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Sex differences in [3H]nitrendipine binding and effects of sex steroid hormones in rat cardiac and cerebral membranes.

The sex differences and regulation by sex steroid hormones in calcium channels were studied by using [3H]nitrendipine binding to cardiac and cerebral membranes in 15-week old spontaneously hypertensive rats (SHRs). The maximal number of binding sites (Bmax) in the hippocampus of female SHRs increased by 24.1% over that in male SHRs. In the females, the Bmax values in the cardiac, striatal, thalamic and hippocampal membranes from ovariectomized SHRs decreased by 34.7, 29.9, 29.3 and 26.9%, respectively, compared to normal SHRs. This phenomenon, except for the hippocampus, was inhibited by estradiol but not by testosterone. In the male, the Bmax values in cardiac and cerebral membranes showed almost no changes after orchidectomy or treatment with estradiol or testosterone. After gonadectomy, the Bmax values in the cardiac, striatal and thalamic membranes of females decreased by 30.2, 33.0 and 35.6%, respectively, compared to those in males. The changes in apparent dissociation constant (KD) values were less remarkable than those in the Bmax values. These findings suggest that sex differences exist in the calcium channels of the heart, striatum, thalamus and hippocampus, and they suggest that estradiol, but not testosterone, may play a part in the regulation of the calcium channels in female SHRs.

Animals↗

Are the neurodevelopmental effects of gonadal hormones related to sex differences in psychiatric illnesses?

There are large sex differences in the incidence of many psychiatric diseases. The bases for these sex differences are probably complex and are likely to involve the interaction of both social and biological factors. Probable social factors include child rearing practices, personal expectations and lifestyles, and societal institutions. Biological factors would likely include genetic effects, hormonally mediated neurodevelopmental effects and hormonally mediated neuroregulatory effects. This paper focuses upon the developmental effects of gonadal hormones. The sex differences observed in the neuroanatomy and behavior of nonhuman mammals are reviewed. The instances in which developmental exposure to gonadal hormones has been demonstrated to be involved in establishing these sexual dichotomies are surveyed. The molecular mechanisms by which differences in prenatal and early postnatal levels of gonadal hormones may generate such sex differences are examined. Sex differences in human neuroanatomy and cognitive function are discussed. Finally, we speculate on ways in which similar hormonal mechanisms might act to influence psychiatric disorders.

Animals↗

The LH surge in humans: its mechanism and sex difference.

There is a sex difference in the response to an estrogen challenge test in humans, but, unlike with rats, this sex difference is not permanently imprinted in the central nervous system. Estrogen is not only the important ovarian signal to trigger off the LH surge, but it also probably plays an important role in activating the positive estrogen feedback mechanism in humans. For an LH surge to occur, amplification of the hypothalamic signal (enhanced secretion of GnRH) as well as sensitization of the pituitary responsiveness to GnRH are required. It is unlikely that androgens per se are responsible for suppressing the positive estrogen feedback in humans and the possible role of another gonadal factor other than androgens remains speculative. The LH surge is a neuroendocrine phenomenon involved primarily in the process of ovulation and it is not correlated to sexual identity and orientation. Furthermore, how the hypothalamic-pituitary axis (HPA) responds to the estrogen challenge can be accounted for purely by its exposure to a different steroid milieu without reference to gender identity or sexual orientation of the subject.

Estrogens↗

Sex differences in mortality after myocardial infarction: evidence for a sex-age interaction.

BACKGROUND: Studies of sex differences in mortality after myocardial infarction (MI) have shown conflicting results. OBJECTIVES: To test the hypothesis that sex differences in mortality after MI vary according to patients' age, with younger women, but not older women, having a higher mortality compared with men. METHODS: We performed a retrospective cohort study of 1025 consecutive patients who met accepted criteria for MI in 1992 and 1993 in 15 Connecticut hospitals. Data for the study were abstracted from medical records. RESULTS: Women had a 40% higher hospital mortality rate than men. Simple age adjustment eliminated the sex difference in mortality rate (odds ratio, 0.99; 95% confidence interval, 0.66-1.48). However, when the sample was subdivided into 2 age groups, women younger than 75 years showed twice as high a mortality rate as men in the same age group, while among older patients no difference in mortality was found. In multivariate analyses the interaction of sex with age was highly significant, even after adjusting for comorbid conditions, clinical severity, process of care, and hospital characteristics. In the fully adjusted model, this interaction indicated that among patients younger than 75 years women had 49% higher odds of hospital death than men, while in the age group 75 years or older women had 46% lower odds of death compared with men. CONCLUSIONS: A higher mortality of women compared with men after MI is confined to the younger age groups. The sex-age interaction should be considered when examining sex differences in mortality after MI.

