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PubMed2001

Sex differences in cardiac catheterization: the role of physician gender.

CONTEXT: Many studies indicate that women are less likely than men to undergo cardiac procedures after an acute myocardial infarction (AMI), raising concerns of sexual bias in clinical care. However, no data exist regarding the relationship between patient sex, physician sex, and use of cardiac procedures. OBJECTIVE: To determine whether sex differences in cardiac catheterization after AMI were greater when patients were treated by male attending physicians compared with female attending physicians. DESIGN, SETTING, AND PATIENTS: Analysis of data from the Cooperative Cardiovascular Project, a retrospective medical record review. A total of 104 >231 Medicare fee-for-service beneficiaries who were hospitalized in US acute care hospitals for an AMI between January 1994 and February 1995. MAIN OUTCOME MEASURE: Use of cardiac catheterization within 60 days of admission, compared between the 4 groups of patient sex-physician sex combinations. RESULTS: Women underwent fewer cardiac catheterizations than men when treated by either male physicians (38.6% vs 50.8%; P =.001) or female physicians (34.8% vs 45.8%; P =.001). Sex differences in procedure use were not greater when a patient and physician were of different sexes (P for interaction =.85). After potential confounders in multivariable analysis were accounted for, women were less likely to undergo cardiac catheterization (risk ratio, 0.90 [95% confidence interval (CI), 0.88-0.92]), regardless of the treating physician's sex. Patients treated by male physicians were more likely to undergo cardiac catheterization (risk ratio, 1.06 [95%CI, 1.02-1.10]) than those treated by female physicians, regardless of patient sex. CONCLUSIONS: Women who have had an AMI undergo a cardiac catheterization less often than men, whether treated by a male or female physician. These results suggest that factors other than sexual bias by male physicians toward women account for sex differences in cardiac procedure use.

Aged↗

PubMed2000

Androgen receptor expression is greater in macrophages from male than from female donors. A sex difference with implications for atherogenesis.

BACKGROUND: Male sex is an independent risk factor for the extent and severity of atherosclerosis. The influence of androgens on foam cell formation, a key event in atherogenesis, has not yet been investigated. METHODS AND RESULTS: Primary human monocytes were allowed to differentiate into macrophages. RNA was then extracted from healthy male-donor (n=8) and premenopausal female-donor (n=8) macrophages, and message for the androgen receptor (AR) was examined by RT-PCR. There was a significantly higher level of AR mRNA in macrophages isolated from men than in those from women (0.64+/-0.06 versus 0.15+/-0.02 amol/microgram total RNA; P<0.001). AR mRNA levels were similar in macrophages from postmenopausal and premenopausal women (P=0.16). The functional consequence of this sex difference was then explored. Lipid-loading studies were performed on male (n=9) macrophages treated with the androgen dihydrotestosterone (DHT) and/or the AR antagonist hydroxyflutamide. These showed that DHT caused a dose-dependent and receptor-mediated increase in macrophage cholesteryl ester content (109+/-10%, 117+/-3%, and 120+/-4% for 4, 40, and 400 nmol/L DHT, respectively, as a percentage of control, P=0.002; 95+/-8% for DHT with hydroxyflutamide, P=0.58 versus controls). By contrast, there was no significant effect of androgen on lipid loading in female-donor macrophages (P>0.2 versus controls). CONCLUSIONS: Sex differences in androgen-mediated macrophage lipid loading may contribute to the greater prevalence and severity of atherosclerosis in men.

Adult↗

PubMed1999

Developmental sex differences in amino acid neurotransmitter levels in hypothalamic and limbic areas of rat brain.

