Lack of support for relation between woman's masculinity preference, estradiol level and mating context.

It has been proposed that women's preferences for male facial sexual dimorphism are positively correlated with conception probability and differ between short- and long-term mating contexts. In this study, we tested this assumption by analyzing relationships between estradiol levels to the women's preferences of male faces that were manipulated to vary in masculinity. Estradiol was measured in daily saliva samples throughout the entire menstrual cycle collected by Polish women with regular menstrual cycles. In our analyses, we included the three most commonly used definitions of the fertile window in the literature. After computing the overall masculinity preference of each participant and measuring hormone levels, we found that i) the timing of ovulation varied greatly among women (between -11 and -17days from the onset of the next menses, counting backwards), ii) there was no relationship between daily, measured during the day of the test (N=83) or average for the cycle (N=115) estradiol levels and masculinity preferences, iii) there were no differences in masculinity preferences between women in low- and high-conception probability phases of the cycle, and iv) there were no differences in masculinity preferences between short- and long-term mating contexts. Our results do not support the idea that women's preferences for a potential sexual partner's facial masculinity fluctuate throughout the cycle.

Cyclic endogenous estrogen and progesterone vary by mammographic density phenotypes in premenopausal women.

Estrogen and progesterone are key factors in the development of breast cancer, but it remains unclear whether these hormones are associated with mammographic density phenotypes in premenopausal women. We measured percent mammographic density, nondense area, and absolute mammographic density using computer-assisted breast density readings (Madena) from digitized mammograms taken on a scheduled day of the menstrual cycle (day 7-12) among 202 healthy, premenopausal women (Energy Balance and Breast cancer Aspects Study-I). Daily salivary concentrations of 17ß-estradiol and progesterone throughout an entire menstrual cycle and fasting morning serum concentrations of hormones on 3 specific days of the menstrual cycle were assessed. Salivary and serum 17ß-estradiol and progesterone were positively associated with percent mammographic density, we observed by 1 SD increase in overall salivary estradiol (ß-value equal to 2.07, P=0.044), luteal salivary progesterone (ß-value equal to 2.40, P=0.020). Women with above-median percent mammographic density had a 20% higher mean salivary 17ß-estradiol level throughout the menstrual cycle. The odds ratio for having above-median percent mammographic density (>28.5%) per 1 SD increase in overall salivary 17ß-estradiol was 1.66 (95% confidence interval 1.13-2.45). Women in the top tertile of the overall average daily 17ß-estradiol concentrations had an odds ratio of 2.54 (confidence interval 1.05-6.16) of above-median percent mammographic density compared with women in the bottom tertile. Our finding of a relationship between estrogen, progesterone, and percent mammographic density and not with other mammographic density phenotypes in premenopausal women is biologically plausible, but needs to be replicated in larger studies.

Alcohol consumption, endogenous estrogen and mammographic density among premenopausal women.

INTRODUCTION: Alcohol consumption may promote aromatization of androgens to estrogens, which may partly explain the observations linking alcohol consumption to higher breast cancer risk. Whether alcohol consumption is associated with endogenous estrogen levels, and mammographic density phenotypes in premenopausal women remains unclear. METHODS: Alcohol consumption was collected by self-report and interview, using semi quantitative food frequency questionnaires, and a food diary during seven days of a menstrual cycle among 202 premenopausal women, participating in the Energy Balance and Breast Cancer Aspects (EBBA) study I. Estrogen was assessed in serum and daily in saliva across an entire menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms taken between days 7-12 of the menstrual cycle. Multivariable regression models were used to investigate the associations between alcohol consumption, endogenous estrogen and mammographic density phenotypes. RESULTS: Current alcohol consumption was positively associated with endogenous estrogen, and absolute mammographic density. We observed 18 % higher mean salivary 17ß-estradiol levels throughout the menstrual cycle, among women who consumed more than 10 g of alcohol per day compared to women who consumed less than 10 g of alcohol per day (p = 0.034). Long-term and past-year alcohol consumption was positively associated with mammographic density. We observed a positive association between alcohol consumption (past year) and absolute mammographic density; high alcohol consumers (≥7 drinks/week) had a mean absolute mammographic density of 46.17 cm(2) (95 % confidence interval (CI) 39.39, 52.95), while low alcohol consumers (<1 drink/week) had a mean absolute mammographic density of 31.26 cm(2) (95 % CI 25.89, 36.64) (p-trend 0.001). After adjustments, high consumers of alcohol (≥7 drinks/week), had 5.08 (95 % CI 1.82, 14.20) times higher odds of having absolute mammographic density above median (>32.4 cm(2)), compared to low (<1 drink/week) alcohol consumers. CONCLUSION: Alcohol consumption was positively associated with daily endogenous estrogen levels and mammographic density in premenopausal women. These associations could point to an important area of breast cancer prevention.

