Young Premenopausal Women Research Articles

Granzyme B-based cytolytic fusion protein targeting EpCAM specifically kills triple negative breast cancer cells in vitro and inhibits tumor growth in a subcutaneous mouse tumor model

Triple-negative breast cancer (TNBC) is associated with poor prognosis and high prevalence among young premenopausal women. Unlike in other breast cancer subtypes, no targeted therapy is currently available. Overexpression of epithelial cell adhesion molecule (EpCAM) in 60% of TNBC tumors correlates with poorer prognosis and is associated with cancer stem cell phenotype. Thus, selective elimination of EpCAM+ TNBC tumor cells is of clinical importance.Therefore, we constructed a fully human targeted cytolytic fusion protein, designated GbR201K-αEpCAM(scFv), in which an EpCAM-selective single-chain antibody fragment (scFv) is genetically fused to a granzyme B (Gb) mutant with reduced sensitivity to its natural inhibitor serpin B9. In vitro studies confirmed its specific binding, internalization and cytotoxicity toward a panel of EpCAM-expressing TNBC cells. Biodistribution kinetics and tumor-targeting efficacy using MDA-MB-468 cells in a human TNBC xenograft model in mice revealed selective accumulation of GbR201K-αEpCAM(scFv) in the tumors after i.v. injection. Moreover, treatment of tumor-bearing mice demonstrated a prominent inhibition of tumor growth of up to 50 % in this proof-of-concept study. Taken together, our results indicate that GbR201K-αEpCAM(scFv) is a promising novel targeted therapeutic for the treatment of TNBC.

A Retrospective Study Evaluating the Impact of Preoperative Breast MRI on Surgical Decision-Making in Young Patients (≤50 Years) with Invasive Breast Cancer.

INTRODUCTIONBreast magnetic resonance imaging (MRI) is considered a more sensitive diagnostic test for detecting invasive breast cancer than mammography or breast ultrasound. Breast MRI may be particularly useful in younger premenopausal women with higher density breast tissue for differentiating between dense fibroglandular breast tissue and breast malignancies. The main objective of this study was to determine the impact of preoperative breast MRI on surgical decision-making in young women with breast cancer.METHODSA retrospective review of patients with newly diagnosed invasive breast cancer and age of ≤50 years was performed. All patients underwent physical examination, preoperative mammogram, breast ultrasound, and bilateral breast MRI. Two breast cancer surgeons reviewed the preoperative mammogram report, breast ultrasound report, and physical examination summary and were asked if they would recommend a lumpectomy, a quandrantectomy, or a mastectomy. A few weeks later, the two surgeons were shown the same information with the breast MRI report and were asked what type of surgery they would now recommend. In each case, MRI was classified by two adjudicators as having affected the surgical outcome in a positive, negative, or neutral fashion. A positive impact was defined as the situation where breast MRI detected additional disease that was not found on physical examination, mammogram, or breast ultrasound and led to an appropriate change in surgical management. A negative impact was defined as the situation where breast MRI led the surgeon to recommend more extensive surgery, with less extensive disease actually found at pathology. No impact was defined as the situation where MRI findings did not alter surgical recommendations or outcomes.RESULTSOf 37 patients whose charts were reviewed, five patients were deemed to be ineligible due to having received neoadjuvant chemotherapy, having previous breast implants, or having had their tumor fully excised during biopsy. In total, 32 patients met the inclusion criteria of this study and were appropriate for analysis. The median age of our study patient population was 42 years. The pathologic diagnosis was invasive ductal carcinoma in 91% (29/32) of patients and invasive lobular carcinoma in 9% (3/32) of patients. For surgeon A, clinical management was altered in 21/32 (66%) patients, and for surgeon B, management was altered in 13/32 (41%) patients. The most common change in surgical decision-making after breast MRI was from breast-conserving surgery to a mastectomy. Mastectomy rates were similar between both surgeons after breast MRI. After reviewing the pathology results and comparing them with the breast MRI results, it was determined that breast MRI led to a positive outcome in 13/32 (41%) patients. Breast MRI led to no change in surgical management in 15/32 (47%) patients and resulted in a negative change in surgical management in 4/32 (13%) patients. Bilateral breast MRI detected a contralateral breast cancer in 2/32 (6%) patients.CONCLUSIONSPreoperative breast MRI alters surgical management in a significant proportion of younger women diagnosed with breast cancer. Prospective studies are needed to confirm these findings and to help determine if this change in surgical decision-making will result in improved local control.

