Healthy Premenopausal Women Research Articles

Do external female genital measurements affect genital perception and sexual function and orgasm?

Objective:To provide baseline data for the anatomy of the external female genitalia and to investigate the correlation between those measurements and sexual function and genital perception.Materials and Methods:This prospective cohort study consisted of 208 healthy premenopausal women. The Female Sexual Function index (FSFI) and the Female Genital Self-image scale (FGSIS) questionnaires were administered. Participants were divided into two groups according to their female sexual dysfunction (FSD) status. External genital measurements and anterior and posterior vaginal length were measured.Results:The external female genital measurements were (cm, mean ± standard deviation): clitoral prepuce length 2.05±0.48; clitoral glans length 0.87±0.21; clitoral glans width 0.60±0.15; clitoris to urethra 2.24±0.55; anterior fornix depth 7.75±0.92; posterior fornix depth 9.25±0.75; labia minora width, right 2.12±0.86, left 2.20±0.96. A weak negative correlation was found between total FGSIS scores and clitoral prepuce length (p=0.01, r=-0.17), whereas a weak positive correlation was seen between total FGSIS scores and anterior-posterior vaginal lengths (p=0.04, r=0.13; p=0.02, r=0.15, respectively). No statistically significant difference was found between the genital measurements of participants with FSD (n=82, 39.4%) and those without FSD (n=126, 60.6%), and the total FSFI scores and orgasm subdomain scores.Conclusion:The female genital measurements were found to be distributed over a wide range. Although the relationship between genital measurements and genital perception varied, no significant relationship was found between genital measurements and sexual functions or orgasm. These findings suggest that a more cautious approach should be taken towards genital surgeries for cosmetic purposes.

Anti-carbamylated protein antibodies in premenopausal rheumatoid arthritis women: relation to disease activity and bone loss.

Anti-carbamylated protein antibodies (anti-CarP Abs) are present in patients with RA, however, their association with bone loss is not confirmed. The purpose of this study was to determine the relation between the serum level of anti-CarP Abs in premenopausal RA women and disease activity and bone loss. This case-control study was conducted on 48 premenopausal women with RA and 48 matched healthy premenopausal women. All RA women were subjected to clinical examination, disease activity assessment using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), functional assessment using the HAQ, physical activity assessment using the International Physical Activity Questionnaire (IPAQ), fatigue assessment using the Modified Fatigue Impact Scale (MFIS), serological tests as well as anti-CarP Abs using ELISA. Moreover, the BMD was measured by DXA and plain X-ray of both hands was done to assess juxta-articular osteopenia and erosions. The anti-CarP Abs level was significantly higher in RA patients than in healthy controls. The serum level of anti-CarP Abs had a significant positive correlation with the RA DAS28, CDAI, HAQ, MFIS and original Sharp score, while a significant negative correlation was present with the IPAQ. Anti-CarP Abs were negatively correlated with either spine BMD or Z-score and positively correlated with the original Sharp score. Anti-CarP Abs were higher in premenopausal RA women compared with older and BMI matched healthy women. Anti-CarP Abs are associated with higher RA disease activity, increased disability and fatigability and decreased physical activity. Moreover, anti-CarP Abs are associated with systemic trabecular bone loss as well as local bone loss.

Mammographic density change in a cohort of premenopausal women receiving tamoxifen for breast cancer prevention over 5 years

BackgroundA decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations.MethodsMammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year.ResultsAnalysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17–25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2–7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60–300% worse than using mean change at 1year.ConclusionsAll measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.

Changes of intestinal microflora of breast cancer in premenopausal women.

Breast cancer is one of the most common malignant tumors in women. More than half of breast cancer patients are not menopausal at the time of diagnosis. The occurrence and development of premenopausal breast cancer are affected by many factors. Intestinal flora, especially SCFA-producing bacteria, participates in the development of various tumors, and there is a lack of in-depth research in premenopausal breast cancer patients. We used 16S rRNA gene sequencing, targeted metabolomics, and cell culture methods to analyze the changes in the intestinal flora and metabolites of premenopausal breast cancer patients. In addition, we treated breast cancer cells with significantly altered propionate and butyrate in vitro to examine their effects on cell activity. This study followed STROBE guidelines. We found that compared with healthy premenopausal women, the composition and symbiosis of intestinal flora in patients with premenopausal breast cancer changed significantly. The abundance of short-chain fatty acid (SCFA)-producing bacteria was significantly reduced, and the key SCFA-producing enzymes were also significantly reduced. Pediococcus and Desulfovibrio could distinguish premenopausal breast cancer patients from normal premenopausal women. The related propionate and butyrate had a certain ability to inhibit breast cancer cell viability in vitro. As SCFA-producing bacteria, Pediococcus and Desulfovibrio showed potential reference value for the diagnosis of premenopausal breast cancer. The ability of propionate and butyrate to inhibit breast cancer cell lines in vitro suggests that the relevant SCFA receptor may be a new target for the treatment of premenopausal breast cancer.

