Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis

Stress-induced reproductive dysfunction is a relatively common cause of infertility in women. In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. Female cynomolgus monkeys, when exposed to mild combined psychosocial and metabolic stress (change in social environment + 20% reduced calorie diet), can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). In this study, we examined whether increased sensitivity to stress-induced reproductive dysfunction is associated with elevated adrenal axis activity by measuring 1) the diurnal release of ACTH and cortisol, 2) ACTH and cortisol in response to an acute psychological stress, 3) the percent suppression of cortisol in response to dexamethasone negative feedback, 4) the diurnal release of ACTH and cortisol following exposure to mild psychosocial and metabolic stress, 5) the concentration of cortisol in hair, and 6) adrenal weight. SS monkeys (n = 5) did not differ from MSR (n = 5) or HSR (n = 7) monkeys in any measurement of baseline HPA axis activity or the integrated measurements of chronic HPA axis activity. However, MSR + SS monkeys (n = 10) did secrete more cortisol than HSR monkeys during the daytime hours (1000-1800) following exposure to a novel social environment and reduced diet. We conclude that increased activity of the HPA axis is unlikely to be the primary mechanism causing increased sensitivity to stress-induced reproductive dysfunction.     

季节性变化对雌性恒河猴生殖功能的影响

目的　研究季节性变化对雌性恒河猴生殖功能的影响。方法　采用随机抽样法和放射免疫测定法 ,分析了不同时期雌性恒河猴性皮肤变化、月经周期和生殖激素变化的特点。结果　 ( 1)性征的季节性变化 :在生殖季节雌性恒河猴几乎都出现性皮肤反应 ,出现比较规则月经周期 ,在非生殖季节只有部分雌性恒河猴出现性皮肤反应 ,月经周期不规则 ,行经频率低 ,有的出现长时间的闭经 ;( 2 )生殖激素的季节性变化 :在生殖季节促性腺激素和性类固醇激素的分泌水平都出现周期性的变化 ,而非生殖季节促性腺激素和性类固醇激素的分泌水平没有显著的差异。结论　雌性恒河猴性皮肤变化、月经周期和生殖激素存在明显的季节性差异 ,这种差异导致了雌性恒河猴生殖功能的季节性变化     

Pulsatility of serum LH in pathological conditions

LH pulsatility changes throughout the normal menstrual cycle. The number of LH pulses increases during the first days after menstruation, remains unchanged thereafter until after ovulation and declines progressively during the luteal phase. LH pulse amplitude is highest during midcycle. In hypothalamic amenorrhea, gonadotropin levels are reduced. This appears to be a consequence of a reduction of hypothalamic Gn-RH secretion which is reflected by a diminished frequency and amplitude of LH pulses during the 24-hour span. Administration of an opiate antagonist, naloxone, increases LH pulse frequency in those patients, and in patients with secondary hypothalamic amenorrhea the daily oral administration of naltrexone, another specific opiate antagonist, induces ovulatory cycles. Patients suffering from hyperandrogenemia may present with eumenorrhea, oligomenorrhea or amenorrhea. There is an increase in mean LH levels and of the LH/FSH ratio with increasing severity of the ovarian disturbance. The increase in mean LH levels is a consequence of an increase in LH pulse amplitude while LH pulse frequency is not changed compared to the early follicular phase of the menstrual cycle.     

Menstrual disorders associated with hyperprolactinemia

In hyperprolactinemia, menstrual disorders ranging from irregular bleeding, insufficient luteal phase, spanio-amenorrhea, to anovulatory cycles and amenorrhea, are frequent. Multiple mechanisms are involved in these disorders: hyperprolactinemia could act at the hypothalamic level on LHRH secretion and directly on LH and sex steroids secretion. Hyperprolactinemia could also act by impairing fertilization or implantation at the endometrial level.     

Aetiological approach of female reproductive physiology in lactational amenorrhoea.

