Workshop summary: National Institutes of Health (NIH) 2022 scientific workshop on gender and health.

In this manuscript, we summarize the goals, content, and impact of the Gender and Health: Impacts of Structural Sexism, Gender Norms, Relational Power Dynamics, and Gender Inequities workshop held by the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) in collaboration with 10 NIH Institutes, Centers, and Offices. Specifically, we outline the key points emerging from the workshop presentations, which are the focus of the collection of articles in this supplement. The overarching goals of the workshop were to convene NIH staff, the external scientific community, and the public to discuss methods, measurement, modifiable factors, interventions, and best practices in health research on gender as a social and cultural variable and to identify opportunities to advance research and foster collaborations on these key topics. Themes emerging from the workshop include the need for intersectional measures in research on gender and health, the role of multilevel interventions and analyses, and the importance of considering gender as a social and structural determinant of health. Careful, nuanced, and rigorous integration of gender in health research can contribute to knowledge about and interventions to change the social and structural forces that lead to disparate health outcomes and perpetuate inequities.

Personality structure and social style in macaques.

Why regularities in personality can be described with particular dimensions is a basic question in differential psychology. Nonhuman primates can also be characterized in terms of personality structure. Comparative approaches can help reveal phylogenetic constraints and social and ecological patterns associated with the presence or absence of specific personality dimensions. We sought to determine how different personality structures are related to interspecific variation in social style. Specifically, we examined this question in 6 different species of macaques, because macaque social style is well characterized and can be categorized on a spectrum of despotic (Grade 1) versus tolerant (Grade 4) social styles. We derived personality structures from adjectival ratings of Japanese (Macaca fuscata; Grade 1), Assamese (M. assamensis; Grade 2), Barbary (M. sylvanus; Grade 3), Tonkean (M. tonkeana; Grade 4), and crested (M. nigra; Grade 4) macaques and compared these species with rhesus macaques (M. mulatta; Grade 1) whose personality was previously characterized. Using a nonparametric method, fuzzy set analysis, to identify commonalities in personality dimensions across species, we found that all but 1 species exhibited consistently defined Friendliness and Openness dimensions, but that similarities in personality dimensions capturing aggression and social competence reflect similarities in social styles. These findings suggest that social and phylogenetic relationships contribute to the origin, maintenance, and diversification of personality.

Rhesus macaques (Macaca mulatta) as living fossils of hominoid personality and subjective well-being.

Personality dimensions capturing individual differences in behavior, cognition, and affect have been described in several species, including humans, chimpanzees, and orangutans. However, comparisons between species are limited by the use of different questionnaires. We asked raters to assess free-ranging rhesus macaques at two time points on personality and subjective well-being questionnaires used earlier to rate chimpanzees and orangutans. Principal-components analysis yielded domains we labeled Confidence, Friendliness, Dominance, Anxiety, Openness, and Activity. The presence of Openness in rhesus macaques suggests it is an ancestral characteristic. The absence of Conscientiousness suggests it is a derived characteristic in African apes. Higher Confidence and Friendliness, and lower Anxiety were prospectively related to subjective well-being, indicating that the connection between personality and subjective well-being in humans, chimpanzees, and orangutans is ancestral in catarrhine primates. As demonstrated here, each additional species studied adds another fold to the rich, historical story of primate personality evolution.

Color signal information content and the eye of the beholder: a case study in the rhesus macaque.

