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Sex differences in the vomeronasal system.

In the early eighties we found sex differences in the vomeronasal organ (VNO) and hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. At that time sex differences had already been described for some structures that receive VNO input, such as the medial amygdala, the medial preoptic area, the ventromedial hypothalamic nucleus, and the ventral region of the premammillary nucleus. Since then, we have shown sex differences in the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT), and the bed nucleus of the stria terminalis (BST). When new VNS connections were found, all of them ended in nuclei that present sex differences. In general, sex differences in the olfactory system show two morphological patterns: one in which males present greater morphological measures than females, and just the opposite. To explain the morphometric measures of males in the latter, it has been hypothesized that androgens serve as inhibitors. Our work on the involvement of the GABA(A) receptor in the development of AOB and maternal behavior sex differences also suggests that neonatal changes in neuronal membrane permeability to the ion Cl- differences. This might be the first animal model to help us to understand the situation in which human genetic and gonadal sex do not agree with brain and behavioral sex. Finally, we stress that sex differences in the VNS constitute a neurofunctional model for understanding sex differences in reproductive behaviors.

Animals↗

Orofacial pain symptom prevalence: selective sex differences in the elderly?

This study investigated sex differences in orofacial pain symptoms in a sample of elderly adults. Furthermore, differences across sex were tested on symptom continuity, overall duration, pain severity, activity reduction, and health care utilization, related to each specific symptom. Telephone interviews were conducted with a stratified random sample of community dwelling older (65+) north Floridians. A total of 5860 households were contacted and screened, with 75.3% participating to the point where their eligibility for the study could be determined. Of the remaining households, 1636 completed the interview. Of the total sample, 17.4% reported experiencing at least one of the four target orofacial pain symptoms (jaw joint pain, face pain, oral sores, burning mouth) during the past year, suggesting that orofacial pain symptoms are common in older adults. Our findings for prevalence of each specific symptom (jaw joint pain, 7.7%; face pain, 6.9%; oral sores, 6.4%; toothache, 12.0%; burning mouth, 1.7%) are similar to those estimated by the 1989 National Health Interview Survey, for the US adult population. Consistent with other epidemiological and clinical studies, we found that females were more likely to report jaw joint pain and face pain than males. In contrast to clinical studies, no differences were found on subjective ratings of pain severity, for any symptom. Differences across sex were most likely to be reported for jaw joint pain related variables, suggesting undetermined sex-uniqueness for these symptoms. In contrast to previous studies, older females tended to report lower levels of health care utilization than older males. This is the first study to our knowledge that reports orofacial symptom-specific sex differences among the elderly.

Adult↗

Sex differences in mandibular movements during opening and closing.

This study evaluated the sex differences in maximum 3-dimensional opening and closing movements. The sample included 29 men (ages, 23-39 years) and 27 women (ages, 23-35 years), who were selected for normal Class I occlusion, temporomandibular function, and skeletal patterns. Condylar (hinge axis) translation and mandibular incisor movements, were recorded with an optoelectric jaw-tracking system; each participant performed 4 maximum opening/closing cycles. The results showed significant (P <.05) sex differences for incisor opening and closing movements, with most of the differences in the vertical component. Male incisor straight-line distances and curvilinear pathways averaged 52.1 mm and 54.8 mm, respectively. Female straight-line distances and curvilinear pathways averaged 46.0 mm and 48.1 mm, respectively. There were significant (P <.05) sex differences for condylar translation, with most of the differences in the anteroposterior component. Male condyles translated 15.4 to 17.6 mm (straight-line distances) and 20.5 to 20.7 mm (curvilinear pathways); female condyles translated 12.4 to 12.7 mm (straight-line distances) and 16.2 to 17.9 mm (curvilinear pathways). Mandibular length accounted for some of the sex difference in interincisal opening and for most of the sex differences in condylar translation. Closing movements showed the same pattern of sex differences as opening movements. Mandibular opening rotation was approximately 4 degrees larger in men than in women. The shapes of the condylar opening and closing pathways also differed significantly between men and women. For both sexes, condylar translation did not correlate with incisor opening or closing movements. It was concluded that (1) significant sex differences exist in incisor opening movements that are independent of mandibular size, (2) sex differences in condylar translation are dependent on mandibular size, (3) incisor opening movements should not be used as an indicator of condylar translation, and (4) sex differences in the shapes of the condylar pathways indicate sex differences in articular eminence morphologic features.