Bone density and frame size in adult women: Effects of body size, habitual use, and life history.

Bone mineral density (BMD) and frame size are important predictors of future bone health, with smaller frame size and lower BMD associated with higher risk of later fragility fractures. We test the effects of body size, habitual use, and life history on frame size and cortical BMD of the radius and tibia in sample of healthy adult premenopausal women. We used anthropometry and life history data from 123 women (age 18-46) from rural Poland. Standard techniques were used to measure height, weight, and body fat. Life history factors were recorded using surveys. Grip strength was measured as a proxy for habitual activity, wrist breadth for skeletal frame size. Cortical BMD was measured at the one-third distal point of the radius and mid-point of the tibia using quantitative ultrasound (reported as speed of sound, SoS). Radial SoS was high (mean t-score 3.2 ± 1.6), but tibia SoS was average (mean t-score 0.35 ± 1.17). SoS was not associated with age, although wrist breadth was positively associated with age after adjusting for height. Radius SoS was not associated with measures of body size, habitual use, or life history factors. Wrist breadth was associated with body size (p < .05 for all), lean mass, and grip strength. Tibia SoS was associated with height. Life history factors were not associated with frame size or cortical SoS. Habitual use and overall body size are more strongly associated with frame size and cortical SoS than life history factors in this sample of healthy adult women.

Association between lipid and thyroid function parametersin premenopausal euthyroid healthy women and women on levothyroxine replacement therapy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Reference Intervals for Bone Histomorphometric Measurements Based on Data from Healthy Premenopausal Women.

This study has established the normal reference intervals for bone histomorphometric measurements derived from healthy premenopausal women, which is rarely available. We presented the static and dynamic bone histomorphometric data from trans-iliac bone biopsies in 62 healthy premenopausal women (19 blacks and 43 whites, ages 20-53years). There were no significant differences in age and BMI between black and white women. Since there was no significant difference in bone remodeling between the two ethnic groups, we pooled data of all 62 premenopausal women to establish normal reference intervals for bone histomorphometry. The results provide normal reference intervals for both static and dynamic histomorphometric variables in cancellous and cortical bone of the ilium. None of the bone remodeling-related variables correlated with age or BMI. This study provides reference intervals for bone histomorphometric measurements in both cancellous and cortical bone of the ilium, which would behelpful inthe evaluation of bone health in women.

The effects of vilaprisan on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive-A randomized controlled trial.

AimsThe primary objective was to explore whether the suppression of ovarian activity induced by a combined oral contraceptive (COC) is influenced by the simultaneous intake of the selective progesterone receptor modulator (SPRM) vilaprisan (VPR).MethodsIn this exploratory randomized, double‐blind, parallel‐group study, 71 healthy premenopausal women were randomized (1:1) to receive either 2 mg/d VPR or placebo for 3 months. Concomitantly, a COC (0.15 mg levonorgestrel, 0.03 mg ethinyloestradiol) was administered in a cyclic regimen. Ovarian activity (Hoogland score based on follicle size and hormone concentrations), cervical function (Insler score), bleeding pattern and endometrial thickness/histology were assessed before treatment, in treatment cycle 3 and during follow‐up.ResultsThe known COC‐driven suppression of ovarian activity was mildly affected by VPR. COC+VPR group: 22, 0 and 6% of the subjects had Hoogland scores of 4 (active follicle‐like structures), 5 or 6 (ovulation). COC+placebo group: 14% of the subjects had a score of 4 and none a score of 5 or 6 (Bayesian analysis for Hoogland score = 4, median difference in response rate: 7.5%; 90% credible interval [−8.5; 23.5%]). COC effects on cervical function were moderately affected (mucus more sperm permeable under COC+VPR). COC withdrawal bleeding, in contrast, was absent in 81% of the subjects receiving COC+VPR vs 0% receiving COC+placebo.ConclusionThe SPRM VPR interfered with the pharmacodynamic effects of the COC. Therefore, full contraceptive effectiveness cannot be assumed without final judgement by a Pearl index study. Women on SPRMs should be advised to use nonhormonal contraception methods.

Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women.

Observed sex differences in the epidemiology of cardiovascular disease incidence and the efficacy of clinical intervention strategies, coupled with recent mandates from the National Institutes of Health (NIH), and its international counterparts to consider sex as a biological variable in all preclinical and clinical work (15), have led to increased enrollment of women in human physiology studies of vascular function with the goal of improving external validity and clinical applicability of the findings. However, standard practice in these studies is to test women during the early follicular phase (~days 1-5) of the menstrual cycle, during which estrogen and progesterone concentrations are lowest, and either exclude or limit testing of women who use hormonal contraceptives to the placebo phase. This approach seeks to control for, or limit, differences in circulating hormone concentrations between men and women and is based on the dogmatic theory that cyclic changes in estrogen and progesterone concentrations lead to greater variability in study outcomes and uninterpretable datasets. Contrary to this common approach, we propose that limiting testing of women to this single phase 1) decreases external validity of the findings, 2) obfuscates potential physiological differences contributable to differences in sex hormone concentrations between men and women, and 3) is, in many instances, contradicted by literature that demonstrates limited or no variability in vascular measurements across the menstrual cycle.

Anal Sphincter Length as Determined by 3-Dimensional Endoanal Ultrasound and Anal Manometry: A Study in Healthy Nulliparous Women.

The normal female external anal sphincter (EAS) is shorter anteriorly than laterally and posteriorly. Furthermore, the thickness of the very proximal part of the circular EAS is thinner than 50% of the lateral and posterior EAS thickness. The extent of these features is not fully explored. The aim of this prospective study was to assess the normal anal sphincter with 3-dimensional (3D) endoanal ultrasound (EAUS) and to relate 3D EAUS length measurements to sphincter length determined by anal manometry. Healthy premenopausal nulliparous women underwent anal manometry and 3D EAUS examinations. Two experienced colorectal surgeons independently assessed all scans, blinded to any patient data. A total of 43 women were included. Four scans were incomplete and excluded from the analysis. Interobserver agreement was fair to very good for the various length measurements. The mean length from the distal border of the puborectal muscle to the very proximal border of the anterior EAS (the anterior gap) was 4.4 (95% confidence interval, 3.9-4.9) mm, whereas the length to the level where the anterior EAS thickness was at least 50% of the lateral and posterior EAS thickness was 7.2 (95% confidence interval, 6.5-7.9) mm. Manometric sphincter length at rest did not correlate with any 3D EAUS length measurements. In the normal anterior female anal canal, the EAS is not present or appears with less than 50% of the thickness of the lateral and posterior EAS for the first 7.2 mm below the distal border of the puborectal muscle.

Obesity and Breast Cancer: Circulating Adipokines and Their Potential Diagnostic as Risk Biomarkers

Obesity and cancer are two major epidemics of this century. Obesity is related to a higher risk of many types of cancer. Studies have accessed circulating adipokines, as key-mediators in obesity and breast cancer. The study is aimed to examine the circulating levels of insulin-like growth factor-1, leptin, adiponectin, and resistin in premenopausal Iraqi women with breast cancer. The current study was performed during the period from June 2019 to December 2019 at Oncology unit/ Medical City Hospital-Baghdad. A total of 90 premenopausal women with BC/ stage II and III after 2nd dose of chemotherapy were contributed in this study as patients group. Their ages ranged from (35- 50) years in addition to 90 premenopausal healthy women were designated as a control group. There was a substantial rise (p &lt; 0.05) in fasting serum glucose, total serum cholesterol, triacylglycerol, low-density lipoprotein cholesterol, CA15-3, insulin-like growth factor-1, leptin, leptin/adiponectin ratio, and resistin. While there was a substantial decrease (p= 0.01) in serum adiponectin in patients as paralleled to healthy. There was a considerable rise (p ≤ 0.05) in serum insulin-like growth factor-1, leptin, and resistin, while there was a reduced in serum adiponectin in obese patients as paralleled to overweight, but it was not significant. Additionally, circulating levels of insulin-like growth factor-1, leptin, and resistin were significantly increased (p= 0.001) in patients who had tumour size &gt; 5 cm paralleled to those with tumour size 2-5 cm.Higher levels of serum leptin, resistin, and leptin to adiponectin ratio are related to improved breast cancer risk in Iraqi women. The clinical and pathological features of the tumour recommended that these adipokines might affect the development of breast cancer. Thus adipokines, in complicated and interrelated mechanisms, maybe drive breast cancer instigation and progression.