Age Factors↗

Sex differences in disease anorexia.

Sexually differentiated responses occur in molecular, cellular, physiologic, and organismic aspects of immune-system function in relation to acquired and innate immunities. These sex differences apparently include activational effects, which depend on gonadal hormone levels in adults, and lifelong effects, which arise directly from genetic differences or organizational effects of gonadal hormones early in development that lead to lifelong sex differences. Sex differences in immune function also can have great biological significance. Despite this, the mechanisms of these effects rarely have been analyzed extensively. This is especially true of anorexia during illness or disease. Therefore, this review briefly considers 1) the biological mechanisms of sex differences; 2) sex differences in immune function; 3) clinical and experimental data related to sex differences in four diseases or disease models that involve anorexia, Crohn's inflammatory-bowel disease, cancer, turpentine inflammation, and lipopolysaccharide bacteremia; and 4) sex differences in anorexia after interleukin-1 administration.

Anorexia↗

The contribution of smoking to sex differences in mortality.

The contribution of smoking to sex differences in mortality is estimated on the basis of data from 12 studies of the mortality of nonsmoking men and women, together with mortality data for comparable general population samples. Most of the data are for samples drawn from the U.S. population from the late 1950s to 1980. The findings from different studies are generally consistent, once methodological factors are taken into account. The findings indicate that, for total mortality, the proportion of sex differences attributable to smoking decreases from about two-thirds at age 40 to about one-quarter at age 80. Over the adult age span, it appears that about half of the sex difference in total mortality is attributable to smoking. Findings for ischemic heart disease mortality show a similar pattern. For lung cancer, it appears that about 90 percent of the sex difference in mortality is attributable to smoking. The estimated contributions of smoking include both the effects of sex differences in smoking habits and the effects of sex differences in the increase in mortality caused by smoking. The quantitative results should be interpreted with caution, since several lines of argument suggest that multivariate analyses controlling for other relevant factors would produce lower estimates of the contribution of smoking to sex differences in mortality. Despite this limitation, the findings analyzed in this review, together with additional evidence from related research, strongly support the conclusion that cigarette smoking makes a major contribution to men's higher mortality, but other factors also play an important role.

Adolescent↗

Sex, sex differences, and social behavior.

Sex differences in social behavior are center stage in recent formulations of evolutionary psychology. Evolutionary psychology, with its emphasis on the long-term consequences of early adaptations, offers itself as an alternative meta-theory to mainstream social psychology, which emphasizes the importance of social structures in determining the existence and extent of social and cognitive sex differences. Using a range of examples, we argue that evolutionary psychology is open to criticism on several fronts: It does not (a) include a role for mediating and moderating variables or test predictions rigorously; (b) appreciate the importance of the difference between first- and second-order effects; (c) offer a truly interactionist theory; or (d) seriously consider the social implications of sex-based inequities. We also argue that social psychology has, in its turn, failed to appreciate the non-intuitive richness of some evolutionary hypotheses or that there is a role for evolutionary psychology in a genuinely interactionist theory This paper restates the need for that perspective, and suggests how it may be achieved.

Biological Evolution↗

On the elusive nature of sex differences in cognition: hormonal influences contributing to within-sex variation.

We argue that within-sex variation resulting from the prenatal organizational and adult activational effects of gonadal steroid hormones has the potential to obscure between sex differences in cognitive performance and functional cerebral asymmetry. Two putative markers for prenatal testosterone, finger ridge count (FRC) asymmetry and the 2D:4D finger length ratio, have been linked to within-sex variation in cognitive performance. In particular, FRC allows the identification of men and women who show a reversal of the typical sex-related pattern of task performance. Three paradigms for the study of activational effects--seasonal, menstrual, and diurnal hormonal cycles--have evaluated changes in task performance and functional cerebral asymmetry. The performance of sex-dimorphic, but not sex-neutral, tasks changes with estrogen across the menstrual cycle and with testosterone across its seasonal and diurnal cycles. Functional cerebral asymmetry also changes systematically across both the menstrual cycle and the diurnal testosterone cycle in such a way that suggests left hemisphere performance increases as testosterone levels decline whereas right hemisphere performance increases as estrogen levels decline. In studies of sex differences, such correlates of within-sex hormone-related differences are rarely measured or controlled. Whatever the explanation for the associations of putative markers and hormone cycles with differences in cognitive abilities and cerebral asymmetry, it is clear that these relationships have the potential to contribute to the elusive nature of sex differences in cognition and functional brain organization.

