Human Sex Differences Research Articles

Abstract 075: Sex Differences in the Development of Autoimmune-Associated Hypertension

Systemic lupus erythematosus (SLE) is an autoimmune disorder with prevalent hypertension and is a novel disease model to study the link between chronic inflammation and hypertension. Because SLE is female-dominant, studies are usually conducted in female NZBWF1 mice, a well-established model of SLE. However, men are also diagnosed with SLE and the late onset and different clinical features draws interest. We hypothesize that sex differences exist in SLE and that female SLE mice have heightened disease, hypertension, and renal injury earlier than males. Female and male SLE and control ( NZW ) mice were monitored for albuminuria starting at 30 weeks of age and then at 35 weeks implanted with vascular catheters to allow measurement of blood pressure in conscious mice. At 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies, the hallmark of SLE, compared to male SLE (4.6e5 ± 1.3e5 vs. 6.3e4 ± 2.7e4 U/mL; n=3-5; all p<0.05), female controls (8.9e4 ± 3.3e4), and male controls (4.8e4 ± 9.3e3). At this same time point, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 20) of male SLE, 5% (1 out of 22) of female controls, and no male controls. Although male SLE mice did not reach similar levels of dsDNA autoantibodies as SLE females (2.0e5 ± 4.6e4 vs. 3.9e5 ± 4.3e4; n=8-13; p=0.015), by 35 weeks, the autoantibodies were increasing in SLE males (2.0e5 ± 4.6e4 vs. 6.3e4 ± 2.7e4; p=0.157) and higher than male controls (4.3e4 ± 9.3e3; p=0.046). At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 19) of male SLE, 5% (1 out of 22) of female controls, and no male controls. Importantly, both female and male SLE mice were hypertensive at 35 weeks: blood pressure was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3 mmHg; n=6-8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6-11; p=0.041). These data confirm the development of hypertension and renal injury in female SLE mice and suggest that male SLE mice develop hypertension with no renal involvement. Future studies will allow us to investigate the divergent mechanisms involved in autoimmune-induced hypertension in female and male mice, which will ultimately provide clues in sex differences in hypertensive humans with underlying chronic inflammation.

The reality and evolutionary significance of human psychological sex differences.

The aims of this article are: (i) to provide a quantitative overview of sex differences in human psychological attributes; and (ii) to consider evidence for their possible evolutionary origins. Sex differences were identified from a systematic literature search of meta-analyses and large-sample studies. These were organized in terms of evolutionary significance as follows: (i) characteristics arising from inter-male competition (within-sex aggression; impulsiveness and sensation-seeking; fearfulness; visuospatial and object-location memory; object-centred orientations); (ii) those concerning social relations that are likely to have arisen from women's adaptations for small-group interactions and men's for larger co-operative groups (person-centred orientation and social skills; language; depression and anxiety); (iii) those arising from female choice (sexuality; mate choice; sexual conflict). There were sex differences in all categories, whose magnitudes ranged from (i) small (object location memory; negative emotions), to (ii) medium (mental rotation; anxiety disorders; impulsivity; sex drive; interest in casual sex), to (iii) large (social interests and abilities; sociosexuality); and (iv) very large (escalated aggression; systemizing; sexual violence). Evolutionary explanations were evaluated according to whether: (i) similar differences occur in other mammals; (ii) there is cross-cultural consistency; (iii) the origin was early in life or at puberty; (iv) there was evidence for hormonal influences; and (v), where possible, whether there was evidence for evolutionarily derived design features. The evidence was positive for most features in most categories, suggesting evolutionary origins for a broad range of sex differences. Attributes for which there was no sex difference are also noted. Within-sex variations are discussed as limitations to the emphasis on sex differences.