Animal coloration has provided many classical examples of both natural and sexual selection. Methods to study color signals range from human assessment to models of receiver vision, with objective measurements commonly involving spectrometry or digital photography. However, signal assessment by a receiver is not objective but linked to receiver perception. Here, we use standardized digital photographs of female rhesus macaque (Macaca mulatta) face and hindquarter regions, combined with estimates of the timing of the female fertile phase, to assess how color varies with respect to this timing. We compare objective color measures (camera sensor responses) with models of rhesus vision (retinal receptor stimulation and visual discriminability). Due to differences in spectral separation between camera sensors and rhesus receptors, camera measures overestimated color variation and underestimated luminance variation compared with rhesus macaques. Consequently, objective digital camera measurements can produce statistically significant relationships that are probably undetectable to rhesus macaques, and hence biologically irrelevant, while missing variation in the measure that may be relevant. Discrimination modeling provided results that were most meaningful (as they were directly related to receiver perception) and were easiest to relate to underlying physiology. Further, this gave new insight into the function of such signals, revealing perceptually salient signal luminance changes outside of the fertile phase that could potentially enhance paternity confusion. Our study demonstrates how, even for species with similar visual systems to humans, models of vision may provide more accurate and meaningful information on the form and function of visual signals than objective color measures do.

Do females pay attention to secondary sexual coloration in vervet monkeys (Chlorocebus aethiops)?

Several primate species show sexual dichromatism with males displaying conspicuous coloration of the pelage or skin. Studies of scrotal coloration in male vervet monkeys (Chlorocebus aethiops) suggest that it is an important intrasexual signal, with relatively dark, colourful males dominating paler males. To date, no studies have examined the influence of male colour on intersexual social interactions in vervet monkeys. The primary goal of the present study was to evaluate whether female vervet monkeys attend to male coloration. We experimentally introduced females, housed with either "pale" or "dark" males, to stimulus males whose scrota were pale, dark, or pale but painted to look dark. Overall, during introductions, females did not differ in time spent directing affiliative behaviour toward pale, dark, and painted males; however, females, permanently housed with dark males, spent significantly more time directing affiliative behaviour toward pale than painted males. When the stimulus male was pale, affiliative exchanges between males and females were longer than when the stimulus male was painted. Home male colour was not related to female-initiated aggression. Home male colour was also not related to male-initiated aggression, although painted stimulus males were more likely to initiate aggression than pale stimulus males. These findings lead us to conclude that females pay attention to male coloration, but do not bias their interactions toward males solely on the basis of natural male coloration.

Bystanders affect the outcome of mother-infant interactions in rhesus macaques.

Animal communication involves the transfer of information between a sender and one or more receivers. However, such interactions do not happen in a social vacuum; third parties are typically present, who can potentially eavesdrop upon or intervene in the interaction. The importance of such bystanders in shaping the outcome of communicative interactions has been widely studied in humans, but has only recently received attention in other animal species. Here, we studied bouts of infant crying among rhesus macaques (Macaca mulatta) in order to investigate how the presence of bystanders may affect the outcome of this signalling interaction between infants and mothers. It was hypothesized that, as crying is acoustically aversive, bystanders may be aggressive to the mother or the infant in order to bring the crying bout to a close. Consequently, it was predicted that mothers should acquiesce more often to crying if in the presence of potentially aggressive animals. In line with this prediction, it was found that mothers gave infants access to the nipple significantly more often when crying occurred in the presence of animals that posed a high risk of aggression towards them. Both mothers and infants tended to receive more aggression from bystanders during crying bouts than outside of this time, although such aggression was extremely rare and was received by less than half of the mothers and infants in the study. Mothers were also found to be significantly more aggressive to their infants while the latter were crying than outside of crying bouts. These results provide new insight into the complex dynamics of mother-offspring conflict, and indicate that bystanders may play an important role in shaping the outcome of signalling interactions between infants and their mothers.

Pregnancy coloration in macaques may act as a warning signal to reduce antagonism by conspecifics.

