Androgens and eye movements in women and men during a test of mental rotation ability

Eye movements were monitored in 16 women and 20 men during completion of a standard diagram-based test of mental rotation ability to provide measures of cognitive function not requiring conscious, decisional processes. Overall, women and men allocated visual attention during task performance in very similar, systematic ways. However, consistent with previous suggestions that sex differences in attentional processes during completion of the mental rotation task may exist, eye movements in men compared to women indicated greater discrimination and longer processing of correct alternatives during task performance. Other findings suggested that androgens may enhance cognitive processes that are recruited differentially by women and men as a function of the task. Specifically, smaller (i.e., more masculine) digit ratios were associated with men's shorter fixations on distracters, suggesting that perinatal androgen action may influence brain systems that facilitate the identification of relevant task stimuli. In women, higher circulating testosterone levels appeared to contribute to more general processes engaged during task performance, for example higher levels of visual persistence. It is possible that variability in the relative contribution of such hormone sensitive cognitive processes to accuracy scores as a function of different sample characteristics or assessment methods may partially account for the inconsistent findings of previous research on hormonal factors in mental rotation ability.     

Evidence for the influence of testosterone in the performance of spatial navigation in a virtual water maze in women but not in men

Testosterone (T) may be associated with enhanced spatial navigation in a number of rodent species, although the nature of the relation is equivocal. Similarly, numerous studies in humans generally have found that T is associated with enhanced spatial ability on a variety of paper and pencil tasks that may relate to navigational ability. However, relatively few studies have reported effects of T on navigational ability in humans. We investigated the relationship between endogenous T and performance on a virtual water maze (vWM) and mental rotations test (MROT). ELISA for T was performed on salivary samples that were obtained from participants before and after completion of both spatial tasks. Results indicated that women with low T required more time to locate the hidden platform in the vWM than either group of men or women with high T. Significant negative correlations were found for the entire sample between vWM performance and T, and between vWM latency to escape and MROT. Similar significant correlations were found in women but not men. Thus, our data support the position that T improves performance in the vWM in a linear fashion, most strongly in women. However, further work is needed to confirm this hypothesis in humans.     

Sex hormones influence human cognitive pattern

The major sex differences in cognitive skills are summarized, and the role of sex hormones in early organization and possible maintenance of these differences is discussed. Using animal models and human hormonal anomalies, a good case can be made that prenatal androgens strongly influence adult cognitive pattern, though the relation between baseline androgens and spatial ability, for example, need not be linear. Moreover, men and women remain sensitive to variation in hormonal state, as evidenced in the fluctuations in cognitive and motor performance across natural diurnal, menstrual and circannual rhythms. Evidence from administration of exogenous hormones in humans is more equivocal, though this field ultimately should yield useful information.     

Sex steroid hormones and cognitive functioning in healthy, older men

The precise impact of age-related changes in hormone levels on cognition in men is still unclear due to differing study designs and contradictory findings. This study was undertaken to examine the relationship between endogenous sex hormone levels and cognitive functioning in healthy older men using a comprehensive battery of neuropsychological tests and measurement of serum sex hormone levels. Verbal learning and memory, visual-motor processing, spatial abilities, working memory and attention, and levels of testosterone and estradiol were evaluated in 54 healthy older men. Regression analyses revealed significant curvilinear associations between working memory function and both free and bioavailable testosterone levels, suggesting that an optimal hormone level may exist for maximal performance on tasks of executive/frontal lobe functioning. However, no other relationships were evident between either estradiol or testosterone levels and any of the other cognitive functions evaluated. Hormone assays performed at the end of the study revealed that a considerable portion of the healthy elderly men in our sample met criteria for hypogonadism and suggests that their low hormone levels may have mitigated against discovering other significant hormone-cognition relationships.     

Age-Related Differences in Multiple Task Monitoring

Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults'' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.     