The duration of postpartum amenorrhea and return of ovulation varies on an individual and population basis. In 1980, in Senegal, the relationship of chronic malnutrition and female fertility was investigated for 2 years. The stability of the female body regarding weight and arm circumference despite a heavy annual workload was a surprising finding. The mean female body mass index was higher for lactating women in amenorrhea than required for restoring menstruation in European women. The mean duration of postpartum amenorrhea was 18.2 +or- .6 months. The difference between those who resumed menstruation (20.9 +or- .9 months) and who still had amenorrhea (25.4 +or- 2.2 months) was significant. The duration of breast feeding determined the duration of amenorrhea. Studies have found a link between ovarian dysfunction and women in harsh third world environments and sportswomen under intensive training with both showing irregular menstruation and amenorrhea. Long duration of cycles in New Guinean women, high amount of anovulation in Zairian forest women, and suppression of testosterone and estradiol levels in hunter-gatherers were found. In affluent Europeans and urbanized women in developing countries postpartum amenorrhea dropped drastically. Long distance runners are often vegetarians with low calorie consumption and with a high degree of menstrual trouble owing to low body fat and weight-for-height. The role of beta-endorphins in the hypothalamic blockade of the gonadotropin releasing hormone pulse generator and high stress or physical training is proven. The functioning of the hypothalamo-pituitary-ovarian axis can be hurt by intensive training. Short-term fasting also suppressed the pulsatile luteinizing hormone and testosterone secretion. The protocol and methodology of an etiological study is outlined regarding the factors of this hypothesis on amenorrhea.     

Effects of 12-hour rotating shifts on menstrual cycles of photoelectronic workers in Taiwan

12 h rotating shifts are common in high-tech industries in Taiwan. The aim of this longitudinal study was to evaluate the effect of the disruption of circadian rhythms by the shift schedule on menstrual cycle length (MCL) and regularity of female workers at an optoelectronic company in Taiwan. We recruited females who worked rotating shifts in a clean room environment as the shift-work group and female office workers who worked normal business hours as the comparison group. Every participant recorded their MCL for each menstruation cycle up to eight consecutive months prospectively and provided demographic characteristics, reproductive history, and menstrual characteristics. We collected data on 1,135 and 117 menstruation cycles in the shift-work (n = 280) and comparison groups (n = 49). Whereas the two groups had similar group means for MCL and number of menstrual bleeding days, the prevalence of menstrual cycle irregularity (cycles <25 or >35 days) was higher in the shift-work group ( p = 0.04). Univariate and multivariate logistic regression analyses demonstrated that rotating shift work was an independent predictor of menstrual cycle irregularity (odds ratio = 1.71, 95% confidence interval: 1.03-2.88) after adjusting for shift-work history, employment duration, coffee consumption,and pre-employment menstrual cycle irregularity. Although further study is required to confirm our findings plus to explore prevention and control measures, our data indicate rotating shift work can increase the risk of MCL irregularity.     

Effects of an antiprogestin onapristone on the endometrium of bonnet monkeys: morphometric and ultrastructural studies

Our previous studies demonstrated the ability of low doses of antiprogestin ZK 98.299 (onapristone) to inhibit fertility in bonnet monkeys. In the present study cumulative effects of low doses of ZK 98.299 on the endometrial cytoarchitecture of bonnet monkeys were analyzed. Treatment with either the vehicle (n = 3) or onapristone at 2.5 mg (n = 4) or 5.0 mg (n = 3) was initiated on Day 5 of the first menstrual cycle and thereafter repeated every third day for four to seven consecutive cycles. The last treatment cycles were anovulatory in two animals treated with 2.5 mg and all animals treated with 5.0 mg. Endometrial biopsies were collected on Day 8 after the midcycle estradiol peak in ovulatory menstrual cycles and on Day 20 in anovulatory menstrual cycles during the last treatment cycle. Ultrathin sections of the fixed endometrium were stained with toluidine blue for morphometric analysis and uranyl acetate and lead citrate for ultrastructural analysis. The ZK 98.299-treated animals showed a dose-dependent endometrial atrophy as evident by a decrease in the height and diameter of the glands and early signs of compaction in the stroma. Ultrastructural analysis also revealed dose-dependent degenerative changes in the subcellular organelles such as the nucleus, mitochondria, endoplasmic reticulum, lysosomes, and Golgi apparatus. This suggests that long-term treatment with low doses of ZK 98.299 leads to the suppression of estrogen-dependent endometrial proliferation. However, this blockade operates independent of estradiol receptor (ER) and progesterone receptor (PR) concentrations as the expressions of these steroid receptors did not show any significant changes even after prolonged treatment. The study demonstrated an antiestrogenic effect of ZK 98.299 on endometrium after prolonged treatment in bonnet monkeys.     

