Number Of Menstrual Cycles Research Articles

Selectively Training in a Single Sport is Not Associated with Increased Injury in High School Female Athletes

Competing predominately in one sport instead of multiple sports has become increasingly prevalent in young athletes. However, there is a lack of data focused on female athletes who compete exclusively in one sport. We hypothesized that female athletes who selectively train in a single sport (SS) have higher rates of injury, body image concerns, and menstrual dysfunction compared to female athletes who play multiple sports (MS). Retrospective data was collected from a pre-physical questionnaire distributed among female athletes from five local high schools (n=611; 13-18 years of age). Odds ratios, 95% confidence intervals (CI), and effect size were calculated to investigate the association between SS training and injuries, irregular menses, and body image concerns (a priori p< 0.05). SS training was not associated with higher rates of injury (p=0.48) and were less likely to have a history of stress fractures compared to MS athletes (p=0.03). There was a decrease in the number of menstrual cycles within the last 12 months among SS athletes (p=0.02, d=0.34). Exclusively competing in a single sport is not associated with higher injury rates in female high school athletes but is associated with dissatisfaction with one’s weight.

Visceral Adiposity Index as an Indicator for Menstrual Disturbance, Hormonal and Metabolic Dysfunction in Polycystic Ovarian Syndrome.

Increase in visceral adiposity is characteristic of polycystic ovarian syndrome (PCOS) and is the main cause of insulin resistance and hyperandrogenism. This study tried to compare the visceral adiposity index (VAI) in PCOS women and control population, thereby exploring its correlation with ovarian morphology, hormonal and metabolic dysfunction. Reproductive-age women who fulfilled the Rotterdam criteria for PCOS constituted the cases. Control population consisted of the same number of non-PCOS women. History of menstrual irregularity and features of hyperandrogenism were noted. Overnight fasting serum hormonal profile on second day of the cycle, oral glucose tolerance test (OGTT) and serum fasting insulin and lipid profile were obtained. Ultrasound evaluation was done simultaneously. Free androgen index (FAI), homeostatic model assessment of insulin resistance (HOMA-IR) and VAI were calculated. Serum androgen levels and OGTT were greater in PCOS women. No significant difference was noted in serum fasting glucose, fasting insulin and lipid profile between cases and controls. Both systolic and diastolic blood pressures were significantly higher among women with PCOS. Mean ovarian volume, antral follicle count, FAI and HOMA-IR were higher in PCOS women. VAI was significantly higher in cases compared to controls. VAI demonstrated a strong negative correlation with number of menstrual cycles per year. Increasing VAI was associated with longer menstrual cycles and correlated positively with greater severity of anovulation. VAI also showed highly significant correlation with fasting blood glucose and statistically significant moderately strong positive correlation with OGTT values at two hours post glucose challenge, systolic blood pressure and mean ovarian volume.There was no demonstrable correlation between androgen levels or HOMA-IR values. VAI is higher in women with PCOS. It correlates positively with features of disease severity and ovarian morphology. An assessment of VAI in PCOS women could be predictive of a greater propensity for development of classical metabolic risk factors.

Anti-Müllerian hormone has limited ability to predict fecundability in Chinese women: a preconception cohort study

Research questionCan anti-Müllerian hormone (AMH) level predict female fecundity in healthy reproductive-aged Chinese women? DesignPreconceptional couples (n = 993) attempting pregnancy without contraception provided information on serum AMH concentrations and essential covariates. They were followed up for 12 months or until a clinically recognized pregnancy occurred between August 2013 and April 2015. Fecundability was indirectly assessed by time-to-pregnancy, defined as the number of menstrual cycles taken to conceive by a sexually active couple without using birth control. Discrete-time Cox proportional hazards model was used to estimate fecundability ratios in relation to AMH levels. Potential effect modifications by woman's age, BMI and menstrual cycle irregularity were examined through stratified analyses. Restricted cubic splines were applied to model the potential non-linear relationship between AMH and fecundability. ResultsAfter adjusting for woman's age, BMI, education status, smoking status, alcohol consumption and parity, AMH level (either as a continuous or categorical variable) was not significantly associated with fecundability. Stratified analyses revealed that, compared with intermediate AMH level (2.78–6.94 ng/ml), low AMH level (<2.78 ng/ml) was associated with reduced fecundability among women with menstrual cycle irregularity; the estimate did not reach statistical significance (adjusted fecundability ratio 0.43, 95% CI 0.16 to 1.15, P for interaction <0.1). ConclusionsSerum AMH levels were not associated with fecundability in Chinese women of childbearing age. A suggestive association, however, was observed among women with cycle irregularity. Regular monitoring of AMH in fecundity prediction may be of limited value among healthy reproductive-aged Chinese women.

