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Immunoglobulins in healthy controls: HLA-B8 and sex differences.

Serum immunoglobulins were measured in one hundred and eighty-four healthy controls. One hundred and fifty-nine of these were also HLA typed. IgG levels did not differ with sex or HLA-B8 status. IgM levels did not differ with HLA-B8 status but were significantly higher in females than males. IgA levels were lower in females than males; they were also lower in HLA-B8 positive compared with HLA-B8 negative individuals; the lowest IgA levels were found in HLA-B8 positive females. The IgA variation may be relevant to the higher incidence of certain disorders among HLA-B8 positive individuals and among females.

Adult↗

Sex differences in the distribution of axon types within the genu of the rat corpus callosum.

Neuroanatomical sex differences have been documented in the rat neocortex, including dimorphism of its predominant commissure, the corpus callosum (CC). In particular, CC sex differences have been reported in the ultrastructure of the posterior callosal region, the splenium. Since the CC is a heterogeneous fiber tract with its axons arising from distinct cortical areas and passing through restricted regions along its length, it became of interest to ascertain whether cellular sexual dimorphisms may also be present in another division of the CC. To test this hypothesis, electron microscopy was used to examine axon composition in adult male and female rats in the anterior portion, the genu. The number and size of axons, the thickness of the myelin sheath, and the area within the genu occupied by these constituents, were quantified. Results showed a significant sex difference in the ratio of unmyelinated to myelinated axons, with females having a larger proportion of unmyelinated fibers. This effect was present for both (1) the number of axons, and (2) the area taken up by axonal fibers. No differences were found in the size of either axon type, or for myelin thickness. Comparison of these results with those from the splenium and possible mechanisms underlying this dimorphism are discussed.

Analysis of Variance↗

Symptom sensitivity and sex differences in physical morbidity: a review of health surveys in the United States and The Netherlands.

Health surveys have found higher female morbidity rates, as reflected by indices such as general health status, number of acute conditions or physical symptoms and medical care utilization. Such findings can lead to the conclusion that women are the "sicker sex" in terms of objective health status. However, the size of the sex difference varies with the different indices used to operationalize the morbidity concept. Apart from sex specific conditions, the female morbidity excess seems most substantial with regard to general health status, acute and mild chronic conditions and physical symptoms. Findings from a large health survey in the Netherlands, presented in this article, confirm this picture. Some major methodological sources of bias, that have been held responsible for part of the sex differences found in health surveys, such as the poor definition of the morbidity concept and aspects of the data collection process, are discussed. One explanation for the higher morbidity of women, i.e., the differential perception of physical symptoms by men and women, is elaborated in more detail. The authors suggest that part of the sex differences found in health surveys can be explained by a higher female symptom sensitivity, defined as a readiness to perceive physical sensations as symptoms of illness. Research supporting this symptom sensitivity hypothesis is reviewed and explanations are given. It is suggested that further research on sex differences in morbidity should control for methodological sources of sex bias and should focus explicitly on differences in the perception of physical symptoms by men and women.

Bias↗

Reversal of sex differences in morphine analgesia elicited from the ventrolateral periaqueductal gray in rats by neonatal hormone manipulations.

Male rats display significantly greater analgesic responses than female rats following systemic, ventricular and intracerebral morphine administration into either the ventrolateral periaqueductal gray (vlPAG) or the rostral ventromedial medulla, and following beta-endorphin administration into the vlPAG. Although adult gonadectomy severely reduces nonopioid forms of swim stress-induced analgesia, the marked sex differences in morphine analgesia were minimally affected by either male or female adult gonadectomy. Since very little is known about neonatal effects of gonadal hormones upon sex differences in morphine analgesia elicited from the vlPAG, the present study evaluated the effects of neonatal (within 1 day of birth) castration in male rat pups relative to sham-operated controls, and systemic androgenization with testosterone propionate in female rat pups relative to vehicle-injected controls upon baseline nociceptive thresholds and morphine analgesia elicited from the vlPAG in rats tested as adults. Significant sex differences in morphine analgesia elicited from the vlPAG were observed with adult males receiving neonatal sham surgeries displaying significantly greater morphine analgesia on two nociceptive measures than adult females tested during the estrous phase and receiving neonatal vehicle injections. Neonatal gonadectomy essentially reversed the pattern of sex difference effects upon morphine analgesia elicited from the vlPAG. Neonatally-castrated male rats tested in adulthood displayed dramatic reductions in morphine analgesia elicited from the vlPAG on both the tail-flick (approximately 15-fold rightward shift) and jump (6-fold rightward shift) tests relative to sham-operated males, and essentially mirrored those of vehicle-treated females. Conversely, neonatally-androgenized female rats tested in adulthood displayed dramatic increases in morphine analgesia elicited from the vlPAG on the tail-flick (5-fold leftward shift) and jump (12-fold leftward shift) tests relative to vehicle-treated females, and approximated those observed in sham-operated males. The potent differences between neonatally-castrated and sham-operated male rats and between neonatally-androgenized and vehicle-treated female rats suggest a possible 'organizational' role of gonadal hormones in mediating sex differences in morphine analgesia elicited from the vlPAG.