Urine Organic Acids Can Determine the Metabolic Effects of Traditional Korean Diet, a Cardiometabolic Diet

Abstract Objectives Urine organic acids are water-soluble chemical compounds excreted in the urine that are intermediates in many metabolic pathways. Because excess metabolites are excreted in the urine, they may reflect the metabolic status. We investigated whether urine organic acids can determine the metabolic influence of traditional Korean diet (K-diet), a cardiometabolic diet. Methods Fifty two healthy premenopausal women were recruited into a 2 × 2 crossover study with two different diets, K diet and control diet (Westernized current Korean diet). Each diet was provided alternately to all subjects for 1 month with 1 month washout period. Blood and urine samples were collected with anthropometric measurements. Sixty five urine organic acids were measured by LC-MS/MS. Results In the K-diet group, the mean difference of triglyceride (−6.58 ± 4.80 vs −26.35 ± 6.05 mg/dL, P = 0.012), total cholesterol (−12.77 ± 2.78 vs −30.02 ± 2.65 mg/dL, P &amp;lt; 0.001) and LDL- cholesterol (−5.52 ± 2.30 vs −15.88 ± 2.29 mg/dL, P = 0.002) were significantly lower compared to the control group. Body weight and body mass index were also lowered in the K-diet group. Among 65 urine organic acids, TCA cycle associated α-ketoglutarate (21.73 ± 1.27 vs 19.05 ± 1.15 ug/mg creatinine, P = 0.008), malate (1.61 ± 0.10 vs 1.34 ± 0.09, P = 0.008) and isocitrate (22.90 ± 0.68 vs 21.27 ± 0.54, P = 0.014) were lowered in the K-diet group, while citrate (249.16 ± 16.96 vs 324.42 ± 21.18, P = 0.001) and furmarate (0.51 ± 0.03 vs 0.65 ± 0.06, P = 0.029) were elevated in the control group. α-Keto-β-methylvalerate (1.46 ± 0.09 vs 1.09 ± 0.07, P = 0.001), α-ketoisovalerate (0.22 ± 0.02 vs 0.16 ± 0.02, P = 0.012) and methylmalonate (1.30 ± 0.06 vs 1.00 ± 0.06, P &amp;lt; 0.001), which are associated with branched chain amino acid metabolism, were decreased in the K-diet group. Adipate (0.90 ± 0.07 vs 0.65 ± 0.04, P &amp;lt; 0.001) and α-ketoisocaproate (0.46 ± 0.02 vs 0.38 ± 0.02, P = 0.002), which are associated with fatty acid metabolism, were also decreased in the K-diet group. Conclusions K-diet improves clinical parameters and alters urine organic acids associated with TCA cycle and metabolisms of fatty acids and branched-chain amino acid, suggesting that urine organic acids can be useful endpoints to determine the metabolic effects of K-diet and even other diets. Funding Sources Korea Food Research Institute.

SUN-LB58 Repeated Once-Daily Administration of the Non-Hormonal Neurokinin 1,3 Receptor Antagonist NT-814 Reduces LH, Estradiol and Progesterone in Healthy Women

