Effects of menstrual cycle on background parenchymal enhancement and detectability of breast cancer on dynamic contrast-enhanced breast MRI: A multicenter study of an Asian population.

PURPOSE: To evaluate the effect of the menstrual cycle on BPE and cancer detectability in an Asian population. MATERIAL AND METHODS: 266 premenopausal patients with regular menstrual cycles from 24 centers were included, and 176 of them were diagnosed by pathology as having breast cancer. Thirty-five patients were examined in the menstrual phase (days 1-4), 105 in the proliferative phase (days 5-14), and 126 in the secretory phase (days 15-30). Measurement of the following signal intensities (SIs) were obtained: breast tissue on the unaffected side on a pre-contrast image (SI1) and an early-phase image (SI2); the SIs of breast tissue on the affected side on a pre-contrast image (SI3) and an early-phase image (SI4); and the SIs of breast cancer on a pre-contrast image (SI5) and an early-phase image (SI6). We calculated the BPE ratio, i.e., (SI2- SI1)/SI1 and the cancer/background enhancement ratio (C/B) ratio, i.e., (SI6- SI5) / (SI4- SI3). The BPE was classified as minimal, mild, moderate, or marked, and the cancer detectability was classified as excellent, good, or poor independently by two radiologists. RESULTS: The average C/B ratio was 20.1, 15.7, and 9.1 at the menstrual, proliferative, and secretory phases (p < 0.001). BPE was determined as moderate or marked in 0% and 5.4% at the menstrual phase, 10.3% and 11.0% at the proliferative phase, and 17.5% and 21.7% at the secretory phase by the two observers, respectively (p = 0.01, p = 0.01). The detectability of breast cancer was classified as poor in 0% and 0%, 1.4% and 13.0%, and 8.0% and 22.1% at the menstrual, proliferative, and secretory phases by the two observers, respectively (p = 0.07, p = 0.02). CONCLUSION: The menstrual phase and the proliferative phase seem to be suitable for breast MRI of Asian women.

Menstrual Cycle Hormone Changes in Women Traversing Menopause: Study of Women's Health Across the Nation.

Context: Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. Objective: To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation Daily Hormone Study (DHS). Design: DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. Setting: Seven sites across the United States. Participants: A total of 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. Intervention: Time-to-FMP measurement. Main Outcome Measures: Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle, and segment integrated urinary luteinizing hormone, follicle-stimulating hormone, estrone conjugates, and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Results: Mean menstrual cycle length was remarkably preserved at 26 to 27 days in ELA cycles; non-ELA cycles had greater variability. The percentage of cycles that were ELA remained high until 5 years before the FMP (87.9%); only 22.8% of cycles within 1 year of the FMP were ELA. Whole cycle hormones remained relatively stable up to 3 years before the FMP, when gonadotropins began to increase. Pdg excretion declined slowly with progress to the FMP, but Pdg patterns of ELA cycles remained distinguishable from non-ELA. Conclusions: Menstrual cycle hormone patterns in perimenopausal women resemble those of midreproductive-aged women until 5 years before menopause, and presumably ovulatory cycles retain a potentially fertile pattern up to the end of reproductive life.

Circulating androgens and SHBG during the normal menstrual cycle in two ethnic populations.

The objective of this study was to study possible ethnic differences in steroid hormones and sex hormone-binding globulin (SHBG) during the menstrual cycle. Serum levels of the ovarian steroids estradiol (E2) and progesterone (P) and of follicle-stimulating hormone (FSH), luteinizing hormone (LH), SHBG, dehydroepiandrosterone (DHEA) and testosterone (T-ria) were all measured by immunoassay during the menstrual cycle in 15 Swedish and 11 West Asian regularly menstruating women. Testosterone (T-ms) was also measured by LC-MS/MS and so were 4-androstene-3,17-dione (A-4) and 17-alpha-hydroxyprogesterone (17-OHP). There were no ethnic differences in levels of ovarian steroids, gonadotrophins, A-4, 17-OHP and T-ms. DHEA were significantly higher and SHBG significantly lower in West Asian than in Swedish women. Surprisingly, T-ria was significantly higher in West Asian than in Swedish women and higher than T-ms (47% in Swedish and 107% in West Asian women). The difference (T-ria - T-ms) showed strong positive correlations to DHEA in the total and in West Asian but not in Swedish women, indicating an influence of DHEA/DHEAS metabolites on the T-ria results. In conclusion, ethnic differences in cross reacting steroids may cause erroneous results in one ethnic group by a steroid immunoassay having reasonable specificity in another. The reasons for the lower SHBG and the higher DHEA levels in West Asian women are not known. The results raise the question about establishing different reference values for certain analytes in different ethnic groups.