Analgesics, Opioid↗

The behavior of male and female Wistar rats pressing a lever for food is not affected by sex differences in food motivation.

Male rats both eat more and weigh more than females. Differences in food intake and body weight result, at least partly, from differences in gonadal hormone secretions. The present experiments were designed to investigate whether sex differences in food motivation might contribute to the behavioral differences observed when food-deprived male and female rats are exposed to appetitively motivated operant learning tasks. Male and female Wistar rats were exposed to different progressive ratio schedules of reinforcement which have been shown to generate reliable indices of 'motivational' conditions. In progressive ratio schedules, subjects are required to make a systematically increasing number of responses for each successive reinforcer, until the requirement becomes so large that the subjects stop responding. Expt. Ia was designed to investigate whether or not food-deprived males would be more motivated than food-deprived females to obtain food. Expt. Ib investigated whether gonadectomy might differentially affect food motivation of male and female rats exposed to a progressive ratio schedule of reinforcement. Motivational differences between males and females were not observed. Males and females obtained an equal number of reinforcers, while differences in the total number of responses and response rate were not observed. Gonadectomy did not affect the total number of responses in the final completed ratio. The results of the present experiments do therefore not support the hypothesis that sex differences in food motivation might underlie sex differences in behavior when food-deprived male and female rats are exposed to operant schedules of positive reinforcement.

Animals↗

The human corpus striatum and dentate nucleus: volumetric analysis for hemispheric asymmetries, sex differences, and aging changes.

The corpus striatum and the dentate nucleus were examined for volumetric asymmetries, sex differences in volume, and for aging changes in volume in a sample of 27 human brains ranging in age from 281 days of gestation to 94 years of age. No statistically significant hemispheric asymmetries were found, and no sex differences in volume or in degree of hemispheric asymmetry were found. It was found that the volumes of the corpus striatum and the dentate nucleus decrease in relation to the volume of the whole hemisphere with aging, but the rate of decrease is different before than after sexual maturity. The significance of these findings is discussed in relation to lateralization of motor functioning, sex differences in the brain, and aging changes in the brain.

Adolescent↗

Sex differences in diabetes induced by neonatal streptozotocin treatment in spontaneously hypertensive rats.

We examined the sex differences in the development of diabetes due to neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) which are more prone to diabetes than normotensive rats. Male and female SHR were intraperitoneally injected with various doses of STZ at 2 days after birth. In those treated with vehicle or 25 mg/kg of STZ, there were no sex differences in plasma glucose levels, which changed little during the 12 weeks of observation. When treated with 50 mg/kg of STZ, however, male SHR developed overt hyperglycemia greater than 300 mg/dl plasma glucose after 8 weeks of age, while females showed a minimal change in plasma glucose levels. When given 75 mg/kg of STZ, female rats developed overt hyperglycemia at 4-6 weeks of age, during which time male SHR showed no apparent hyperglycemia. At 8 weeks or later, however, both males and females had similarly high levels of plasma glucose. Glycosylated hemoglobin at 12 weeks was compatible with plasma glucose levels in each group. The present results indicate that there are sex differences in susceptibility to neonatal STZ treatment and in development of hyperglycemia.

Aging↗

Sex differences in patients with mesial temporal lobe epilepsy.

Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.

Adult↗

[Sex differences in the physical dependence on barbital in rats].

Sex differences in physical dependence on barbital (BAR), which is not readily metabolized in rats, were studied by the drug-admixed food method. The concentration of BAR in the food was gradually increased from 1 and 2 up to 6 and 8 mg/g food concurrently available to each rat over a period of 36 days in both male and female Sprague-Dawley rats. Sedation and muscle relaxation were observed in males at the 4 and 6 mg/g condition and to a greater degree at 6 and 8 mg/g of food. This effect was seen only at the highest drug concentration, 6 and 8 mg/g food, in females. Physical dependence was assessed in both sexes after substitution of normal food for the BAR-admixed food. Various signs of BAR withdrawal were observed including vocalization, irritability, muscle rigidity, tremors and convulsions. The incidence of convulsions was 76.9% in females and 45.5% in males, respectively. Maximum weight loss was 15.4% in females and 12.1% in males. However, brain BAR concentrations in the male rats were higher than that in the female rats 9 hours before onset of withdrawal and at all later time points tested. Thus, we have demonstrated that weak sex differences in physical dependence on BAR exist and suggest that this difference resulted from a difference in CNS sensitivity to BAR.