Cognitive performance in rhesus monkeys varies by sex and prenatal androgen exposure

Men and women differ on performance and strategy on several spatial tasks. Rodents display similar sex differences, and manipulations of early hormone exposure alter the direction of these differences. However, most cognitive testing of nonhuman primates has utilized sample sizes too small to investigate sexually differentiated behaviors. This study presents an investigation of sex differences and the effects of prenatal androgen on spatial memory and strategy use in rhesus monkeys. Monkeys prenatally exposed to vehicle, testosterone, or the androgen receptor blocker flutamide performed a search task in which 5 of 12 goal boxes contained food rewards. Spatial consistency and the presence of local landmarks were varied. Performance when both spatial and marker cues were available did not differ by sex or prenatal treatment. Contrary to predictions, females easily solved the task when local markers were removed, and their performance outscored males. Although eliminating spatial consistency and requiring subjects to use local markers impaired performance by all monkeys, females continued to locate correct goal boxes at higher than chance levels and scored better than males. Blocking prenatal androgen exposure in males improved use of local markers. These findings suggest that the tendency to attend to landmarks and to use them in solving spatial problems is typical of females across many species, including rodents, humans, and rhesus monkeys. In rhesus monkeys and rodents, developmental androgen eliminates this specialization. However, these results are the only known example of better performance of females than males when salient markers are removed.     

Sex differences in mushroom gathering: men expend more energy to obtain equivalent benefits

Some of the strongest evidence for sex differences in human cognition relate to spatial abilities, with men traditionally reported to outperform women. Recently, however, such differences have been shown to be task dependent. Supporting the argument that a critical factor selecting for sex differences in spatial abilities during human evolution is likely to have been the division of labor during the Pleistocene, evidence is accumulating that women excel on tasks appropriate to gathering immobile plant resources, while men excel on tasks appropriate to hunting mobile, unpredictable prey. Most research, with the exception of some recent experimental field studies, has been conducted in the laboratory, with little information available on how men and women actually forage under natural conditions. In a first study, we GPS-tracked the foraging pathways of 21 pairs of men and women from an indigenous Mexican community searching for mushrooms in a natural environment. Measures of costs, benefits and general search efficiency were analyzed and related to differences between the two sexes in foraging patterns. Although men and women collected similar quantities of mushrooms, men did so at significantly higher cost. They traveled further, to greater altitudes, and had higher mean heart rates and energy expenditure (kcal). They also collected fewer species and visited fewer collection sites. These findings are consistent with arguments in the literature that differences in spatial ability between the sexes are domain dependent, with women performing better and more readily adopting search strategies appropriate to a gathering lifestyle than men.     

Evidence that androgenic and estrogenic metabolites contribute to the effects of dehydroepiandrosterone on cognition in postmenopausal women

Prior studies of the effects of dehydroepiandrosterone (DHEA) on cognition have produced complex and inconsistent results. We hypothesize that these results may arise, in part, because of DHEA's metabolism into estrogens and androgens that produce opposing effects on cognition. Our study administered 50 mg of oral DHEA daily for 4 weeks in a placebo-controlled crossover design to six postmenopausal women. We measured blood levels of androgens (total testosterone, free testosterone, DHEA, DHEAS), estrogens (estradiol, estrone), and cognitive performance on recognition memory, perceptual identification, digit span memory, and visual attentional vigilance under both drug and placebo conditions. Multiple regression models incorporating the factors of age and body mass index (BMI) were used to ascertain the relation between sex steroids and cognitive performance. Our results demonstrated that estrogens produced a positive effect on recognition memory, while androgens produced a negative effect. This pattern reversed in perceptual identification with estrogens producing a negative effect and androgens producing a positive effect. In addition, BMI produced a negative effect on digit span memory, age produced a negative effect on perceptual identification, and androgens produced a negative effect on visual attentional vigilance. These results help, in part, to explain DHEA's complex effects on cognition. The diverse effects of sex steroids across tasks underscore the importance of identifying the specific cognitive mechanisms influenced by sex steroids and emphasizes that one should not expect sex steroids to produce homogeneous effects across cognitive tasks.     