Abstract A126: Taking out the trash: Efferocytosis in the tumor microenvironment

Abstract We have examined the malignant tumor microenvironment (TME) from a perspective that is often noted but overlooked: tissue repair. It has long been observed that tumors resemble ‘wounds that do not heal,’ but the reasons remain obscured. We found that macrophages in the tumor microenvironment orchestrate wound healing and immune tolerance in response to tumor cell death, a feature common to all solid tumors. We used genetic and pharmacological methods to block macrophage-mediated engulfment of dying tumor cells, a process referred to as efferocytosis. We found that MerTK-mediated efferocytosis of dying tumor cells induces macrophage-mediated production of Th2-like cytokines, including IL-4, IL-13, IL-10, and TGF-beta. Blockade of the receptor tyrosine kinase MerTK through pharmacological tyrosine kinase inhibition or through genetic MerTK abalation blocked macrophage-mediated efferocytosis in the tumor microenvironment, impairing M2-like macrophage polarization and expression of Th2-like cytokines in the tumor microenvironment. Because cell death is a major histological feature of the breast during post-partum involution of milk-producing breast epithelia, we studied the impact of MerTK-mediated efferocytosis in a model of post-partum breast cancer (ppBC). Currently, ppBC accounts for nearly 25% of all breast cancers in young (pre-menopausal) women. In contrast to breast cancers diagnosed during pregnancy, which correlate with a favorable prognosis, ppBCs are highly aggressive, metastatic, and life-threatening, even when corrected for molecular breast cancer subtype and for the age of the woman at diagnosis. We used genetic and pharmacological methods to block MerTK-mediated efferocytosis in ppBCs, demonstrating that efferocytosis increased ppBC metastasis by nearly 10-fold, but that genetic or pharmacological MerTK inhibition markedly decreased metastasis in ppBCS. Similarly, targeted inhibition of efferocytosis-induced cytokines, including TGF-beta, substantially reduced metastasis of efferocytosis-competent ppBCs. Collagen deposition, TReg expansion, and Th2 cytokine upregulation were found to be dependent on efferocytosis-induced TGF-beta signaling. These findings in ppBC, in which widespread tumor cell death was initiated by physiological post-partum involution, prompted our interest in the impact of therapeutically-induced cell death and subsequent efferocytosis on pro-malignant leukocyte behaviors in the tumor microenvironment. As many as 70-80% of primary breast tumors treated with cytotoxic chemotherapy show a partial response in the pre-surgical (neoadjuvant) setting, and lack of a pathological complete response (pCR) is a strong predictor of tumor recurrence following surgical tumor excision. We tested the hypothesis that efferocytosis, the immune system's inherent response to cell death, results in tumor repair (increased ‘wound healing’) in response to cytotoxic treatment. In support of this hypothesis, a single dose of doxorubicin or lapatinib induced a transient wave tumor cell death within 24 hours, followed at post-treatment day 4 with increased M2 macrophages and TRegs within the tumor microenvironment, and increased expression of Th2-like cytokines. Importantly, increased metastases were seen in tumor-bearing mice treated once with doxorubicin over what was seen in untreated mice. However, targeted inhibition of efferocytosis using a MerTK kinase inhibitor (TKIs) in combination with doxorubicin blocked expression of Th2-like cytokines, limited the number of M2-like macrophages in the tumor microenvironment, and prevented therapy-enhanced tumor metastasis. These findings support continued investigation into the role of MerTK and efferocytosis in therapeutic tumor responses. Note:This abstract was not presented at the conference. Citation Format: Rebecca S. Cook. Taking out the trash: Efferocytosis in the tumor microenvironment. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A126.