Adult↗

Minireview: Sex differences in adult and developing brains: compensation, compensation, compensation.

Despite decades of research, we do not know the functional significance of most sex differences in the brain. We are heavily invested in the idea that sex differences in brain structure cause sex differences in behavior. We rarely consider the possibility that sex differences in brain structure may also prevent sex differences in overt functions and behavior, by compensating for sex differences in physiological conditions, e.g. gonadal hormone levels that may generate undesirable sex differences if left unchecked. Such a dual function for sex differences is unlikely to be restricted to adult brains. This review will entertain the possibility that transient sex differences in gene expression in developing brains may cause permanent differences in brain structure but prevent them as well, by compensating for potentially differentiating effects of sex differences in gonadal hormone levels and sex chromosomal gene expression. Consistent application of this dual-function hypothesis will make the search for the functional significance of sex differences more productive.

Animals↗

Epidemiology of childhood injuries. II. Sex differences in injury rates.

The development of sex differences in children's injury rates was explored by analyzing data from 197,516 consumer product-related injuries reported in 1978. The results indicated that sex differences in injury rates appear within the first year of life for most types of injuries. Burns, ingestions, and poisonings were important exceptions. The sex differences were not completely explained by differences in exposure to risk. Sex differences in behavior begin to appear at the same age as the differences in injury rates and correlate with injury type. Injury prevention efforts should take these developmental differences into account and focus attention on the high-risk child.

Accidents, Home↗

Galton and sex differences: an historical note.

The psychological study of sex differences is a special area of interest within differential psychology. Differential psychology was launched as a scientific field of research in the latter half of the nineteenth century by Sir Francis Galton. Galton's early research on sex differences in psychological traits gives him the distinction of being the "father" of the modern study of sex differences. Galton's empirical findings and his interpretation of sex differences were heavily influenced by his Victorian sexist attitudes. The early history of the modern study of sex differences exemplifies the intimate relation between facts and values.

England↗

Increasing sex difference in bone strength in old age: The Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK).

INTRODUCTION: It is important to identify possible pathological mechanisms that underlie the known sexual dimorphism in bone fragility in old age. In this cross-sectional population-based study, we use data from three different skeletal sites to examine sex differences in volumetric bone density, geometry and strength indices and determine whether sex differences in these bone strength measures continue to increase into very old age. MATERIALS AND METHODS: A total of 1715 elderly individuals (807 men and 908 women) age 67-93 years, participants in a population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were studied. Quantitative computed tomography (QCT) was performed in the lumbar spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and integral BMD, bone geometry and bone strength indices. Regression models were used to assess the effects of age and gender-adjustment for standing midlife height and current weight. RESULTS: At age 67-69 years, men had 24.9-31.7% larger cross-sectional bone size at measured sites than women. At all bone sites, women had two- to fivefold diminution in net bone mass with age compared to men but had comparable increments in bone size (1.8-6.0% per 10 years). This was reflected in significantly worse (more than twofold) bone strength measures with age in women, including compressive strength indices at the spine, femoral neck and trochanter and bending strength indices at the femoral neck. CONCLUSION: With the limitations of a cross-sectional study, our data support the hypothesis that sex differences in bone strength continue into old age. These sex differences appear to be due to greater net bone loss in women rather than due to greater bone gain in men.

Age Distribution↗

Sex differences in WAIS item performance.

Although the WAIS IQ scores of males and females differ only negligibly, significant sex differences do exist on many WAIS subtests. The purpose of the present investigation was to identify any WAIS items within these subtests that showed reliable sex differences. Within a cross-validation methodology that employed 521 adults (264 males; 257 females), 21 items were found to show reliable sex differences. A reanalysis by age groups provided similar results. The nature of the items was discussed, and an index of stereotyped sex-role experiences was proposed.

