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PubMed2002

Sex differences in temporo-limbic and frontal brain volumes of healthy adults.

Sex differences have been observed in neurobehavioral measures and in neuroanatomic studies. Men and women differ in emotion processing, including perception, experience and expression, most notably reflected in greater male aggression. We examine temporo-limbic and prefrontal structures volumetrically in a large well-characterized sample of healthy adults, applying morphometric methods across cerebral regions that regulate emotions. Quantitative magnetic resonance imaging (MRI) was performed in 116 healthy adults, 57 men and 59 women, age range 18-49 years. We used reliable methods of region of interest identification to examine sex differences in volume of temporo-limbic and frontal regions. An automated tissue segmentation procedure was used to obtain separate measurements for gray and white matter. After correcting for cranial volume, men and women had identical volumes of amygdala and hippocampus, as well as dorsal prefrontal cortex. However, women had larger orbital frontal cortices than men, resulting in highly significant difference in the ratio of orbital gray to amygdala volume (P = 0.002). The larger volume of cortex devoted to emotional modulation may relate to behavioral evidence for sex differences in emotion processing.

Adolescent↗

PubMed2004

"Not a university type": focus group study of social class, ethnic, and sex differences in school pupils' perceptions about medical school.

OBJECTIVE: To investigate what going to medical school means to academically able 14-16 year olds from different ethnic and socioeconomic backgrounds in order to understand the wide socioeconomic variation in applications to medical school. DESIGN: Focus group study. SETTING: Six London secondary schools. PARTICIPANTS: 68 academically able and scientifically oriented pupils aged 14-16 years from a wide range of social and ethnic backgrounds. MAIN OUTCOME MEASURES: Pupils' perceptions of medical school, motivation to apply, confidence in ability to stay the course, expectations of medicine as a career, and perceived sources of information and support. RESULTS: There were few differences by sex or ethnicity, but striking differences by socioeconomic status. Pupils from lower socioeconomic groups held stereotyped and superficial perceptions of doctors, saw medical school as culturally alien and geared towards "posh" students, and greatly underestimated their own chances of gaining a place and staying the course. They saw medicine as having extrinsic rewards (money) but requiring prohibitive personal sacrifices. Pupils from affluent backgrounds saw medicine as one of a menu of challenging career options with intrinsic rewards (fulfillment, achievement). All pupils had concerns about the costs of study, but only those from poor backgrounds saw costs as constraining their choices. CONCLUSIONS: Underachievement by able pupils from poor backgrounds may be more to do with identity, motivation, and the cultural framing of career choices than with low levels of factual knowledge. Policies to widen participation in medical education must go beyond a knowledge deficit model and address the complex social and cultural environment within which individual life choices are embedded.

Adolescent↗

PubMed2002

Child sex differences in primary care clinicians' mental health care of children and adolescents.

BACKGROUND: Sex differences in the medical and mental health care of adults are well established. OBJECTIVE: To study the effect of child patient's sex on whether primary care clinicians (PCCs), including pediatricians, family physicians, and nurse practitioners, found or treated mental health problems in primary care settings. DESIGN: The data were collected by clinicians and parents from 21 065 individual child visits (50.3% girls) in 204 primary care practices. METHODS: Each PCC enrolled a consecutive sample of approximately 55 children and adolescents aged 4 to 15 years. Parents filled out questionnaires, including the Pediatric Symptom Checklist, before seeing the clinician. Clinicians completed a survey after the visit about the psychosocial problems and recommended treatments, but they did not see the results of the Pediatric Symptom Checklist or any other data collected from the parents. RESULTS: Boys were more likely to be seen for a mental health-related visit and by a clinician who identified them as "my patient." Boys with parent-reported symptom profiles that were similar to those of girls were more likely to be identified as having attention-deficit/hyperactivity problems or behavior or conduct problems and less likely to be identified as having internalizing problems. Adjusting for parent-reported symptoms, PCCs were more likely to prescribe medications for boys. Child sex differences in referrals to mental health specialists and the provision of counseling to families were not statistically significant. CONCLUSION: There are substantial sex differences in the mental health care of children in the primary care system.

Adolescent↗

PubMed2004

Sex differences in respiratory exercise physiology.

