Menopause in female rhesus monkeys

Fifteen female rhesus monkeys (Macaca mulatto), ranging in age from 8 to 34 years, were studied for one year to characterize the endocrine and menstrual changes associated with menopause in this species. Five monkeys were premenopausal; these younger monkeys, ages 8–11 years, menstruated and showed cyclic ovarian activity during the 12–month study period, as evidenced by menses and periodic elevations of serum estradiol (E₂) and luteinizing hormone (LH) concentrations. Four females, ages 24–26 years, were in transition to menopause. Two of these perimenopausal females menstruated and secreted E₂ and LH in a periodic fashion; the other two females showed elevated LH concentrations, consistently low E₂ levels, and no evidence of menstruation. Six females, ages 27–34 years, were clearly postmenopausal; LH concentrations were high, whereas E₂ concentrations were uniformly low. There was a significant inverse correlation between basal E₂ concentrations and age, and a significant positive correlation between age and LH concentrations across all 15 animals. Hormonal changes indicative of ovulation, when they occurred, were generally restricted to the winter and early spring months. Histological analysis of ovaries from four postmenopausal females revealed little or no evidence of active folliculogenesis. These data indicate that menopause in female rhesus monkeys does not occur until the second half of thethird decade of life. © 1995 Wiley-Liss, Inc.     

Relation between the dominance rank of female rhesus monkeys and their access to males

Systematic observations were made on 12 measures of the sexual, aggressive, and social interactions of 24 male–female pairs of rhesus monkeys in six social groups, each consisting of one male and four ovariectomized females tested in a large room. Each female in a group was treated in turn first with estradiol alone and then with estradiol and progesterone in combination. When hormone-treated, the female was also observed during pair tests with the male in the same large observation room (four males, eight females, 240 group tests, 240 pair tests). The dominance ranks of females during group tests were determined post hoc by means of the dominance index [Zumpe & Michael, American Journal of Primatology 10:291–300, 1986]. In all six groups, the most dominant female virtually monopolized the male, and the subordinate females' interactions with the male, assessed during pair tests, were almost completely suppressed during group tests. This “dominant female effect” was a robust phenomenon that depended solely on female dominance rank. It was independent of the identity and hormonal status of females and of the social preferences of males as expressed in pair tests. These findings demonstrate the existence of female mate competition in an Old World primate.     

Social status modifies estradiol activation of sociosexual behavior in female rhesus monkeys

Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions.     

Social status modifies estradiol activation of sociosexual behavior in female rhesus monkeys

Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions.     

Expression of male-typical behavior in adult female pseudohermaphroditic rhesus: Comparisons with normal males and neonatally gonadectomized males and females

Two types of pseudohermaphroditic female rhesus produced by exposure to either testosterone propionate (TP) or dihydrotestosterone propionate (DHTP) prior to birth were ovariectomized postpuberally and evaluated for the display of male-typical sexual behavior in response to exogenous TP in adulthood (2 mg/kg/day for 12 weeks). Their performance in standardized tests with estrogenized female partners was compared to that of neonatally gonadectomized males and females identically tested and treated with exogenous TP as adults. In addition intact adult males not given exogenous TP were tested with the same estrogenized female partners. There were no reliable differences between the two types of pseudohermaphrodites on any measure of behavior shown during the tests. Accordingly results were combined. Reliable behavioral changes induced by the TP given in adulthood were limited to increases in purse-lip responses, the induced increases were similar in pseudohermaphrodites and castrated males, and increases were reliably greater in these two groups of subjects than in females. Pseudohermaphrodites and castrated males did not differ reliably from intact males in performance of purse-lip gestures during TP treatment. In the performance of mounting, however, pseudohermaphrodites and castrated males remained consistently below the standard of the intact males. The estrogenized female partners displayed proceptive responses most frequently to the intact males and least frequently to the females. Their proceptive responses with castrated males resembled their performance with intact males, but with pseudohermaphrodites their proceptive responses more closely resembled their performance with females. Receptive behavior of the female partners was displayed most frequently to intact males, at intermediate levels to castrated males, and least often to pseudohermaphrodites. Results are completely consistent with the notion that androgens in high concentrations before birth alter mechanisms related to the later display of masculine behavior. These alterations in behavioral mechanisms are of such a nature that the display of male-typical behavior induced by androgens in adulthood is more pronounced and more frequent than it would have been otherwise. The alterations in masculine behavior observed in pseudohermaphroditic rhesus are not different in kind or scope than those reported extensively for lower mammals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expression of adult female patterns of sexual behavior by male, female, and pseudohermaphroditic female rhesus monkeys