Influence of race/ethnicity, body mass index, and proximity of menopause on menstrual cycle patterns in the menopausal transition: the Study of Women's Health Across the Nation.

OBJECTIVE: Few studies have evaluated factors that influence menstrual cycle length (MCL) during the menopausal transition (MT), a life stage during which very long cycles become more likely to occur. The objective of this article was to assess how body mass index and race/ethnicity--factors associated with MCL in young women--influence MCL during the MT. METHODS: Study of Women's Health Across the Nation menstrual calendar substudy data of African-American, white, Chinese, and Japanese women were available for three sites (southeastern Michigan, Los Angeles, and northern California). Self-recorded monthly menstrual calendars with end-of-the-month questions on hormone therapy use and smoking were collected from 1996 to 2006. Height and weight were measured at annual study visits. We used quantile regression to model MCL at the 25th, 50th, 75th, and 90th percentiles with bootstrap sampling to construct 95% CIs. Models evaluated MCL with time indexed to the start of the MT (n = 963) and to the final menstrual period (n = 431). RESULTS: During the MT, increases in MCL occurred mostly at the right tail of the distribution, reflecting a lengthening of long menstrual cycles, not of the median MCL. After adjustment for smoking, education, physical activity, and time, Chinese and Japanese women had 1 day to 6 days longer MCLs compared with white women. Obese women had 1 day to 5 days longer MCLs compared with nonobese women. CONCLUSIONS: As occurs in younger women, menstrual characteristics during the MT are influenced by race/ethnicity and obesity. The long menstrual cycles characteristic of the MT are longer in obese women and in Chinese and Japanese women.

In the secretory endometria of women, luminal epithelia exhibit gene and protein expressions that differ from those of glandular epithelia.

OBJECTIVE: To characterize the transcriptome of luminal epithelia (LE) of fertile secretory endometria and compare the results with those from glandular epithelia (GE). DESIGN: Endometrial samples were collected at 2 and 7 days after initial blood LH surge in separate menstrual cycles. LE were obtained with the use of laser microdissection. mRNA was amplified with the use of linear polymerase chain reaction and hybridized to Agilent 4×44 microarrays. Gene analysis was used to identify differentially expressed mRNAs. Immunohistochemistry was used to assess nine proteins. SETTING: One IVF clinic. PATIENT(S): Seven Caucasian fertile cycling women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycle dating with the use of blood endocrinologic markers, microarrays of laser-microdissected LE, immunohistochemical analysis. RESULT(S): One hundred sixty-one (of 401) differentially expressed mRNAs in LE were identified from the metabolism pathway. Increased selective protein expression in LE at 7 days after initial LH surge was observed. LE mRNA expression was the converse of that in GE. The two cell types each had a different significant biologic pathway identified. CONCLUSION(S): Our results introduce a new concept that LE differentially expressed mRNAs are in the converse direction to that of GE, indicating different biologic processes despite the GE being continuous with the luminal monolayer. This probable distinction of biologic roles has not been noted previously. Further investigations must take cognizance of this observation.

Edad de menarquia y ascendencia indígena: Un estudio poblacional en Chile / Age at menarche and indigenous ancestry: A population study in Chile

Background: The age at menarche may influence decisively health and disease in women. It also indicates the beginning of the reproductive period and, as a consequence, the possibility of biological continuity for the human species. Genetic and environmental determinants define the age of menarche and can explain differences found among different populations. Aim: To determine the age at menarche among adolescents with different levels of indigenous descent (parental indigenous surnames), considering the effect of socioeconomic and demographic factors. Material and Methods: An observational study of historic cohorts of8.624 girls from the Arauca-nía Region (central-southern Chile) was carried out. Data were collected by health professionals using a previously validated questionnaire. Occurrence of menarche was estimated through survival analysis and compared between groups (according to indigenous parental surnames) adjusted for parents' income and educational level and provenance (rural/urban). Results: Estimated median age of menarche was 151 months (95% Cl: 150-151). In female with four indigenous surnames, menarche occurred two months later than girls without indigenous surnames and with two indigenous surnames (p < 0,001). In girls whose parents had lowest level of schooling, the difference increased to eight months later (p < 0,005). Conclusions: Age at menarche in the group with higher indigenous descent is later even if socio-economic conditions remain stable. Genetic factors might play an important role, however conditions of vulnerability can influence and further delay the onset of reproductive competency.

