Malignant Ovarian Tumors with Induced Expression of Carbonyl Reductase Show Spontaneous Regression

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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

Successful laparoscopic resection of virilizing ovarian steroid cell tumor, not otherwise specified, in a 22-year-old woman: a case report and evaluation of the steroidogenic pathway

Objective: Ovarian steroid cell tumor (SCT) is a rare tumor with steroid-producing ability. We report a 22-year-old woman with secondary amenorrhea and hirsutism caused by an ovarian SCT-not otherwise specified (NOS), who underwent successfully laparoscopic resection of the tumor. Case report: A 22-year-old null gravida woman presented to a hospital, having amenorrhea for 18 months and increasing facial hair. Physical examination revealed obesity (body mass index, 37.3 kg/m2) with evident facial and trunk hair. Total and free serum testosterone, and dehydroepiandrosterone sulfate levels were found to be elevated. Levels of serum adrenocorticotropic hormone, gonadotropins, cortisol, aldosterone, and ovarian steroids were observed to be within reference intervals. Although polycystic ovaries were not found, a hyperechogenic solid tumor (3 cm) was detected on transvaginal ultrasonography. Laparoscopic resection of the tumor was performed. One month post-surgery, total and free testosterone levels were observed to have decreased, and menstruation resumed two months thereafter. The patient was histologically diagnosed with ovarian SCT-NOS. Expression of ovarian steroidogenic enzymes, which are related to hyperandrogenism, was observed. No disease recurrence has been reported for more than 5 years post-surgery

Efficacy and safety of monthly oral minodronate in patients with involutional osteoporosis

Summary Monthly minodronate at 30 or 50 mg had similar efficacy as 1 mg daily in terms of change in bone mineral density (BMD) and bone turnover markers with similar safety profiles. This new regimen provides patients with a new option for taking minodronate. Introduction Minodronate at a daily oral dose of 1 mg has been proven to have antivertebral fracture efficacy. In the present study, the efficacy and safety of oral minodronate at monthly doses of either 30 mg or 50 mg were compared with a daily dose of 1 mg. Methods A total of 692 patients with involutional osteoporosis were randomized to receive minodronate at either 30 or 50 mg monthly or a daily dose of 1 mg. The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at 12 months. Total hip BMD, bone turnover markers, serum calcium (Ca), and parathyroid hormone (PTH) levels were also evaluated. Results Minodronate at monthly doses of 30 or 50 mg were noninferior to the 1 mg daily dose in terms of change in LS-BMD. Changes in total hip BMD were also comparable. Although a transient decrease in serum Ca and increase in PTH levels were observed in all three groups at slightly different magnitudes and time courses, changes in bone turnover markers were comparable among the differentdosage groups with a similar time course. Safety profiles were also comparable. Conclusion Minodronate at monthly doses of 30 or 50 mg has similar efficacy to the daily 1 mg dose in terms of BMD and bone turnover markers with similar tolerability

Early Menarche, Nulliparity, and the Risk for Premature and Early Natural Menopause

Study question: How the timing of menarche and parity link with premature and early natural 42 menopause? Summary answer: Early menarche (≤11 years) is a risk factor for both premature menopause (final 44 menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women. What is known already: Women with either premature or early menopause face increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, adjustment for confounding factors, and statistical power. Study design, size, duration: This pooled study comprises 51,450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia, and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Participants/materials, setting, methods: Age at menarche (categorised as ≤11, 12, 13, 14, and 15 56 or more years) and parity (categorised as no children, one child, and two or more children) were exposure of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorised as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years, and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% confidence intervals (95%CI) for associations between menarche, parity and age at FMP adjusting for within-study correlation. Main results and the role of chance: The median age at FMP was 50 years (interquartile range 48 to 53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53 to 2.12) and early menopause (1.31, 1.19 to 1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84 to 2.77) and early menopause (1.32, 1.09 to 1.59). Women having early menarche and nulliparity were at over five folds increased risk of premature menopause (5.64, 4.04 to 7.87) and two folds increased risk of early menopause (2.16, 1.48 to 3.15) compared with women who had menarche at ≥12 years and two or more children. Limitations, reasons for caution: Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche which may have led to some degree of recall bias. Wider implications of the findings: Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause

Malignant transformation arising from mature cystic teratoma of the ovary presenting as ovarian torsion: a case report and literature review

Objective: Ovarian torsion is an acute gynecological condition. Torsion is more likely to occur with benign rather than malignant tumors. Mature cystic teratoma of the ovary (MCTO) is frequent in women of reproductive age; however, the incidence of malignant transformation is approximately 2%. We report a case of malignant transformation of MCTO presenting as ovarian tumor torsion. Case report: A 51-year-old premenopausal woman was diagnosed with mature cystic teratoma in the left ovary 7 years ago. The patient visited our hospital because she had been experiencing of pain in left lower abdomen for the past two days. She was diagnosed with ovarian tumor torsion and underwent emergency surgery. The left ovarian tumor was twisted, and left salpingo-oophorectomy was performed. Histopathological examination revealed squamous cell carcinoma arising from the MCTO. We carefully followed the patients without performing staging laparotomy. On postoperative day 112, multiple lymph node metastases in the pelvic and para-aortic areas were found by positron-emission tomography and computed tomography. After referral to a university hospital, total hysterectomy, right salpingo-oophorectomy, partial omentectomy, and pelvic and paraaortic lymphadenectomy were performed. Metastases of squamous cell carcinoma were confirmed in the pelvic and para-aortic lymph nodes. Six courses of adjuvant chemotherapy with paclitaxel and carboplatin were given following radical surgery to prevent the recurrence of malignant transformation of MCTO. No recurrence of the disease has been observed during 2 years of follow-up. Conclusio: When physicians diagnose large ovarian tumor torsion cases, preoperative examinations should be performed, with the possibility of malignancy in mind

The InterLACE study: design, data harmonization and characteristics across 20 studies on women's health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE

FOXP1 forkhead transcription factor is associated with the pathogenesis of endometrial cancer

Endometrial cancers are mostly estrogen-dependent. FOXP1 is a P subfamily of forkhead box (FOX), and known as an estrogen-responsive transcription factor. The aims of this study were to examine histological location of FOXP1 in normal and malignant endometrium, and to investigate a possible association between FOXP1 and other factors considered to be involved in pathogenesis of endometrial cancer. The levels of FOXP1, estrogen receptor (ER)α, and ERβ expression were examined immunohistochemically in normal and malignant endometrium obtained from 75 women (8 normal, 8 atypical endometrial hyperplasia, and 59 endometrial cancers from grade 1 to 3). The effects of estrogen on ERα, FOXP1, KRAS, and PTEN expression were analyzed in telomerase-immortalized human endometrial stromal cells (T HESCs) by Western blotting. Western blotting was also used to examine the effect of FOXP1 plasmid DNA or siRNA transfection on KRAS and PTEN expression in Ishikawa cells (well differentiated endometrioid adenocarcinoma), HEC-50B cells (poorly differentiated endometrioid adenocarcinoma), and T HESCs, respectively. FOXP1 was expressed in normal and malignant endometrium, but the rate of expression was different depending upon menstrual cycle and pathological grade of malignancy. FOXP1 expression in nucleus and cytoplasm of grade 3 endometrioid cancers was significantly lower than that of grade 1 and 2 ones. Estradiol increased levels of FOXP1 and KRAS expression in a dose- and time-dependent manner in T HESCs cells, and FOXP1 transfection or knockdown led to increase or decrease of KRAS expression but not PTEN. KRAS expression level was significantly related to FOXP1 and ERα levels in cancer tissues. Estradiol did not affect KRAS expression in T HESCs cells transfected with FOXP1 siRNA. These results suggest that FOXP1 is involved in estrogen dependent endometrial cancers through KRAS pathway