Introduction: Uterine fibroids (UF) affect up to 25% of women and endometriosis (EM) 10% of women worldwide. An ideal therapy would lower estradiol concentrations to reduce hormonal drive to the endometrium and myometrium, but not to the levels which cause the hot flashes and bone loss associated with current treatments. A target estradiol range of 110-180 pmol/L has been proposed1. GnRH secretion is modulated by neurokinin B (NKB) acting at the NK3 receptor via hypothalamic neurons expressing kisspeptin, NKB & dynorphin (KNDy neurons). In addition, Substance P acting at the NK1 receptor may also stimulate reproductive hormone release. We hypothesised that NT-814, a dual NK1,3 receptor antagonist, would reduce GnRH release and hence LH, estradiol and progesterone levels in women. This preliminary clinical study in healthy pre-menopausal women evaluated this hypothesis. Methods: We undertook a randomized, single-blind, placebo-controlled study. 32 healthy women attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3/4, 9/10, 15/16 and 21/22 to measure serum sex hormone concentrations. No treatment was given in cycle 1 (baseline). During cycle 2, participants received placebo or one of three doses of NT-814 once per day; 40mg, 80mg or 120mg (n=8 per group) for up to 21 days. Results: Compared to placebo, NT-814 reduced LH, estradiol and progesterone concentrations in a dose-related manner. The median changes in average LH (IU/L) during cycle 2 compared to cycle 1 were: placebo, 0.16; 40mg, -0.13; 80mg, -0.46; 120mg, -0.58. Median change in average estradiol (pmol/L) in cycle 2 was: placebo, -16.5; 40mg, -9.3; 80mg, -92.1; 120mg, -141.4. The median changes in progesterone (nmol/L) on day 21/22 in cycle 2 compared to cycle 1 were: placebo, 3.2; 40mg, 8.0; 80mg, -5.7; 120mg, -19.4. The reductions in estradiol and progesterone with 120 mg NT-814 were significant (p=0.038 & p=0.046, respectively). There were no clear changes in FSH concentrations. Of note, in women treated with 120mg NT-814, the average estradiol level reduced from 310.8 pmol/L in cycle 1 to 179.8 pmol/L in cycle 2. Cycle length was extended by at least 6 days in 5 of 8 women receiving the 120 mg dose. NT-814 was well tolerated; no participant experienced hot flashes during treatment. Conclusions: Once-daily administration of the non-hormonal NK1,3 receptor antagonist NT-814 reduced serum LH, estradiol and progesterone in healthy women in a dose-related manner without causing vasomotor symptoms. The 120 mg dose of NT-814 lowered estradiol levels to potentially ideal levels for UF and EM treatment. These preliminary data support further studies with NT-814 to establish its efficacy and safety in treating patients with these hormone driven disorders.

The body composition analysis as a complementary tool in the screening of bone structural abnormalities.

Purpose. The importance of early diagnosis, bone-healthy lifestyle and medication is required for remaining fracture free. Dual-energy X-ray absorptiometry and ultrasound densitometry are widely used to screen osteoporosis and other bone structural diseases. Bioelectrical impedance analysis (BIA) devices can also estimate bone mineral content (BMC), but it has not been recommended for diagnostic purposes. The aim was to analyse whether low levels of the body composition' components and low bone mineral content can predict bone structural risk. Methods. Healthy pre- (n: 235, 18-45 years) and postmenopausal women (n: 137, 46-78 years) were enrolled to the analysis. BMC (kg) was estimated by InBody 720 analyser. Bone structure was measured by ultrasound DTU-One osteometer. Broadband ultrasound attenuation (BUA, dB/MHz), which estimates structural characteristics of trabecular bone, was used to assess bone structure. Body mass components were estimated by Drinkwater-Ross method. Results. Age changes of BMC, absolute and relative bone mass, muscle mass and bone structural parameters were analysed in women. BMC (r = 0.43, p < 0.01), absolute muscle mass (r = 0.41, p < 0.01) and absolute bone mass (r = 0.37, p < 0.01) were highly correlated (Pearson correlation) with BUA in premenopausal women. In postmenopausal women weaker relationship was identified between BUA and its hypothetical predictive factors. Conclusion. BMC and other studied body mass components alone do not provide enough information to identify osteoporosis, but can complete and widen the screening methods for bone structural diseases. Bone mineral density of healthy premenopausal women with low BMC, low bone mass and/or low muscle mass values should be measured regularly.

Augmented sympathetic neural responses to a cold pressor test during salt loading in healthy premenopausal women