Respiratory exercise physiology research has historically focused on male subjects. In the last 20 years, important physiological and functional differences have been noted between the male and female response to dynamic exercise where sex differences have been reported for most of the major determinants of exercise capacity. Female participation in competitive and recreational sport is growing worldwide and it is universally accepted that participation in regular physical activity is of health benefit for both sexes. Understanding sex differences is of potential importance to both the clinician-scientist and the exercise physiologist since differences could impact upon exercise rehabilitation programmes for patient populations, exercise prescription for disease prevention in healthy individuals and training strategies for competitive athletes. Sex differences have been shown in resting pulmonary function, which may impact on the respiratory response to exercise. Women typically have smaller lung volumes and maximal expiratory flow rates even when corrected for height relative to men. Differences in resting and exercising ventilation across the menstrual cycle and relative to men have also been reported, although the functional significance remains unclear. Expiratory flow limitation and a high work of breathing are seen in women. Pulmonary system limitations, in particular exercise-induced arterial hypoxia, have been reported in both men and women; however, the prevalence in women is not yet known. From the available literature, it appears that there are sex differences in some areas of respiratory exercise physiology. However, detailed sex comparisons are difficult because the number of subjects studied to date has been woefully small.

Canada↗

PubMed1995

Sex differences in mesolimbic dopamine responses to ethanol and relationship to ethanol intake in rats.

Sex differences in ethanol intake in rats suggest that there may be sex differences in brain dopamine systems believed to mediate ethanol's reinforcing properties. To test this hypothesis, we used in vivo microdialysis to examine changes in nucleus accumbens and striatal dopamine, DOPAC and HVA following acute administration of several doses of ethanol in male and female Long-Evans rats. Following dialysis, rats were trained to bar press for oral ethanol reinforcement. In nucleus accumbens, females showed greater increases in dopamine than males at low to intermediate doses. In striatum, both sexes showed increased dopamine at the low to intermediate doses. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. Correlations between neurochemical measures and subsequent ethanol consumption indicated that among males, both basal and peak ethanol-induced nucleus accumbens dopamine levels were inversely related to later ethanol intake. No such relationship was observed for females. Striatal neurochemical measures were not significantly related to ethanol intake. These findings supported the hypothesis of sex differences in mesolimbic responses to ethanol and suggested that the relationship of those responses to subsequent ethanol intake may differ for males and females.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Sex differences in the cerebral BOLD signal response to painful heat stimuli.

There are limited data addressing the question of sex differences in pain-related cerebral processing. This study examined whether pain-related blood oxygenation level-dependent (BOLD) signal change measured with functional magnetic resonance imaging (fMRI) demonstrated sex differences, under conditions of equivalent pain perception. Twenty-eight healthy volunteers (17 women, 11 men) were subject to a fMRI scan while noxious heat stimuli were applied to the dorsum of the left foot. Significant BOLD signal modulation was observed in several nociceptive processing regions of interest (ROIs) in all subjects. There were no sex differences in the spatial extent of BOLD signal change for any ROI, but the signal amplitude was lower for women in most ROIs and significantly so for the primary somatosensory cortex (S1), the midanterior cingulate cortex, and the dorsolateral prefrontal cortex (DLPFC). The BOLD signal response could be positive or negative, and frequently, both polarities were observed within a single ROI. In most ROIs, women show proportionately more voxels with negative signal change than men, and this difference was statistically significant for the S1 and the DLPFC. The time course of the negative signal change was very similar to that of the positive signal change, suggesting that the latter was not "driving" the former. The location of negative and positive clusters formed distinct patterns in several of the ROIs, and these patterns suggest something other than a local "steal" phenomenon as an explanation for the negative signal changes. Sex differences in baseline cerebral blood flow may contribute to the BOLD signal differences observed in this study.

Adult↗

PubMed2002

Sex differences in cognitive impairment in multiple sclerosis.

Multiple sclerosis (MS) is twice as prevalent in females as in males, but the possibility of sex differences in the cognitive sequellae of the disease has not been considered. In this study male patients with MS performed more poorly than female patients on tests of verbal and nonverbal memory, visuospatial construction, and on the Mini Mental State Exam (MMSE) and the Wisconsin Card Sorting Test (WCST). The groups of male and female patients were similar in age, education, and on several measures of neurologic and emotional disturbance. Among normals there are no sex differences on the MMSE and WCST. Sex differences on the memory and visuospatial construction tests were larger in magnitude for the patients than for normal controls, implying that male patients are somehow especially vulnerable to cognitive deficits. Reanalysis of existing databases could clarify questions about the existence and source of cognitive sex differences in MS.

Cognition Disorders↗

PubMed2004

Postnatal apoptosis, development, and sex difference in the lateral septum of rats.