Adult↗

Sex differences in opioid analgesia: clinical and experimental findings.

Sex differences in analgesic responses to opioids have received increasing attention in recent years. This article examines the literature on sex differences in opioid analgesia, including the results of studies from the authors' own laboratories. In general, nonhuman animal studies suggest more robust opioid analgesic responses in males relative to females; however, the human studies completed to date seem to indicate greater opioid analgesia among females. The most consistent evidence of sex differences in analgesia comes from studies of kappa-agonist-antagonists administered to patients following oral surgery. These data indicate more robust analgesia in females, and dose-response characteristics suggest that these agents possess both analgesic and antianalgesic properties, and the agonists may produce these effects in different proportions for women versus men. In contrast, the data from laboratory pain models in humans suggest greater analgesic effects in women in response mu-opioid agonists but not kappa-agonist-antagonists. Multiple mechanisms may explain sex differences in opioid analgesia, including gonadal hormonal effects, pharmacokinetics and pharmacodynamics, genetic influences, balance of analgesic/antianalgesic processes, and psychological factors. However, the disparity of results obtained from different pain models--animals versus humans and clinical pain versus experimental pain in humans--suggests that the models themselves are mechanistically different. Additional investigation is warranted in order to further explicate the nature of sex differences in opioid analgesia and to elucidate the underlying mechanisms.

Analgesics, Opioid↗

Sex differences in adolescent chronic pain and pain-related coping.

Sex differences exist in pain and the strategies used to cope with pain. Although it is has been proposed that such differences become apparent around puberty, somewhat surprisingly very little research has specifically investigated sex as a moderator of pain within adolescents. The primary aim of the current study was to investigate sex differences in pain and coping within a group of 46 male and 115 female adolescent chronic pain sufferers. All were aged between 11 and 19 years and had been referred to the Pain Management Unit at the Royal National Hospital for Rheumatic Diseases, United Kingdom. Patients completed a battery of measures including pain experiences and a pain coping questionnaire. No sex differences were found in pain chronicity, although males and females did differ in self-reported pain experiences (females reported higher pain). Sex differences were also found in coping behaviours. Females used more social support, positive statements and internalizing/catastrophizing, whereas males reported engaging in more behavioural distraction. Of these strategies internalizing/catastrophizing was found to mediate the relationship between sex and pain. This suggests that not only do sex differences exist in the pain experiences and pain-coping strategies of adolescents with chronic pain, but that internalizing/catastrophizing may be an important mechanism in understanding such differences. More research examining potential sex differences in children and adolescents is recommended.

Adaptation, Psychological↗

Sex differences in the activation of language cortex during childhood.

Sex differences have been well documented in the behavioral literature but have occurred inconsistently in the neuroimaging literature. This investigation examined the impact of subject age, language task, and cortical region on the occurrence of sex differences in functional magnetic resonance imaging. Two hundred and five (104 m, 101 f) right handed, monolingual English speaking children between the ages of 5 and 18 years were enrolled in this study. The study used fMRI at 3T to evaluate BOLD signal variation associated with sex, age, and their interaction. Children completed up to four language tasks, which involved listening to stories, prosody processing, single word vocabulary identification, and verb generation. A sex difference for behavioral performance was found for the prosodic processing task only. Brain activation in the classical left hemisphere language areas of the brain and their right homologues were assessed for sex differences. Although left lateralization was present for both frontal and temporal regions for all but the prosody task, no significant sex differences were found for the degree of lateralization. Sex x age interaction effects were found for all but the task involving single word vocabulary. However effect sizes associated with the sex differences were small, which suggests that relatively large sample sizes would be needed to detect these effects reliably.

Adolescent↗

Sex differences in the genetic and causal relationships between depression, smoking, and alcohol use: the role of socioeconomic status.

