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.

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.

Pooled energy budget and human life history.

Human life history contains a series of paradoxes not easily explained by classical life history theory. Although overall reproductive output is higher than in related primates, juvenile growth is slower and age-specific reproductive rates decline faster with age. A simple energetic model would predict that growth and reproductive rates should be positively correlated and that reproductive effort should not decelerate with age. The pattern of negative correlations in humans suggest the presence of trade-offs among peak reproductive rate, childhood growth, and reproductive rate at older ages. To address this puzzle, we propose a synthesis of reproductive ecology and behavioral ecology focused on intra- and inter-somatic energy transfers. This integration includes three concepts: the mother as final common pathway through which energy must pass to result in offspring; a distinction between direct and indirect reproductive effort, proposing the latter as a novel net energy allocation category relative to growth and direct reproductive effort; and a pooled energy budget representing the energetic contributions and withdrawals of all members of a breeding community. Individuals at all reproductive life stages are considered in light of their contributions to the pooled energy budget.

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.

Social variables predict between-subject but not day-to-day variation in the testosterone of US men.

Previous research has shown lower testosterone (T) levels associated with involvement in committed, romantic relationships ("paired" men) and paternal care in eight studies of North American men. An unanswered question is whether differences in male T levels associated with relationship status better reflect state (e.g., a man has lower T levels because he is involved in a relationship) or trait (e.g., low T men are more inclined toward such relationships) effects. Toward addressing this question, this paper presents data on male salivary T levels among a sample of 65 men varying in marital and parental status. Subjects collected saliva samples (at approximately waking, 17:00 and 21:00 h) and filled out questionnaires concerning their activities on four days. Each subject collected samples in two settings that varied in social interactions: for unmarried men, two working and two non-working days; for married non-fathers, two days spent mostly with their wives and two days spent mostly away from their wives; and for married fathers, two days spent mostly with their young children and two days spent mostly away from their children. Analyses revealed no significant within-subject T differences between these different conditions. However, between-group analyses revealed that married men had lower evening T levels than unmarried men, corroborating existing North American studies of male T and relationship status. These results suggest that day-to-day differences in social interactions may not be associated with differences in T levels, and lend further support to the growing body of evidence that hormone-behavior effect sizes may be greater in the afternoon and evening than in the morning.

Human male pair bonding and testosterone.

Previous research in North America has supported the view that male involvement in committed, romantic relationships is associated with lower testosterone (T) levels. Here, we test the prediction that undergraduate men involved in committed, romantic relationships (paired) will have lower T levels than men not involved in such relationships (unpaired). Further, we also test whether these differences are more apparent in samples collected later, rather than earlier, in the day. For this study, 107 undergraduate men filled out a questionnaire and collected one saliva sample (from which a subject's T level was measured) at various times across the day. As in previous studies, men involved in committed, romantic relationships had lower salivary T levels, though only during later times of the day. Furthermore, additional analysis of the variation among unpaired subjects indicated that men without prior relationship experience had lower T levels than experienced men. Finally, while paired men as a group had lower T levels than unpaired men, those men at the earliest stage (less than six months) of a current relationship had higher T levels than unpaired men as well as men in longer-term relationships. These results suggest that variation in male testosterone levels may reflect differential behavioral allocation to mating effort.

Effects of developmental and adult androgens on male abdominal adiposity.

We present results from 42 gay men who completed a survey including self-measurement of waist circumference, height, and weight, in addition to providing saliva samples for the assay of testosterone, and a photocopy of the right hand for the measure of second-to-fourth digit length ratio (2D:4D), proposed as a means of approximating androgenic effects during development. The analyses were conducted as a test of the recent hypothesis, proposed by Abbott et al. ([2002] J Endocrinol 174:1-5), that high prenatal androgen exposure causes greater deposition of fat on the abdomen relative to other depots. We found support for this hypothesis in men, albeit in a limited sample and with self-reported and self-collected data.

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.

Diurnal patterns of urinary steroid excretion in wild chimpanzees.

Urinary testosterone and cortisol concentrations were quantified in a large number of samples (>500) collected from wild male chimpanzees (n=11) over the course of 1 year. For both steroids, urinary concentrations were higher and more variable in the morning than in the afternoon. Urinary creatinine levels showed no such diurnal pattern. These patterns are consistent with studies of steroid excretion in humans and gorillas. This study emphasizes the importance of considering time of day as a confounding variable in field studies of primate endocrine function. It also suggests that if a small number of samples are to be used to characterize an individual's basal steroid levels, afternoon samples may be preferable because they show less intra-individual variability.

Population variation in age-related decline in male salivary testosterone.

BACKGROUND: Age-related declines in free and bioavailable testosterone are frequently reported for Western populations, but interpopulation variation in this pattern has not previously been investigated. METHODS: Salivary testosterone was measured using a consistently applied protocol on morning samples collected from men in four populations (USA, Congo, Nepal, and Paraguay) representing different geographical, ecological, and cultural settings. RESULTS: Mean testosterone levels varied significantly between the four populations. The mean testosterone differences between populations were greatest for young men (aged 15-30 years) and insignificant for older men (aged 45-60 years). The slope of age-related decline in testosterone was significant in the USA and Congolese participants, but not in the Nepalese or Paraguayan participants. CONCLUSIONS: Age patterns of testosterone decline vary between populations primarily as a result of variation in the peak levels attained in young adulthood. The potential consequences of this variation for other aspects of male health deserve investigation.

Ovarian function in the latter half of the reproductive lifespan.

The relationship of age to four aspects of ovarian function was investigated: daily progesterone levels, pulsatile progesterone secretion, follicular and luteal estradiol levels, and preovulatory estradiol levels. Daily progesterone levels decrease after age 40. Pulsatile progesterone secretion remains approximately stable with age, though older women have somewhat higher late luteal activity. Daily follicular and luteal estradiol levels decrease with advancing age, but preovulatory peak estradiol remains stable. Some of these changes undoubtedly have negative effects on fecundity, such as lower follicular estradiol and average progesterone, via effects on endometrial development and support. But other changes identified, such as stability of preovulatory estradiol levels and thereby presumptive capacity to stimulate a luteinizing hormone (LH) surge despite lower follicular and luteal levels, as well as increased pulsatile progesterone secretion around the time of implantation, appear designed to conserve and maintain function. Thus, ovarian endocrine function over the course of reproductive life represents a process of change, but not one of generalized functional decline. Rather, aging with respect to ovarian endocrine function may proceed on a track, or on multiple tracks, which are largely separable from the continual depletion of oocyte stores which occurs over the lifetime. © 1996 Wiley-Liss, Inc.