Endometrial adenocarcinoma in a 13-year-old girl

Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature.

Using the health belief model to predict breast self examination among Saudi women.

BackgroundIn the Kingdom of Saudi Arabia, breast cancer (BC) usually presents at advanced stages and more frequently in young pre-menopausal women in comparison to western countries. There is controversy surrounding the efficacy of breast self examination (BSE) for early detection of BC in countries where other methods are available. This study aims to explore the perception towards breast cancer and towards BSE among Saudi women, using the Health Belief Model (HBM).MethodsA convenient sample of adult Saudi female employees, working at King Abdulaziz Medical City, Riyadh, Saudi Arabia (n = 225), and their non-working adult female family members (n = 208), were subjected to the Arabic version of revised Champion’s Health Belief Model Scale (CHBMS) and the Arabic version of Breast Cancer Awareness Measure (CAM), to assess their knowledge and attitude on BC respectively. Percentage mean score (PMS) for each HBM domain was calculated. Significant predictors of BSE practice were identified using logistic regression analysis and significance was considered at p < 0.05.ResultsThe majority of women heard about BSE (91.2 %), only 41.6 % reported ever practicing BSE and 21 % performed it regularly. Reported reasons for not doing BSE were: not knowing how to examine their breast (54.9 %), or untrusting themselves able to do it (24.5 %). Women were less knowledgeable about BC in general, its risk factors, warning signs, nature and screening measures (PMS:54.2 %, 44.5 %, 61.4 %, 53.2 %, 57.6 % respectively). They reported low scores of; perceived susceptibility, seriousness, confidence and barriers (PMS: 44.8 %, 55.6 %, 56.5 % & 41.7 % respectively), and high scores of perceived benefits and motivation (PMS: 73 % & 73.2 % respectively) to perform BSE. Significant predictors of BSE performance were: levels of perceived barriers (p = 0.046) and perceived confidence (p = 0.001) to BSE, overall knowledge on BC (p < 0.001), work status (p = 0.032) and family history of BC (p = 0.011).ConclusionsSaudi women had poor knowledge on BC, reported negative attitude towards BSE and their practice was poor. Working women and those with family history of BC, higher perceived confidence and lower perceived barriers on HBM, and those with high level of knowledge on BC were more likely to perform BSE. Breast awareness as an alternative to BSE needs further investigations. HBM was shown as a valid tool to predict BSE practice among Saudi women.

Osteoporosis in Gastrointestinal Diseases.

Secondary osteoporosis occurs as an isolated pathology or co-exists with types I and II osteoporosis. The gastroenterologist may come across osteoporosis or osteopenia in a patient with a gastrointestinal disease. This is often a young patient in whom investigations should be carried out and appropriate treatment initiated, aimed at preventing bone fractures and the formation of the best peak bone mass. Osteoporosis occurs in patients with the following conditions: Crohn's disease, ulcerative colitis, celiac disease, post gastrectomy patients, patients with short bowel syndrome, chronic hepatitis and cirrhosis, treated with steroids (steroid-induced osteoporosis) and patients using proton pump inhibitors chronically (state of achlorhydria). It is therefore necessary to approve a list of risk factors of secondary osteoporosis, the presence of which would be an indication for screening for osteoporosis, including a DXA study and the development of a separate algorithm for the therapeutic management of secondary osteoporosis accompanying gastrointestinal diseases, especially in premenopausal young women and young men, because there are currently no registered drugs with proven antifracture activity for this group of patients.

Status of the pelvic floor in young primiparous women.