Instances of bright, hormonally induced coloration among females during gestation have been reported in a few reptile and primate genera. Gravid coloration in lizards has been linked to female aggression but the influence of color changes associated with pregnancy has not yet been experimentally pursued for primates. As a first step to determine whether the crimson to magenta hues common to pregnancy coloration in rhesus macaques (Macaca mulatta) contains information, to which conspecifics of either sex attend, we evaluated whether male and female rhesus macaques discriminate between pregnant and non-pregnant female faces. To these ends, we presented 19 adult rhesus macaques with color-manipulated digital images of female faces where pregnancy coloration was present or absent, and measured visual attention and behavioral reactions. Males were significantly more attentive to female faces with pregnancy coloration over those without pregnancy coloration. Both sexes engaged in higher levels of appeasement behavior toward stimulus with pregnancy coloration, and males showing signs of anxiety did so exclusively when exposed to faces with pregnancy coloration. Our results suggest that pregnancy coloration might be an attention grabbing stimulus to males and a warning stimulus to both male and female rhesus macaques. The findings provide a comparative perspective on the use of color in intra-specific communication, and suggest similarity in female similarity in signalling properties in distantly related taxa.

Sex differences in survival costs of reproduction in a promiscuous primate.

In sexually promiscuous mammals, female reproductive effort is mainly expressed through gestation, lactation, and maternal care, whereas male reproductive effort is mainly manifested as mating effort. In this study, we investigated whether reproduction has significant survival costs for a seasonally breeding, sexually promiscuous species, the rhesus macaque, and whether these costs occur at different times of the year for females and males, namely in the birth and the mating season, respectively. The study was conducted with the rhesus macaque population on Cayo Santiago, Puerto Rico. Data on 7,402 births and 922 deaths over a 45-year period were analyzed. Births were concentrated between November and April, while conceptions occurred between May and October. As predicted, female mortality probability peaked in the birth season whereas male mortality probability peaked in the mating season. Furthermore, as the onset of the birth season gradually shifted over the years in relation to climatic changes, there was a concomitant shift in the seasonal peaks of male and female mortality. Taken together, our findings provide the first evidence of sex differences in the survival costs of reproduction in nonhuman primates and suggest that reproduction has significant fitness costs even in environments with abundant food and absence of predation.

Plasma cortisol responses to stress in lactating and nonlactating female rhesus macaques.

Lactating female rats without their pups exhibit lower HPA responsiveness to stress than nonlactating females. However, responsiveness to stress is similar when lactating females are tested with their pups and the stressor involves a potential threat to the offspring. This study constitutes the first comparison of stress responsiveness in lactating and nonlactating female nonhuman primates. Subjects were 53 multiparous female free-ranging rhesus macaques. Approximately half of the females were lactating and half were nonpregnant/nonlactating. Blood samples were obtained after capture and after overnight housing in an individual cage. Lactating females were tested with their infants. Lactating females had significantly higher plasma cortisol levels than nonlactating females on both days. Having or not having an infant was also a better predictor of plasma cortisol levels among all females than their age, dominance rank, group of origin, time of day at which the sample was obtained, and time elapsed since beginning of the sampling procedure or since anesthesia. Plasma cortisol levels of lactating females were not significantly correlated with post-partum stage or with the cortisol levels of their infants. Capture, handling, and individual housing in a cage are powerful psychological stressors for free-ranging primates. We suggest that the higher plasma cortisol levels exhibited by lactating females reflect greater responsiveness to stress associated with perception of risks to infants. Hyporesponsiveness to stress may not be a general characteristic of lactation in all mammalian species, but a short-term effect of infant suckling that is most apparent with stressors unrelated to the offspring.

Effects of parity and age on female attraction to faces of infants and neonates in rhesus macaques.

This study investigated the effects of parity and age on female rhesus macaque attention toward infants, and assessed whether the faces of neonates are more attractive than those of older infants. Six nulliparous and six multiparous females were shown digitized images of neonates' and 5- to 6-month-old infants' faces. Attention and preferences for images were measured by gaze duration and other picture-directed behaviors, including lip smacking, approaches, and presentations. As predicted, nulliparous females displayed significantly longer gaze durations for images than did multiparous females. There were no significant differences in gaze duration for faces of neonates and those of infants, but images of infants were approached more frequently than images of neonates. This difference is tentatively explained on the basis of differences in female familiarity with neonates' and infants' faces and differences in opportunities for allomothering with neonates and infants.