ВЛИЯНИЕ МАССЫ ТЕЛА НА МЕНСТРУАЛЬНЫЙ ЦИКЛ

Any changes in body weight (excess or deficiency) negatively affect the menstrual cycle. Violations manifest themselves in the form of a decrease in the number of menstrual cycles per year, the duration of which is more than 35 days. These disorders in the future lead to a violation of reproductive function.

The effect of chamomile on menstruation pattern and serum androgens in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with menstrual disorders and hyperandrogenism, which is considered to be a common cause of hirsutism and infertility. Chamomile has been used as a medicinal herb known for its menstrual property. This study aimed to investigate the effect of chamomile on the menstruation pattern and serum androgens in PCOS women. This study was a randomized clinical trial, conducted on 80 women during their reproductive age with PCOS from April 2014 to August 2015. They were divided into intervention and control groups. The intervention group received a chamomile capsule (containing 370 mg dried powder of German chamomile flower) three times a day for 12 weeks, while the control group received placebo (starch-based capsules) with the same prescription order. Menstrual questionnaires as well as the androgens of testosterone and dehydroepiandrosterone were examined before and after 3 months. The primary outcome in the chamomile capsules user group, the number of participants with normal menstrual cycles significantly increased (p<0.001). In addition, a significant improvement in the number of menstrual cycles after the chamomile therapy was observed. A significant decrease was observed in testosterone levels in the intervention group. However, there was no significant change in the level of hormone dehydroepiandrosterone sulfate in both intervention and control groups (P = 0.423). Chamomile can have a significant impact on menstrual regulation and decrease the total testosterone levels in women of reproductive age with polycystic ovary syndrome. It is recommended that careful, large randomized controlled trials should be conducted to understand the mechanisms of action of chamomile and its effects on menstruation process.

Variability in Contraceptive Clinical Trial Design and the Challenges in Making Comparisons Across Trials.

Clinical trials of contraceptives have often differed in their study designs, making cross-trial comparisons difficult. This brief report outlines some of the technical design features that can vary from trial to trial. For example, the overall number of menstrual cycles in a study has substantial impact on the final efficacy determination; however, the rules related to qualifying cycles can differ based on the length of the study and the statistical analysis plan. In two commonly used methods of calculating efficacy, the Pearl Index and the time-to-event analysis, inclusion of fewer menstrual cycles results in higher calculated failure rates. Statistical analysis plans for contraceptive trials have sometimes excluded menstrual cycles because of an absence of documented vaginal intercourse and the concomitant use of another birth control method. Other design features that have varied between contraceptive trials relate to body mass index inclusion/exclusion criteria and the definition of “on-treatment” pregnancy. In addition, study designs of non-hormonal products can differ from those of hormonal products in their length and rules for qualifying cycles. The Draft Guidance for Hormonal Contraception, published in 2019 by the US Food and Drug Administration (FDA), will hopefully lead to more uniform trial design in the future, particularly for hormonal products. In the meantime, health care providers and patients should be aware of the nuances in trial design that make direct comparisons about relative efficacy challenging.

Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application to Plan a Pregnancy.

Background: Time to pregnancy (TTP) is a biomarker of fecundability and has been associated with behavioral and environmental characteristics; however, these associations have not been examined in a large population-based sample of application (app) users.Materials and Methods: This observational study followed 5,376 women with an age range of 18 to 45 years who used an app to identify their fertile window. We included women who started trying to conceive between September 30, 2017 and August 31, 2018. TTP was calculated as the number of menstrual cycles from when the user switched to “Plan” mode up to and including the cycle in which they logged a positive pregnancy test. We examined associations with several characteristics, including age, gravidity, body mass index, cycle length and cycle length variation, frequency of sexual intercourse, and temperature measuring frequency. Discrete time fecundability models were used to estimate fecundability odds ratios.Results: For the complete cohort the 6-cycle and 12-cycle cumulative pregnancy probabilities were found to be 61% (95% confidence interval [CI]: 59–62) and 74% (95% CI: 73–76), respectively. The median TTP was four cycles. The highest fecundability was associated with an age of less than 35 years, with cycle length variation <5 days and logging sexual intercourse on at least 20% of days added (the proportion of days in which intercourse was logged) (11.5% [n = 613] of entire sample). This group achieved a 6- and 12-cycle cumulative pregnancy probability of 88% (95% CI: 85–91) and 95% (95% CI: 94–97), respectively, and a TTP of 2 cycles.Conclusions: Natural Cycles was an effective method of identifying the fertile window and a noninvasive educational option for women planning a pregnancy. Women under age 35 with regular cycles showed a high pregnancy rate.