GABA, glutamate and aspartate are the predominant amino acid neurotransmitters in the mammalian brain. We have previously reported a developmental sex difference in messenger RNA levels of glutamate decarboxylase, the rate-limiting enzyme in GABA synthesis [Davis A. M. et al. (1996) Horm. Behav. 30, 538-552]. Males were found to have significantly higher levels of messenger RNA in many steroid-concentrating regions of the hypothalamus and limbic system on day 1 of life. Therefore, in this study, we have examined levels of amino acid neurotransmitters during early postnatal development in many of the same or related brain areas. We found that levels of all three transmitters change as animals age. While both GABA and aspartate concentrations increase, glutamate levels decrease. In addition, there are sex differences in neurotransmitter levels in several areas examined, including the ventromedial and arcuate nuclei of the hypothalamus, and the CA1 region of the hippocampus. Sex differences for GABA occur only on postnatal days 1 and 5. However, sex differences in aspartate occur later in development (postnatal day 20). The CA1 region of males has a significantly greater concentration of GABA, glutamate and aspartate than females on postnatal day 1. In addition, treatment of females with testosterone propionate on the day of birth results in increased GABA levels, suggesting that these sex differences may be the result of hormone exposure during development. We hypothesize that these hormonally mediated sex differences in amino acid transmitters early in development contribute to the establishment of sexually dimorphic neuronal architecture in the adult.

Aging↗

PubMed2002

Sex differences in chronic stress effects on memory in rats.

Recent studies in rodent models and in humans have shown that the status of both the gonadal and adrenal axes (hypothalamic-pituitary-gonadal, HPG and hypothalamic-pituitary-adrenal, HPA, respectively) can influence learning and memory function. In this article, the effects of activating the HPA axis (stress) on performance of memory tasks in rats are reviewed. More importantly, results are presented which show that chronic stress has a different impact on performance of these tasks depending upon the sex of the rat. These observations are novel and potentially important since few studies, animal or human, have utilized females as subjects in studies of the stress response. Sex differences in the effects of chronic stress on memory were investigated in rats using an object recognition task and two spatial memory tasks, radial arm maze and object location. Given the same chronic stress--21 days of restraint for 6 h each day--males were impaired in all of the memory tests while females showed enhanced performance of the spatial memory tasks and no changes in object recognition performance. Levels of neurotransmitters and metabolites were measured in brain areas important for cognition in the subjects in order to determine neural systems that may respond to stress and mediate the cognitive responses. These results show that responses of monoamine and amino acid containing neural systems may contribute to or underlie sex differences in stress effects on cognition. Stress decreased dopaminergic activity in the frontal cortex and amygdala of males but not females; whereas, in CA3 of the hippocampus, stress increased levels of 5-HT and norepinephrine in females, but not males, and increased GABA in males, but not females. Finally, a possible role for estradiol in mediating sexually differentiated responses to stress was examined. Behavioral and neurochemical evaluations in ovariectomized, stressed females, with or without estrogen replacement, suggest that sex differences in response to stress are influenced by both the organizing and activating effects of estradiol. A few, recent studies in humans, that show sexually dimorphic relationships between chronic stress and cognition, are also highlighted. These results in humans are consistent with the pattern of results in rats. Clearly, further studies are necessary to substantiate sex differences in stress effects on memory function in humans and to understand mechanisms whereby estrogen may influence the stress response in rats. Nonetheless, recent studies show sexually differentiated cognitive responses to chronic stress and underline the importance of considering the sex/gender of subjects when studying the stress response.

Animals↗

PubMed2004

No evidence for sex differences in the severity and treatment of cancer pain.

While chronic pain is experienced by approximately 50-90% of patients with metastatic cancer, little is known about sex differences in chronic cancer pain. Therefore, the purposes of this study, in a sample of oncology outpatients (n=187) who were experiencing pain from bone metastasis, were: 1) to determine if there were sex differences in various pain characteristics, including pain intensity, and 2) to determine if there were sex differences in the prescription and consumption of analgesic medications. No significant sex differences were found in any of the baseline pain characteristics. In addition, no significant sex differences were found in analgesic prescriptions or intake of analgesic medications. Of note, men reported significantly higher pain interference scores for sexual activity than women. The study findings are important because they suggest that, unlike in acute pain, sex may not influence patients' perceptions of and responses to chronic cancer pain.