An experimental examination of female responses to infant face coloration in rhesus macaques.

In many primates, infants possess distinctive coloration that changes as a function of age. This colour is thought to serve the purpose of eliciting caretaking behaviour from the mother as well as other conspecifics. The present study investigated the responses of adult female rhesus macaques (Macaca mulatta) to pictures of infant faces in relation to infant age and facial coloration. Study animals were shown digitized images of neonates and 5-6-month-old infants displaying either unaltered facial colour, pink neonatal colour, or novel (green) facial colour. While infant and neonate faces of all colours elicited the attention of adult females, pink neonatal facial coloration did not appear to be especially attractive to subjects in contrast with the findings from an earlier study [Higley, J.D., Hopkins, W.D., Hirsch, R.M. Marra, L.M. Suomi S.J., 1987. Preferences of female rhesus monkeys (Macaca mulatta) for infantile coloration. Dev. Psychobiol. 20, 7-18]. The results suggest that infant facial colour is not particularly important in mediating infant attractiveness to rhesus macaque females as previously suggested or that other infantile facial characteristics might be more important than colour in eliciting caretaking behaviours amongst females.

Tetanus antibody titers and duration of immunity to clinical tetanus infections in free-ranging rhesus monkeys (Macaca mulatta).

Prior to 1985 tetanus was a major cause of mortality in the free-ranging colony of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual deaths. In 1985 and 1986 all animals (except infants) received primary and booster doses, respectively, of tetanus toxoid. In subsequent years primary immunizations were given to all yearlings, and boosters were administered to all 2-year-old animals during the annual capture of the colony. The main objectives of the tetanus immunization program were to reduce the pain and suffering caused by tetanus infections and to decrease mortality in the colony. Other objectives were to evaluate the efficacy of the two-dose tetanus toxoid immunization protocol and to determine whether additional boosters might be required to provide adequate long-term protection against tetanus infections. The immediate effect of the mass immunization program was the elimination of clinical tetanus infections in the population and a 42.2% reduction in the overall mortality rate. Since the immunization program began, no cases of tetanus have been observed in the colony, except in two unimmunized infants, and it has not been necessary to give tertiary injections of tetanus toxoid to maintain protection against infection. A sample collected in 2004 of the original cohort of monkeys immunized in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers (>0.01 IU/ml) at the ages of 20-23 years, which is close to the life expectancy of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid provided long-term, if not lifelong, protection against tetanus for rhesus monkeys living in a tropical clime where tetanus is enzootic and the risk of infection is great.

Selective attention toward female secondary sexual color in male rhesus macaques.

Pink-to-red anogenital and facial sexual skin occurs in females of many primate species. Since female sexual skin color varies with reproductive state, it has long been assumed that color acts to stimulate male sexual interest. Although there is supportive evidence for this as regards anogenital skin, it is unclear whether this is also the case for facial sexual skin. In this study we experimentally manipulated digital facial and hindquarter images of female rhesus macaques (Macaca mulatta) for color within the natural range of variation. The images were presented to adult male conspecifics to assess whether the males exhibited visual preferences for red vs. non-red female coloration, and whether preferences varied with anatomical region. The males displayed significantly longer gaze durations in response to reddened versions of female hindquarters, but not to reddened versions of faces. This suggests that female facial coloration may serve an alternative purpose to that of attracting males, and that the signal function of sexual skin and the intended recipients may vary across anatomical regions.

Herpes B-virus seroreactivity in a colony of Macaca mulatta: data from the Sabana Seca Field Station, a new specific pathogen-free program.