Disordered Eating, Development of Menstrual Irregularity, and Reduced Bone Mass Change After a 3-Year Follow-Up In Female Adolescent Endurance Runners.

This prospective study evaluated the 3-year change in menstrual function and bone mass among 40 female adolescent endurance runners (age 15.9 ± 1.0years) according to baseline disordered eating status. Three years after initial data collection, runners underwent follow-up measures including the Eating Disorder Examination Questionnaire and a survey evaluating menstrual function, running training, injury history, and prior sports participation. Dual-energy X-ray absorptiometry was used to measure bone mineral density and body composition. Runners with a weight concern, shape concern, or global score ≥4.0 or reporting >1 pathologic behavior in the past 28 days were classified with disordered eating. Compared with runners with normal Eating Disorder Examination Questionnaire scores at baseline, runners with disordered eating at baseline reported fewer menstrual cycles/year (6.4 ± 4.5 vs. 10.5 ± 2.8, p = .005), more years of amenorrhea (1.6 ± 1.4 vs. 0.3 ± 0.5, p = .03), and a higher proportion of menstrual irregularity (75.0% vs. 31.3%, p = .02) and failed to increase lumbar spine or total hip bone mineral density at the 3-year follow-up. In a multivariate model including body mass index and menstrual cycles in the past year at baseline, baseline shape concern score (B = -0.57, p value = .001) was inversely related to the annual number of menstrual cycles between assessments. Weight concern score (B = -0.40, p value = .005) was inversely associated with lumbar spine bone mineral density Z-score change between assessments according to a multivariate model adjusting for age and body mass index. These finding support associations between disordered eating at baseline and future menstrual irregularities or reduced accrual of lumbar spine bone mass in female adolescent endurance runners.

Fertility outcomes after preconceptional laparoscopic abdominal cerclage for second-trimester pregnancy losses

Objective(s)Cervical incompetence is an important cause of recurrent pregnancy loss, typically presenting in the second trimester with silent cervical dilation and premature delivery of the fetus. We aimed to evaluate the conception rate and time to conception or failure to conceive after preconceptional laparoscopic abdominal cerclage (LAC). Study DesignWe conducted this retrospective observational cohort study at a tertiary referral center. Patients who underwent LAC in the nonpregnant state for a second-trimester pregnancy loss between June 2012 and February 2020 were included. ResultsThe subjects were 40 patients with a history of one or more second-trimester pregnancy losses despite the placement of vaginal cerclage, who had undergone LAC before contemplating a future pregnancy. The mean number of second-trimester pregnancy losses before LAC was two per woman. The ages of the women at the time of cerclage ranged from 21 to 42 years. The time to pregnancy, which was the primary outcome of the study, was determined as the number of menstrual cycles before the patient became pregnant after LAC and the number of cycles needed for the patient to achieve her latest pregnancy before LAC. Of the 40 women, 22.5 % were noted during the LAC operation to have a pelvic peritoneal pathology that might have affected fertility, and all such pathologies were treated concomitantly during the procedure. Spontaneous pregnancy rates before and after LAC were 96.4 % and 89.3 % (p = 0.299), and times to pregnancy before and after LAC were 6.3 ± 8.4 and 6.6 ± 8.1 cycles (p = 0.897). Neither difference was statistically significant. In more than 84 % of patients who became pregnant after LAC, pregnancy was sustained to the stage of viability. Conclusion(s)In patients with cervical incompetence, LAC is a very effective intervention to sustain pregnancy to the stage of viability. If placed during the preconceptional period, it does not delay achieving pregnancy and does not have a negative impact on the chances of conception. This may be reassuring to women undergoing this procedure before they achieve a pregnancy.