Aged↗

PubMed1995

Magnitude of sex differences in spatial abilities: a meta-analysis and consideration of critical variables.

In recent years, the magnitude, consistency, and stability across time of cognitive sex differences have been questioned. The present study examined these issues in the context of spatial abilities. A meta-analysis of 286 effect sizes from a variety of spatial ability measures was conducted. Effect sizes were partitioned by the specific test used and by a number of variables related to the experimental procedure in order to achieve homogeneity. Results showed that sex differences are significant in several tests but that some intertest differences exist. Partial support was found for the notion that the magnitude of sex differences has decreased in recent years. Finally, it was found that the age of emergence of sex differences depends on the test used. Results are discussed with regard to their implications for the study of sex differences in spatial abilities.

Aptitude↗

PubMed2002

Sex differences in visceral adipose tissue volume among African Americans.

BACKGROUND: Men are believed to have more visceral adipose tissue (VAT) than women have, but studies in African Americans that measured VAT from a single computed tomography (CT) slice found no sex difference. OBJECTIVE: We used a serial-slice CT scan to investigate whether there is a sex difference in VAT volume among African Americans. DESIGN: Single-slice CT measurements of VAT area at lumbar spine L2-3 and L4-5 levels were taken in 110 African Americans (44 men, 66 women). In 59 subjects (24 men, 35 women), VAT volume was also measured with contiguous CT slices from the diaphragm to the iliac crest. Fat mass was determined by dual-energy X-ray absorptiometry. RESULTS: Men and women had similar ages (x +/- SD: 36.1 +/- 7.8 and 35.6 +/- 7.8 y, respectively) and body mass indexes in kg/m(2) (29.5 +/- 6.9 and 32.0 +/- 8.9). The percentage of body fat was lower (P < 0.0001) in men (21.8 +/- 7.3%) than in women (37.4 +/- 7.9%). The VAT volume was greater (P = 0.01) in men (1443 +/- 931 cm(3)) than in women (940 +/- 821 cm(3)). There was no sex difference in unadjusted VAT area at L2-3 (men, 88.6 +/- 63.5 cm(2); women, 57.2 +/- 45.4 cm(2)) or L4-5 (men, 65.6 +/- 53.3 cm(2); women, 55.0 +/- 38.3 cm(2)). After adjustment for percentage of body fat or fat mass, men had larger VAT area at both levels (P < 0.01). After adjustment for body mass index, the sex difference in VAT area was detectable at L2-3 (P < 0.001) but not at L4-5 (P = 0.22). CONCLUSIONS: VAT volume is greater in men than in women. Detection of sex differences in VAT area among African Americans on single-slice CT requires adjustment for body fat content. At L2-3, adjustment for body mass index alone is adequate to detect sex differences in VAT.

Absorptiometry, Photon↗

PubMed2006

Sex differences in sleep: the response to sleep deprivation and restraint stress in mice.

STUDY OBJECTIVES: Numerous clinical studies and sleep surveys have shown pronounced sex differences in the occurrence of insomnia and other sleep pathologies. It has been suggested that sex differences in sleep, while subtle under baseline conditions, may increase in magnitude under biological or environmental challenges. However, controlled and experimental studies on sleep under challenged conditions rarely include female subjects. In this context, we examined sex differences in sleep in the mouse, not only under baseline conditions, but also after sleep deprivation and restraint stress. DESIGN: Adult male and female C57BL/6J mice were implanted with electrodes to record sleep-wake architecture and sleep electroencephalogram under baseline conditions and after 6 hours of sleep deprivation or 1 hour of restraint stress at the beginning of the daily light phase. RESULTS: Although baseline sleep patterns slightly differed between the sexes, the homeostatic recovery response to sleep deprivation was similar. In contrast, the changes in sleep after restraint stress were markedly different between male and female mice, with males displaying a stronger initial suppression of sleep and a stronger rebound of rapid-eye-movement sleep later in the recovery phase. CONCLUSIONS: In mice, the fundamental homeostatic properties of sleep regulation may not differ between the sexes, but the way sleep is affected and disrupted by environmental influences may be sex dependent. The latter may reflect sex differences in stress sensitivity.