BackgroundExcessive salt intake is considered a risk factor for the development of hypertension. Previous studies have demonstrated that augmented neural and pressor responses to a cold stimulus are associated with an increased risk of hypertension. This study aimed to determine whether salt loading impacts sympathetic neural responses during the cold pressor test (CPT) in healthy young and middle‐aged women.MethodsNine healthy premenopausal women [42±3 (SD) yr] were given a standardized isocaloric high‐salt (HS; 250 mEq sodium, 100 mEq potassium, and 1000 mg calcium per day) or low‐salt diet (LS; 50 mEq sodium, 100 mEq potassium, and 1000 mg calcium per day) for 1 week each (~2‐month apart with the order randomized), while water intake was ad libitum. Twenty‐four‐hour urine was collected and laboratory testing was performed following each HS and LS period in the mid‐luteal phase of the menstrual cycle. Subjects were in the supine position and beat‐by‐beat BP, heart rate (HR) and muscle sympathetic nerve activity (MSNA) were measured during baseline, 2‐minute CPT, and 3‐minute recovery. Blood sample was taken to calculate the change in plasma and blood volume by using the Dill’s equation. Salt sensitive was defined as more than 10% changes in mean arterial pressure between HS and LS, and below this cutoff was defined as non‐salt‐sensitive.ResultAll subjects were non‐salt‐sensitive (salt sensitivity range: −7.78 to 6.49%). Urine osmolality and 24‐h urine sodium were higher during HS than LS (572±174 vs. 443±153 mOs/kg and 150.8±72.1 vs. 65.2±38.5 mmol/day, both P&lt;0.05). Plasma and blood volume increased by 6.9±1.8% (p=0.006) and 4.3±1.2% (p=0.008) in HS compared with LS. Baseline systolic and diastolic BP (103±12 vs. 105±10 mmHg and 59±6 vs. 69±9 mmHg), HR (66±10 vs. 63±9 bpm), or MSNA (burst frequency: 14±11 vs. 16±10 bursts/min and total activity: 156±118 vs.184±115 a.u./min) did not differ between HS and LS (all P&gt;0.05). Systolic and diastolic BP and HR increased during the CPT (all P&lt;0.001) with no salt effects (all P&gt;0.05). MSNA increased during the CPT in both conditions (both P&lt;0.001), but the increases in burst frequency and total activity were greater during HS than LS (Δ burst frequency: 26±20 vs. 14±15 bursts/min and Δ total activity: 644±480 vs.368±402 a.u./min, P=0.042 and 0.002 for interaction, as figure ).ConclusionSalt loading augments sympathetic neural responses to the cold pressor stimulus with no significant impact on blood pressure responses in healthy premenopausal non‐salt‐sensitive women. Whether similar results can be obtained in salt‐sensitive women remains to be determined.Support or Funding InformationThe Harry S. Moss Heart Trust awardChanges (Δ) from baseline in muscle sympathetic nerve activity (MSNA) burst frequency, total activity, mean arterial pressure and heart rate during cold pressor test (CPT) and recovery in high salt and low salt diet. Values are means ± SD. *, high salt vs low salt at P&lt;0.05.Figure 1

Diabetes Attenuates the Increase in Estrogen‐Mediated Endothelial Function

BackgroundApparently healthy premenopausal women are protected against cardiovascular disease (CVD) compared to men; and estrogen has been thought to play a key role. In the presence of diabetes; however, this overall sex‐dependent cardiovascular protection is lost. The increase in vascular function throughout the menstrual cycle in healthy premenopausal women has been established. The present investigation sought to test the hypothesis that the increase in vascular function from menses to the late follicular phase of the menstrual cycle is lost in premenopausal women with type 1 diabetes (T1D).MethodsPremenopausal women with a clinical diagnosis of T1D (n=22, HbA1c=8.2±1.7%, age=26±8 years, BMI=26.9±5.4 kg/m2) and seemingly healthy, age‐ and sex‐matched controls (n=10, HbA1c=5.2±0.3%, age=26±9 years, BMI=23.3±4.1 kg/m2) were recruited to participate. Flow mediated dilation (FMD), a measure of endothelial function, was assessed during the menses (cycle day=4±1) and late follicular phases (cycle day=13±1) of the menstrual cycle to represent periods of low and high concentrations of estrogen, respectively. Visit 1 (menses) was confirmed by a positive hemolytic urological multistix test and visit 2 (late follicular) was scheduled based on indications from an ovulation prediction kit. A small venous blood sample was collected at each visit to measure concentrations of estrogen. Endothelial independent vasodilation was determined by administration of sublingual nitroglycerin after each FMD test.ResultsThe increase in estrogen from menses to the follicular phase was similar (p=0.73) in both groups (Δ estrogen: T1D=78.3±92.6 vs Controls=85.6±30.0 pg/mL). Baseline brachial artery diameter was similar between T1D and controls (p=0.25) and was not different between visit 1 and visit 2 (p=0.76). Fasting blood glucose was higher (p&lt;0.01) in women with T1D compared to controls at both visits; however, the change within groups was similar (p=0.49) across time. A near significant interaction (p=0.07) for endothelial function was observed such that FMD increased from the menses to follicular phase in controls (ΔFMD=1.151±1.603%), whereas no change was observed in patients with T1D (ΔFMD=−0.633±2.126%). Endothelial independent vasodilation was not different between groups (p=0.82). Additionally, the endothelial independent response was similar across the menstrual cycle (p=0.97).ConclusionThese data suggest that the presence of diabetes may attenuate the beneficial effects of estrogen on endothelial function in premenopausal women. The loss of estrogen’s cardiovascular protective effect on the vasculature in diabetes may explain the increased risk of CVD observed in women with T1D.Support or Funding Information1RO1HL137087‐01A1.