Gonadally intact pseudohermaphroditic female and normal female and neonatally castrated male rhesus monkeys were given estrogen treatment as adults and evaluated for attractivity, proceptivity, and receptivity during tests with a tethered stud male. Pseudohermaphrodites were produced by injecting their mothers during pregnancy with either testosterone propionate (TP) or dihydrotestosterone propionate (DHTP). Castrated males had reliably lower attractivity than normal females on all indicator responses shown by the tethered males. Additionally, castrated males showed reliably fewer proceptive responses on 4 of 5 measures than normal females. Receptivity could not be assessed in this situation for castrated males, because tethered males never contacted them unless the castrated males were displaying presentation. No reliable differences were observed between pseudohermaphrodites produced by prenatal treatments with TP or DHTP. Pseudohermaphrodites generally showed reliably less attractivity and proceptivity than normal females and reliably more of these traits than castrated males. Attractivity scores for pseudohermaphrodites were not different from those for normal females until proximity to the tethered male was established. Receptivity was not different in pseudohermaphrodites compared with normal females. Results indicate prenatal androgenization and its developmental sequelae lead to a defeminization in adulthood which, in this testing situation, was principally manifested by a deficiency in the performance of proceptive behaviors. Additionally, defeminization in rhesus monkeys, unlike that demonstrated in rodents, does not depend upon actions of an aromatizable androgen.     

Seasonal changes in reproductive behavior in two ovariectomized female rhesus monkeys treated year-round with estradiol

Two ovariectomized female rhesus monkeys treated year-round with estradiol-filled capsules were used in hour-long behavioral tests with male rhesus monkeys both in and out of the normal breeding season. The study was designed primarily to test male hormonal responses to copulatory behavior and it was expected that behavior of the females would be essentially the same under both seasonal conditions. Several behaviors of the female, however, were found to fluctuate on a seasonal basis, namely (1) proximity to the male, (2) grooming of the male, (3) sexual presentations, and (4) threatening away (a form of sexual invitation). All of these behaviors, except proximity, were found to be positively correlated with the male partner's testosterone levels before and after the behavior test in the only test condition in which most males ejaculated. The preliminary suggestion is made that these females responded to some cue, either from the environment or from the males, that caused a change in their behavior between breeding and nonbreeding seasons despite the constant hormonal environment provided by the estradiol capsules. Since the same behaviors which were sensitive to seasonal effects were positively correlated with male testosterone levels, it is possible that the male's hormonal status affects affects female behavior.     

Infant-directed behavior of rhesus monkeys during their first pregnancy and parturition

To determine whether pregnancy influences the response of rhesus monkeys towards infants, 11 females were observed during 15-min exposures to a 1- to 15-day-old infant at 1- to 2-week intervals throughout pregnancy. No evidence was found for increasing willingness to contact infants as pregnancy progressed. The parturition of 5 of these females was observed, which included 1 live breech birth. These primiparae all established ventral contact with their infants at birth, though most of them appeared to passively allow the infant to initiate contact while their own attention was directed at licking the birth fluids.     

Estimation of body fat in female rhesus monkeys

Measurement of height (crown–rump length), body weight, and abdominal subcutaneous fat depth, based on skinfold thickness taken from 13 female rhesus monkeys comprising two age groups were correlated with body fat values derived from tritiated water determinations of total body water. The manner with which each measure was related to percent body fat differed as a function of age of the animal. In the young, nulliparous females, crown–rump length was the single best predictor of body fat, whereas in the older, multiparous females, skinfold thickness correlated most highly with body fat. When all measurements, including the Quetelet index [(wt/ht)² × 1,000], were combined statistically and regressed against percent body fat, a significant increase in predictive ability was obtained. When each age group was considered separately, the resulting equations again reflected the agegroup biases. In addition, as an internal check on the validity of the regression equations, an additional regression analysis was performed using morphometric data from selected animals in each age group. These equations yielded accurate estimates of body fat when compared to determinations made from total body water. These analyses indicate that the predictive accuracy of morphometric data is greatly enhanced by using these measurements in concert. Furthermore, the utility of such predictions is influenced by the specific physical characteristics of the subject population.     

Increased cage size does not alter heart rate or behavior in female rhesus monkeys

Newly proposed federal regulations will mandate that singly caged non-human primates be kept in cages larger than the current minimum standard, or be given 4 hours in an exercise cage per week. In order to evaluate the effectiveness of increasing cage size in improving well-being, the behavioral and heart rate responses of 10 female rhesus monkeys (Macaca mulatta) to three different cage sizes were measured. With the exception of vocalizations, no significant differences in behavior were obtained. Grunts increased in the largest cage, following the birth of an infant in a cage within view of the test cages. No differences with respect to cage size were found in heart rate or activity level, although there were significant variations at different times of day. We conclude that modest increases in cage size are less likely to enrich the environment of singly caged laboratory primates than are changes in social opportunities or increases in environmental complexity.     