Serum leptin concentrations during the menstrual cycle in Iranian healthy women.

Leptin, a circulating 16-kd polypeptide consisting of 167 amino acids, appears to be involved in the body weight homeostasis. Moreover leptin plays an important role for the reproductive system, early embryogenesis, and fat metabolism during pregnancy and puberty. Significant correlations have been found between leptin and sexual hormones, which is a cytokine and has hormonal properties. The aim of this study was to determine serum leptin levels during the menstrual cycle, and the association between serum leptin and reproductive hormones in young, healthy Iranian women. 42 healthy women volunteered for the study. They all had regular menstrual cycles, with cycle length varying between 26 and 32 days. None of them used oral contraceptives. All were of normal weight, with body mass index ( BMI) < 25 Kg/m2. Fasting blood samples were collected during the follicular phase, mid cycle and luteal phase of the menstrual cycle. FSH and LH were measured with coated tube immunoradiometric assay. Estrogen and progesterone were measured using antibody -coated tubes. Serum Leptin concentration were measured by Leptin (sandwich) ELISA. In menstruating women, serum leptin increased from 13.15+/-1.60 ng/ml in the early follicular phase to 16.57+/-1.68 ng/ml (P<0.01) at the luteal phase. Serum leptin concentration negatively correlated with LH and progesterone (P<0.05). Mean serum leptin levels correlated with body mass index (BMI) (r =0.78, P<0.001).

Helping midlife women predict the onset of the final menses: SWAN, the Study of Women's Health Across the Nation.

OBJECTIVE: Women approaching menopause often ask their doctors, "When are my periods going to end?" The objective of this study was to predict time to the final menstrual period (FMP). DESIGN: This multiethnic, observational cohort study, the Study of Women's Health Across the Nation, has been ongoing since 1996. Data collected from seven annual study visits were used. The community-based cohort from seven national sites included 3,302 white, African American, Hispanic, Chinese, and Japanese women aged 42 to 52 years at baseline with a uterus and at least one ovary, who were not pregnant or taking reproductive hormones, and had at least one menstrual period within the past 3 months at baseline. The time to the FMP was defined retrospectively after 12 months of amenorrhea. Uni- and multivariable Cox proportional hazard models, hazard ratios (HRs), and 95% CIs were computed for variables of interest. RESULTS: A total of 2,662 women, of whom 706 had an observed FMP, were included. Age, menstrual cycles that had become farther apart (HR = 2.56, 95% CI = 1.94-3.39) or more variable (HR = 1.79, 95% CI = 1.45-2.21), and current smoking (HR = 1.68, 95% CI = 1.35-2.08) were all associated with shorter time to the FMP. Higher (log) follicle-stimulating hormone (HR = 2.32, 95% CI = 2.02-2.67) was related to a shorter time to the FMP, but the highest estradiol category (>or=100 pg/mL [367 pmol/L]) was associated with an earlier onset of the FMP (HR = 2.16, 95% CI = 1.63-2.89). The number of vasomotor symptoms was related to an earlier FMP, whereas higher physical activity and educational levels were associated with a later FMP. CONCLUSIONS: Age, menstrual cycle recall, smoking status, and hormone measurements can be used to estimate when the FMP will occur, allowing for more precise estimates for older midlife women: in the most extreme cases, ie, age 54, high estradiol level, current smoking, and high follicle-stimulating hormone level, the FMP can be estimated to within 1 year.

Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of Women's Health across the Nation (SWAN) Daily Hormone Study.

The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women. The Study of Women's Health across the Nation (SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42-52 yr at baseline. All participants are seen annually to assess a variety of endpoints. A subcohort of 848 women undergoes further investigation of their daily patterns of reproductive hormones in the Daily Hormone Study (DHS). DHS enrollees annually complete a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 d (whichever comes first). Chemiluminescent assays measured urinary LH and FSH, as well as metabolites of estradiol [estrone conjugates (E1c)] and progesterone [pregnanediol glucuronide (Pdg)]. Cycles were assessed for evidence of luteal activity and day of luteal transition using previously developed algorithms. Midreproductive-aged women who underwent similar daily urinary analyses served as historical controls. Correlates of cycle features were identified. Eight hundred thirty-three cycles were evaluable and had complete data on covariates. Six hundred seventy-four (80.9%) cycles had evidence of luteal activity, and 159 (19.1%) did not. Women who were at least 49 yr old were less likely to have cycles with luteal activity and had more variable cycle length, higher total-cycle FSH, and lower total-cycle Pdg. Compared with heavier women, those with body mass index less than 25 kg/m2 had shorter cycles and higher total-cycle LH, FSH, and Pdg but not E1c. Chinese- and Japanese-American women had overall lower adjusted total-cycle E1c excretion. Smoking was not significantly associated with cycle length or hormones. When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition. In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve.