Physical activity of adult female rhesus monkeys (Macaca mulatta) across the menstrual cycle

Physical activity is an important physiological variable impacting on a number of systems in the body. In rodents and several species of domestic animals, levels of physical activity have been reported to vary across the estrous cycle; however, it is unclear whether such changes in activity occur in women and other primates across the menstrual cycle. To determine whether significant changes in activity occur over the menstrual cycle, we continuously measured physical activity in seven adult female rhesus monkeys by accelerometry over the course of one menstrual cycle. Monkeys were checked daily for menses, and daily blood samples were collected for measurement of reproductive hormones. All monkeys displayed ovulatory menstrual cycles, ranging from 23 to 31 days in length. There was a significant increase in estradiol from the early follicular phase to the day of ovulation (F(1.005,5.023) = 40.060, P = 0.001). However, there was no significant change in physical activity across the menstrual cycle (F(2,12) = 0.225, P = 0.802), with activity levels being similar in the early follicular phase, on the day of the preovulatory rise in estradiol and during the midluteal phase. Moreover, the physical activity of these monkeys was not outside the range of physical activity that we measured in 15 ovariectomized monkeys. We conclude that, in primates, physical activity does not change across the menstrual cycle and is not influenced by physiological changes in circulating estradiol. This finding will allow investigators to record physical activity in female primates without the concern of controlling for the phase of the menstrual cycle.     

Changes in social dynamics associated to the menstrual cycle in the vervet monkey (Cercopithecus aethiops)

Behavioral changes associated to the menstrual cycle in a social group of vervet monkeys (Cercopithecus aethiops) were studied. Three adult females were used as experimental subjects and in these, vaginal smears were taken every other day in order to detect their menstrual cycles. Only the dominant and the mid-ranking female showed regular cycles while the low-ranking female showed amenorrhea. The menstrual cycles were divided into five periods (menstrual, premenstrual, luteal, ovulatory and follicular) which were related to the behavioral data. Social behavior recordings were taken during one hour daily for five consecutive months; the data were adjusted twice in order to follow the cycles of the females with regular menstruations. By plotting in a matrix the relative frequencies of joins and displacements, the social position of each animal as well as the group's social organization and dynamics were evaluated. A clear tendency towards social rejection (emitting less joins and increasing the amount of displacements) was detected during the premenstrual periods of the dominant female which abruptly changed towards affiliation during menstruation. This observation was detected in all group members no matter their age-sex class or social position during the five months of observation. When the data were analyzed following the mid-ranking female's cycle, no consistent changes were apparent. The importance of social stimuli in the modulation and expression of hormone-related behavior is stressed, as well as the need of using social settings in the experimental analyses of premenstrual mood and behavior disorders.     

Menstrual cycle and some other related aspects of Japanese monkeys (Macaca fuscata)

The menstrual cycle and some other related aspects of Japanese monkeys (Macaca fuscata) were dealt with in this paper. Almost all the monkeys had regular menstrual cycles only in the mating season, and had no menstrual cycles, or only irregular ones, in the non-mating season. The average length of the menstrual cycle in the mating season was 26.3 ±5.4 days. Many monkeys had a tendency to have their own individual and relatively regular cycles. Ninety out of 108 monkeys kept in the air-conditioned quarters for five years showed “periodical changes” essentially coincident with the changes of outdoor season, and this fact suggests that the rhythm of the seasonal change of Japanese monkeys remains for a relatively long period even if the monkeys are kept in air-conditioned quarters where room temperature and lighting are kept constant throughout the year. Vaginal smear, cervical mucus, sexual skin, etc. were observed in relation to ovulation. These characters showed cyclic changes with menstrual cycles in about half of all cases observed, but ovulation occurred even in the cases in which no cyclic change was observed. Therefore, it was not necessarily easy to estimate the ovulation by observing these characters.     