To investigate the postnatal prevalence of sonographically diagnosed pelvic floor trauma, and the correlations with various antenatal/intrapartum predictors in primiparous women. This was a prospective cohort study performed in a tertiary hospital with 9000 deliveries per annum. Of those invited, 202 (23.2%) primiparous participants were assessed clinically at least 1 year after delivery by Pelvic Organ Prolapse Quantification (POP-Q), two/three-dimensional transperineal sonography and quantification of serum collagen type III levels. There was a high prevalence of clinically significant pelvic organ prolapse (POP) on POP-Q staging: uterine prolapse, 63%; cystocele, 42%; and rectocele, 23%. Ballooning of the levator ani muscle (LAM) hiatus was detected in 33% and LAM avulsion in 29% of participants, with partial LAM avulsion occurring in 15% and complete avulsion in 14%. Postnatal POP symptoms (odds ratios (ORs) given here for presence of multiple prolapse symptoms) were positively associated with similar prepregnancy symptoms (OR, 7.2 (95% CI, 1.19-44.33)), LAM avulsion (OR, 4.8 (95% CI, 1.99-11.34)) and forceps delivery (borderline significance; OR, 1.8 (95% CI, 0.96-3.25)) and negatively associated with elective (OR, 0.2 (95% CI, 0.09-0.63)) and emergency (OR, 0.3 (95% CI, 0.12-0.83)) Cesarean section. LAM abnormality was associated with forceps delivery (OR, 4.9 (95% CI, 1.44-16.97)) and prolapse (OR, 6.8-11.7 (95% CI, 2.34-78.51)), whereas collagen levels did not play a role (OR, 1.001 (95% CI, 0.99-1.02)). Clinically significant POP was common in relatively young premenopausal primiparous women. Partial or full levator avulsion was seen in 29% of participants and was associated with POP and related symptoms. Congenital factors seem to play little role in the etiology of LAM trauma, and the main risk factor seems to be forceps delivery. Avoidance of difficult vaginal deliveries may prevent severe pelvic floor trauma.

Sociodemographic Factors Related to Quality of Life Among Premenopausal Women in Ibadan, Nigeria

Quality of life (QoL) of premenopausal women (PW) was assessed using primary data collected between September and December 2011. A 26-item questionnaire (WHO-QoL BREF) was administered to 285 apparently healthy women selected from two local government areas in Ibadan. The scores were categorized into poor (≤79.53) and good (>79.53) QoL. Multiple logistic regressions were used to study factors associated with QoL. The mean score for the overall QoL (OQoL) was 65.18 ± 11.35 (range = 81.25). The Cronbach’s alpha for all domains as well as the OQoL were within an acceptable range. The proportion of women with good OQoL was significantly higher in the urban areas (18.2 percent) than in the rural areas (9.2 percent) (p < .05). The proportion of respondents with good OQoL was significantly higher for women aged <20 years (37.5 percent) than older women (p < .01). Teenage participants were almost ten times as likely to have a good social relationship than participants above 35 years of age (odds ratio: 9.52; 95% confidence interval: 1.83–49.40). The authors’ results suggest that the WHO-QoL BREF is a reliable instrument for measuring QoL among PW in Nigeria. Younger PW and women in the urban areas were more likely to have good QoL.

Efficacité d’un dispositif médical à base d’acide hyaluronique liposomé contre la sécheresse vulvo-vaginale

ObjectivesHyaluronic acid (HA) is present in the vulval and vaginal conjonctive tissue. It possesses hydrating and healing properties and is indicated to treat menopause induced vulvo-vaginal atrophy. The goal of this study is to evaluate the efficacy of a medical device containing liposomal HA upon patients of different ages suffering from vulvo-vaginal dryness (VVD). MethodsTested product Mucogyne® was applied 3 times a week for 84 days by 47 patients, 28 premenopausal young women (mean age: 32 years old) and 19 post-menopausal women (mean age: 57.5 years old) all suffering from VVD associated to spontaneous pain and dyspareunia. Clinical evaluations and Vaginal Health Index (VHS) were calculated at 0, 1 and 3 months. ResultsA significant clinical improvement (P<0.001) occurred at 1 month (−25 % for dryness and −46 % for pain) and at 3 months (respectively −86 and −79 %). VHS was significantly improved (P<0.001) from 30 % at 1 month to 72 % after 3 months. ConclusionLiposomal AH significantly decreases symptoms and clinical signs of VVD at all ages and represents a safe and efficient alternative to topical and/or systemic hormonal therapy after menopause.