Cognition↗

Sex differences in parasite infections: patterns and processes.

Sex differences in parasite infection rates, intensities, or population patterns are common in a wide range of taxa. These differences are usually attributed to 1 of 2 causes: (1) ecological (sociological in humans); and (2) physiological, usually hormonal in origin. Examples of the first cause include differential exposure to pathogens because of sex-specific behavior or morphology. The second cause may stem from the well-documented association between testosterone and the immune system; sexually mature male vertebrates are often more susceptible to infection and carry higher parasite burdens in the field. Although many researchers favor one explanation over the other, the requisite controlled experiments to rule out confounding variables are often neglected. We suggest that sex differences in disease have evolved just as sex differences in morphology and behavior, and are the result of selection acting differently on males and females. Research has often focused on proximate mechanistic explanations for the sex difference in infection rates, but it is equally important to understand the generality of the patterns in an evolutionary context. Because males potentially gain more than females by taking risks and engaging in competition, sexual selection pressure has shaped male behavior and appearance to maximize competitive ability and attractiveness. Many of the classic male attributes such as antlers on deer are testosterone-dependent, putting males in what appears to be a cruel bind: become vulnerable to disease by developing an attractive secondary sexual ornament, or risk lowered mating success by reducing it. A variety of hypotheses have been put forward to explain why males have not circumvented this dilemma. The mating system of the host species will influence the likelihood of sex differences in parasite infection, because males in monogamous species are subject to weaker sexual selection than males in polygynous species. Whether these evolutionary generalizations apply to invertebrates, which lack testosterone, remains to be seen.

Animals↗

Sex differences in brain and behavior: emphasis on nicotine, nitric oxide and place learning.

Although males and females are unmistakably different, the recognition of sex as a key variable in science and medicine is considered a revolution in some circles. Sex differences transcend reproductive functions, are evident in the structural and functional organization of the brain, and are reflected in group differences in cognitive abilities and behavior. Males and females have different neural organizational patterns for information processing and different strategies in problem solving. Research on sex differences not only provides descriptive data, but also allows us to elucidate mechanisms that underlie our behavior. In this review, sex differences in the central actions of nicotine (an addictive substance) and nitric oxide, and performance on active avoidance and place learning tasks are discussed as examples, and biobehavioral approaches relating to these topics are presented.

Animals↗

Small sex differences in song control dendrites are associated with minimal differences in song capacity.

Previous work on canaries and zebra finches has shown that large differences between the sexes exist in the structure of dendrites in n. robustus archistriatalis (RA), one of the principal nuclei involved in the control of song. This sex difference is associated with a general or complete absence of song in females. If dendritic morphology in RA is causally related to capacity for song, large sex differences in structure should not occur in avian species in which both sexes sing. We now report this prediction confirmed for buff-breasted wrens (Thryothorus leucotis), a species in which the members of a breeding pair sing duets with each other. Total dendritic length and number of dendritic branches in RA do not differ in this species. Dendrites from males project about 8 micron further from the cell body than dendrites from females, apparently because of longer dendritic segments near the cell body. We argue that this suggests that differential influences on the structure of RA occurred early in the lives of the wrens.

Animals↗

Labile sex differences in long calling in cotton-top tamarins.

Sex differences in behavior are quite common among nonhuman primates. In sexually monomorphic species, sex differences might be expected to be less evident than in polygynous and highly dimorphic species. Callitrichid primates (marmosets and tamarins) are cooperative breeders that exhibit little sexual size dimorphism. However, several sex differences in the structure and usage of vocalizations have been reported. In one such study, McConnell and Snowdon [Behaviour 97:273-296, 1986] reported that female cotton-top tamarins (Saguinus oedipus) emitted significantly more normal long calls than males during simulated intergroup encounters. In the course of collecting a library of normal long calls, we replicated a portion of that study 20 years later with the same colony and similar methods. To our surprise we found a reversal of sex differences. In the same experimental situation, males gave significantly more normal long calls than females. In a further replication 2 years later, males still called more but the effect was less pronounced. The dramatic change in sex differences within the same species and colony over a 22-year period suggests that behavioral sex differences in callitrichids may be quite labile, and that repeated sampling over several years may be necessary to establish true sex differences.