The relationship between menstrual factors and breast cancer according to estrogen receptor status of tumor: a case-control study in African-American women.

BACKGROUND: Exposure to estrogen is a risk factor for breast cancer. Since estrogen executes its effect through estrogen receptors (ERs), the relationship between menstrual factors, which are estrogen-related, and breast cancer may be different depending upon ER status of tumors. This case-control study aimed to examine such a relationship according to ER status of breast cancer in African-American women. METHODS: Cases were 304 African-American patients pathologically diagnosed with breast cancer during 1995-1998, who were 20-64 years old and lived in 3 Tennessee counties. Controls were 305 African-American women without breast cancer, selected through random-digit dialing and frequency matched to cases by age and county. Information on menstrual factors (age at menarche, age at menopause, time from menarche to menstrual regularity, cycle length, and length of flow) and other risk factors were collected through telephone interviews. Estrogen receptor status of tumor samples was defined based on immunohistochemical measurement. Logistic regression analysis was used to calculate odds ratios and 95% confidence interval (CI). RESULTS: Compared to women with an average cycle length less than 28 days, the risks of breast cancer for those with longer length were 0.62 (95% CI, 0.36-1.06) and 0.56 (95% CI, 0.32-1.00) for ER-positive and ER-negative tumors, respectively. The corresponding odds ratio (OR) estimates were 0.42 (95% CI, 0.20-0.86) and 0.38 (95% CI, 0.16-0.90) for postmenopausal women. Other menstrual factors were not significantly associated with breast cancer for either ER status. CONCLUSIONS: Our results did not show a different menstrual factor/breast cancer relationship in terms of ER status in African-American women, although there might be an association between menstrual cycle length and the disease.

Progesterone, estradiol and their receptors in leiomyomata and the adjacent normal myometria of black Kenyan women.

The contents of progesterone and oestrogen, and their respective receptors in uterine leiomyomata and adjacent normal myometrial tissue in indigenous black women in Kenya were studied. A random selection of twenty women undergoing hysterectomy for uterine fibroids at Kenyatta National Hospital was used for the studies. The myometria contained higher levels of E(2 ) (181% : P < 0.001); and P(4 ) (240.6 % : P < 0.001); as compared to the leiomyomata. On the other hand uterine leiomyomata contained significantly higher levels of ER (147.6% : P < 0.001); and PR (178.7% : P < 0.001 ); than normal myometria. These findings differ slightly from those reported in black women in developed countries, but support the proposal that manipulation of sex steroids may be useful in the treatment and management of uterine leiomyomata.

A comparison of menstrual cycle profiles of salivary progesterone in British and Thai adolescent girls.

Menstrual-cycle profiles of salivary progesterone concentration, obtained by radioimmunoassay of daily samples collected throughout the cycle, were obtained from Thai (n = 232) and British (n = 130) adolescent girls up to 4 years postmenarche. These profiles were graded from 1 to 5 ranging, respectively from concentrations at the detection limit of the assay to profiles generally observed for the mature premenopausal woman. Contingency table analysis of the grade frequencies for Thai-British pairs of girls matched for chronological age and age at menarche (n = 2 x 90) demonstrated that British girls had more mature cycles (22/90) than Thais (11/90) (P less than 0.05) particularly in the first 2 years postmenarche (P less than 0.01). For these matched pairs of girls there was no evidence to support the view that girls with an early age of menarche develop their profiles more quickly following menarche than those with a late age of menarche, as previously reported and which was thought to be important in the development of breast cancer. The findings of this study also suggest that adolescent girls in Britain develop their menstrual cycle profiles of salivary progesterone more quickly than their Thai counterparts and this may be of value in formulating hypotheses regarding any role that ovarian progesterone secretion may have on subsequent breast cancer risk.