Evidence that prenatal testosterone transfer from male twins reduces the fertility and socioeconomic success of their female co-twins

During sensitive periods in utero, gonadal steroids help organize biological sex differences in humans and other mammals. In litter-bearing species, chromosomal females passively exposed to prenatal testosterone from male littermates exhibit altered physical and behavioral traits as adults. The consequences of such effects are less well understood in humans, but recent near-doubling of twinning rates in many countries since 1980, secondary to advanced maternal age and increased reliance on in vitro fertilization, means that an increasing subset of females in many populations may be exposed to prenatal testosterone from their male co-twin. Here we use data on all births in Norway (n = 728,842, including 13,800 twins) between 1967 and 1978 to show that females exposed in utero to a male co-twin have a decreased probability of graduating from high school (15.2%), completing college (3.9%), and being married (11.7%), and have lower fertility (5.8%) and life-cycle earnings (8.6%). These relationships remain unchanged among the subsets of 583 and 239 females whose male co-twin died during the first postnatal year and first 28 days of life, respectively, supporting the interpretation that they are due primarily to prenatal exposure rather than to postnatal socialization effects of being raised with a male sibling. Our findings provide empirical evidence, using objectively measured nation-level data, that human females exposed prenatally to a male co-twin experience long-term changes in marriage, fertility, and human capital. These findings support the hypothesis of in utero testosterone transfer between twins, which is likely affecting a small but growing subset of females worldwide.

Gendered genetics: How reading about the genetic basis of sex differences in biology textbooks could affect beliefs associated with science gender disparities

AbstractThe belief that men and women differ in science ability because of genetics contributes to gender disparities in science, technology, engineering, and math (STEM) in complex ways. In this field experiment, we explored how the content of the genetics curriculum affected beliefs about science ability through its impact on a social–cognitive bias known as neurogenetic essentialism. Students (n = 460, 8th–10th grade) were randomized to read a genetics text that (a) explained plant sex differences, (b) explained human sex differences, or (c) refuted neurogenetic essentialism. After reading, students in the two genetics of sex conditions had significantly greater belief in neurogenetic essentialism and the innate basis of science ability compared with students who read the text that refuted neurogenetic essentialism. Structural equation modeling (SEM) of the experimental data demonstrated that the effect of the readings on the belief that science ability is innate was mediated by neurogenetic essentialism and this indirect effect was significant for girls but not boys. In turn, the belief that science ability is innate predicted lower future interest in STEM for girls, but not for boys. These findings suggest that learning about human genetic difference is not a socially neutral endeavor. Implications for mitigating gender disparities in STEM are discussed.

Sex related biases for attending to object color versus object position are reflected in reaction time and accuracy.

Processing of visual features related to objects and space relations occurs within separate cortical streams that interact with selective attention. Such separation has implications for cognitive development because the perception of ‘what’ and ‘where’ provide a neural foundation for the development of aspects of higher cognition. Thus, a small attentional bias in early development for attending to one aspect over the other might influence subsequent higher cognitive processing in tasks involving object recognition and space relations. We examined 134 men and women for evidence of an inherent sex-related bias for attending to basic perceptual features related to object discrimination versus object position. Each stimulus consisted of a circle located in one of 9 positions within a surrounding frame. Circles were one of three shades of blue or red. These stimuli were used in a match-to-sample paradigm where participants were required to match circles on the basis of color or spatial position. The first stimulus appeared in the center of the screen for 400 msec and the matching stimulus subsequently appeared for 400 msec oriented 5 degrees to the right or left of center. The same stimuli were used to test the perception of color and position, with order of testing counterbalanced across participants. Results showed significantly longer reaction times in females compared with males, with better accuracy to discriminate color when that color was tested before position. Males showed better accuracy when object position was tested before color discrimination. A second experiment employed the same procedure, but enhanced selective attention by adding an endogenous cue that predicted the right or left location for the appearance of the matching stimulus. This manipulation greatly attenuated the sex differences in reaction time and accuracy compared to Experiment 1, suggesting that the sex-related attentional biases are strongly coupled to bottom-up processing. Overall, the sex related attentional biases toward processing object characteristics versus object position location suggest a differential manifestation of biased competition between the weighted systems of dorsal and ventral stream processing. Results are discussed with how a developmental bias in the processing objects versus space relations may contribute to adult cognitive sex differences in humans and animals.