Heterogeneity of Endocrinologic and Metabolic Parameters in Reproductive Age Polycystic Ovary Syndrome (PCOS) Women Concerning the Severity of Hyperandrogenemia-A New Insight on Syndrome Pathogenesis.

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, infertility, obesity, and insulin resistance, which results in increased concentrations of testosterone (T), which disturbs follicular growth and ovulation. This study aimed to assess PCOS women’s clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity. Results: 314 women (mean age 27.3 ± 4.6; mean body mass index (BMI) 25.7 ± 5.6) with PCOS, were divided into terciles according to T concentrations: <0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and >0.84 ng/mL (group 3). The mean concentration of T in all women was 0.59 ng/mL and correlated negatively with the number of menstrual cycles per year (MPY) (r = −0.36; p < 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33; p < 0.0001), luteinizing hormone (LH) (r = 0.19; p < 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52; p < 0.0001). Positive correlation between BMI and hirsutism (r = 0.16; p < 0.0001), total cholesterol (TC) (r = 0.18; p < 0.0001), low-density lipoprotein (LDL) (r = 0.29; p < 0.0001), and triglycerides (TG) (r = 0.40; p < 0.0001) was demonstrated. The division into subgroups confirmed the lowest MPY, highest LH, and hirsutism in group 3. BMI, insulin sensitivity indices, and lipid profile parameters were not different between the three T subgroups. Conclusions: We found no correlation between testosterone levels and insulin sensitivity or dyslipidemia in women with PCOS. Metabolic abnormalities may contribute more significantly than hyperandrogenemia to PCOS development.

Serum kisspeptin levels correlated with anti-mullerian hormone levels in women with and without polycystic ovarian syndrome

Objective: To determine serum kisspeptin and anti-mullerian hormone (AMH) levels in women with and without polycystic ovary syndrome (PCOS). Materials and methods This was a prospective, cross-sectional, comparative study that included 70 women with PCOS and 58 non PCOS controls. PCOS patients were diagnosed according to the Rotterdam criteria. Age, body mass index (BMI), number of menstrual cycles per year, and the Ferriman-Gallwey Score were determined for each woman. Serum levels of kisspeptin, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), estradiol, total testosterone, dehydroepiandrosterone sulfate (DHEA-S), AMH, fasting glucose and insulin were determined. Results Women with PCOS were younger (p < .001), with higher BMI (p = .027) and glucose values (p < .001); while displaying less number of menstrual cycles per year (p < .001). Although serum kisspeptin levels were similar in both groups, age was negatively (r= −0.33, p = .00018) and serum AMH levels were positively correlated (r = 0.25, p = .0039) with the serum kisspeptin levels in women with the PCOS. After adjusting for age, serum kisspeptin levels were comparable in both groups (p > .05). Serum LH, AMH, DHEA-S and total testosterone glucose, insulin levels and HOMA-IR values were significantly higher in women with PCOS as compared to controls (all p < .05). Conclusions Serum kisspeptin levels were similar in women with and without PCOS but positively correlated with AMH serum levels in PCOS women.

Coadministration of metformin or spironolactone enhances efficacy of rosiglitazone in management of PCOS

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women (n = 138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as – rosiglitazone (R), rosiglitazone with spironolactone (R + S), and rosiglitazone with metformin (R + M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2 h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R + S in improving hyperandrogenism whereas R + M was most effective in decreasing body weight and plasma insulin levels compared to R and R + S (p<.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.

Determining Optimal Time Interval Between Operative Hysteroscopy for Intrauterine Adhesions and Transfer of Single Euploid Embryos