Animals↗

PubMed1999

Sex differences in heat pain thresholds as a function of assessment method and rate of rise.

Studies of sex differences in the responses to experimentally induced pain demonstrate greater pain sensitivity among females than males. However, studies investigating heat pain responses have produced inconsistent results. Differences in stimulus characteristics and assessment methods probably account for this variability. This study examined sex differences in the heat pain threshold as a function of two different assessment methods and varying rates of rise. Nineteen female and 18 male healthy volunteers underwent heat pain threshold assessment via the method of levels and the method of limits. In addition, both fast (4.0 degrees C/s) and slow (0.5 degrees C/s) rates of rise were used for the method of levels assessments. In order to examine the reliability of threshold values, each subject participated in two sessions, separated by approximately 8 days. Females evinced lower thresholds than males for the method of levels assessments with both slow and fast rates of rise (ps < 0.05), while no sex differences emerged for the threshold assessed via the method of limits. Test-retest reliability coefficients were relatively high. However, thresholds generally increased significantly from session 1 to session 2. Between method correlations were generally low to moderate. These findings indicate that the method of levels may be more sensitive to sex differences than the more commonly used method of limits. Also, thresholds appear to increase from session 1 to session 2, and thresholds assessed via different methods are not strongly correlated. Potential implications of these results for experimental pain assessment are discussed.

Adult↗

PubMed2006

Aged rats: sex differences and responses to chronic stress.

Cognitive, as well as physiological, sex differences exist in young adult rats under both basal conditions and following chronic stress; however, few studies have examined whether sex differences remain in aged subjects and whether responses to stress are altered. We compared aged male and female Fischer 344 rats (21.5 months at testing) without stress and when given 21 days of restraint for 6 h/day on locomotion, anxiety-related behaviors, object recognition (non-spatial memory), object placement (spatial memory), body weight and serum steroid hormone levels. Control (unstressed) females had lower levels of estradiol and testosterone and higher corticosterone than males, and stress had no lasting effect on hormone concentrations. Females weighed less than males and showed less weight loss with stress. Locomotion measures on an open field were similar in the sexes and unaffected by stress. Anxiety-related behavior measures on the field showed that males were generally more anxious and that stress increased male, but decreased, female anxiety-related behaviors. In memory testing, exploration of objects was not different between the sexes, with or without stress, while stress increased exploration in both sexes during object recognition trials. Both males and females, regardless of treatment, discriminated between old and new objects at short, but not long, inter-trial delays. The typical advantage of young males for spatial memory performance was not observed in aged subjects on the object placement tasks. Stress-dependent enhancements in females and impairments in males for object placement are reported for young rats, but in aged rats, neither sex was altered by stress. Current data suggest that aging is associated with changes in the pattern of sex differences present in young adult rats in some behaviors and in the behavioral responses to stress.

Aging↗

PubMedDate not supplied

Sex differences in the pharmacologic effects of antiretroviral drugs: potential roles of drug transporters and phase 1 and 2 metabolizing enzymes.

Sex differences in the pharmacologic effects of antiretroviral drugs are increasingly being reported. Emerging evidence suggests that women may be at increased risk of developing adverse effects of antiretroviral drugs. Several mechanisms have been proposed to explain sex differences in drug effects, including physiologic differences between men and women and the influence of sex hormones on drug metabolism. This article reviews sex-related variations in the levels of expression and activities of drug transporters and metabolizing enzymes involved in the disposition of the antiretroviral drugs, and postulates that these variations may partly explain sex differences in the responses to these drugs. Studies that explore relationships between levels of expression and activities of relevant enzymes and drug transporters and observed sex-related differences in treatment responses to antiretroviral drugs will help clarify the extent to which molecules involved in drug disposition affect sex differences in treatment response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

A study of sex differences in presentation for care of HIV.