Animals↗

Six-hydroxydopamine induced hyperactivity: neither sex differences nor caffeine stimulation are found.

We investigated possible sex differences in the development of locomotor activity in rats treated neonatally with desmethylimipramine (DMI) followed by intraventricular 6-hydroxydopamine (6-HDA). In addition, the locomotor response to the stimulant caffeine was investigated in the male rats after they had reached adulthood. Both male and female 6-HDA-treated rats exhibited increased activity relative to controls. No sex differences were seen in either the development or magnitude of this effect. Male rats were used to determine the dose effects function for caffeine (0.5, 5, 15, 30 mg/kg) on locomotor activity. Control rats exhibited increased locomotor activity whereas 6-HDA-treated rats showed no increases with any dose of caffeine. Large decreases in the dopamine content of the olfactory tubercle (-88%, -82%), nucleus accumbens (-96%, -95%), and striatum (-99%, -99%) were found in both male and female rats. Choline acetyltransferase and glutamic acid decarboxylase activities were unchanged.

Aging↗

Sex differences in interest in infants in juvenile rhesus monkeys: relationship to prenatal androgen.

Yearling rhesus monkey females interact more with infants than do males. However, the continuity of this sex difference throughout the juvenile period is unknown. Human females display similar sexually differentiated interest in infants, and studies of girls with congenital adrenal hyperplasia suggest that this sex difference may be modulated by prenatal androgen exposure. We investigated infant interest in 1- to 3-year-old juvenile rhesus monkeys. Hormonal influences on this behavior were investigated by treating pregnant females with an androgen-receptor blocker (flutamide), testosterone enanthate, or vehicle, early or late in gestation. Subjects were reared in their well-established natal groups, composed of species-typical matrilineal social structures, including members of all ages. Yearling control females interacted with infants more than did yearling control males. At 2 and 3 years of age, the magnitude of the sex difference in interactions with infants increased markedly, producing effect sizes of more than 2.5 standard deviations. These effects are larger than those reported in humans. Androgen treatment did not affect male or female interactions with infants, but late gestation flutamide masculinized aspects of females' interest in infants. Although early flutamide prevented complete masculinization of male genitalia, this treatment was not accompanied by any alterations in the masculine pattern of infant interest. We found no evidence that the robust juvenile sex difference in frequency of infant interactions results from socialization. However, it was largely unaffected by our hormone manipulations. Whether this reflects characteristics of our specific treatments or is evidence of nonhormonal influences on infant interest remains unanswered.

Age Factors↗

Sex differences in the activational effects of gonadal hormones on food intake and body weight.

Estrogens have been shown to decrease, and androgens to increase body weight (BWt) of guinea pigs (GPs). The magnitude of the BWt sex difference shown by intact adult GPs is due primarily to these concurrent, or activational, effects of gonadal steroids. However, a small but significant sex difference in BWt persists in animals gonadectomized at birth, indicating that early hormonal exposure may permanently influence certain steroid sensitive weight regulatory mechanisms in the two sexes. Three experiments were therefore designed to investigate the short term effects of estradiol and testosterone on food intake (FI) and BWt of gonadectomized adult male and female GPs. In the first experiment, GPs gonadectomized in adulthood were given a single injection of 6 micrograms estradiol benzoate (EB). Although EB treatment reduced FI and BWt of both females and males, significantly larger reductions occurred in females. In the second experiment, GPs gonadectomized at birth received treatments of oil or 2 micrograms EB for 7 days. EB treatment also produced significantly larger effects on FI and BWt in the neonatally gonadectomized females. The third experiment involved GPs gonadectomized as adults who were injected with either oil or 1 mg/day testosterone propionate in oil (TP) for 32 days. Compared to changes in oil injected controls, TP produced significantly larger increases in male BWt than female BWt. Therefore, although GPs show only minor sex differences in BWt which might relate to prenatal gonadal hormonal exposure, significant sex differences remain in their responsiveness to the activational effects of gonadal steroids on FI and BWt in adulthood.

Animals↗

Sex differences in the expression of haemorheological determinants in individuals with atherothrombotic risk factors and in apparently healthy people.