Major depressive disorder (MDD), smoking, and drinking frequently co-occur, with evidence suggesting these relationships may differ by sex. However, the direction of causality and the extent of sex-specific associations remain unclear. We investigated sex-specific genetic relationships between MDD and substance use phenotypes using genome-wide association studies (GWAS) from the UK Biobank and publicly available sex-stratified GWAS for MDD and problematic alcohol use (PAU). Causal effects were assessed using bidirectional, sex-stratified Mendelian randomization (MR). We further applied multivariable MR (MVMR) to evaluate the influence of socioeconomic status (SES). Genetic correlation analyses indicated significant shared genetic architecture between MDD and all substance use traits in sex-combined GWAS. In sex-specific analyses, the correlation between cigarettes per day and MDD was significantly stronger in females, and drinks per week were correlated with MDD only in females. MR analyses showed that genetic liability to MDD increased the risk of smoking initiation and PAU in females, and was associated with reduced alcohol drinking frequency in males. In contrast, no tested substance use trait showed evidence of a causal effect on MDD in either sex. MVMR adjusting for SES attenuated the association between MDD and smoking initiation. The effect on PAU in females remained. In males, the negative association between MDD and drinking frequency became non-significant after SES adjustment. These findings reveal sex-specific genetic and causal relationships between smoking, drinking, and MDD, and highlight the role of SES as a potential confounder. Incorporating sex and socioeconomic context is critical when examining these associations.

Humans↗

Sex differences in locomotor effects of morphine in the rat.

Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into a photobeam apparatus for 3-5 h to measure activity. Modulation of morphine's effects by gonadal hormones and by handling (either during the test session or for 4 days before the test session) were examined. Morphine initially suppressed and later increased locomotor activity in both sexes relative to their saline-injected controls, but males were more sensitive than females to the initial locomotor suppressant effect of morphine. Intermittent, brief handling during the 3-h test session blunted morphine-induced locomotor activation in both sexes. Females in proestrus were the most sensitive to morphine's locomotor-stimulant effect, with females in estrus showing the least response to morphine. Gonadectomized (GDX) males with or without testosterone were equally sensitive to morphine's effects, whereas GDX females treated with estradiol showed a blunted response to morphine's effects, similar to intact females in estrus. Brief handling on each of 4 consecutive days pre-test attenuated morphine's locomotor suppressant effect in males but had no effect in females, thereby eliminating the sex difference. These data suggest that sex differences in morphine's effects on locomotor activity can be attributed to gonadal hormones in females, and to differential stress-induced modulation of morphine's effects in males vs. females.

Analgesics, Opioid↗

Surprising lack of sex differences in normal cognitive aging in twins.

Sex differences in the etiology of normal cognitive functioning in aging remain largely unexplored. We conducted an investigation of genetic and environmental contributions to sex differences in level of cognitive performance and rate of decline in the Swedish Adoption/Twin Study of Aging (SATSA) (Finkel & Pedersen, 2004) data set. Behavioral genetic parameterizations of a latent growth curve model were fit to longitudinal data on 11 cognitive measures. Seven hundred and ninety-eight non-demented individuals had cognitive data across four waves of measurement covering 13 years. Participants ranged in age from 44 to 88 at first testing wave; 60% were female. Results indicated sex differences in mean performance for five cognitive measures and in rates of decline for Information and Card Rotations. Only Synonyms demonstrated sex differences in genetic and environmental contributions to mean performance: heritability was higher in men than women. Despite differential longevity and susceptibility to disease, there are no consistent indications that men and women show different patterns of cognitive aging.

Adult↗

Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats.