Menstrual Cycle Influences the Protective Effects of Remote Ischemic Preconditioning Against Endothelial Ischemia‐Reperfusion injury

PURPOSEA promising therapeutic intervention to counteract endothelial ischemia/reperfusion (I/R) injury is ischemic preconditioning (IPC). Limited data from ovariectomized animal models shows that estrogen deficiency abolishes the cardioprotective effects of IPC, whereas estrogen replacement restores protection. This suggests that alterations in female sex hormones, particularly estrogens, that occur naturally during the menstrual cycle is likely to influence the vascular protective properties of IPC. The aim of the present study was to identify how changes in female sex hormones that occur naturally during the menstrual cycle interfere with IPC to provide vascular endothelial protection in women.METHODSTen healthy premenopausal eumenorrheic women (age 21±1 yr) not taking any contraceptive medications were studied in a within‐subjects design. Primary outcomes with respect to the assessment of vascular endothelial function were measured during the early follicular (after onset of menses; days 1–6) and at mid‐cycle during ovulation (days 10–14 after positive urine ovulation test). Endothelium‐dependent vasodilation was assessed by the forearm blood flow (FBF) response to reactive hyperemia using strain‐gauge venous occlusion plethysmography in the absence and presence of endothelial I/R injury (20 min brachial artery ischemia followed by 15 min reperfusion) when preceded by remote IPC (right arm: 3×5 min cycles of ischemia).RESULTSIn the absence of endothelial I/R injury, peak FBF to reactive hyperemia was similar (P=0.19) between the early follicular (19.9±6.1 ml/100ml tissue/min) and ovulation phases (22.1±5.9 ml/100ml tissue/min). In contrast, there was a significant main effect (P=0.001) of menstrual cycle phase on the capacity of IPC to protect against endothelial I/R injury. For example, during the early follicular phase, peak FBF was significantly (P=0.02) diminished with endothelial I/R injury (from: 19.9±6.1 to 17.1±4.1 ml/100ml tissue/min) despite remote IPC. As a result, total FBF during the initial 30 sec of reactive hyperemia (area under the curve) was decreased ~18% (P=0.027) after (41.0±11.4 ml/100ml tissue) compared with before (49.6±15.1 ml/100ml tissue) endothelial I/R injury. However, during ovulation, remote IPC provided a level of endothelial protection from I/R injury that was not observed in the early follicular phase. With endothelial I/R injury, peak FBF increased 15% (from: 22.1±5.9 to 25.3±6.4 ml/100ml tissue/min; P=0.012). As a result, total FBF was well preserved (P=0.859) after (58.2±14.6 ml/100ml tissue) compared with before (58.0±13.3 ml/100 ml tissue) endothelial I/R injury.CONCLUSIONSThese data suggest that the menstrual cycle differentially influences the capacity of remote IPC to protect against endothelial I/R injury. Greater circulating estrogens during ovulation may be an important mediator contributing to the protective benefits of remote IPC in women.Support or Funding InformationSouth Dakota State University Research Scholarship Support Fund

Acute High Phosphate Intake Impairs Endothelial‐Dependent Vasodilation in Young Premenopausal Women