Digit ratio (2D:4D) does not correlate with daily 17ß-estradiol and progesterone concentrations in healthy women of reproductive age.

OBJECTIVES: Second-to-fourth digit ratio (2D:4D) is proposed as a proxy for the prenatal balance of sex hormones, is related to hormone-dependent characteristics in adult life, and is a possible predictor of disease later in life. Here, we studied the relationship between 2D:4D and ovarian steroid hormones (17ß-estradiol and progesterone) among women of reproductive age. METHODS: From 186 healthy premenopausal women, aged 24-37 years, we collected saliva samples daily during the entire menstrual cycle. Data on reproductive and lifestyle characteristics were collected via questionnaires, and anthropometric measurements were performed. RESULTS: No statistically significant relationships were detected between adult women's sex hormone concentrations (17ß-estradiol and progesterone) during the menstrual cycle and 2D:4D, in either left or right hand, when controlling for size at birth, body mass index, and physical activity. CONCLUSIONS: This study shows, for the first time in a large sample of women of reproductive age, that 2D:4D is not a predictor of adult women's sex hormone concentration. The lack of relationship may be because 2D:4D might be genetically determined and is not related to maternal nutritional environment during fetal development. These results support the hypothesis that, in contrast to the nutritional quality of the fetal environment, the fetal hormonal environment (reflected by 2D:4D) does not determine reproductive physiology in later life.

High-density lipoprotein-cholesterol, daily estradiol and progesterone, and mammographic density phenotypes in premenopausal women.

High-density lipoprotein-cholesterol (HDL-C) may influence the proliferation of breast tumor cells, but it is unclear whether low HDL-C levels, alone or in combination with cyclic estrogen and progesterone, are associated with mammographic density, a strong predictor of breast cancer development. Fasting morning serum concentrations of HDL-C were assessed in 202 premenopausal women, 25 to 35 years of age, participating in the Norwegian Energy Balance and Breast Cancer Aspects (EBBA) I study. Estrogen and progesterone were measured both in serum, and daily in saliva, throughout an entire menstrual cycle. Absolute and percent mammographic density was assessed by a computer-assisted method (Madena), from digitized mammograms (days 7-12). Multivariable models were used to study the associations between HDL-C, estrogen and progesterone, and mammographic density phenotypes. We observed a positive association between HDL-C and percent mammographic density after adjustments (P = 0.030). When combining HDL-C, estradiol, and progesterone, we observed among women with low HDL-C (<1.39 mmol/L), a linear association between salivary 17ß-estradiol, progesterone, and percent and absolute mammographic density. Furthermore, in women with low HDL-C, each one SD increase of salivary mid-menstrual 17ß-estradiol was associated with an OR of 4.12 (95% confidence intervals; CI, 1.30-13.0) of having above-median percent (28.5%), and an OR of 2.5 (95% CI, 1.13-5.50) of having above-median absolute mammographic density (32.4 cm(2)). On the basis of plausible biologic mechanisms linking HDL-C to breast cancer development, our findings suggest a role of HDL-C, alone or in combination with estrogen, in breast cancer development. However, our small hypothesis generating study requires confirmation in larger studies.

Perfluoroalkyl substances and ovarian hormone concentrations in naturally cycling women.

OBJECTIVE: To examine associations between environmental exposure to perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women. DESIGN: E2 and P were measured in saliva samples collected daily for a single menstrual cycle and concentrations of PFASs (including perfluoroctane sulfonate [PFOS] and perfluoroctanoic acid) were measured in serum samples collected during the same cycle. SETTING: Not applicable. PATIENT(S): A total of 178 healthy, naturally cycling women, aged 25-35 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean follicular E2 (cycle days -7 to -1, where 0 is the day of ovulation); mean luteal P (cycle days +2 to 10). RESULT(S): Among nulliparous, but not parous women, PFOS concentrations were inversely associated with E2 (ß = -0.025, 95% CI -0.043, -0.007) and P (ß = -0.027, 95% CI -0.048, -0.007). Similar, but weaker results were observed for perfluorooctanesulfonic acid. No associations were observed between other PFASs (including perfluoroctanoic acid) and ovarian steroid concentrations, nor were any associations noted in parous women. CONCLUSION(S): Our results demonstrate that PFOS and perfluorooctanesulfonic acid may be associated with decreased production of E2 and P in reproductive age women. These results suggest a possible mechanism by which PFASs affect women's health, and underscore the importance of parity in research on PFASs and women's reproductive health.