Abstract P4-04-02: Cell death and efferocytosis generate a pro-metastatic landscape during mammary gland involution that increase dissemination of post-partum breast cancers

Abstract Although pregnancy at a young age decreases a woman’s lifetime breast cancer risk, the first five years following a pregnancy at any age are associated with increased breast cancer risk, a risk that continues to increase with age. Given societal trends to postpone child-birth later into women’s lives, the incidence of malignant post-partum breast cancer is expected to increase. Currently, breast cancers diagnosed 2-5 years post-partum account for nearly 25% of all pre-menopausal breast cancers. Importantly, breast cancers diagnosed 2-5 years post-partum are diagnosed more frequently as metastatic disease and correlate with decreased disease-free survival (DFS) versus breast cancers occurring in other young pre-menopausal women. In contrast, many studies show that breast cancers diagnosed during pregnancy do not correlate with decreased DFS, although there remains some debate about this conclusion. The observation that post-partum breast cancers correlate with reduced DFS suggests that events occurring in the post-partum breast augment the malignant severity of tumors existing therein. This hypothesis is supported by studies in which breast cancer cells transplanted into involuting mouse mammary fatpads grow and invade more rapidly than cells transplanted into mammary glands of nulliparous mice, demonstrating a unique mammary micro-environment during involution versus other reproductive stages. We aimed to study how the changing landscape of the post-partum breast accelerates cancer progression. Although the molecular mechanisms underlying the malignant severity of post-partum breast cancers (ppBCs) are unclear, they relate to stromal wound healing events during post-partum involution, a dynamic process characterized by widespread cell death in milk-producing mammary epithelial cells (MECs). Using both spontaneous and allografted mammary tumors in fully immune-competent mice, we discovered that post-partum involution increased mammary tumor metastasis 10-fold. Widespread cell death occurred not only in MECs, but also in tumor epithelium. Dying tumor cells were cleared through MerTK-dependent efferocytosis, which robustly induced transcription of wound healing cytokines interleukins (IL)-4, -10, and -13, and transforming growth factor (TGF)-beta. Genetic models of MerTK ablation and pharmacologic MerTK inhibition impaired efferocytosis in post-partum tumors, reduced M2-like macrophages without altering total macrophage levels, decreased TGF-beta expression and reduced post-partum tumor metastasis to levels seen in nulliparous mice. TGF-beta blockade reduced post-partum tumor metastasis. These data suggest that widespread cell death during post-partum involution triggers efferocytosis-induced wound healing cytokines in the tumor microenvironment that promote metastatic tumor progression. Citation Format: Rebecca S Cook, Shelton Earp, Jamie Stanford. Cell death and efferocytosis generate a pro-metastatic landscape during mammary gland involution that increase dissemination of post-partum breast cancers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-02.

Circuit resistance training attenuates acute exertion-induced reductions in arterial function but not inflammation in obese women.

Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response. Eighteen obese [body mass index (BMI) 30.0-40.0 kg · m(-2)] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed. Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics. This study shows that CRT alleviates acute exertion-induced reductions in endothelial function among obese sedentary women in the absence of changes in inflammation.