Seasonal modulation of luteinizing-hormone secretion in female rhesus monkeys

The seasonal restriction of ovulations in rhesus monkeys is thought to be due to enhanced estradiol (E2)-negative feedback suppression of luteinizing hormone (LH) during the spring and summer anovulatory months. This hypothesis was examined in seven ovariectomized monkeys housed in an outdoor environment and treated with various doses of E2 in a counterbalanced design during both the anovulatory season (May-Jul) and the breeding season (Sep-Nov). Subcutaneous implants of E2 produced levels that mimicked late follicular (LF-100 pg/ml) or periovulatory concentrations (PO-190 pg/ml). Analyses of twice weekly serum samples revealed that during the period of no E2 treatment (NT), basal levels of bioactive LH were significantly lower in the summer than the fall. Although treatment with both doses of E2 lowered basal LH levels during both seasons, the decrease in LH was significantly greater during the summer. Samples collected at 15-min intervals for 2 h revealed that during NT, LH pulses were significantly slower during the summer than in the fall, whereas pulse amplitude did not differ between seasons. Treatment with both doses of E2 either abolished or significantly reduced both LH pulse amplitude and frequency in the summer. In contrast, LH pulses during the fall were not affected by E2 treatment. Response to treatment with LH-releasing hormone (5 micrograms/kg i.v.) revealed that release was significantly reduced during E2 treatment in the summer. These data indicate that seasonal changes in the environment influence both nongonadal control and E2-negative feedback inhibition of LH secretion. The reduced ability of E2 to maximally suppress LH release in the fall can thus account for the seasonally delimited pattern of ovulations observed in rhesus monkeys.     

Sexual behavior and hormone levels during the menstrual cycles of rhesus monkeys.

The sexual interactions of 10 pairs of rhesus monkeys were observed during a control and an experimental menstrual cycle of each female. During the experimental cycle the females were treated with an antiandrogen, flutamide. Daily peripheral serum levels of estradiol, testosterone, and progesterone in each female were determined by radioimmunoassay. Sexual behavior did not correlate reliably with female serum concentrations of any hormone measured nor with the menstrual cycle stage. Administration of the antiandrogen to the females did not affect the sexual behavior of the pairs, although female serum levels of estradiol and testosterone were reduced. It was concluded that although female ovarian hormones may influence rhesus sexual interactions under some circumstances, the normal hormonal fluctuations during the menstrual cycle need not regulate this behavior; a knowledge of an intact rhesus female's hormonal condition does not allow accurate predictions about behavior displayed during laboratory pair tests with a male.     

Impact of a privacy panel on the behavior of caged female rhesus monkeys living in pairs

Thirty paired female rhesus monkeys were tested in a control situation when companions had no privacy, and in an experimental situation when they were offered the option to move behind a panel and be alone. Paired partners spent significantly more time in close proximity (same half of the cage) when the privacy panel was provided (means with panel = 76.0%/h vs. means no panel = 60.8%/h; p less than 0.005). At the same time, they were more engaged in affiliative interactions (means with panel = 37.4%/h vs. means no panel = 26.5%/h; p less than 0.025) while the incidence of agonistic interactions tended to decrease (means with panel = 0.3/h vs. means no panel = 2.2/h; p less than 0.1). It was concluded that rhesus monkeys have a need for companionship. They prefer to stay in close proximity with a compatible partner even though this may reduce their available cage space. It was further concluded that companions have no need for prolonged periods of visual seclusion, but occasional privacy is beneficial for their relationship.     

The effect of season on the induction of sexual behavior by estradiol in female rhesus monkeys