Chronic stress effects on memory: sex differences in performance and monoaminergic activity

Increasing evidence suggests that the time course of advantageous versus deleterious effects of stress on physiologic function is also apparent in some brain functions, including learning and memory. This article reviews the effects of chronic stress on behavioral performance and, more importantly, shows that sex of the subject, as well as duration and intensity of stress, is an important determinant of the functional/behavioral, neurochemical, and anatomical consequences of the stress. Following chronic stress (7-28 days of restraint, 6 h/day), male and female rats were tested on a visual memory task (object recognition) and two spatial memory tasks (object placement and radial arm maze). At 21 days, stress impaired males on all tasks while females were either enhanced (spatial memory tasks) or not impaired (nonspatial memory tasks). Additionally, the influence of the hypothalamic-pituitary-adrenocortical axis in mediating the sex-specific responses to stress is considered. Behavioral and neurochemical assessments following chronic stress in ovariectomized females, with and without estradiol, suggest that estrogen exerts both organizational and activational influences on the observed sex differences in response to stress. Furthermore, stress differentially affected central transmitter levels in the frontal cortex, hippocampus, and amygdala depending on sex. The possible role of these sex-specific changes in neurotransmitter levels in mediating behavioral differences in response to stress is discussed. While these results are thus far limited to a few studies and require both further investigation and verification, chronic stress appears to be associated with distinct, sex-differentiated behavioral/cognitive and neurochemical responses. We conclude that sex differences must be taken into account when investigating or describing stress and associated sequalae.     

Virtual navigation in humans: the impact of age, sex, and hormones on place learning

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.     

Androgens and body fat distribution

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.     

The contribution of the androgen receptor (AR) in human spatial learning and memory: A study in women with complete androgen insensitivity syndrome (CAIS)

Few studies have examined the impact of androgen insensitivity on human spatial learning and memory. In the present study, we tested 11 women with complete androgen insensitivity syndrome (CAIS), a rare genetic disorder characterized by complete absence of AR activity, and compared their performance against 20 comparison males and 19 comparison females on a virtual analog of the Morris Water Maze task. The results replicated a main sex effect showing that men relative to women were faster in finding the hidden platform and had reduced heading error. Furthermore, findings indicated that mean performance of women with CAIS was between control women and control men, though the differences were not statistically significant. Effect size estimates (and corresponding confidence intervals) of spatial learning trials showed little difference between women with CAIS and control women but CAIS women differed from men, but not women, on two variables, latency to find the platform and first-move latency. No differences between groups were present during visible platform trials or the probe trial, a measure of spatial memory. Moreover, groups also did not differ on estimates of IQ and variability of performance. The findings are discussed in relation to androgen insensitivity in human spatial learning and memory.     

Women Who Know Their Place

Differences between men and women in the performance of tests designed to measure spatial abilities are explained by evolutionary psychologists in terms of adaptive design. The Hunter-Gatherer Theory of Spatial Ability suggests that the adoption of a hunter-gatherer lifestyle (assuming a sexual division of labor) created differential selective pressure on the development of spatial skills in men and women and, therefore, cognitive differences between the sexes. Here, we examine a basic spatial skill-wayfinding (the ability to plan routes and navigate a landscape)-in men and women in a natural, real-world setting as a means of testing the proposition that sex-based differences in spatial ability exist outside of the laboratory. Our results indicate that when physical differences are accounted for, men and women with equivalent experience perform equally well at complex navigation tasks in a real-world setting. We conclude that experience, gendered patterns of activity, and self-assessment are contributing factors in producing previously reported differences in spatial ability.     

Testosterone levels and cognitive functioning in women with polycystic ovary syndrome and in healthy young women

We investigated the possible influence of testosterone (T) on cognitive functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder associated with elevated levels of free testosterone (free T). Performance on a battery of neuropsychological tests in 29 women with elevated free T levels due to PCOS was compared to the performance of 22 age- and education-matched, healthy control women with free T levels in the normal female range. Women with PCOS had significantly higher levels of free T (estimated by the free androgen index) and demonstrated significantly worse performance on tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory than the healthy control women. No differences between the groups were found on tests of mental rotation, spatial visualization, spatial perception, or perceptual speed. These results suggest that, in women, elevations in free T may be associated with poorer performance on cognitive tasks that tend to show a female advantage.     