To determine whether apoptosis is involved in the formation of the structure and morphological sex difference of the lateral septum (LS), the postnatal developmental changes in the number of apoptotic cells were examined in the LS on postnatal day 1 (PD1 = birth day), 4, 6, 8, 11, 16, and 31 in male and female rats. Apoptotic cells were immunohistochemically detected by antibody against single-stranded DNA (ssDNA) or active caspase-3. The volume of the LS was also measured and was found to increase with age. The number of apoptotic cells detected by anti-ssDNA in the LS increased from PD1 to PD8 but decreased after PD11. Also, the LS was divided into dorsal, intermediate, and ventral parts (LSd, LSi, and LSv), and the volume and number of ssDNA-immunoreactive cells in each part were measured on PD6, 8, 11, 16, and 31. In both sexes, a large number of ssDNA-immunoreactive cells was found in the LSd and LSi on PD8 (but not on PD6) and in the LSv on PD6 and PD8. On PD6, the number of active caspase-3-immunoreactive cells was significantly greater in the LSv than in the LSd or LSi, in both sexes. Only the LSi of males had a high number of ssDNA-immunoreacitve cells on PD16; the number was significantly greater than that of females of the same age. However, there was no significant sex difference in the number of active caspase-3-immunoreacitve cells in the LSi on PD16. On PD31, the volume of the LSi was significantly greater in females than in males. There was no sex difference in volume or number of apoptotic cells in the LSd or LSv. These findings indicate that loss of cells due to apoptosis, which is partially caused by activation of caspase-3, occurs in the LS during postnatal development, with regional differences. They also indicate that sex difference in caspase-3-independent apoptosis contributes to morphological sexual differentiation of the LSi.

Aging↗

PubMed1986

Occupational and sex differences in smoking and smoking cessation.

Occupational and sex differences in the prevalence of smoking, smoking cessation, and attempts to quit smoking were studied cross-sectionally among employees of ten work sites (N = 3035). Comparisons by sex, occupation, and work site, controlling for age, were made using analysis of covariance. For both sexes, smoking prevalence was highest among blue collar workers and lowest among professionals. Successful cessation was most prevalent among professionals. At all occupational levels, smoking prevalence was higher in women than men. Although men were more likely to be exsmokers, no significant sex differences were found in the rate of recent cessation. Also, significant differences between work sites were found in the prevalences of smoking and overall cessation and in quit rates in the last two years. The high prevalence of smoking and the low interest in quitting among blue collar respondents indicate an important target for future work site interventions.

Adult↗

PubMed1987

Sex difference in the effect of mating on the pulsatile secretion of luteinizing hormone in a reflex ovulator, the ferret.

Sex differences in the pulsatile secretion of LH were examined in male and female ferrets after mating. Female ferrets which were either gonadally intact and in estrus or gonadectomized and maintained on a pulsed regimen of daily estradiol (E2) injections exhibited a prolonged rise in plasma LH, characterized by an elevation in mean LH levels and an increase in the number of LH pulses after receiving an intromission from a stud male. By contrast, no such increase in LH secretion occurred in males which achieved an intromission with a female, regardless of whether they were gonadally intact and in breeding condition or gonadectomized and given pulsed estrogen. In fact, intact breeding males which achieved an intromission had significantly fewer LH pulses 1-5 h later than unmated males bled serially over the same time period. This decrease in LH pulse frequency was followed by a significant rise in mean plasma levels of androgen 5-12 h later. When a sexually dimorphic LH response to intromission was observed in gonadectomized E2-treated ferrets, we asked whether this could reflect a sex difference in pituitary responsiveness to the endogenous release of GnRH. Thus, plasma LH levels were measured in gonadectomized and gonadectomized E2-treated ferrets for 2 h after iv injection of GnRH. In the absence of gonadal steroids, ferrets exhibited a sex-specific difference in LH responsiveness to GnRH; however, no sex difference was apparent under the influence of E2. These findings demonstrate that ferrets' sexually dimorphic LH responses to intromission probably reflect a sex difference in the processing of somatosensory inputs from the genitalia or in the neural control of GnRH release into the pituitary portal vessels.

Androgens↗

PubMed1999

Sex differences in cholinergic analgesia I: a supplemental nicotinic mechanism in normal females.