In the United States, the growing abundance of processed foods has led to Americans consuming more than double the recommended dietary intake of inorganic phosphate (Pi). Chronic consumption of Pi is associated with a higher risk of cardiovascular disease in the general population; however, studies investigating underlying mechanisms are limited. Recently, our lab has reported an impairment in brachial artery flow‐mediated dilation (FMD) following acute high Pi consumption in young, healthy men. To our knowledge, the effect of acute high Pi on vascular function in women remains unknown. This becomes important, as previous longitudinal work suggests that women may be protected from the greater cardiovascular risk associated with high serum phosphorus. Therefore, the aim of this study was to determine the effect of acute high Pi consumption on vascular function in young, healthy women. Eight healthy premenopausal women ingested a high‐Pi drink containing 2,000 mg of phosphorus (23 ± 2 yrs; mean ± SEM). Heart rate (HR) (ECG) and arterial blood pressure (BP) (finger photoplethysmography and automated sphygmomanometer) were measured during a 10 min baseline. FMD was used to assess conduit artery endothelial function and microvascular function was quantified as reactive hyperemic velocity AUC following cuff release. In addition, Pulse Wave Velocity (PWV) was used to assess large artery stiffness. All measures were performed before (pre) and 60 min after (post) Pi drink consumption (a time period our lab has shown to elicit peak elevations in serum phosphate following Pi consumption). Resting mean arterial BP and HR were not different pre‐ vs. post‐ Pi consumption (BP= pre, 80 ± 1; post, 81 ± 2 mmHg; p=0.28; HR= pre, 62 ± 4; post, 62 ± 4 beats/min; p=0.64). In contrast, FMD was significantly attenuated post‐Pi consumption, (pre, 6.7 ± 0.5%; post, 4.8 ± 0.8%; p=0.04), whereas, reactive hyperemic velocity AUC remained unchanged (pre, 2590 ± 488 arbitrary units; post, 2056 ± 221 arbitrary units; p=0.30), indicating that acute high Pi consumption had no effect on microvascular function. In addition, PWV was also unaffected by acute high Pi (p=0.18). Collectively, our preliminary findings suggest that, similar to men, exposure to acute high Pi impairs conduit artery endothelial function, but not microvascular function, in young healthy women.Support or Funding InformationUniversity of Texas at Arlington College of Nursing and Health Innovation

Asymptomatic Bacteriuria and Pyuria in Premenopausal Women.

Asymptomatic bacteriuria and pyuria in healthy women often trigger inappropriate antimicrobial treatment, but there is a paucity of data on their prevalence and persistence. To evaluate the prevalence and persistence of asymptomatic bacteriuria and pyuria in women at high risk of recurrent urinary tract infection, we conducted an observational cohort study in 104 healthy premenopausal women with a history of recurrent urinary tract infection with daily assessments of bacteriuria, pyuria, and urinary symptoms over a 3-month period. The mean age of participants was 22 years, and 74% were white. Asymptomatic bacteriuria events (urine cultures with colony count ≥105 CFU/mL of a uropathogen on days with no symptomatic urinary tract infection diagnosed) occurred in 45 (45%) women on 159 (2.5%) of 6283 days. Asymptomatic bacteriuria events were most commonly caused by Escherichia coli, which was present on 1.4% of days, with a median duration of 1 day (range, 1-10). Pyuria occurred in 70 (78%) of 90 evaluable participants on at least 1 day and 25% of all days on which no symptomatic urinary tract infection was diagnosed. The positive predictive value of pyuria for E. coli asymptomatic bacteriuria was 4%. In this population of healthy women at high risk of recurrent urinary tract infection, asymptomatic bacteriuria is uncommon and, when present, rarely lasts more than 2 days. Pyuria, on the other hand, is common but infrequently associated with bacteriuria or symptoms. These data strongly support recommendations not to screen for or treat asymptomatic bacteriuria or pyuria in healthy, nonpregnant women.

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment.

Breast cancer (BC) is the most common cancer in women worldwide. Approximately 70–80% of BCs express estrogen receptors (ER), which predict the response to endocrine therapy (ET), and are therefore hormone receptor-positive (HR+). Endogenous cannabinoids together with cannabinoid receptor 1 and 2 (CB1, CB2) constitute the basis of the endocannabinoid system. Interactions of cannabinoids with hypothalamic–pituitary–gonadal axis hormones are well documented, and two studies found a positive correlation between peak plasma endogenous cannabinoid anandamide with peak plasma 17β-estradiol, luteinizing hormone and follicle-stimulating hormone levels at ovulation in healthy premenopausal women. Do cannabinoids have an effect on HR+ BC? In this paper we review known and possible interactions between cannabinoids and specific HR+ BC treatments. In preclinical studies, CB1 and CB2 agonists (i.e., anandamide, THC) have been shown to inhibit the proliferation of ER positive BC cell lines. There is less evidence for antitumor cannabinoid action in HR+ BC in animal models and there are no clinical trials exploring the effects of cannabinoids on HR+ BC treatment outcomes. Two studies have shown that tamoxifen and several other selective estrogen receptor modulators (SERM) can act as inverse agonists on CB1 and CB2, an interaction with possible clinical consequences. In addition, cannabinoid action could interact with other commonly used endocrine and targeted therapies used in the treatment of HR+ BC.