Sexual Differentiation of Cognitive Abilities in Women Exposed to Diethylstilbestrol (DES) Prenatally

In nonhuman animals, prenatal exposure to androgens or estrogens enhances development of male-typical characteristics (masculinizes) and impairs development of female-typical characteristics (defeminizes). We investigated the hypothesis that prenatal exposure to the synthetic estrogen, diethylstilbestrol (DES), similarly masculinizes or defeminizes cognitive development in women. Forty-two DES-exposed women and 26 of their unexposed sisters were studied. No group differences were seen for abilities at which females excel on average (verbal fluency, perceptual speed and accuracy, and associative memory), for abilities at which males excel on average (visuospatial abilities), or for abilities that do not show sex differences (vocabulary, nonverbal intelligence). The time of prenatal exposure to DES correlated with visuospatial performance with later exposure associated with better performance. However, the subgroup of women exposed to DES late in gestation did not differ from unexposed women on these measures. Results support the conclusion that prenatal exposure to DES has little or no influence on cognitive development in women. However, they do not preclude other types of early hormonal influences on human cognition, such as prenatal influences of androgen or influences of androgens or estrogens during the early postnatal period.     

Sex Differences in Hypertension: Contribution of the Renin–Angiotensin System

Numerous studies have shown that female human beings exhibit lower blood pressure levels over much of their life span compared with their age-matched counterparts. This sexual dimorphism is apparent in human beings as well as most, if not all, mammals. However, after the onset of menopause blood pressure levels in women increase and become similar to those in men, suggesting an important role of sex hormones in the regulation of blood pressure. The lower blood pressure levels in premenopausal women are associated with a lower risk of development and progression of cardiovascular disease and hypertension compared with age-matched men. This clear female advantage with respect to lower incidence of cardiovascular disease no longer exists after menopause, again highlighting the importance of sex hormones in the pathophysiology of cardiovascular disease in both men and women. In fact, both estrogens and androgens have been implicated in the development of cardiovascular disease and hypertension, with estrogens, in general, being protective and androgens being detrimental. Although the exact mechanisms by which sex hormones contribute to the regulation of cardiovascular function and blood pressure are still being investigated, there is increasing evidence that modulating the activity of locally active hormonal systems is one of the major mechanisms of sex hormone actions in target organs, including the vasculature and kidneys. Indeed, several studies have demonstrated the importance of the interaction between sex hormones and the renin–angiotensin system in regulating cardiovascular function and blood pressure. Furthermore, the differential effects of estrogens and androgens on the expression and activity of the components of the renin–angiotensin system could possibly explain the sex differences in blood pressure levels and the development and progression of cardiovascular disease and hypertension.     

Menstrual cycle variation in spatial ability: relation to salivary cortisol levels

This study examined whether menstrual cycle phase was associated with performance on the Primary Mental Abilities Test of Spatial Relations, a test of mental rotation, in undergraduate students (N = 82). As cortisol levels also vary across the menstrual cycle under conditions of stress and influence cognitive performance, saliva samples were obtained before and after the test session to examine whether cortisol levels were related to between- and within-group differences in spatial performance. Men scored higher on the spatial test than all the groups of women, although the difference between men and women in the menstrual phase was not significant. Women in the luteal phase scored lower than the menstrual, follicular, and oral contraceptive user groups of women. There were no sex or menstrual cycle differences in cortisol levels, and no association between cortisol levels and spatial performance. The poorer performance of women in the luteal phase was not related to differences in ratings of perceived stress, perceived success on the test, or mood. Although menstrual cycle phase accounted for a significant proportion of the variance (15%) in performance on the spatial test, this does not explain why men outperformed women regardless of the phase of the cycle. Thus, there are clearly several other variables, sociocultural and physiological, involved in mediating individual differences in spatial performance.     