Study Objective There is limited data assessing optimal timing between operative hysteroscopy for intrauterine adhesions (IUAs) and embryo transfer (ET). Prior studies have demonstrated an association between IUAs and infertility. This study aims to assess whether increasing time intervals between hysteroscopy for IUAs and ET affects pregnancy outcomes in the ideal study group of those undergoing euploid frozen ET. Design Retrospective cohort. Setting Academic center. Patients or Participants 375 women undergoing hysteroscopy prior to single euploid ET over a 3 year period. Interventions hysteroscopy for IUAs and single euploid ET. Measurements and Main Results 55.6% (n=99) had a diagnosis of IUAs and 44.4% (n=79) had normal intrauterine findings. Patients were stratified based on number of menstrual cycles (1, 2, or 3 cycles) between hysteroscopy and ET and categorized by outcome of pregnant, not pregnant, and ongoing pregnancy. Student's and nonparametric t-tests, and Chi-square tests were used with p There was no difference in baseline demographics between groups. In those undergoing hysteroscopy for IUAs, 68.7% were pregnant overall and 46.5% were ongoing. There were an insufficient number of patients undergoing ET 1 menstrual cycle after hysteroscopy for intrauterine adhesions to draw conclusions in this group. There was no difference in the pregnancy rate between groups who underwent ET after 2 or 3 menstrual cycles from hysteroscopy for IUAs as compared to those who waited a longer period or as compared to those who underwent diagnostic hysteroscopy. These same findings were also confirmed for the rate of ongoing pregnancy between groups. Conclusion The time between hysteroscopy for IUAs and single euploid ET did not have an effect on pregnancy outcome. Clinicians can proceed with ET as early as in the second menstrual cycle after hysteroscopy for IUAs. Further research is needed to examine patients undergoing ET in shorter intervals given small sample size.

Identifying menstrual migraine\u2013 improving the diagnostic criteria using a statistical method

ObjectiveTo develop a robust statistical tool for the diagnosis of menstrually related migraine.BackgroundThe International Classification of Headache Disorders (ICHD) has diagnostic criteria for menstrual migraine within the appendix. These include the requirement for menstrual attacks to occur within a 5-day window in at least frac {2}{3} menstrual cycles (frac {2}{3}-criterion). While this criterion has been shown to be sensitive, it is not specific. Yet in some circumstances, for example to establish the underlying pathophysiology of menstrual attacks, specificity is also important, to ensure that only women in whom the relationship between migraine and menstruation is more than a chance occurrence are recruited.MethodsUsing a simple mathematical model, a Markov chain, to model migraine attacks we developed a statistical criterion to diagnose menstrual migraine (sMM). We then analysed a data set of migraine diaries using both the frac {2}{3}-criterion and the sMM.ResultssMM was superior to the frac {2}{3}-criterion for varying numbers of menstrual cycles and increased in accuracy with more cycle data. In contrast, the frac {2}{3}-criterion showed maximum sensitivity only for three cycles, although specificity increased with more cycle data.ConclusionsWhile the ICHD frac {2}{3}-criterion is a simple screening tool for menstrual migraine, the sMM provides a more specific diagnosis and can be applied irrespective of the number of menstrual cycles recorded. It is particularly useful for clinical trials of menstrual migraine where a chance association between migraine and menstruation must be excluded.

Fecundity and human birth seasonality in Sweden: a register-based study

BackgroundIt is well-established that couples’ fecundities vary widely. Each couple has a relatively constant monthly probability of conceiving, which can vary from zero to quite high. This underlying probability is usually expressed as the time (number of menstrual cycles) the couple requires to conceive. Couples with high fecundity will, on average, need fewer cycles than couples with low fecundity. It is also well-documented that almost all human populations exhibit seasonal variation in births. Most European countries show seasonal variation that usually peak in the spring and are the lowest during the last quarter of the year. The increasingly strong pattern of depressed birth rates in November and December is likely explained by the December–January cut-off threshold for Swedish pupils’ school entry and their parents increasing awareness of the negative effects on school outcomes for children who are juniors in the school-entry cohort they belong to. To actively plan births for a specific time of the year, couples need to have some knowledge of the time required for them to conceive.MethodsWe use the duration between marriage of childless couples and first birth as a proxy measure of couples’ fecundity. Based on this time-to-pregnancy measure we study to what extent couples’ capacity to conceive affects the seasonality of their second births. We hypothesize that in a society with highly controlled fertility and a strong norm of having at least two children, sub-fertile couples will on average show less seasonal variation in second births. Sub-fertile couples, requiring more time to conceive the first time, will be less likely to try to target a desired birth month for their second child because doing so could jeopardize fulfilling their desired family size. We apply multinomial logistic regressions on 81,998 Swedish couples who married while being childless and subsequently gave birth to at least two children between 1990 and 2012, to investigate fecundity’s role in seasonal variation in second births.ResultsWe found that seasonal variation in second births was strongly associated with couples’ observed fecundity, measured as the duration between marriage formation and first birth. Our results support the hypothesis that sub-fertile couples, requiring more time to conceive the first time, show less seasonal variation in second births. The seasonal variations in second order births among couples with normal fecundity shows some similarities to traditional patterns as seen in agricultural and industrial societies of the past, with high numbers of births during the spring, and low numbers during the last quarter of the year. However, two important differences are notable. The characteristic Christmas peak in September has vanished, and the low birth rates in November and December come out much stronger than in the past.ConclusionsThe birth seasonality among couples with normal fecundity are what we would expect if couples actively plan their births according to the cut-off date for Swedish pupils’ school entry. We argue that our findings support the notion that scheduled childbirth is a reality in contemporary sociality.