Women who are married or living as married have higher salivary estradiol and progesterone than unmarried women.

OBJECTIVES: Extensive research has demonstrated that marriage and parenting are associated with lower testosterone levels in men, however, very little is known about associations with hormone concentrations in women. Two studies have found lower testosterone in relation to pair-bonding and motherhood in women, with several others suggesting that estradiol levels are lower among parous women than nulliparous women. Here, we examine estradiol and progesterone concentrations in relation to marriage and motherhood in naturally cycling, reproductive age women. METHODS: In 185 Norwegian women, estradiol and progesterone concentrations were assayed from waking saliva samples collected daily over the course of a menstrual cycle. Cycles were aligned on day 0, the day of ovulation. Mean periovulatory estradiol (days -7 to +6) and luteal progesterone (day +2 to +10) indices were calculated. Marital status and motherhood (including age of youngest child) were reported in baseline questionnaires. Multivariable linear regression models were used to examine associations between ovarian hormones, marital status, and motherhood. RESULTS: Women who were married or living as married had higher estradiol than unmarried women (ß = 0.19; 95% CI: 0.02, 0.36) and higher luteal progesterone as well (ß = 0.19; 95% CI: -0.01, 0.39). There were no notable differences in hormone levels in relationship to motherhood status. CONCLUSIONS: Our results indicate that ovarian steroid hormones may be higher among women who are married or living as married, and suggest several possible explanations, however, additional research is needed to elucidate any causal relationships.

Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

Gene variations in oestrogen pathways, CYP19A1, daily 17ß-estradiol and mammographic density phenotypes in premenopausal women.

INTRODUCTION: High mammographic density is an established breast cancer risk factor, and circulating oestrogen influences oestrogen-regulating gene expression in breast cancer development. However, less is known about the interrelationships of common variants in the CYP19A1 gene, daily levels of oestrogens, mammographic density phenotypes and body mass index (BMI) in premenopausal women. METHODS: Based on plausible biological mechanisms related to the oestrogen pathway, we investigated the association of single nucleotide polymorphisms (SNPs) in CYP19A1, 17ß-estradiol and mammographic density in 202 premenopausal women. DNA was genotyped using the Illumina Golden Gate platform. Daily salivary 17ß-estradiol concentrations were measured throughout an entire menstrual cycle. Mammographic density phenotypes were assessed using a computer-assisted method (Madena). We determined associations using multivariable linear and logistic regression models. RESULTS: The minor alleles of rs749292 were positively (P = 0.026), and the minor alleles of rs7172156 were inversely (P = 0.002) associated with daily 17ß-estradiol. We observed an 87% lower level of daily 17ß-estradiol throughout a menstrual cycle in heavier women (BMI >23.6 kg/m(2)) of rs7172156 with minor genotype aa compared with major genotype AA. Furthermore, the rs749292 minor alleles were inversely associated with absolute mammographic density (P = 0.032). Lean women with rs749292 minor alleles had 70 to 80% lower risk for high absolute mammographic density (>32.4 cm(2)); Aa: odds ratio (OR) = 0.23 (95% CI 0.07 to 0.75). Lean women with rs7172156 minor homozygous genotype had OR 5.45 for high absolute mammographic density (aa: OR = 5.45 (95% CI 1.13 to 26.3)). CONCLUSION: Our findings suggest that two SNPs in CYP19A1, rs749292 and rs7172156, are associated with both daily oestrogen levels and mammographic density phenotypes. BMI may modify these associations, but larger studies are needed.

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women.

BACKGROUND: Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear. MATERIALS AND METHODS: Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models. RESULTS: Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17ß-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5%). The odds ratios (ORs) per standard deviation increase in 17ß-estradiol were 1.81 [95% confidence interval (CI) 1.08-3.03] in the high IGF-1 stratum and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17ß-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95 % CI 1.33-12.83) and GH 4.17 (95 % CI 1.41-12.28). CONCLUSION: Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.