A Life History Approach to the Female Sexual Orientation Spectrum: Evolution, Development, Causal Mechanisms, and Health.

Women's capacity for sexual fluidity is at least as interesting a phenomenon from the point of view of evolutionary biology and behavioral endocrinology as exclusively homosexual orientation. Evolutionary hypotheses for female nonheterosexuality have failed to fully account for the existence of these different categories of nonheterosexual women, while also overlooking broader data on the causal mechanisms, physiology, ontogeny, and phylogeny of female nonheterosexuality. We review the evolutionary-developmental origins of various phenotypes in the female sexual orientation spectrum using the synergistic approach of Tinbergen's four questions. We also present femme-specific and butch-specific hypotheses at proximate and ultimate levels of analysis. This review article indicates that various nonheterosexual female phenotypes emerge from and contribute to hormonally mediated fast life history strategies. Life history theory provides a biobehavioral explanatory framework for nonheterosexual women's masculinized body morphology, psychological dispositions, and their elevated likelihood of experiencing violence, substance use, obesity, teenage pregnancy, and lower general health. This pattern of life outcomes can create a feedback loop of environmental unpredictability and harshness which destabilizes intrauterine hormonal conditions in mothers, leading to a greater likelihood of fast life history strategies, global health problems, and nonheterosexual preferences in female offspring. We further explore the potential of female nonheterosexuality to function as an alloparental buffer that enables masculinizing alleles to execute their characteristic fast life history strategies as they appear in the female and the male phenotype. Synthesizing life history theory with the female sexual orientation spectrum enriches existing scientific knowledge on the evolutionary-developmental mechanisms of human sex differences.

Gender-Based Occupational Segregation and Sex Differences in Sensory, Motor, and Spatial Aptitudes.

Research on sex differences in humans documents gender differences in sensory, motor, and spatial aptitudes. These aptitudes, as captured by Dictionary of Occupational Titles (DOT) codes, predict the occupational choices of men and women in the directions indicated by this research. We simulate that eliminating selection on these skills reduces the Duncan index of gender-based occupational segregation by 20 % to 23 % in 1970 and 2012, respectively. Eliminating selection on DOT variables capturing other accounts of this segregation has a smaller impact.

Let's call the whole thing off: evaluating gender and sex differences in executive function.

The executive functions allow for purposeful, deliberate, and intentional interactions with the world-attention and focus, impulse control, decision making, and working memory. These measures have been correlated with academic outcomes and quality of life, and are impacted by deleterious environmental events throughout the life span, including gestational and early life insults. This review will address the topic of sex differences in executive function including a discussion of differences arising in response to developmental programming. Work on gender differences in human studies and sex differences in animal research will be reviewed. Overall, we find little support for significant gender or sex differences in executive function. An important variable that factors into the interpretation of potential sex differences include differing developmental trajectories. We conclude by discussing future directions for the field and a brief discussion of biological mechanisms.

Human Sex Differences in Emotion Prediction: Evidence from Event-Related Potentials

Women and men process emotion stimuli in different ways. Few of the previous researchers who have examined how emotion recognition differs between the sexes, looked at sex differences in emotion prediction. Thus, I investigated women's and men's perceptions of emotional faces in predictable and unpredictable conditions. Results showed that behaviorally, women's response accuracy was higher than men's. In contrast, neurally, men had greater P1 amplitudes for happy faces compared with angry faces in right hemisphere electrodes, suggesting that men have a perceptual bias toward happy faces. Further, women exhibited larger N170 amplitudes for predictable versus unpredictable angry faces in right hemisphere electrodes. This may reflect enhanced sensitivity to detecting anger. Finally, there was a significant positive correlation between behavioral and N170 predictability effects. This result may indicate that emotion prediction enhances neural responses while improving recognition efficiency at the behavioral level. In this respect, the electrophysiological results and behavioral data were consistent.