Evaluation of efficacy and safety of spironolactone on clinical, metabolic and insulin sensitivity parameters among vitamin D replete women with PCOS: An observational study

Objective: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting 5-10% women in the reproductive age. PCOS is characterized by irregular menstrual cycles, chronic an-ovulation and hyperandrogenism in addition to many metabolic manifestations and some cancers. The study aimed to evaluate the efficacy and safety of spironolactone among PCOS women supplemented with vitamin D to make them vitamin D replete.&#x0D; Material &amp; methods: Sixty eligible women who qualified Rotterdam 2003 criteria and satisfied inclusion /exclusion criteria and had been assigned two groups: Group I: spironolactone (50 mg daily) and cholecalciferol 60000 IU every two weeks and group II: spironolactone 50 mg daily. All women were assessed for clinical, laboratory, and safety parameters before, 3 and 6 months after the treatment.&#x0D; Results: Mean age, number of menstrual cycles per year, anthropometric parameters; FG score, metabolic parameters and hormonal profiles were comparable in the groups at baseline. Menstrual cycle frequency improved (8.2±4.6 to 14±4.5 cycles/year vs. 7.9 ± 3.2 to 12.9 ± 6.214.0 ± 4.5) significantly at 6 months after therapy with combination of spironolactone and cholecalciferol vs. spironolactone alone while as FG score decreased significantly (12.4±4.3 to 8.6±1.4 6 vs. 12 ± 3.88 to 10.7 ± 2.9 at 6 months) in the combination. Serum total testosterone levels also showed a significant decline (56.5±20.3 to 38.7±13.6 vs. 57.4 ± 52.1 to 43.8 ± 29.7 at 6 months in the combination. Insulin sensitivity showed a non-significant favorable trend in the combination. There was no significant effect on weight, BMI, BP, LH and FSH levels.&#x0D; Conclusion: The results of the observational study that women with PCOS rendered vitamin D replete have better efficacy of spironolactone on clinical, metabolic and insulin sensitivity parameters among women with PCOS without increasing adverse event rate.

PO-085 MiR-424(322)/503 regulates Wnt/b-catenin pathway and resistance to treatment in breast cancer

IntroductionThe female mammary gland is a very dynamic organ that undergoes continuous tissue remodelling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy increase the risk of breast cancer, the reasons are unclear. Clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy and that miR-424(322)/503 is commonly lost in a subset of aggressive breast cancers. Through the use of a knockout mouse model, we demonstrated for the first time that loss of miR-424(322)/503 promotes breast tumorigenesis in vivo. Remarkably, we found that loss of miR-424(322)/503 promotes chemoresistance due to the up-regulation of two of its targets: BCL-2 and insulin-like growth factor-1 receptor (IGF1R). Importantly, targeted therapies blocking the aberrant activity of these targets restore sensitivity to chemotherapy.Material and methodsPatient data were assessed from METABRIC and TCGA corresponding to breast cancer samples with available whole-genome DNA CNAs, mRNA expression data, and clinicopathological data.Targets of the miR-424(322)/503 were validated by western blot, 3’UTR reporter assays and PAR-CLIP. Wnt localization and activity was assessed by cell fractionation and qRT-PCR.Results and discussionsTumours generated in the miR-424(322)/503 knock out mouse model present morphological and molecular characteristics of metaplasic squamous cell carcinoma (SSC) of the breast. These include the presence of a non-glandular component, spindle cells and expression of cytokeratin 6. Primary SSC of the breast is a very aggressive tumour with high metastatic activity and refractory to treatment. It has been reported that nearly all the primary metaplasic carcinomas present activation of Wnt pathway, and about 40% of them carry mutations in genes of the Wnt pathway. By analysing the expression data of over 3000 breast tumours, we have determined that the loss of mir-424(322)/503 contributes to the activation of Wnt/b-catenin pathway in SSC. We also show that the miR-424(322)/503 directly targets the Wnt receptor LRP-6, preventing the translocation of b-catenin to the nucleous and inhibiting the transcription of b-catenin-regulated genes.ConclusionMiR-424(322)/503 is a tumour suppressor in breast cancer and provide a link between mammary epithelial involution, tumorigenesis, and chemoresistance.