Ovarian function in Samoan women shows stronger association with signals of energy metabolism than fat reserves.

OBJECTIVES: The relative influence of prominent energetic hormones such as insulin and leptin on ovarian steroid production has yet to be determined and demonstrated consistently in vivo. This study reports preliminary findings on the relationship between insulin, leptin, and estradiol, a major ovarian steroid, in a sample of Samoan women. METHODS: Participants were 34 regularly cycling, nonlactating, premenopausal women in the follicular phase of their menstrual cycle with indicators of normal glucose tolerance. Fasting serum samples provided one-time, cross-sectional measures of glucose, insulin, leptin, and estradiol. Main statistical analyses consisted of Student's t-tests, used to determine significant differences in mean estradiol level between contrasting groups of insulin and leptin. RESULTS: Relatively high insulin levels within the normal range of variation showed a positive association with estradiol levels whereas relatively high leptin levels did not. The association between insulin and estradiol appeared to conform to a step-like categorical relationship--with the highest insulin levels exerting the greatest positive effect--rather than a dose-response linear relationship. CONCLUSIONS: This study adds to the growing evidence that peripheral regulation of ovarian function likely involves permissive signals that emphasize a state of energy surplus, related primarily to energy metabolism rather than energy reserves, and warrant more extensive study.

Puberty as a life history transition.

BACKGROUND: James Tanner's landmark publication, Growth at Adolescence, was not only the first and most comprehensive treatise on the subject of human pubertal development of its time, its core insights have held up remarkably well over time. REVIEW: This review connects Tanner's contributions to contemporary understanding of puberty as a process fundamentally driven by neuroendocrine maturation. It introduces the concepts of the 'hour-glass of puberty' and 'somatic strategy' as heuristic constructs. The 'hour-glass of puberty' describes the converging pathways of information flow influencing the timing of the neuroendocrine events of puberty and its ramifying consequences throughout the body. Somatic strategy refers to the pattern of sex-specific, adult body morphology that develops at puberty as the individual undergoes a life history transition from juvenile to adult.

Genetic polymorphism CYP17 rs2486758 and metabolic risk factors predict daily salivary 17ß-estradiol concentration in healthy premenopausal Norwegian women. The EBBA-I study.

CONTEXT: The relationship between low-penetrance genes, metabolic risk factors, and levels of endogenous 17ß-estradiol and progesterone, which play a role in breast cancer risk, remains unclear. OBJECTIVE: The aim of this study was to determine whether common polymorphisms in CYP17, in combination with metabolic risk factors (individually or clustered), alter salivary concentrations of free biologically active 17ß-estradiol and progesterone among healthy premenopausal Norwegian women. DESIGN: Eight single nucleotide polymorphisms in CYP17 were genotyped in 203 healthy premenopausal women aged 25-35 yr in the Norwegian EBBA-I Study, conducted in 2000-2002. Daily salivary concentrations of 17ß-estradiol and progesterone were measured throughout one menstrual cycle. A clustered metabolic score was calculated, including waist circumference, mean arterial pressure, insulin resistance, fasting triglycerides, and total cholesterol/high-density lipoprotein cholesterol ratio. The study hypothesis was tested in multivariable linear regression and generalized estimating equation models. RESULTS: Women in the upper tertile of clustered metabolic score with the CYP17 rs2486758 minor allele had daily salivary 17ß-estradiol concentrations that were 53% higher than other study women throughout the menstrual cycle (P < 0.001). Similarly, women in the upper tertile of total cholesterol/high-density lipoprotein cholesterol ratio, fasting triglycerides, and insulin resistance had 44, 32, and 24% higher daily salivary 17ß-estradiol concentrations, respectively (all P < 0.05). CONCLUSION: The CYP17 rs2486758 minor allele may predispose to higher 17ß-estradiol levels, particularly in premenopausal women with a high clustered metabolic score. Thus, modification of metabolic risk factors may have significant implications for the prevention of breast cancer in women with the minor allele of CYP17 rs2486758.

Adult height, insulin, and 17beta-estradiol in young women.