BACKGROUND: Cholinergic agents produce analgesia after systemic and intrathecal administration. A retrospective review showed that intrathecal neostigmine was more potent in women than in men, suggesting a sex difference in this response. The purpose of this study was to determine whether such a sex difference exists in normal rats and to examine the pharmacologic mechanisms that underlie this difference. METHODS: Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), or RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), or phentolamine alpha-adrenergic antagonist) with antinociception determined to a noxious heat stimulus to the hind paw. Time versus subcutaneous paw temperature relationships were defined for males and females. RESULTS: Neostigmine produced dose-dependent antinociception with five times greater potency in female than in male rats. Neostigmine-induced antinociception was reversed in male rats by atropine and unaffected by mecamylamine, whereas it was partially reduced by each antagonist alone in females and completely reversed after injection of both. RJR-2403 was more potent in females than in males, whereas there was no sex difference to bethanechol. Phentolamine partially reversed antinociception from RJR-2403 in females. Paw temperature increased more rapidly in females than in males for the same lamp intensity. CONCLUSIONS: These data demonstrate a large sex difference in antinociception to intrathecal neostigmine that is primarily the result of a nicotinic component in females. Phentolamine reversal suggests that part of this nicotinic component may rely on spinal norepinephrine release. A better understanding of this sex difference could lead to development of novel pain therapy for women.

Analgesics↗

PubMed2004

Sex differences in Mongolian gerbils in four tests of anxiety.

Animal models or test paradigms for predominantly female disorders, such as anxiety, often use only male animals, with little or no investigation of sex differences. Thus, this study was conducted to compare the behaviour of males and females in four widely used tests of anxiety. The behaviour of male and female Mongolian gerbils was assessed in the elevated plus maze (EPM), black-white box (BWB), open-field and social interaction tests. In the elevated plus maze, females spent proportionally less time in the centre square and greater time in the closed arms compared with males. In the black-white box, they showed significantly greater entries into the black compartment, whilst in the open field, females spent less time sniffing the arena compared with males. Thus, in these three models, there are no conclusive sex differences in anxiety-like behaviour. However, in the social interaction test, females showed more exploratory/cage-orientated behaviour and less active social and aggressive behaviour. In addition, females terminated social contact more frequently. These results can be interpreted as true sex differences, as behaviour in the open-field and social interaction tests did not differ across the oestrous cycle. In conclusion, the results show that sex differences in anxiety-like behaviour in gerbils are best detected using the social interaction test, which suggests that females show a more anxious profile. It also further highlights the need for sex differences to be investigated in tests of anxiety.

Animals↗

PubMed1987

Eye diseases in northern Nigeria: prevalence, age and sex differences.

This study presents the prevalence, age, and sex differences of eye diseases in northern Nigeria using the records of 1677 eye hospital patients. The most common eye disease are cataract, refractive error and presbyopia, and diseases of the conjunctiva and sclera. There are no significant age and sex differences in the prevalence of most eye conditions.

Adolescent↗

PubMed1985

Estradiol and progesterone influence L-5-hydroxytryptophan-induced myoclonus in male guinea pigs: sex differences in serotonin-steroid interactions.

The effects of castration in males and sex differences in the effects of estradiol and progesterone on L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus in guinea pigs were examined. Castration had no effect on L-5-HTP-induced myoclonus in males. There were sex differences in sensitivity to L-5-HTP. In the absence of steroids, L-5-HTP-induced myoclonus was higher in gonadectomized males than females. A low dose of estradiol benzoate (EB; 3.5 micrograms) given 46 h before L-5-HTP (100 mg/kg) enhanced myoclonus in gonadectomized females but not males. However, at a higher dose of EB (10 micrograms) and a lower dose of L-5-HTP (80 mg/kg), myoclonic responding was enhanced in males. These findings indicate that estradiol has a similar effect on L-5-HTP-induced myoclonus in males and females, but do not rule out the possibility of sex differences in sensitivity to L-5-HTP when both sexes are given estradiol priming. When L-5-HTP was given 6 h after 0.5 mg progesterone in estradiol-primed males, myoclonus was enhanced. Progesterone treatment reverses the facilitative effect of EB on L-5-HTP-induced myoclonus in females. Therefore, progesterone has opposite effects on L-5-HTP-induced myoclonus in males and females. These findings were discussed with respect to the interaction of steroids and 5-HT transmission in the regulation of steroid-dependent reproductive behavior.

5-Hydroxytryptophan↗

PubMed1999

Sex differences in nicotine effects and self-administration: review of human and animal evidence.