PO-089 135 Targeting treatment resistance in breast cancer subtypes via LMTK3 inhibition

IntroductionThe female mammary gland is a very dynamic organ that undergoes continuous tissue remodelling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy increase the risk of breast cancer, the reasons are unclear. Clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy and that miR-424(322)/503 is commonly lost in a subset of aggressive breast cancers. Through the use of a knockout mouse model, we demonstrated for the first time that loss of miR-424(322)/503 promotes breast tumorigenesis in vivo. Remarkably, we found that loss of miR-424(322)/503 promotes chemoresistance due to the up-regulation of two of its targets: BCL-2 and insulin-like growth factor-1 receptor (IGF1R). Importantly, targeted therapies blocking the aberrant activity of these targets restore sensitivity to chemotherapy.Material and methodsPatient data were assessed from METABRIC and TCGA corresponding to breast cancer samples with available whole-genome DNA CNAs, mRNA expression data, and clinicopathological data.Targets of the miR-424(322)/503 were validated by western blot, 3’UTR reporter assays and PAR-CLIP. Wnt localization and activity was assessed by cell fractionation and qRT-PCR.Results and discussionsTumours generated in the miR-424(322)/503 knock out mouse model present morphological and molecular characteristics of metaplasic squamous cell carcinoma (SSC) of the breast. These include the presence of a non-glandular component, spindle cells and expression of cytokeratin 6. Primary SSC of the breast is a very aggressive tumour with high metastatic activity and refractory to treatment. It has been reported that nearly all the primary metaplasic carcinomas present activation of Wnt pathway, and about 40% of them carry mutations in genes of the Wnt pathway. By analysing the expression data of over 3000 breast tumours, we have determined that the loss of mir-424(322)/503 contributes to the activation of Wnt/b-catenin pathway in SSC. We also show that the miR-424(322)/503 directly targets the Wnt receptor LRP-6, preventing the translocation of b-catenin to the nucleous and inhibiting the transcription of b-catenin-regulated genes.ConclusionMiR-424(322)/503 is a tumour suppressor in breast cancer and provide a link between mammary epithelial involution, tumorigenesis, and chemoresistance.

Preconception Blood Pressure Levels and Reproductive Outcomes in a Prospective Cohort of Women Attempting Pregnancy.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00467363.

Increased Incidence of Endometrial Cancer Following the WHI: An Assessment of Risk Factors [18OP

INTRODUCTION: The US incidence of Type I Endometrial cancer (EC) dramatically increased following the Women’s Health Initiative (WHI). While most cancer rates are decreasing, EC incidence increased from 2003 to 2013. EC rates were stable 1992 to 2002, prior to the announcement of WHI results. Potential etiologies for this increase are examined, including compounded hormone therapy use, which may not provide adequate endometrial protection. METHODS: EC incidence was obtained from Surveillance, Epidemiology, and End Result Program database from 1975 through 2013. The incidence of risk factors thought to be associated with EC, including age, obesity, race, number of menstrual cycles, gravidity and parity, metabolic syndromes (diabetes mellitus, PCOS), diet and exercise, and medications (hormone therapy including FDA-approved and unapproved [compounded] estrogens and progesterone, tamoxifen, and hormonal contraceptives) were evaluated and temporal trends were compared to EC trends. RESULTS: Endometrial cancer rates were constant from 1992 to 2002 in women 50-74 years of age, but have increased 2.5% annually with a 10% increase from 2006 to 2012 (test for trend 0.82). The greatest percentage of new cases was in women 55-64 years of age. Use of estrogen and progestin combinations have decreased while risk factors remained constant or decreased during the same time; however, obesity and compounded hormone use have increased coincident with the EC increase. CONCLUSION: EC increased post-2002 following the WHI, which may be multifactorial. The combination of an increase in obesity concurrent with decreasing exogenous progesterone and an increase in compounded hormone therapy is a public health issue requiring further evaluation.