Respiratory symptoms, lung function decrement and chronic obstructive pulmonary disease in pre-menopausal Indian women exposed to biomass smoke

Background: The impact of chronic exposure to smoke from biomass burning on respiratory health has been examined.Methods: Six-hundred and eighty-one non-smoking women (median age 35 years) from eastern India who cook exclusively with biomass (wood, dung and crop residues) and 438 age-matched women from similar neighborhood who cook with liquefied petroleum gas (LPG) were examined. Pulmonary function test was done by spirometry. The concentrations of particulate matter having diameter of < 10 µm (PM10) and < 2.5 µm (PM2.5) in indoor air was measured by real-time aerosol monitor.Results: Compared with LPG users, biomass users had greater prevalence of upper (50.9 versus 28.5%) and lower respiratory symptoms (71.8 versus 30.8%) and dyspnea (58.4 versus 19.9%). They showed reduction in all parameters measured by spirometer especially in mid-expiratory volume. PM10 and PM2.5 concentration in biomass using kitchen were 2–3-times more than LPG-using kitchen, and the decline in spirometry values was positively associated PM10 and PM2.5 levels in indoor air after controlling education, family income and kitchen location as potential confounders. Overall, 29.7% of biomass users and 16.4% of LPG users had deficient lung function, and restrictive type of deficiency was predominant. Chronic obstructive pulmonary disease (COPD) was diagnosed in 4.6% of biomass and 0.9% of LPG users. Women who predominantly used dung cake and did not possess separate kitchen had poorer lung function.Conclusion: Cumulative exposure to biomass smoke causes lung function decrement and facilitates COPD development even in non-smoking and relatively young pre-menopausal women.

Markers of subclinical atherosclerosis in premenopausal women with vitamin D deficiency and effect of vitamin D replacement

Background: Recent studies have revealed a relationship between vitamin D deficiency and atherosclerosis. This study aims to investigate the impact of vitamin D deficiency and replacement on markers of subclinical atherosclerosis in young premenopausal women in whom vitamin D deficiency is prevalent. Methods: Thirty-one premenopausal vitamin D deficient women and 27 age and gender-matched control subjects were enrolled in this study. Markers of subclinical atherosclerosis including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD), endothelial progenitor cell (EPC) count and cytokine levels were determined at baseline. All measurements were repeated at 6-month follow-up in vitamin D-deficient subjects after vitamin D replacement. Results: Vitamin D deficient premenopausal women had lower FMD (9.9 ± 1.3 vs. 13.8 ± 1.7%, p < 0.001) and EPC counts at baseline. This population also had lower IL-10 and higher IL-17 levels. A 6-month vitamin D replacement therapy resulted in a significant increase in FMD (9.9 ± 1.3 vs. 11.4 ± 1.4%, p < 0.001) and EPC counts. Furthermore, cytokine profile shifted toward a more anti-inflammatory phenotype including elevated IL-10 and decreased IL-17 levels. cIMT was not different between patient and control groups and did not change following vitamin D replacement. Change in 25(OH)D and IL-17 levels were independent predictors of the change in FMD measurements following vitamin D replacement. Conclusion: This study demonstrates that endothelial function is impaired in otherwise healthy vitamin D deficient young premenopausal women and improves with 6-month replacement therapy. Immune-modulatory effects of vitamin D may, at least partly, be responsible for its beneficial effects on vascular health.

Past sporting activity during growth induces greater bone mineral content and enhances bone geometry in young men and women

We aimed to determine the effect of past sporting activity on bone mineral content (BMC), areal bone mineral density (aBMD) in the lumbar spine and proximal femur, and bone geometry of the mid femur in young men and women. We assessed 142 subjects, comprising 79 young men (21.2±0.8years) and 63 premenopausal young women (21.4±0.6years). The subjects were classified into three groups, two on the basis of the age of starting to participate in sport [elementary school starters (6-12years), junior high school to university starters (13-22years)], and the third group had no participation in sport. We measured BMC and aBMD by dual-energy X-ray absorptiometry (DXA) in the lumbar spine and proximal femur, and bone geometric characteristics of the mid femur by magnetic resonance imaging (MRI), and calculated the osteogenic index (OI) of previous sporting activity. The OI correlated significantly with many MRI-determined measures of bone geometry; DXA-measured BMC and aBMD were effective indicators of previous sporting activity in both sexes. The female elementary school starters had significantly greater femoral mid-diaphyseal perimeters (vs the no-sport group), bone cross-sectional area (vs the 13-22-year-old starters and the no-sport group), and maximum and minimum second moment of area at the mid-diaphysis point of the femur (vs the no-sport group). The OI is a proven practicable and useful index. DXA- and MRI-determined geometric characteristics showed that high-impact, weight-bearing exercise before and in early puberty induces greater total proximal femur BMC and enhances femoral mid-diaphyseal size and shape, and that these benefits persisted in young adult women.