Rhesus monkeys housed in an outdoor environment are seasonal breeders, with ovulations and concomitant sexual behavior limited to the fall and winter months. To determine if there is a seasonal difference in the capacity of physiological levels of estradiol (E2) to induce sexual behavior in ovariectomized rhesus monkeys housed outdoors, subjects living in a social group were treated with subcutaneous E2 implants in a counter-balanced design during the nonbreeding season (May-July) and during the breeding season (September-November). Serum E2 levels were monitored by obtaining blood samples twice a week. Three levels of E2 were studied: baseline (less than 30 pg/ml), follicular (100 pg/ml), and periovulatory (200 pg/ml). Two of five adult males in the group were injected with human chorionic gonadotropin (hCG) twice a week to insure that males with high testosterone levels were present during each season. Focal observations of behavior of 15 minutes' duration on each subject were conducted 5 days per week, with frequencies and durations of social, sexual, and solitary behaviors recorded. Concomitant 2-h group scans were made to record all occurrences of mounting behavior. Neither heterosexual serial mounting nor seminal plugs were ever observed in E2-treated females during the summer months. In contrast, copulation and seminal plugs were observed in subjects at both treatment levels during the fall. While E2-treated females engaged in homosexual mounting behavior during both summer and fall, E2 treatment resulted in heterosexual copulation only during the fall. Changes in patterns of social behavior paralleled changes in sexual behavior and were significantly affected by treatment and season, with more male-female interactions during the fall months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Periovulatory changes in female sexual behavior and patterns of ovarian steroid secretion in group-living rhesus monkeys

The behavior of nine intact group-living adult female rhesus was observed for 30 min daily with each of four adult male rhesus across a verified ovulatory menstrual cycle. Blood samples collected from females daily or on alternate days were analyzed for estradiol, testosterone, and progesterone. Female patterns of approach, follow, and initiate proximity increased several days prior to the estradiol peak, peaked on the day of the estradiol peak, then declined completely or to very low frequencies. Mounts, intromissions, and ejaculations increased significantly on the day of the estradiol peak, remained elevated for 2 more days, then declined completely by the fifth day after peak estradiol. Ejaculations never occurred outside of a 10-day period starting 4 days before the estradiol peak and ending 5 days after the estradiol peak. During this period females initiated over 90% of all approaches. Female hand slap, threaten away, and stand up increased significantly on the first day of increased copulation, remained elevated while copulation was significantly elevated, then decreased along with the decline in copulation. Ten of eleven patterns of female behavior correlated significantly with estradiol level prior to the estradiol peak. All were significantly inversely correlated with progesterone level after the estradiol peak. No pattern of female behavior correlated significantly with testosterone either before or after the estradiol peak. Similarly, male patterns of behavior correlated with female levels of estradiol and progesterone, but not testosterone. These results demonstrate a relationship between increased serum estradiol and increased female initiation of sexual behavior. The finding that some patterns of female behavior increase several days prior to copulation, whereas other behaviors increase coincident with increased copulation suggests that the behavior of group-living rhesus females serves two functions. The first is to communicate sexual interest and the second is to maintain the consort pair and increase the probability that ejaculation will occur. In addition, the strong correlation between preovulatory female behavior and estradiol level suggests that the female's behavior provides precise information about her reproductive state and could thus coordinate copulation with maximal fertility.     

Comparative pharmacokinetics of frusemide in female rhesus monkeys, cynomolgus monkeys and baboons

1. The pharmacokinetics of frusemide have been compared in 3 non-human primate species after single intravenous dose of 3 mg/kg of the drug. 2. Peak mean plasma concentrations of frusemide were 31.6, 33.6, 43.6 micrograms/ml in the rhesus monkey, cynomolgus monkey and baboon respectively, and concentrations declined with a half-life of about 20 min. 3. There were no notable differences in the pharmacokinetic parameters estimated from either a one-compartment or two-compartment open model. 4. There were statistically significant species-related differences in clearance, half-lives and volumes of distribution adjusted for bodyweight. 5. The pharmacokinetics of frusemide in the cynomolgus monkey are closer to those in man than are those in the rhesus monkey, the baboon or other commonly used laboratory animal species.     

Social and hormonal influences on behavior of adult male, female, and pseudohermaphroditic rhesus monkeys

We previously demonstrated that in a simple pair test situation the expression of adult male sexual behavior by rhesus monkeys depends on both prenatal (organizational) and adult (activational) androgen exposure. In the present study we used a more complex social situation (trio tests) to evaluate the behavior of males, females, and female pseudohermaphrodites. In these trio tests, the experimental subjects were tested with two estrogenized stimulus females simultaneously. Sex differences in behavior were made apparent by this complex testing situation that could not have emerged in the pair test. Gonadectomized males and female pseudohermaphrodites, but not ovariectomized females that were concurrently receiving TP, exhibited increased male sexual behavior in trio tests compared to pair tests. In trio tests, the males and pseudohermaphrodites showed evidence of partner preference by interacting almost exclusively with one of the two stimulus females. These "preferred females" in turn were responsible for the majority of the proceptive behavior exhibited in these tests. Ovariectomized females rarely displayed male sexual behavior in either test situation. These results further support the hypothesis that prenatal androgen exposure predisposes monkeys to exhibit masculine behavior traits when they reach adulthood and are exposed to the activational influences of androgens.