The demand for B-virus-free animals for biomedical research is increasing, while at the same time the availability of such animals is decreasing. The establishment of Specific Pathogen-Free (SPF) breeding macaque colonies is a priority of the National Institutes of Health. Nevertheless, it is well known that seroreactivity to B-virus can be difficult to interpret, particularly as it can vary over time in a single animal. The aim of the present study was to implement a reliable algorithm to examine B-virus reactivity among the rhesus monkey population of the Caribbean Primate Research Center. The sensitivity and specificity of our assay were determined using reports from two different laboratories as references. Whereas 95.4% of animals showed consistent serological status and 4.6% of animals recruited to this SPF program showed serovariability to B-virus over the initial 2 years of examination. Implications for all SPF programs are discussed in this article.

Behavioral, adrenal, and sympathetic responses to long-term administration of an oral corticotropin-releasing hormone receptor antagonist in a primate stress paradigm.

CRH is a main regulator of the stress response. This neuropeptide and its specific receptors, CRHR-1 and CRHR-2, are disseminated throughout the central nervous system. There is a significant interspecies difference in the distribution of CRHR within the central nervous system. CRH-R1 antagonists may attenuate stress-related behavior in rats without compromising adrenal function, but few studies have addressed the same question in higher mammals. Antalarmin (AA) is a specific CRHR-1 antagonist suitable for oral administration. Social separation is a potent stressor for rhesus monkeys. Therefore, we sought to investigate the hormonal responses to chronic administration of AA using a primate stress model. Eight preadolescent (4-6 kg) male rhesus monkeys received AA (20 mg/kg.d) or placebo (PBO) orally. All animals were on a regular day/light cycle and were fed with standard monkey chow daily. The study (114 d) was comprised of the following consecutive phases: adaptation, baseline, separation (stress), recovery, and cross-over. During social separation, solid panels separated the individuals. Cerebrospinal fluid (CSF) and femoral venous blood samples were obtained once a week on the fourth day of separation under ketamine anesthesia. Serum samples were also obtained 1 and 2 h after separation. CSF samples were assayed for CRH, AA, norepinephrine (NE) and epinephrine (EPI). Plasma was assayed for ACTH, cortisol, NE, and EPI. AA was detected in the plasma of each monkey while they were taking the active drug and in none of the animals on PBO. Among the behaviors assessed, environmental exploration, a behavior inhibited by stress, was increased during AA administration. However, AA at this dose did not affect other anxiety-related behavioral end points, including self-directed behavior, vocalization, or locomotion. We also observed that: 1) ACTH decreased between adaptation and baseline, indicating that the animals had adjusted to the novel environment; 2) ACTH and cortisol increased significantly after social separation, indicating that social separation was an adequate model for acute stress; 3) NE and EPI increased significantly during acute stress in the AA and PBO groups (P < 0.005, NE; P < 0.001, EPI); 4) after chronic stress, by d 4 of separation, ACTH levels were no longer significantly different from baseline, and NE and EPI remained slightly elevated when compared with baseline (P < 0.05, NE; P < 0.01, EPI); and 5) all the animals remained healthy and gained the expected weight during the study. In summary, oral chronic administration of a specific CRH-R1 antagonist to rhesus monkeys does not blunt the sympathoadrenal response to stress while increasing environmental exploration, a behavior that is normally suppressed during stressful events. Taken together, these findings suggest that CRHR-1 antagonists may be a valid treatment for stress-related disorders.

Body composition, age and fertility among free-ranging female rhesus macaques (Macaca mulatta).

The relationship of morphometric measures and birth status among 93 females on Cayo Santiago trapped during the 2001 and 2002 seasons was assessed. The proportion of females giving birth differed between the two seasons (0.58 vs. 0.38; P = 0.006) with a prominent decline among older females. Most morphometric measures increased from adolescent to adult groups, but bicep circumference showed a significant decrease among adults. When controlled for age differences, females with infants during the 2002 season exhibited greater bicep circumference, but no difference in abdominal fat than those without. Members of the socially dominant group did not have a higher rate of birth in either 2001 or 2002, despite being significantly longer and weighing more than those of the subordinate group. Abdominal skinfold and bicep circumference were significant predictors of birth status during the 2002 season, controlling for age group, social group membership, and parity in the previous year. Bicep circumference was also a significant predictor of birth status for the 2001 birth season. These findings suggest that individual variation in body composition among females of Cayo Santiago is associated with differences in fertility.

