients, and it provides no visible scar.

Secular trends in age at menarche and time to establish regular menstrual cycling in Japanese women born between 1930 and 1985.

BACKGROUND: Early life-stage exposure to estrogen increases the risk of breast cancer. The objective of this study was to investigate the age at menarche and time to onset of regular menstrual cycles for Japanese women born between 1930 and 1985. METHODS: A cross-sectional study was designed using data from the baseline survey of the Japan Nurses' Health Study. The data from 48,104 female nurses were analyzed. To view trends in age at menarche, the distribution of age at menarche was calculated for each birth year cohort. The distribution of time to onset of regular menstrual cycles was calculated for each birth year cohort. To estimate whether high-risk group of the estrogenic dependent disorders increase with succeeding generations, we defined the women who experienced menarche at ten years old or younger and started a regular cycle within one year as early age onset of ovulatory cycles. RESULTS: Average ages at menarche were as follows: 13.8 years for those born in the 1930s (n = 113), 13.3 years for the 1940s (n = 4,751), 12.8 years for the 1950s (n = 15,844), 12.3 years for the 1960s (n = 20,547), 12.2 years for the 1970s (n = 6,568), and 12.2 years for the 1980s (n = 281). The proportion of women who experienced the onset of regular menstrual cycles 1 year after menarche was 29.3% for those born in the 1930s, but decreased to 11.9% for the 1980s. On the other hand, the proportion of women who did not have regular menstrual cycles was 10.4% for those born in the 1930s, but rose to 19.8% in 1980s. The proportion of women who experienced menarche at 10 years old and started regular menstrual cycles within one year increased over time: the percentage was 0.0%, 0.4%, 0.6%, 1.1%, 1.3%, and 2.1% for the women born in 1930s, 1940s, 1950s, 1960s, 1970s, and 1980s, respectively. CONCLUSIONS: The age at menarche of Japanese women born between 1930 and 1985 decreased, but the onset of regular menstrual cycling is delayed; so that the distribution of the start time of ovulatory cycles may have spread for younger generations. Those suggest that the high-risk group of estrogenic dependent diseases among Japanese women may increase in the near future.