Person:

Ellison, Peter

BACKGROUND: Ovarian hormones, parity and length of 'menarche-to-first birth' time interval are known risk factors for breast cancer, yet the associations between I 7(\beta)-estradiol, progesterone and these reproductive factors remain unclear. METHODS: A total of 204 women (25-35 years) who participated in the Norwegian EBBA-I study collected daily saliva samples for one complete menstrual cycle, and filled in a reproductive history questionnaire. Anthropometry was measured and saliva samples were analyzed for ovarian hormones. Associations between parity, the interval and ovarian hormones, and effects of hormone-related lifestyle factors were studied in linear regression models. RESULTS: Mean age was 30.7 years, and age of menarche 13.1 years. Parous women had on average 1.9 births, and age at first birth was 24.5 years. No association was observed between parity and ovarian steroids. In nulliparous women, higher waist circumference ((\ge))77.75 cm) and longer oral contraceptive (OC) use ((\ge))3 years) were associated with higher levels of I 7(\beta)-estradiol. Short (< 10 years) versus long (>13.5 years) 'menarche-to-first birth' interval was associated with higher overall mean (P(_{trend}) = 0.029), 47% higher maximum peak and 30% higher mid-cycle levels of I 7(\beta)-estradiol. We observed a 2.6% decrease in overall mean salivary I 7(\beta)-estradiol with each 1-year increase in the interval. CONCLUSIONS: Nulliparous women may be more susceptible to lifestyle factors, abdominal overweight and past OC use, influencing metabolic and hormonal profiles and thus breast cancer risk. Short time between 'menarche-to-first birth' is linked to higher ovarian hormone levels among regularly cycling women, suggesting that timing of first birth is related to fecundity.

The introduction of the ‘fetal programming hypothesis’, first in epidemiology, subsequently in a broad range of disciplines concerned with developmental biology, has generated new interest in phenotypic plasticity, the mechanisms that govern it, and its place in evolutionary biology. A number of epidemiological studies link small size at birth, assumed to be a consequence of constrained prenatal energy availability, with adverse effects on the risk of chronic diseases later in life. The cluster of chronic diseases associated with the metabolic syndrome and alterations of glucose metabolism are particularly implicated. Recent evidence suggests that epigenetic modification of gene expression affecting the hypothalamic-pituitary-adrenal (HPA) axis may be involved in these effects. In animal studies epigenetic alteration of HPA axis activity and responsiveness is associated with changes in adult behaviour and stress responsiveness. The potential for similar effects to contribute to psychological and psychiatric outcomes in humans has been explored in a number of contexts, including famine exposure, observed covariance with birth weight, and prenatal dexamethasone treatment of fetuses at risk of congenital adrenal hyperplasia. While fetal programming effects have now been widely demonstrated across species and human populations, the adaptive significance of these effects is still a matter of debate.

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 17β-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 cm2 (95 % confidence interval (CI) 39.39, 52.95), while low alcohol consumers (<1 drink/week) had a mean absolute mammographic density of 31.26 cm2 (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 cm2), 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. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0620-1) contains supplementary material, which is available to authorized users.

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, 17β-estradiol and mammographic density in 202 premenopausal women. DNA was genotyped using the Illumina Golden Gate platform. Daily salivary 17β-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 17β-estradiol. We observed an 87% lower level of daily 17β-estradiol throughout a menstrual cycle in heavier women (BMI >23.6 kg/m2) 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 cm2); 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. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0499-2) contains supplementary material, which is available to authorized users.

Background and objectives: Life history theory predicts a shift in energy allocation from growth to reproductive function as a consequence of puberty. During adolescence, linear growth tapers off and, in females, ovarian steroid production increases. In this model, acquisition of lean mass is associated with growth while investment in adiposity is associated with reproduction. This study examines the chronological and developmental predictors of energy allocation patterns among adolescent women under conditions of energy constraint. Methodology: Fifty post-menarcheal adolescent women between 14 and 20 years old were sampled for weight and body composition at the beginning and end of 1 month in an energy-adequate season and 1 month in the subsequent energy-constrained season in a rural province of The Gambia. Results: Chronologically and developmentally younger adolescent girls gain weight in the form of lean mass in both energy-adequate and energy-constrained seasons, whereas older adolescents lose lean mass under conditions of energetic stress (generalized estimating equation (GEE) Wald chi-square comparing youngest tertile with older two tertiles 9.750, P = 0.002; GEE Wald chi-square comparing fast- with slow-growing individuals for growth rate 19.806, P < 0.001). When energy is limited, younger adolescents lose and older adolescents maintain fat (GEE Wald chi-square for interaction of age and season 6.568, P = 0.010; GEE Wald chi-square comparing fast- with slow-growing individuals for interaction of growth rate and season 7.807, P = 0.005). Conclusions and implications: When energy is constrained, the physiology of younger adolescents invests in growth while that of older adolescent females privileges reproductively valuable adipose tissue.

Among other things, sexual selection theory posits that in species with limited male parental investment, males should evolve biological mechanisms to competitively dominate or otherwise compete with one another. It is unclear whether such proposed mechanisms would influence status hierarchies in small human groups. We report the results of a study investigating possible effects of prenatal (index-to-ring finger length ratio or 2D:4D) and salivary testosterone, and masculine identification, on status among 71 male college students living in nine residential groups. The results indicate no role of either prenatal or salivary testosterone in maintaining status hierarchies in these groups. A possible explanation is that peer-assessed status in these groups was arrived at cooperatively rather than through dominance contests.

Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤ 3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes.

A commentary is offered on the chapters that comprise the section on Theoretical Foundations, emphasizing novel contributions of each. Three additional points are then made. First, while the biology of reproductive aging may be common to all human populations, its actual course can be expected to vary between individuals and between populations depending on ecological conditions and developmental histories. Second, increasing fertility (such as that typical of humans compared with hominoid relatives and imputed ancestral species) decreases the opportunity and impact of contributions from ascendant relatives and increases the opportunity and impact of contributions from collateral and descendent relatives in promoting the fitness of a focal individual. Finally, an argument is made that the major change in human life history physiology in the Pleistocene has been the extension of adult lifespan, not any change in ovarian physiology or rate of reproductive senescence, and that extended lifespan created a selection pressure for the emergence of indirect reproductive effort among postreproductive individuals, not the reverse.

Relative finger lengths, especially the second-to-fourth finger length ratio, have been proposed as useful markers for prenatal testosterone action. This claim partly depends on an association of relative finger lengths in adults with related sex differences in children and infants. This paper reports the results of a study using serial radiographs to test for both sex differences in the fingers of infants and children and for a relationship between sex differences in the children and infant finger and adult finger length ratios. This is the first study using long-term serial data to evaluate the validity of finger length ratios as markers. We found not only that sex differences in finger length ratios arise prior to puberty, but that sex differences in the fingers of children are highly correlated with adult finger length ratios. Our results strongly encourage the further use of finger length ratios as markers of perinatal testosterone action.