Sex differences in search and gathering skills

The hunter–gatherer theory of sex differences states that female cognition has evolutionarily adapted to gathering and male cognition to hunting. Existing studies corroborate that men excel in hunting-related skills, but there is only indirect support for women excelling in gathering tasks. This study tested if women would outperform men in laboratory-based computer tests of search and gathering skills. In Experiment 1, men found target objects faster and made fewer mistakes than women in a classic visual search study. In Experiment 2, participants gathered items (fruits or letters presented on screen), and again, men performed significantly better. In Experiment 3, participants' incidental learning of object locations in a search experiment was studied, but no statistically significant sex differences were observed. These findings found the opposite of what was expected based on the hypothesis that female cognition has adapted to gathering. Alternative interpretations of the role of object location memory, female gathering roles and the division of labor between the sexes are discussed.     

Digit length ratios predict reactive aggression in women, but not in men

Considerable evidence suggests that digit length and dermatoglyphic asymmetry patterns in the hand are affected by early exposure to androgens. Because androgens play an important role in sexual differentiation of morphological and behavioral traits, digit length patterns often display sex differences. When present, sex differences in digit lengths are more pronounced on the right side as compared to the left side. Moreover, the ratio of the second to fourth digit length (2D:4D) in the right hand is inversely correlated with testosterone (T) in men. Because T is implicated in agonistic behavior, 2D:4D may be used as a marker of androgen exposure and subsequent behavioral variation in adulthood. Consequently, we investigated the relationships among 2D:4D, directional asymmetry of 2D:4D (left hand 2D:4D minus right hand 2D:4D) as a variant of T, and human reactive aggression. One hundred young men (n = 51) and women (n = 49) participated in our experiments (mean age = 20.1 years). Participants called two noncompliant confederates to solicit donations for a fictitious charity organization and selected follow-up letters after the calls. The force exerted when hanging up the phone and the "tone" of the follow-up letters were used to assess reactive aggression. High aggression scores were associated with high directional asymmetry of 2D:4D and masculinized (low) right hand 2D:4D, only in females and under high provocation. Directional asymmetry of 2D:4D was positively correlated with T in males (pooled data, n = 97). Taken together, these data confirm the predominantly right-sided influence of androgens on digit length and suggest that digit length ratios may be associated with female reactive aggression when sufficient provocation is present.     

Cognitive outcome in adult women affected by congenital adrenal hyperplasia due to 21-hydroxylase deficiency

BACKGROUND: Some research suggests that girls with congenital adrenal hyperplasia (CAH), who are exposed to higher than normal levels of prenatal androgens, perform better on spatial tasks, worse on verbal tasks and have a greater incidence of left-handedness than unaffected controls, all of which suggests the development of a more male-typical cognitive pattern. However, research in all three areas has produced inconsistent findings. OBJECTIVES: To determine if prenatal androgen exposure has an organizing effect on female cognitive development and to what extent. METHODS: 24 women, 21-71 years, with either the salt-losing (SL) or simple virilizing (SV) forms of CAH due to 21-hydroxylase deficiency, and 18 controls, 21-73 years, who were unaffected female relatives or women with polycystic ovary syndrome, were assessed with IQ, handedness, executive function, verbal learning and memory, non-verbal learning and memory, perceptual speed, visuospatial processing and visuomotor ability measures. The battery included tests known to elicit sex differences and control measures. RESULTS: The findings did not support the hypothesis that women with CAH develop a more male-typical cognitive pattern. CONCLUSION: This study differs from others in the older age of its participants, grouping by SL/SV diagnosis and assessment of medical treatment and compliance as determined through hormone assays. Our findings provide additional support for the conclusion that, in adult women with CAH, previous prenatal androgen exposure does not enhance spatial abilities, impair verbal abilities nor alter hand preferences in a long-lasting way.