BACKGROUND: Adult height and insulin are thought to modify the development of breast cancer. However, little is known about the association between height and 17beta-estradiol, a key factor in breast carcinogenesis, and whether insulin modifies such an association. METHODS: Among 204 healthy women, ages 25 to 35 years, who participated in the Energy Balance and Breast Cancer Aspect I study, adult height (in centimeters) and fasting serum concentrations of insulin (pmol/L) were measured. 17beta-Estradiol concentrations were measured in daily saliva samples throughout an entire menstrual cycle through RIA. Age and multivariate linear regression models were used to study the association between adult height and 17beta-estradiol levels throughout an entire menstrual cycle and whether serum levels of fasting insulin may modify such an association. RESULTS: The women had a mean age of 30.7 years, adult height of 166.9 cm, and serum insulin of 85.7 pmol/L. For each increase of one SD in insulin levels in the upper tertile of adult height, the adjusted level of 17beta-estradiol increased by 3.1 pmol/L (95% confidence interval, 1.1-5.2), equivalent to a 17.3% higher mean average concentration of 17beta-estradiol. Women with an adult height > or =170 cm (upper tertile) and insulin levels >101 pmol/L (upper quartile) experienced, on average, 41% higher 17beta-estradiol levels throughout the entire menstrual cycle compared with women with the same adult height and insulin levels <101 pmol/L. CONCLUSION: Our findings support that premenopausal levels of 17beta-estradiol vary in response to adult height and insulin levels, of possible importance for breast cancer risk.

Influence of birth weight and adult body composition on 17beta-estradiol levels in young women.

BACKGROUND: Estrogens induce cellular proliferation and are associated with an increased risk of breast cancer. Birth weight and adult body weight have independently been associated with both estrogen levels and breast cancer risk. Thus, we hypothesize that low birth weight, in combination with adult overweight, may influence premenopausal 17beta-estradiol over an entire menstrual cycle of possible importance for breast cancer. METHODS: Among 204 healthy women, aged 25-35 years, who participated in the Norwegian EBBA-I Study, birth weight and age at menarche were assessed. Levels of 17beta-estradiol were measured in daily saliva samples over one menstrual cycle using radioimmunoassay (RIA). Measurements of body composition; waist circumference (cm), body mass index (BMI, kg/m(2)), and total fat percentage (DEXA, %) were assessed. Fasting blood samples were drawn, and serum concentrations of lipids and hormones were determined. RESULTS: The participating women had mean birth weight of 3,389 g and age at menarche 13.1 years. Women within the highest tertile of birth weight had the lowest 17beta-estradiol throughout the menstrual cycle (p = 0.03), and they tended to have a later age at menarche (p = 0.06). When we looked into birth weight in combination with adult-attained weight, we found that women with lower birth weights, combined with excess weight during adulthood, had higher levels of free 17beta-estradiol over an entire menstrual cycle compared with women with high birth weights and adult overweight. Women with birth weights <3,530 g, who later developed excess body weight (waist >or= 84 cm), showed 33% higher 17beta-estradiol concentrations over a menstrual cycle compared with women with higher birth weights (>or=3,530 g) and adult excess body weight (p = 0.03). The association was even more pronounced in women with birth weights <3,220 g, early age at menarche (<12 years), and adult overweight. CONCLUSION: Our findings support variation of premenopausal levels of 17beta-estradiol in response to birth weight and energy status in adult life, suggesting that women with low birth weight in combination with adult overweight are put at risk for higher estradiol levels throughout menstrual cycles, which is of possible importance for breast cancer risk.

Weight change and ovarian steroid profiles in young women.

OBJECTIVE: To investigate possible short-term effects of voluntary weight loss on ovarian steroid profiles in young women, in light of better established long-term effects in older women. DESIGN: We tested for an association of voluntary weight change over the course of a menstrual cycle with salivary E(2) and P profiles in the same menstrual cycle. SETTING: Students were recruited in a college residence hall, and they provided daily saliva samples to a researcher living nearby. PATIENT(S): The 65 women who participated were all college students and ranged in age between 18 and 23 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Weight was assessed in the first week of the menstrual cycle and first week of the following menstrual cycle. Estradiol and P were measured by radioimmunoassay in daily saliva samples. RESULT(S): We did not detect a suppressive effect of weight loss on the overall level of either hormone. However, we did find evidence for more distinct follicular and luteal E(2) peaks in women who gained weight. Peak luteal P also arrived about 2 days earlier in women who gained weight. CONCLUSION(S): This finding adds to evidence that short-term response of ovarian function to weight loss in young women is less pronounced than long-term response in older women.

Low estradiol levels in women of reproductive age having low sleep variation.