Forearm vasodilator responses to a β-adrenergic receptor agonist in premenopausal and postmenopausal women.

Beta‐adrenergic vasodilator responses may be blunted in humans who are at an increased risk for hypertension. Because menopause is associated with an increase in blood pressure, we tested the hypothesis that forearm blood flow responses to the β‐adrenergic receptor agonist isoproterenol are blunted in older, postmenopausal women compared to young, premenopausal women. We used venous occlusion plethysmography to measure forearm blood flow in young premenopausal (26 ± 1 years; n = 13) and postmenopausal (61 ± 2 years; n = 12) women. Forearm blood flow and mean arterial pressure were measured at baseline and during isoproterenol infusion at 1.0, 3.0, 6.0, and 12.0 ng/100 mL tissue/min. The two groups did not differ in body mass index or mean arterial pressure. Baseline forearm blood flow was similar between young and postmenopausal women (3.7 ± 0.5 vs. 2.9 ± 0.4 mL/100 mL tissue/min, respectively; P > 0.05). At the lowest dose of isoproterenol, forearm blood flow vasodilator responses were lower in postmenopausal women compared with young women (5.8 ± 0.4 vs. 7.4 ± 0.3 mL/100 mL tissue/min, respectively; P < 0.05). Thereafter, forearm blood flow remained similar between the groups for the remaining isoproterenol doses. In conclusion, β‐adrenergic receptor‐mediated forearm vasodilator responses are blunted in healthy, older postmenopausal women at lower but not higher doses of isoproterenol. This suggests that in aging women, β‐adrenergic receptor‐mediated vasodilator responses may be blunted at a moderate level of stimulation while maximum receptor responses are preserved.

SAT0486 Reference Intervals for Bone Turnover Markers in Spanish Premenopausal Women

BackgroundBone turnover markers (BTMs) are used in clinical practice for assessing patients with osteoporosis and their treatment. In Spain it is necessary to fine-tune the reference intervals, since they were...

Incidence of Chemotherapy‐Induced Ovarian Failure in Premenopausal Women Undergoing Chemotherapy for Breast Cancer

Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients. This study's aim was to find the incidence of chemotherapy-induced ovarian failure (CIOF) and reversible amenorrhea in premenopausal non-metastatic breast cancer patients. This mixed retrospective and prospective study follows premenopausal breast cancer patients receiving chemotherapy between 2008 and 2012. Patients in the prospective arm were followed up with menstrual history and serum ovarian hormones (follicle-stimulating hormone [FSH] and estradiol) until 1 year post-chemotherapy, and patients in the retrospective arm were contacted for their menstrual history. The mean age of the 102 subjects was 43.3 years. Of the patients, 93.1 and 77.9 % were amenorrheic at completion of chemotherapy and at 12 months post-chemotherapy, respectively. Of those who developed amenorrhea, 24.6 % regained menstruation, on average after 7.86 (range 1-15) months post-chemotherapy. Age was the only statistically significant risk factor. CIOF and reversible amenorrhea was 57 and 50 % at <35 years, 95 and 31.6 % at 35-45 years, and 97.9 and 14.9 % at >50 years, respectively. The 33 prospective patients' estradiol and FSH levels seem to correlate well with onset of amenorrhea, with a falling estradiol and rising FSH trend. Tamoxifen use was associated with elevated estradiol levels 1 year post-chemotherapy. This study found a high incidence of CIOF, with a relatively low rate of reversible amenorrhea. Premenopausal patients should be counselled prior to treatment and education and support provided.

