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.

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.

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.

Index-to-ring finger length ratio (2D:4D) predicts levels of salivary estradiol, but not progesterone, over the menstrual cycle.

We tested the association between the index-to-ring finger length ratio (2D:4D) and ovarian steroid hormone concentrations measured over the course of a menstrual cycle in the saliva of 38 young women. Estradiol levels were positively associated with right-hand, but not left-hand, 2D:4D, and also with the difference between right- and left-hand 2D:4D. None of these measures predicted progesterone level.

Ovarian hormones and binge eating in bulimia nervosa.

BACKGROUND: Symptom fluctuation in bulimia nervosa (BN) is related to menstrual cycle phase. However, the relationship between bulimic symptoms and ovarian hormones (estrogens and progesterone) has not been examined directly in women with BN. METHOD: Regularly menstruating women with DSM-IV BN (n=9) and regularly menstruating controls (n=8) collected hormone samples and recorded mood and bulimic symptoms daily for 35 consecutive days. Estradiol and progesterone were measured by radioimmunoassay. Within-subject analyses examined prospective longitudinal associations between changes in ovarian hormones and changes in binge frequency in women with BN. Analyses controlled for the possible influence of negative affect on binge frequency as well as the influence of progesterone when examining estradiol associations and the influence of estradiol when examining progesterone associations. Between-subject analyses examined whether women with BN were more likely to have disrupted hormonal profiles than controls. RESULTS: Increases in binge eating were significantly associated with both decreases in estradiol and increases in progesterone in BN women with intact menstrual cycles. Although BN women were more likely to have disrupted hormone profiles than controls, this difference did not reach statistical significance, and mean estradiol and progesterone levels did not differ between bulimic and control groups. CONCLUSIONS: The results are consistent with those from experimental animal studies and suggest that decreases in estradiol and increases in progesterone may contribute to increases in binge eating. Ovarian hormone function represents a promising candidate for unraveling the neurobiological mechanisms of binge eating.

Habitual physical activity and estradiol levels in women of reproductive age.

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

High ponderal index at birth predicts high estradiol levels in adult women.

Inter-individual variation in levels of sex hormones results from differences in genetic, developmental, and environmental factors. We tested a hypothesis that programming of the fetal neuroendocrine axis may predispose some women to produce higher levels of steroid hormones during their menstrual cycles as adults. One hundred forty-five regularly menstruating 24- to 36- year-old women collected daily saliva samples for one menstrual cycle. Data on women's birth weights and birth lengths were obtained from medical records. A positive relationship was observed between ponderal index at birth (an indicator of nutritional status, calculated as birth weight/(birth length)(3)) and levels of estradiol (E2) in menstrual cycles, after controlling for potential confounding factors. Mean E2 was 16.4 pmol/l in the low ponderal index tertile, 17.3 pmol/l in the moderate ponderal index tertile, and 19.6 pmol/l in the high ponderal index tertile (the high ponderal index group had significantly higher E2 than both low and moderate ponderal index groups, P=0.0001). This study shows a positive association between ponderal index recorded for women at birth and levels of E2 measured during their menstrual cycles as adults. This suggests that conditions during fetal life influence adult production of reproductive hormones and may contribute to inter-individual variation in reproductive function. In addition, because large size at birth is one of the factors linked with an increased risk of breast cancer, our findings provide a physiological link for the observed positive relationship between indicators of energetic conditions during fetal growth and breast cancer in women.

Metabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study.