Focus: Sex and Gender Health: Marijuana,the Endocannabinoid System and the Female Reproductive System

Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.     

Determinants of behavioral rhythmicity during artificial menstrual cycles in rhesus monkeys (Macaca mulatta)

Reproductive success in many mammals depends on synchrony between copulation and ovulation, which is insured by the phenomenon of heat in the female. Certain anthropoid primates including rhesus monkeys do not show heat but may copulate throughout the menstrual cycle, especially when pairs are isolated from conspecifics. In social groups, however, mating mostly occurs around midcycle. We wished to test the hypothesis that copulations are more closely linked to ovulation when males have simultaneous access to several females in different cycle phases. Artificial menstrual cycles were therefore induced by giving hormones to ovariectomized female rhesus monkeys observed in small social groups that each consisted of four females and one male. The cycles of two hormone-treated femlab in each group were either made to synchronize or be offset by 7-day increments so that the estradiol peak of one female occurred 7 days before, and 7 and 14 days after, the estradiol peak of the other. Radioimmunoassay of plasma samples (N = 224) confirmed the timing of the estradiol peaks. Results from eight unique male-female groups (4 males, 8 females, 16 male-female pairs, 718 tests) fully supported the hypothesis. Compared with synchronized cycles, the amplitudes of rhythmic changes in offset cycles were reduced for ejaculations made by males but greatly enhanced for ejaculations received by females. We propose that this socio-hormonal integration of behavior in the group is highly adaptive and enhances the reproductive success of both males and females.     

Neuroendocrine control of ovulation

Modern methods of diagnosis have made the distinction between hypothalamic failure and ovarian failure routine. Failure of the orderly progression of hypothalamic gonadotrophin-releasing hormone (GnRH) → pituitary gonadotrophins → ovarian steroids and inhibin → hypothalamus/pituitary results in anovulation/amenorrhea. The hypothalamic connections that regulate the pattern and amplitude of GnRH pulses are plastic and respond to external/psychological conditions and internal/metabolic factors that may affect the hypothalamic substrate on which estrogen levels can act. We trace the neuroendocrine regulation of the ovarian cycle, concentrating on hypothalamic connections that underlie negative and positive feedback control of GnRH and the complementary role of the adenohypophysis. The main hormone regulating this "central axis" and the development of the endometrium is estradiol which is exported from the developing ovarian follicles and thereby closes the feedback loop with follicle development. Progesterone and inhibin are also involved. Neuroendocrine responses to internal and external factors can cause anovulation and amenorrhea. Generally, these are accompanied by abnormal negative feedback between estradiol and the gonadotrophins; coexistence of low estradiol and luteinizing hormone/follicle-stimulating hormone. There are three main causes: (1) genetic diseases that interfere with the migration of GnRH cells into the brain or result in misfolding of GnRH; (2) input from the brain that interrupts normal feedback (e.g. stress and weight loss amenorrhea); and (3) the effect of agents which alter central neurotransmission and hypothalamic function (e.g. elevated prolactin and psychotropic medications). All types of hypothalamic insufficiency result in insufficient stimulation of the ovaries. In addition to amenorrhea, this central alteration also results in other complications (downstream disease) that make hypothalamic amenorrhea of greater consequence than simply reproductive failure. Thus, there may be more at stake in the diagnosis and treatment of hypothalamic failure than brings the patient to her caregiver.     

Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17β-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.     

Monitoring the reproductive status of Japanese monkeys (Macaca fuscata) by measurement of the steroid hormones in fecal samples

The menstrual cycles as well as the pregnancy in female Japanese monkeys (Macaca fuscata) were monitored by measuring the fecal estradiol concentrations and relative amounts of fecal progesterone. Steroids from fecal samples were extracted by using a previously developed simplified two-step method and then measured by radioimmunoassay. We successfully demonstrated that the two-step method is effective and convenient for monitoring the reproductive status of Japanese monkeys.     