BACKGROUND: Increased red cell aggregation can be detrimental, leading to slow capillary blood flow and tissue hypoxaemia. Sex differences in the degree of erythrocyte adhesiveness/aggregation in the peripheral blood have not been clearly shown. OBJECTIVES: To determine whether there are sex differences in the expression of erythrocyte adhesiveness/aggregation in the peripheral blood in individuals with atherothrombotic risk factors and in apparently healthy people. METHODS: From a cohort of 965 participants in the Tel Aviv Medical Centre inflammation survey, 192 pairs of different sex were matched for age, body mass index, hip and waist circumferences, cardiovascular risk factors, and the intake of active cardiovascular drugs. RESULTS: Women had an enhanced degree of red cell aggregation (p < 0.0005) as well as increased concentrations of inflammation sensitive proteins including fibrinogen and C reactive protein. Women had a lower haemoglobin concentration than men, but this did not affect the degree of erythrocyte adhesiveness/aggregation. CONCLUSIONS: The significant increase in red blood cell adhesiveness/aggregation in the peripheral blood of women with atherothrombosis could be relevant to the more eventful course that some women experience during and following acute ischaemic disease.

Anemia↗

Biological basis of sex differences in drug abuse: preclinical and clinical studies.

The recent focus on drug abuse in women has brought attention to numerous differences between women and men. In this review, we discuss both preclinical and clinical findings of sex differences in drug abuse as well as mechanisms that may underlie these differences. Recent evidence suggests that the progression to dependence and abuse may differ between women and men; thus, different prevention and treatment strategies may be required. Similar sex differences in drug sensitivity and self-administration have been reported in laboratory animal studies. Females appear to be more vulnerable than males to the reinforcing effects of psychostimulants, opiates, and nicotine during many phases of the addiction process (e.g. acquisition, maintenance, dysregulation-escalation, relapse). Male and female animals differ in their behavioral, neurological, and pharmacological responses to drugs. Although the role of sex in the mechanisms of drug action remains unclear, preclinical and clinical studies indicate that ovarian hormones, particularly estrogen, play a role in producing sex differences in drug abuse. Future research is necessary to provide information on how to design more effective drug abuse treatment programs and resources that are sex specific.

Animals↗

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Activities of Daily Living↗

Adult sex differences on a decision-making task previously shown to depend on the orbital prefrontal cortex.

Monkeys and children show sex differences on tasks that depend on the orbital prefrontal cortex. To determine whether similar sex differences exist across the life span, adults were tested on an orbital-dependent decision-making task, the Iowa Card Task, as well as on a control task, the California Weather Task. In addition, estradiol, progesterone, and testosterone were assayed. The 6 groups of participants were college-age men, older men, young low-hormone (menstruating) women, young high-hormone (midluteal) women, older postmenopausal women on estrogen replacement therapy (ERT), and older postmenopausal women not on ERT. Results showed a male superiority on the Iowa Card Task. Among college-age men there was a negative correlation between performance and testosterone levels. There were no significant differences among groups of women on the card task. There were no significant sex differences or hormone correlations on the California Weather Task.

Adult↗

Sex differences in the play behavior of immature spotted hyenas, Crocuta crocuta.

Social, locomotor, and object play were studied in a colony of five male and five female peer-reared spotted hyenas during 12 1-hr tests while the animals were 13-19 months of age. Animals were tested in both same-sex and mixed-sex groups and were stimulated to play by the introduction of fresh straw and sawdust bedding. Each test was videotaped and the frequency of each type of play was determined by a time sampling procedure. Females played more frequently than males, however, the category of play which was elevated depended upon the social context during testing. In same-sex tests the frequency of vigorous social play displayed by females markedly exceeded that by males, but no comparable sex difference appeared in mixed-sex tests. Females engaged in locomotor play more frequently than males in mixed-sex tests, but no comparable sex difference appeared in same-sex tests. No sex difference in object play was observed. Two male and two female hyenas were gonadectomized prior to the initiation of the present sequence of tests. The results suggest that gonadectomy during the prepubertal period does not affect the frequency of play behavior. However, the small sample sizes preclude any conclusive determination of the effects of these gonadectomies on play.

Animals↗

The nature of the sex difference in right hemisphere superiority for face recognition.

Two experiments on right hemisphere superiority for upright face recognition by normal adults are reported. Experiment 1 showed that right hemisphere superiority for face recognition is affected by the ratio of stimuli to trials used in the experiment. A low ratio of stimuli to trials (Condition A) gave right hemisphere superiorities for both male and female subjects, whereas a high ratio of stimuli to trials (Condition C) led to no visual hemifield difference for male or for female subjects. The use of a stimuli to trials ratio intermediate between those of Condition A and Condition C resulted in a sex difference, with males but not females showing right hemisphere superiority in Condition B. It is argued that both males and females possess asymmetrically organised face processing mechanisms whose operation is dependent upon the level of difficulty of the face memory task used in a particular experiment, but that there is a sex difference in the range across which these mechanisms can operate. Experiment 2 demonstrated that this sex difference does not simply reflect an underlying sex difference in the tendency to use configurational or piecemeal strategies in such experiments.

Adult↗