There are sex differences in nociceptive behavior induced by formalin in rats. To determine whether these sex differences are the result of the sexual differentiation of the brain, that is masculinization and defeminization [A.P. Arnold, R.A. Gorski, Gonadal steroid induction of structural sex differences in the central nervous system, Annu. Rev. Neurosci. 7 (1984) 413-442; M.M. McCarthy, A.T.M. Konkle, When is a sex difference not a sex difference? Front Neuroendocrinol. 26 (2005) 85-102], some female rats were injected with testosterone propionate (TP, 100 microg/25 microl/rat) on the day of birth and on the following day. As controls, other female rats and all male rats were injected with the same volume of sesame oil. They were castrated at the age of 8 weeks, and implanted with a silicon tube containing 20% of 17beta-estradiol or cholesterol. Two weeks after the implantation, rats were injected with 50 microl of 2% formalin in the right hind paw and their behavioral changes were observed for 1h. In cholesterol-implanted rats, all rats exhibited three typical phases of pain response and there were no significant differences in the scores of nociceptive behavior. In 17beta-estradiol implanted rats, female and TP-treated female rats had a significantly higher score of nociceptive behavior than male rats. These results indicate that estrogen produces sex differences in nociceptive behavior induced by formalin, and suggest that these differences are not due to the sexual differentiation of the brain, since the dose and the timing of the TP treatment effectively defeminize and masculinize female rats. Alternatively, sexual differentiation of the brain response to formalin-induced nociceptive behavior may be different from ordinary sexual differentiation.

Analysis of Variance↗

Sex differences in the human metabolism of cortisol.

Sex differences in steroid metabolism have been clearly demonstrated in animal studies, but few studies have addressed this question in the human. Our preliminary studies suggested human sex differences in both cortisol production and metabolism. We therefore looked in more detail at indices of cortisol metabolism derived from 24 hour urinary steroid profiles in a group of 20 men and 20 women who were age-matched, drug-free and had no endocrine disorder. Steroid analysis was by high resolution gas chromatography. Men excreted more total cortisol metabolites (7620 +/- 620 v 4750 +/- 380 micrograms/24 h, p < 0.001), 11-oxo metabolites of cortisol (11-oxo FM, 4320 +/- 400 v 2890 +/- 250 micrograms/24 h, p < 0.001) and 11 beta-hydroxy metabolites of cortisol (11-OH FM, 3290 +/- 240 v 1860 +/- 140 micrograms/24 h, p < 0.001). These differences remained significant when corrected for body surface area. The ratio of 11-oxo FM/11-OH FM, an index of 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity, was higher in women (1.57 +/- 0.07 v 1.31 +/- 0.06, p < 0.01). The ratios of 5 alpha/5 beta and 20-oxo/20-OH metabolites of cortisol were both higher in men (1.07 +/- 0.15 v 0.58 +/- 0.04, p < 0.01, and 2.78 +/- 0.06 v 2.27 +/- 0.11, p < 0.01), while the ratio of 20 alpha/20 beta metabolites of cortisol was higher in women (1.79 +/- 0.13 v 1.32 +/- 0.06, p < 0.01). We conclude that there are considerable sex differences in both the production and metabolism of cortisol in healthy men and women. In particular, the data are consistent with a sex difference in 11-HSD activity, with relatively greater conversion of cortisol to cortisone in women.

Chromatography, Gas↗

Human sex differences in sexual psychology and behavior.

Because age and sex constitute the only distinct anatomical and physiological morphs (types) of the human species, universal sex differences ought to be expected. According to Darwinian theory, the most numerous sex differences are likely to be found in the domains of sexuality and reproduction. We first briefly review the basic model of the adaptationist program of modern Darwinian psychology. We then present evidence suggesting substantial sex differences in the following domains of sexual behavior: Mate preferences, interest in casual sex, interest in partner variety, jealousy, fantasy, sexual "plasticity," and magnitude of intrinsic sexual motivation. We then propose a program for research and explanation of sex differences that invokes both proximate and ultimate variables where appropriate. This program is based in modern Darwinian theory, neuroendocrinology, human genetics, and social and behavioral sciences. We conclude by considering sociopolitical implications of research on sex differences.

Adaptation, Psychological↗

[Development of behavior and sex differences in infants; with reference to the formation of sex role].

In order to observe the formation of sex role, an investigation was made on the development of behavior and sex differences in infants aged 1 to 6 at Fukuoka-city. The present study consisted of questionnaire on behavior of daily living and breeding, block construction test and coloring a drawing test. The parents instructed their infants to become masculine for males and feminine for females on the basis of traditional view. No sex differences were observed in construction ability of infants aged 4. Favorite colors were different according to sex.

Age Factors↗