Higher exposure to light at night, for example, owing to night shift work or decrease in sleep duration, may suppress melatonin production, which in turn may increase the reproductive hormone levels. High levels of steroid hormones, especially estrogens, may be associated with an increase of the breast cancer risk. This study investigated whether variation in the sleep duration during one entire menstrual cycle corresponds to estradiol saliva concentrations in healthy, urban women of reproductive age. During 2000-2001, 95 regularly menstruating women aged 24-36 in Poland collected daily saliva samples for one entire menstrual cycle. Saliva samples were analyzed for concentration of 17-beta estradiol (E2) using radio immunoassay. Information on the number of hours of sleep per night (sleep duration) was collected daily by questionnaires for one entire menstrual cycle. Using covariance analysis, after adjustments for sleep duration, we documented a positive relationship between the sleep variation (sleep coefficient of variation) and E2 levels in women of reproductive age. Mean levels of E2 differed significantly in women from the lowest sleep coefficient of variation quartile (13.93 pmol/l) in comparison with other quartiles (22.35 pmol/l), (P<0.001). The low sleep variation group, that is, the women who sleep regularly, had mean E2 levels 60% lower than other groups. These results suggest that sleep variation significantly correlates with E2 levels, whereas sleep duration does not show a statistically significant relationship. This study suggests that sleep variation may influence endogenous estrogens, which is of importance for risk of breast cancer.

Physical activity, heart rate, metabolic profile, and estradiol in premenopausal women.

PURPOSE: To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS: Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical activity (LPA), resting heart rate (HR), blood pressure (BP), anthropometry, and serum glucose, lipids, and insulin [Norwegian Energy Balance and Breast Cancer Aspect (EBBA) study]. E2 was measured in daily saliva samples throughout an entire menstrual cycle. A clustered metabolic risk score [z metabolic syndrome (zMS); total cholesterol-high-density lipoprotein-cholesterol (HDL-C) ratio, insulin resistance, total fat tissue, BP, and triglycerides] was defined. Linear regression and linear mixed models were used, and confounding factors were tested. RESULTS: Physically active women had lower fat percentage (Ptrend = 0.003) and HRs (Ptrend = 0.003) than sedentary women. We estimated an increase in E2 of 1.27 pmol.L [95% confidence interval (CI), 0.06-2.47] for each 11.7 beats.min (1 SD) increase in HR, and this corresponds to the 7% change in mean concentration of E2 for the total group. Associations with E2 were also found for fat tissue, total cholesterol-HDL-C ratio, insulin resistance, and triglycerides. A dose-response relationship was observed among the three levels of LPA and HR and zMS (Ptrend = 0.03 for LPA; Ptrend = 0.004 for HR). Women in the highest tertile of the clustered metabolic risk score had average salivary E2profiles that were markedly higher, throughout the cycle, than those of the other groups, with a cycle peak-day difference in E2 of 22-28%. CONCLUSION: LPA and HR were associated with metabolic risk score, and this score was associated with daily level of E2, pointing to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk.

Moderate anxiety, whether acute or chronic, is not associated with ovarian suppression in healthy, well-nourished, Western women.

The relationship between psychological stress and reduced fecundity has been a matter of speculation and investigation for decades. Most previous studies have been compromised, however, by a number of problems including ambiguous direction of causation, poorly operationalized variables, and the confounding of psychological with energetic stress. We present a two-part study of the relationship between moderate anxiety, both acute and chronic, and daily measures of ovarian steroid and corticosteroid levels in saliva. Anxiety, as a particular form of psychosocial stress, was measured by the Spielberger Stait-Trait Anxiety Inventory as well as by a self-reported daily stress score. In the first part, 23 college juniors taking the Medical College Admissions Test (MCAT) were studied the month before and the month after the test, and again several months later, and compared at the same time points with 27 controls. In the second part, chronic anxiety levels were assessed in 95 women between 27 and 41 years of age and analyzed in relation to daily levels of salivary ovarian and corticosteroids over one menstrual cycle. The sample sizes are sufficient to allow for confidence in negative results. No statistically significant differences in ovarian or corticosteroid levels were observed whether between the MCAT and control subjects in part one, between the MCAT subjects before and after the MCAT test in part one, or between high and low anxiety subjects in part two. The results indicate that moderate levels of anxiety, whether acute or chronic, are not associated with suppressed ovarian function in healthy women.