Animals↗

Sex differences in language dysfunction in schizophrenia.

OBJECTIVE: Normal sex differences in language functions are disrupted in schizophrenia. However, identification of specific language components most vulnerable in schizophrenia and how they may differ by sex remain unexamined. The current study investigated this issue in the domains of phonology, semantics, and grammar, which have been closely linked with neuroanatomic regions for which sex differences have been identified. METHOD: Thirty-one outpatients with DSM-III-R schizophrenia and 27 healthy subjects comparable within sex on age, handedness, parental socioeconomic status, and ethnicity were systematically ascertained from a Boston catchment area. The subjects were administered an extensive language battery in the context of a comprehensive neuropsychological battery that included measures of phonology, semantics, and grammar. RESULTS: Male patients performed significantly worse than their healthy counterparts on all three domains, with phonology least affected. In contrast, language function was relatively preserved in the female patients, compared to their healthy counterparts, with phonology most affected. Across domains, the effect sizes in comparisons of male patients and healthy male subjects had a twofold difference, whereas the difference in effect sizes in comparisons of female patients and healthy female subjects was less in all areas. CONCLUSIONS: Findings were consistent with prior evidence of overall language dysfunction in schizophrenia and may have implications for understanding sex differences in neuroanatomic abnormalities in regions associated with phonological processing.

Adult↗

Sex differences in birth defects: a study of opposite-sex twins.

BACKGROUND: Sex differences in structural birth defects are often confounded by environmental risk factors. Opposite-sex twins provide a unique model for detecting sex differences in birth defects while maximally controlling environmental risk factors in a natural setting. METHODS: Population data from the Florida Birth Defects Registry were analyzed. A total of 4,768 pairs of twins who were discordant for sex and born between 1996 and 2001 were analyzed. The McNemar test was used to compare the differences between a male twin and his twin sister for the risk of developing specific defects and organ-system defects. RESULTS: Of 4,768 twin pairs, 225 males (4.72%) and 175 females (3.67%) had birth defects. Among opposite-sex twin pairs, males had a 29% higher risk for birth defects than their twin sisters. Compared to their twin sisters, males had a 5.4 times higher risk for pyloric stenosis and a 2.4 times higher risk for obstructive genitourinary defect, but only one-tenth the risk for congenital hip dislocation. CONCLUSIONS: Sex differences in birth defects exist between opposite-sex twins.

Congenital Abnormalities↗

Sex differences in the Poggendorff illusion: identifying the locus of the effect.

Extensive research has identified individual differences associated with sex in a range of visual task performances, including susceptibility to visual illusions. The aim of this study was to identify the locus of sex differences within the context of the Poggendorf illusion. 79 women and 79 men participated within a mixed factorial design. Analyses indicated that sex differences were only present in the stimulus context with the full inducing element present. This finding replicates recent research and provides qualifying evidence as to the locus of the effect. The findings are discussed within the functional framework of perceptual processes involved in extrapolating 3-dimensional characteristics from 2-dimensional visual stimuli.

Adolescent↗

Sex differences in pervasive developmental disorders.

Assessed differences in sex ratio, severity of associated mental retardation, and various metrics of severity of autism in autistic, PDD-NOS, and developmentally disordered (non-PDD) cases. Males with autism were more frequent than females, particular at higher IQ levels. The three clinical groups differed, in expected ways, in the various measures of severity of autism with the PDD-NOS cases being intermediate between the strictly diagnosed autistic group and the non-PDD developmental disordered group. Sex differences were primarily confined to IQ; sex differences in other metrics of severity of autism were not prominent. Implications for future research are discussed.

Adolescent↗

Morphine responses and experimental pain: sex differences in side effects and cardiovascular responses but not analgesia.

UNLABELLED: Sex differences in analgesic responses to mu opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to mu opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to mu opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed. PERSPECTIVE: This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

Adult↗

Sex differences in episodic memory: minimal influence of estradiol.

Sex differences exist for several cognitive tasks and estrogen has been suggested to influence these differences. Eighteen men and 18 women were matched on age and estradiol level. Potential sex differences were assessed in episodic memory, semantic memory, verbal fluency, problem solving, and visuospatial ability. Significant sex differences, favoring women, were found for tasks assessing episodic memory. Correlations between estradiol level and cognitive performance were significant for face recognition in females. Since sex differences remained in verbal episodic memory tasks and face recognition despite matched levels of estradiol, circulating estradiol does not appear to be of paramount consequence for observed sex differences in episodic memory.

Cognition↗