Low serum high-density lipoprotein cholesterol (HDL-C) is an important component of the metabolic syndrome and has recently been related to increased breast cancer risk in overweight and obese women. We therefore questioned whether serum HDL-C might be a biologically sound marker of breast cancer risk. We obtained cross-sectional data among 206 healthy women ages 25 to 35 years who participated in the Norwegian EBBA study. We included salivary ovarian steroid concentrations assessed by daily samples throughout one entire menstrual cycle, metabolic profile with measures of adiposity [body mass index (BMI) and truncal fat percentage], serum concentrations of lipids and hormones (insulin, leptin, testosterone, dehydroepiandrostendione sulfate, insulin-like growth factor-I, and its principal binding protein), and mammographic parenchymal pattern. We examined how components of the metabolic syndrome, including low serum HDL-C, were related to levels of hormones, and free estradiol concentration in particular, and studied predictors of mammographic parenchymal patterns in regression models. In women with BMI > or = 23.6 kg/m(2) (median), overall average salivary estradiol concentration dropped by 2.4 pmol/L (0.7 pg/mL; 13.2% change in mean for the total population) by each 0.33 mmol/L (12.8 mg/dl; 1SD) increase in serum HDL-C (P = 0.03; P(interaction) = 0.03). A subgroup of women characterized by both relatively high BMI (> or =23.6 kg/m(2)) and high serum LDL-C/HDL-C ratio (> or = 2.08; 75 percentile) had substantially higher levels of salivary estradiol by cycle day than other women (P = 0.001). BMI was the strongest predictor of overall average estradiol with a direct relationship (P< 0.001). Serum HDL-C was inversely related to serum leptin, insulin, and dehydroepiandrostendione sulfate (P < 0.001, P < 0.01, and P < 0.05, respectively). There was a direct relationship between breast density and healthy metabolic profiles (low BMI, high serum HDL-C; P < 0.001) and salivary progesterone concentrations (P < 0.05). Our findings support the hypothesis that low serum HDL-C might reflect an unfavorable hormonal profile with, in particular, increased levels of estrogens and gives further clues to biomarkers of breast cancer risk especially in overweight and obese women.

Large breasts and narrow waists indicate high reproductive potential in women.

Physical characteristics, such as breast size and waist-to-hip ratio (WHR), function as important features used by human males to assess female attractiveness. Males supposedly pay attention to these features because they serve as cues to fecundity and health. Here, we document that women with higher breast-to-underbreast ratio (large breasts) and women with relatively low WHR (narrow waists) have higher fecundity as assessed by precise measurements of daily levels of 17-beta-oestradiol (E2) and progesterone. Furthermore, women who are characterized by both narrow waists and large breasts have 26% higher mean E2 and 37% higher mean mid-cycle E2 levels than women from three groups with other combinations of body-shape variables, i.e. low WHR with small breasts and high WHR with either large or small breasts. Such gains in hormone levels among the preferred mates may lead to a substantial rise in the probability of conception, thus providing a significant fitness benefit.

Salivary testosterone and body composition among Ariaal males.

To determine if testosterone is negatively related to acute and/or chronic nutritional status among men in a subsistence society, saliva samples and anthropometric measures were compared among nomadic and settled Ariaal pastoralists of northern Kenya. Fifty-six nomadic men and 62 settled men facing drought conditions, estimated ages 22-96 years, were sampled. Measures included height, weight, four skinfolds, and %body fat by bioelectric impedance (BIA). Saliva samples were assayed for testosterone using radioimmunoassay. Overall, both body mass index (BMI) (avg. = 17.8 +/- 6.0 kg/m(2)) and salivary testosterone (T) levels (avg. am value = 176.8 +/- 74.8 pmol/l) were low compared to values from Western populations. Comparison of the two subpopulations revealed no significant difference in height, weight, BMI, or lean body mass. However, nomadic males exhibited significantly smaller skinfolds. Evening, but not morning, salivary T values differed between the subpopulations. Age-related changes in body composition included a significant decline in BMI with age, related to loss of body fat, but with little change in lean body mass. Age-related declines in BMI and %body fat were more pronounced among the nomadic males. am salivary T values declined with age; again, the decline was significantly greater among nomadic males. pm salivary T levels showed no significant decline with age. When controlled for residence and age, salivary T was positively related to %body fat and WHR ratio, but not lean body mass. These results provide evidence that salivary T is related to acute nutritional status among males in an energetically stressed subsistence population, in accordance with life history theories of somatic allocation.