The current study examines sex differences in 183 male and 141 female patients presenting for care of HIV disease at an inner city hospital infectious disease clinic. Females (43%) were found to be less likely to have a history of illicit drug use (relative risk = .77, p < .01) and more likely to have become infected heterosexually (relative risk = 2.38, p < .01). However, a significant number of women reported both intravenous drug use (IVDU) and heterosexual exposure to an IVDU partner which complicates the analysis of the risk factors. Women sought testing because they knew that their sexual partners were HIV-positive (relative risk = 2.88, p < .01) Median CD4 counts at entry were significantly different (females = 340, males = 246; p < .01). Women were less likely to contract tuberculosis, the only infection which presented with a sex difference (relative risk = .38, p < .01) and to have previously had an AIDS defining infection (relative risk = .37, p < .01). Women took longer to progress to AIDS (42 vs. 19 months; p < .05). Survival of patients with AIDS was 51 months for females and 54 for males (p > 0.9). It did appear that the effect of a lower CD4 cell count on risk for death was magnified in patients who acquired their disease through heterosexual transmission. Women presented with higher CD4 counts, were more aware of their risk factors and fared better, with respect to progression to AIDS, than the men. The study underscored the impact of heterosexual transmission of the virus in women as well as the affect of this risk factor on disease progression. Hopefully, this information will initiate further studies on sex differences which will guide interventions and policy development.

AIDS-Related Opportunistic Infections↗

PubMed1993

Sex differences in responsiveness to painful and non-painful stimuli are dependent upon the stimulation method.

Sex differences in thermo- and electrocutaneous responsiveness to painful and non-painful stimuli were investigated in 20 women and 20 men. Heat pain, warmth, and cold thresholds were assessed on the hand and foot with a Peltier thermode system. In addition, subjects used magnitude estimation to judge the sensation intensity evoked by temperatures ranging from 38 degrees C to 48 degrees C applied to the forearm. To measure detection, pain, and tolerance thresholds of electrocutaneous sensitivity, electrical pulses were administered to the hand. Magnitude estimates of sensation intensity were assessed for stimuli ranging from 0.5 mA to 4.0 mA. There were no sex differences in heat pain, warmth and cold thresholds. There were significant sex differences in electrical detection, pain and tolerance thresholds, with lower thresholds in women. Correspondingly, magnitude estimates were similar in women and men when using thermal stimuli while women judged stimuli from 2.5 mA on as more intense than men when using electrical stimuli. Despite these discrepancies, the measures for pain responsiveness from the two stimulation methods correlated significantly. In contrast, no significant correlations between the methods were found when considering the responsiveness to non-painful stimuli. The findings help to clarify controversies in the pain literature about sex differences. Results affirming and denying such differences could be obtained within a single sample, with stimulation method as the critical variable.

Adult↗

PubMed1992

Sex differences in odor-stimulated flank marking in the golden hamster (Mesocricetus auratus).

To determine whether sex differences exist in the frequency of odor-stimulated flank marking, intact male and female hamsters were exposed to the recently vacated home cages of male stimulus hamsters for a 10-min test on 4 consecutive days. Females were found to mark at significantly higher levels than males. To investigate the role of gonadal hormones in the sex differences in flank marking, gonadectomized male and female hamsters were implanted with Silastic capsules containing estradiol or testosterone. Females exhibited twofold higher levels of odor-stimulated flank marking than males, and the amount of flank marking was significantly higher when the hamsters were administered testosterone than when they were administered estradiol. These data demonstrate that sex differences exist in the frequency of flank marking stimulated by the odors of male hamsters, and that these sex differences do not appear to result from the typical sex-specific patterns of circulating levels of estradiol and testosterone.

Animals↗

PubMed2006

How do health and biological age influence chronological age and sex differences in cognitive aging: moderating, mediating, or both?