Although both the human and animal literatures are notable for the general lack of attention paid to possible sex differences in drug self-administration behavior, evidence is accumulating to suggest that males and females may differ in factors that maintain tobacco smoking or nicotine self-administration. Self-administration of nicotine per se may be less robust in women, and women are less sensitive than men to some effects of nicotine that may be reinforcing. Compared to men, smoking behavior of women may be influenced more by non-nicotine stimuli associated with smoking, suggesting greater conditioned reinforcement of smoking in women. Moreover, nicotine replacement, the current standard treatment for smoking cessation, is sometimes less effective in women, further suggesting the need for greater consideration of non-nicotine factors that may maintain women's smoking. Very recent research on rats also indicates sex differences in nicotine self-administration. However, these differences are complex and suggest that nicotine-seeking behavior is composed of several components, including hedonic, incentive-motivational, and conditioning effects; males and females may differ in one or more of these components. Menstrual or estrous cycle phase effects on the maintenance of nicotine self-administration are not particularly apparent in humans or animals, although cycle phase may influence other stages of dependence (e.g., withdrawal symptoms during cessation). Future research should evaluate further the consistency of results across human and non-human species, identify the conditions and procedures under which sex differences are observed, and elucidate the specific components of reinforcement that may differ between males and females. Studies also should examine the possible generalizability of these sex differences to other drugs of abuse. Identification of specific factors responsible for these sex differences may lead to improved interventions for smoking cessation and other substance abuse in women.

Animals↗

PubMed1998

Sex differences in the prevalence and detection of depressive and anxiety disorders in general health care settings: report from the World Health Organization Collaborative Study on Psychological Problems in General Health Care.

BACKGROUND: Understanding the relevance of biological and social factors to sex differences in the prevalence and detection of depressive and anxiety disorders has been impaired by the lack of standardized research methods across cultures. METHOD: Prevalence rates of depressive and anxiety disorders were assessed using a 2-stage design from 26,969 patients attending for primary care in 15 centers from 4 continents. Logistic regression analysis was used to examine sex differences in prevalence and detection across centers. RESULTS: Odds ratios for women compared with men of current depression (1.60; 95% confidence interval [CI], 1.37-1.86) and agoraphobia or panic (1.63; 95% CI, 1.18-2.20) were consistent across centers. The odds ratio for generalized anxiety varied among centers: 3 groups of centers were identified with odds ratios of 0.46 (95% CI, 0.27-0.78), 1.34 (95% CI, 1.08-1.66), and 3.09 (95% CI, 1.60-5.89). There was no sex difference in the detection of depressive and anxiety disorders by physicians across centers. CONCLUSIONS: The absence of a sex-by-center effect for current depression and agoraphobia or panic disorder is consistent with biological and psychosocial factors, either interacting or working alone, that have a similar final effect across cultures. It does not support the idea that sex differences in prevalence are caused by local psychosocial factors that vary from country to country. The variation in the odds ratio for generalized anxiety disorder offers some support to the idea that there are local differences between the centers contributing to the sex difference in rates. Patients' sex does not appear to affect the likelihood of current depression and anxiety being detected by primary care physicians.

Agoraphobia↗

PubMed2005

The development of sex differences in digital formula from infancy in the Fels Longitudinal Study.

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.

Adolescent↗

PubMed1996

Sex differences in androgen responsiveness in the rat brain: regional differences in the induction of aromatase activity.

The transformation of testosterone (T) to estrogens in brain tissue by cytochrome P-450 aromatase is required for the expression of sexual behaviors in adult male rats. Androgens regulate aromatase activity in the medial preoptic nucleus (MPN), as well as in a reciprocally connected group of forebrain nuclei involved in the regulation of male sexual behaviors. The levels of aromatase in these nuclei are generally greater in males than in females due to sex differences in circulating androgen levels. However, the mechanism of enzyme induction also appears to be sexually dimorphic. The current experiments were undertaken: (1) to characterize and compare the kinetic properties of aromatase in male and female rats and (2) to study sex differences in the dose-response relationship between the administered doses of T and the induction of aromatase in microdissected brain regions. Saturation analysis of aromatase activity in the MPN, bed nucleus of the stria terminalis (BNST), periventricular preoptic area (PVPOA), anterior hypothalamus (AH), and ventromedial hypothalamic nucleus (VMN) indicates that the greater aromatase activity observed in intact males reflects a sex difference in the maximal enzyme velocity, and not a sex difference in the apparent affinity of enzyme for substrate (Michaelis constant). The dose-response study of aromatase induction in the BNST, PVPOA, and VMN indicated a sex difference in aromatase activity over a range of circulating T levels varying from 0.3 to 35 ng/ml. No sex difference in inducible aromatase activity in AH was observed at any dose of T. The results of this study clearly demonstrate a sexually dimorphic effect of androgen action in the rat brain. Since T both regulates and is the substrate for aromatase in the brain, this sexual dimorphism is potentially an important limitation to the action of T in females and may relate to the enhanced expression of T-stimulated copulatory behavior in males compared to females.

Animals↗