Characteristics of Men and Premenopausal Women With Burning Mouth Symptoms: A Case–Control Study

To identify possible clinical differences between male, premenopausal, and postmenopausal female patients with burning mouth symptoms. Burning mouth symptoms are known to occur predominantly in postmenopausal women. In some rare cases, however, such symptoms may also appear in men and younger premenopausal women. There is no information on the characteristics of male and premenopausal female patients with burning mouth symptoms. A total of 22 male patients (no age limit) and 19 relatively younger premenopausal female patients (age: ≤45 years) with a burning sensation in the mouth without any visible signs of oral mucosal diseases were included in the experimental groups. Sixty burning mouth patients (postmenopausal females, age: ≥50 years) without oral mucosal diseases were included as a typical older postmenopausal group for comparison. All individuals in the 3 groups were subjected to clinical evaluations including an interview, a comprehensive questionnaire, a simplified psychological evaluation (Symptom Checklist-90-Revision [SCL-90-R]), blood tests, and a measurement of salivary flow rate. The male group reported taste problems less commonly (40.9%, P = .009) and less severely (median visual analog scale [VAS] = 0.00, P = .004) than the postmenopausal group (73.3%, median VAS = 4.50). The younger premenopausal group complained of paresthesia more commonly (68.4%, P = .006) and more severely (median VAS = 0.50, P = .007) than the postmenopausal group (30.0%, median VAS = 0.00). The male group (81.8%) reported discomfort of the tongue less commonly than the postmenopausal group (100.0%, P = .004). The percentage of patients with a symptom triad of oral mucosal pain, dysguesia, and xerostomia was significantly higher in the premenopausal (73.7%, P = .005) and postmenopausal (60.0%, P = .012) groups than the male group (27.3%). The flow rate of unstimulated whole saliva was significantly higher in the premenopausal group (0.27 ± 0.18 mL/min) than the postmenopausal group (0.17 ± 0.16 mL/min, P = .006). None of the 9 symptom dimensions of the SCL-90-R were significantly different among the 3 groups. The percentage of patients with abnormal blood tests and taking medications due to comorbid diseases was the lowest in the premenopausal group. Male and premenopausal female patients with burning mouth symptoms showed different characteristics compared with typical postmenopausal female patients.

Pulmonary Benign Metastasizing Leiomyoma: An Extremely Rare Case.

Benign metastasizing leiomyoma is typically seen in young premenopausal women after a mean period of 15 years following uterine leiomyoma or hysterectomy surgery. They are usually incidentally seen on chest x-rays and are nodular lesions that appear as bilateral nodules with a benign appearance and consist of smooth muscle proliferation. A 44-year-old female presented at her healthcare institution for backache for the last 9 months. Multiple nodules (largest 15 mm) scattered in both lungs and consistent with metastases were detected on computed tomography. The PET-CT results revealed multiple nodular densities with increased metabolic activity (SUVmax: 1.92) in both lungs, with the largest one measuring approximately 15 mm and located in the lower lobe superior segment of the right lung. A benign metastasizing leiomyoma was diagnosed with open wedge biopsy of the lung. We present this case due to its interesting clinical presentation and rarity and emphasize the pathogenesis.

Lymphangioleiomyomatosis: A rare case report

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown etiology that traditionally affects young women of child bearing or premenopausal age. It is characterized by proliferation of atypical smooth muscle cells, preferentially along bronchovascular structures that causes progressive respiratory failure. Due to its unusual and nonspecific presenting symptoms, patients often receive missed or delayed diagnosis. This disease occurs sporadically or in association with the genetic disease tuberous sclerosis complex (TSC). We present 34-year-old young premenopausal woman with LAM.