Much research on cognitive competence in normal older adults has documented age and sex differences. The authors used new cross-sectional data from the Victoria Longitudinal Study (VLS) (n=386; age 61 to 95 years) to examine how health and biological age influence age and sex differences in cognitive aging. The authors found evidence for both moderating and mediating influences. Age differences were moderated by health status, such that the negative effects of age were most pronounced among participants of relatively better health. Sex differences were moderated by health and were more pronounced among participants reporting comparatively poorer health. Although health mediated a notable amount of age-related cognitive variation, BioAge mediated considerably more variance, even after statistical control for differences in health. A complex pattern emerged for the mediation of sex differences: Although BioAge accounted for sex-related variation in cognitive performance, health operated to suppress these differences. Overall, both health and BioAge predicted cognitive variation independently of chronological age.

Aged↗

PubMed1987

Assessing sex differences in neonatal survival: a study of discordant twins.

We identified 1699 liveborn twin pairs, discordant for sex. In this study, which essentially controls for gestational age, race, and maternal risk factors among males and females, there was no significant sex difference (108 male deaths and 103 female deaths) in neonatal mortality (p greater than 0.50). However, there was a sex difference in intrauterine growth, since 53% of the males, but only 42% of the females had birthweights greater than 2499 grams (p = 0.0002). A differential growth pattern can bias birthweight-specific assessments of survival. Such a bias may have been responsible for our finding that low-birthweight white females had better survival than did males in that category, since there was no such sex difference found among white twins born prematurely (greater than 36 weeks gestation). Therefore, we recommend that accurate assessments of sex differences in neonatal survival should be on the basis of gestational age, controlling for race and maternal risk factors.

Birth Weight↗

PubMedDate not supplied

Consistent sex differences in cortisol responses to psychological stress.

In four independent studies, sex differences in cortisol responses to psychological stress were investigated in healthy adolescents and adults (total n = 153). Public speaking and mental arithmetic in front of an audience (Studies 1-3) reliably induced increases in free cortisol levels in both sexes with 2- to 4-fold increases above baseline levels. Mean cortisol responses were 1.5- to 2-fold higher in men compared with women. In Study 3, cortisol profiles were additionally investigated after human corticotropin-releasing hormone (h-CRH) and bicycle ergometry until exhaustion. Here, both sexes showed very similar adrenocortical responses. Furthermore, men showed elevated cortisol levels in anticipation of the psychological stress situation without actually having to perform the tasks (Study 4). Under this condition cortisol concentration was unchanged or decreased in women. From these data we conclude that the observed sex difference does not reflect an overall lower responsiveness of the female adrenal cortex. Although these studies do not provide conclusive data, we suggest sex differences in cognitive and/or emotional responses to distressing psychosocial situations which in turn may influence cortisol secretion.

Adaptation, Psychological↗

PubMed1995

Sex differences and the effect of gonadectomy on morphine-induced antinociception and dependence in rats and mice.

1. Differences between sexes and the effect of bilateral surgical gonadectomy on the response to morphine analgesia and dependence were examined in rats and mice. 2. The analgesic response to morphine (5 mg/kg) was assessed by the hot plate and the abdominal constriction tests. Dependence was induced by injecting morphine at increasing doses (5-160 mg/kg) for 6 consecutive days and withdrawal signs elicited by injecting naloxone (2.5 mg/kg). 3. The base line reaction times in the intact control, sham-operated and gonadectomized animals of either sex were not significantly different from each other. 4. After treatment with morphine, the percentage increase in the reaction time in gonadectomized male and female rats and in gonadectomized male mice was significantly higher than in their respective controls. 5. The increase in the reaction time, after morphine treatment, was significantly higher in gonadectomized female rats than in gonadectomized male rats. 6. Naloxone-induced withdrawal signs in morphine-dependent gonadectomized rats and mice were not significantly different from those in sham-operated controls. However, female rats in both groups exhibited a significantly higher number of escape jumping responses than males.

Analgesia↗