Genomic upregulation of cardiac Cav1.2\u03b1 and NCX1 by estrogen in women

BackgroundWomen have a higher risk of lethal arrhythmias than men in long QT syndrome type 2 (LQTS2), but the mechanisms remain uncertain due to the limited availability of healthy control human tissue. We have previously reported that in female rabbits, estrogen increases arrhythmia risk in drug-induced LQTS2 by upregulating L-type Ca2+ (ICa,L) and sodium-calcium exchange (INCX) currents at the base of the epicardium by a genomic mechanism. This study investigates if the effects of estrogen on rabbit ICa,L and INCX apply to human hearts.MethodsPostmortem human left ventricular tissue samples were probed with selective antibodies for regional heterogeneities of ion channel protein expression and compared to rabbit myocardium. Functionally, ICa,L and INCX were measured from female and male cardiomyocytes derived from human induced pluripotent stem cells (iPS-CMs) with the voltage-clamp technique from control and estrogen-treated iPS-CMs.ResultsIn women (n = 12), Cav1.2α (primary subunit of the L-type calcium channel protein 1) and NCX1 (sodium-calcium exchange protein) levels were higher at the base than apex of the epicardium (40 ± 14 and 81 ± 30%, respectively, P < 0.05), but not in men (n = 6) or postmenopausal women (n = 6). Similarly, in cardiomyocytes derived from female human iPS-CMs, estrogen (1 nM, 1–2 days) increased ICa,L (31%, P < 0.05) and INCX (7.5-fold, − 90 mV, P < 0.01) and their mRNA levels (P < 0.05). Moreover, in male human iPS-CMs, estrogen failed to alter ICa,L and INCX.ConclusionsThe results show that estrogen upregulates cardiac ICa,L and INCX in women through genomic mechanisms that account for sex differences in Ca2+ handling and spatial heterogeneities of repolarization due to base-apex heterogeneities of Cav1.2α and NCX1. By analogy with rabbit studies, these effects account for human sex-difference in arrhythmia risk.

Predation by female chimpanzees: Toward an understanding of sex differences in meat acquisition in the last common ancestor of Pan and Homo

Among modern foraging societies, men hunt more than women, who mostly target relatively low-quality, reliable resources (i.e., plants). This difference has long been assumed to reflect human female reproductive constraints, particularly caring for and provisioning mates and offspring. Long-term studies of chimpanzees (Pan troglodytes) enable tests of hypotheses about the possible origins of human sex differences in hunting, prior to pair-bonding and regular provisioning. We studied two eastern chimpanzee communities (Kasekela, Mitumba) in Gombe, Tanzania and one (Kanyawara) in Kibale, Uganda. Relative to males, females had low hunting rates in all three communities, even where they encountered red colobus monkeys (the primary prey of chimpanzees) as often as males did. There was no evidence that clinging offspring hampered female hunting. Instead, consistent with the hypothesis that females should be more risk-averse than males, females at all three sites specialized in low-cost prey (terrestrial/sedentary prey at Gombe; black and white colobus monkeys at Kanyawara). Female dominance rank was positively correlated with red colobus hunting probability only at Kasekela, suggesting that those in good physical condition were less sensitive to the costs of possible failure. Finally, the potential for carcass appropriation by males deterred females at Kasekela (but not Kanyawara or Mitumba) from hunting in parties containing many adult males. Although chimpanzees are not direct analogs of the last common ancestor (LCA) of Pan and Homo, these results suggest that before the emergence of social obligations regarding sharing and provisioning, constraints on hunting by LCA females did not necessarily stem from maternal care. Instead, they suggest that a risk-averse foraging strategy and the potential for losing prey to males limited female predation on vertebrates. Sex differences in hunting behavior would likely have preceded the evolution of the sexual division of labor among modern humans.