Variation in reproductive outcomes for captive male rhesus macaques (macaca mulatta) differing in CSF 5-hydroxyindoleacetic acid concentrations.

In rhesus macaque males, lower than average cerebrospinal fluid (CSF) concentrations of the principle metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), have been linked to impulsivity, involvement in escalated aggression, failure to elicit consort relationships, production of fewer sperm plugs, and a relatively early age of mortality. Given these potential fitness costs, we performed two studies aimed at elucidating the effects of CSF 5-HIAA on reproduction. Study 1 retrospectively evaluated over a four-year period, the relative reproductive outcome for pairs of adult male rhesus macaques (n = 15) who lived in social groups and who differed in concentrations of CSF 5-HIAA. Study 2 examined the relationship between CSF 5-HIAA and sperm motility and density (n = 12), as a potential mechanism for maintaining variability in CSF 5-HIAA. For Study 1, an average measure from two CSF 5-HIAA samples was calculated for the two males who were present during the time when conception most likely took place (offspring birth date -165 +/- 14 days). Within-pair comparisons of CSF 5-HIAA concentrations between the sire and the non-successful male were drawn for each of the 72 offspring in the study. We found that while sires were typically the male with relatively higher CSF 5-HIAA within the pair, there were no absolute differences in CSF 5-HIAA between males who sired at least one offspring (sires) and those who failed to reproduce (non-sires). Furthermore, while absolute age was not predictive of reproductive outcome, sires with relatively high CSF 5-HIAA also tended to be also relatively older than their competitors. By contrast, for the males with relatively low CSF 5-HIAA who reproduced, sires were relatively younger than the non-sires. These differences in reproductive outcome for males differing in CSF 5-HIAA could not be explained by variability in sperm quantity or quality as we did not find evidence of a relationship between CSF 5-HIAA and either sperm measure. The results of this study suggest that as serotonergic function affects many aspects of behavior and survivorship, it might also be associated with reproductive outcome and different life-history strategies for males differing in concentrations of CSF 5-HIAA.

The finding of an inverse relationship between social dominance and feeding priority among pairs of unfamiliar adult male vervet monkeys (Cercopithecus aethiops sabaeus).

Dominance is often presumed to confer priority of access to resources. This study evaluated the relationship between two assessments of dominance: (1) social dominance, based on agonistic interactions and (2) feeding priority among pairs of unfamiliar adult vervet monkeys (Cercopithecus aethiops sabaeus) differing in scrotal colour, but matched for height, weight and testicular volume, during paired introduction experiments. Results of this investigation showed that neither size differences nor scrotal colour were predictive of feeding priority, and social dominance was inversely related to feeding priority. This finding demonstrates that different assessments of dominance can yield different outcomes even within the same primate taxon. I propose that male dominance rank may best predict access to resources when there is direct contest competition over a resource, which is not immediately exhaustible, whereas highly impulsive low ranking males may gain a competitive edge in scramble competitions for ephemeral and small resources.

Evolutionary underpinnings of excessive alcohol consumption.

Given our close phylogenetic relatedness, non-human primates, in principle, could serve as an ideal model for alcoholism. Indeed, many studies in both humans and rhesus macaques show relationships between excessive alcohol consumption, aggression and serotonergic function, as measured by concentrations of the principal metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). An important behavioral predictor of excessive alcohol consumption in both humans and rhesus monkeys is the propensity toward impulsivity. Integrating behavioral and neuroendocrine data from captive and semi-free-ranging rhesus macaques, we posit that benefits derived from impulsive and aggressive behaviors in some contexts might contribute indirectly to the maintenance of traits involved in alcoholism and excessive alcohol intake.