Sex differences in virtual navigation influenced by scale and navigation experience.

The Morris water maze is a spatial abilities test adapted from the animal spatial cognition literature and has been studied in the context of sex differences in humans. This is because its standard design, which manipulates proximal (close) and distal (far) cues, applies to human navigation. However, virtual Morris water mazes test navigation skills on a scale that is vastly smaller than natural human navigation. Many researchers have argued that navigating in large and small scales is fundamentally different, and small-scale navigation might not simulate natural human navigation. Other work has suggested that navigation experience could influence spatial skills. To address the question of how individual differences influence navigational abilities in differently scaled environments, we employed both a large- (146.4 m in diameter) and a traditional- (36.6 m in diameter) scaled virtual Morris water maze along with a novel measure of navigation experience (lifetime mobility). We found sex differences on the small maze in the distal cue condition only, but in both cue-conditions on the large maze. Also, individual differences in navigation experience modulated navigation performance on the virtual water maze, showing that higher mobility was related to better performance with proximal cues for only females on the small maze, but for both males and females on the large maze.

P.1.g.087 - Behavioral measures of sensitization to repeated d-amphetamine: Preliminary data on sex differences in healthy humans

P.1.g.087 - Behavioral measures of sensitization to repeated d-amphetamine: Preliminary data on sex differences in healthy humans

Immune Responses to Viruses and Vaccines Differ Between Men and Women

Human sex differences extend beyond anatomy to encompass important immune system functions, predisposing men and women to respond differently to infectious diseases. For instance, estrogens tend to promote stronger inflammatory, cellular, and humoral immune responses in women than men. While robust immune responses to pathogens can benefit the host, overexuberant inflammatory responses can damage host tissues—predisposing women more than men to develop immunopathologies, comorbidities, autoimmune disorders, and adverse reactions to vaccines, among other deleterious effects.

Human sex differences in solving a virtual navigation problem

The current study examined sex differences in initial and subsequent strategies in solving a navigational problem within a virtual reality environment. We tested 163 undergraduates on a virtual T-maze task that included probe trials designed to assess whether participants were responding using either a place or response strategy. Participants were also tested on a mental rotation task and memory of the details of the virtual room. There were no differences between the sexes in copying or recalling a map of the room or on first trial performance of the T-maze. However, at trial two, males show a significant advantage in solving the task, and approximately 80% of the males adopt a place strategy to solve the T-maze whereas females at that point showed no strategy preference. Across all testing, both males and females preferentially used a place strategy. We discuss how factors such as spatial priming affect strategy preferences and how such factors may differentially affect males and females.

Sex Has a Meaning and Sex Differences Are Real

In 1871, Charles R. Darwin published his book, The Descent of Man and Selection in Relation to Sex (Darwin 1899). He discussed his ideas on the origins of dimorphic features of anatomy, citing examples of insects, crustaceans, birds, and mammals. Although he did not include behavior in his exhaustive coverage, it was indirectly discussed, because he suggested that male weaponry existed because it had the potential to give specific males an advantage in intrasexual combat. Females were not involved in such agonistic battles and so would not benefit from the burdensome and unused antlers, horns, or tusks. Since these contests were being exhibited by one sex and not by the other, they could certainly qualify as “sexually dimorphic behaviors” even if never presented and discussed by Darwin as such. Mating behavior for species with internal fertilization would also obviously reflect a sexual dimorphism. However, its causal foundations could possibly be attributed to differing internal hormonal environments rather than differing central nervous system organization. Frank Beach (1974) focused upon prepubertal development of urination patterns in dogs as being an example of a sexually dimorphic behavior pattern that is exhibited in the absence of the activational action of gonadal hormones. Field observations on a wide variety of primates have confirmed a wide variety of sexually dimorphic behaviors (Bernstein 1978). Harry Harlow’s work with surrogatereared rhesus monkeys (Macaca mulatta) established that these behavioral differences did not require exposure to adult models for their development and display and since these young rhesus monkeys were all prepubertal, there was confirmation of the independence of these behaviors from circulating hormones (Harlow 1971). Harlow’s work provided the appropriate backdrop for the experimental work with rhesus carried out by Charles Phoenix, Arnold Gerall, Robert Goy, and William C. Young that confirmed the organizational action of gonadal hormone exposure in utero (Goy 1968). The extension of this to humans is more problematic because ethics prevent direct manipulation, and a necessary reliance on clinical conditions is in some respects less than ideal, although congenital adrenal hyperplasia has been a disorder which has allowed for appropriate examination. For a great many people, the validity of sex differences is well-established and beyond question at the level of behavior and the central nervous system. However, the field is experiencing an inappropriate shift where the term “gender” is being substituted for the word “sex” even in situations where it is clearly inappropriate. For example, a 2015 work by Haynh et al. (2015) was published as a paper entitled “Forensic Identification of Gender from Fingerprints.” The very first table in the paper is headed “Average amino acid concentration (mM) values for males and females derived from sweat” and the very first figure has reference to “males” and “females.”Although the terms “man” and “woman” never appear in the article, these terms might have been appropriate under the article’s title. The first thing I want to commend Geary for is his sensitivity to the appropriate use of terminology; the term “gender” does not even appear in the book’s index. I doubt, however, that this was much of an effort for a man who has published an approximately 400-page book with the title Male, Female: the Evolution of Human Sex Differences (Geary 2005). In this reviewed book, the conceptual model which Geary sets up to examine is a simple and straightforward one: “traits that have been elaborated through sexual or social selection * Craig Bielert Craig.Bielert@oneonta.edu

The ‘extreme female brain’: increased cognitive empathy as a dimension of psychopathology

Baron-Cohen's ‛extreme male brain’ theory postulates that autism involves exaggerated male-typical psychology, with reduced empathizing (considered here as social–emotional interest, motivation and abilities) and increased systemizing (non-social, physical-world and rule-based interest, motivation and abilities), in association with its male-biased sex ratio. The concept of an ‘extreme female brain’, involving some combination of increased empathizing and reduced systemizing, and its possible role in psychiatric conditions, has been considerably less well investigated. Female-biased sex ratios have been described in two conditions, depression and borderline personality disorder (BPD), that also show evidence of increases in aspects of empathy in some studies. We evaluated the hypothesis that BPD and depression can be conceptualized in the context of the ‘extreme female brain’ by: (1) describing previous conceptualizations of the extreme female brain model, (2) reviewing evidence of female-biased sex ratios in BPD and depression, (3) conducting meta-analyses of performance on the Reading the Mind in the Eyes test (RMET) among individuals with BPD, clinical or sub-clinical depression, and other psychiatric conditions involving altered social cognition and mood (schizophrenia, bipolar disorder, eating disorders, and autism), in relation to disorder sex ratios, and (4) evaluating previous evidence of increased empathic performance in these, and related, psychiatric conditions, and (5) synthesizing these lines of evidence into models for causes and effects of an ‘extreme female brain’. Our primary empirical results are that RMET performance is enhanced in sub-clinical depression, preserved in borderline personality disorder, and reduced in other disorders (by meta-analyses), and that across disorders, more male-biased patient sex ratios are strongly associated with worse RMET performance of patients relative to controls. Our findings, in conjunction with previous work, suggest that increased cognitive empathizing mediates risk and expression of some psychiatric conditions with evidence of female biases, especially sub-clinical depression and borderline personality disorder, in association with increased attention to social stimuli, higher levels of social and emotional sensitivity, negative emotion biases, and over-developed mentalist thought. These results link evolved human sex differences with psychiatric vulnerabilities and symptoms, and lead to specific suggestions for future work.

Maternal early life adversities and the offspring's epigenome: A M.A.V.A.N. project

Overexposure of the developing fetus to glucocorticoids is a key mechanism linking early development with later life disease. In humans low birthweight, a marker of an adverse in utero environment, associates with increased fasting cortisol, increased hypothalamic-pituitary-adrenal (HPA) axis reactivity and with cardiovascular risk factors, cardiovascular disease and poorer cognitive function. Animal models suggest the HPA axis of female offspring is more susceptible to programming insults. We hypothesised that there would be similar sex differences in humans. We carried out a systematic review, searching Embase, Medline and Web of Science up to June 2014. Two independent researchers screenedarticles for eligibility. The29 includedstudies investigated the consequences of maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology, and HPA axis function in earlyand later-life. Overall, the studies reported sex differences such that female offspring were more responsive to stress both in earlyand later-life: females had lower birthweight, increased therapeutic responsiveness to glucocorticoids, increased diurnal cortisol secretion and HPA axis reactivity, compared to males. Further, in comparison to males, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with downregulation of the enzyme 11-beta-hydroxysteroid dehydrogenase (which converts active cortisol to inactive cortisone) in response to maternal glucocorticoid exposure or maternal asthma. Theobservationsof increasedprogrammedvulnerabilityof theHPA axis in females is consistentwith data fromanimalmodels andmay be a mechanism underlying sex differences in later life diseases including depression and cardiometabolic disease.

Sex differences in early life programming of the hypothalamic-pituitary-adrenal axis in humans suggest increased vulnerability in females

Overexposure of the developing fetus to glucocorticoids is a key mechanism linking early development with later life disease. In humans low birthweight, a marker of an adverse in utero environment, associates with increased fasting cortisol, increased hypothalamic-pituitary-adrenal (HPA) axis reactivity and with cardiovascular risk factors, cardiovascular disease and poorer cognitive function. Animal models suggest the HPA axis of female offspring is more susceptible to programming insults. We hypothesised that there would be similar sex differences in humans. We carried out a systematic review, searching Embase, Medline and Web of Science up to June 2014. Two independent researchers screenedarticles for eligibility. The29 includedstudies investigated the consequences of maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology, and HPA axis function in earlyand later-life. Overall, the studies reported sex differences such that female offspring were more responsive to stress both in earlyand later-life: females had lower birthweight, increased therapeutic responsiveness to glucocorticoids, increased diurnal cortisol secretion and HPA axis reactivity, compared to males. Further, in comparison to males, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with downregulation of the enzyme 11-beta-hydroxysteroid dehydrogenase (which converts active cortisol to inactive cortisone) in response to maternal glucocorticoid exposure or maternal asthma. Theobservationsof increasedprogrammedvulnerabilityof theHPA axis in females is consistentwith data fromanimalmodels andmay be a mechanism underlying sex differences in later life diseases including depression and cardiometabolic disease.

Fulfilling desire: Evidence for negative feedback between men's testosterone, sociosexual psychology, and sexual partner number

Across human societies and many nonhuman animals, males have greater interest in uncommitted sex (more unrestricted sociosexuality) than do females. Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology (attitudes and desires) is mediated by testosterone, whether any relationships between testosterone and sociosexuality differ between men and women, and what the nature of these possible relationships might be. In studies to resolve these questions, we examined relationships between salivary testosterone concentrations and sociosexual psychology and behavior in men and women. We measured testosterone in all men in our sample, but only in those women taking oral contraception (OC-using women) in order to reduce the influence of ovulatory cycle variation in ovarian hormone production. We found that OC-using women did not differ from normally-ovulating women in sociosexual psychology or behavior, but that circulating testosterone mediated the sex difference in human sociosexuality and predicted sociosexual psychology in men but not OC-using women. Moreover, when sociosexual psychology was controlled, men's sociosexual behavior (number of sexual partners) was negatively related to testosterone, suggesting that testosterone drives sociosexual psychology in men and is inhibited when those desires are fulfilled. This more complex relationship between androgens and male sexuality may reconcile some conflicting prior reports.