多囊卵巢综合征猕猴的生殖特性(英文)

多囊卵巢综合征(PCOS)是临床上常见的一种内分泌失调性疾病,也是造成无排卵性不孕的重要原因。对多囊卵巢综合征动物模型的研究有10余年,迄今尚未建立起较为理想的模型动物。该研究的目的在于构建猕猴多囊卵巢综合征动物模型,并分析该模型动物的一些主要生殖特性。将6只成年雌性猕猴(6～10a)平均分成2组:PCOS模型组和对照组。模型组动物的建立方法是:在月经周期的第1、3、5天,分别皮下注射丙酸睾丸酮一次,剂量为3.5mg/kg体重;接着在第7、9、11天,分别肌注人绒毛膜促性腺激素一次,剂量是350IU/kg体重;连续注射2个月经周期。对照组动物注射生理盐水。结果显示:PCOS模型组动物呈现出高血清LH和T,分别为(5.35±0.17)IU/L和(7.58±0.14)ng/mL,而且血清LH/FSH值(5.35/1.30=4.12);模型组动物血清FSH、E2和P的含量与对照组无显著差异。腹部B超扫描结果提示,模型组动物卵巢多囊化。对两组动物进行超排处理后,模型组动物卵巢呈明显的过刺激现象,模型组动物胚胎体外培养的囊胚率为23.53%,显著低于对照组(66.67%)(P<0.05),即用丙酸睾丸酮联合人绒毛膜促性腺激素,能够建立PCOS猕猴模型,该模型动物的一些主要生殖特性与人类PCOS相似。     

Hormonal monitoring of reproductive status in monogamous wild female owl monkeys (Aotus azarai) of the Argentinean Chaco

The Neotropical owl monkeys (Aotus spp.) are a good model for evaluating the hypothesis that monogamy may arise if female reproductive cycles limit the mating potential of males. To evaluate this hypothesis, we first needed to assess the feasibility of using fecal sampling for monitoring the reproductive status of females. We collected fecal samples (n = 242, from 7 females) from wild adult Aotus azarai females in the Gran Chaco forests of Argentina during 3 years. Fecal estrone-1-glucuronide (E(1)C) and pregnenadiol-3-glucuronide (PdG) tended to rise in parallel during the luteal phase. The average cycle length was 22 ± 3 days (n = 5 females, 10 cycles). We identified 2 conceptive cycles and characterized the E(1)C and PdG profiles of 2 pregnancies. This report is the first of its kind on wild female owl monkeys. Despite the difficulties in sample collection and processing in the field and providing a species-specific validation in the laboratory, we show that fecal samples from A. azarai can be used for monitoring female reproductive status and function.     

Effects of 12‐Hour Rotating Shifts on Menstrual Cycles of Photoelectronic Workers in Taiwan

12 h rotating shifts are common in high‐tech industries in Taiwan. The aim of this longitudinal study was to evaluate the effect of the disruption of circadian rhythms by the shift schedule on menstrual cycle length (MCL) and regularity of female workers at an optoelectronic company in Taiwan. We recruited females who worked rotating shifts in a clean room environment as the shift‐work group and female office workers who worked normal business hours as the comparison group. Every participant recorded their MCL for each menstruation cycle up to eight consecutive months prospectively and provided demographic characteristics, reproductive history, and menstrual characteristics. We collected data on 1,135 and 117 menstruation cycles in the shift‐work (n=280) and comparison groups (n=49). Whereas the two groups had similar group means for MCL and number of menstrual bleeding days, the prevalence of menstrual cycle irregularity (cycles<25 or>35 days) was higher in the shift‐work group (p=0.04). Univariate and multivariate logistic regression analyses demonstrated that rotating shift work was an independent predictor of menstrual cycle irregularity (odds ratio=1.71, 95% confidence interval: 1.03–2.88) after adjusting for shift‐work history, employment duration, coffee consumption, and pre‐employment menstrual cycle irregularity. Although further study is required to confirm our findings plus to explore prevention and control measures, our data indicate rotating shift work can increase the risk of MCL irregularity.     

The hypogonadotropic state of the prepubertal male rhesus monkey (Macaca mulatta) is not associated with a decrease in hypothalamic gonadotropin-releasing hormone content

Hypothalamic contents of gonadotropin-releasing hormone (GnRH) in neonatally orchidectomized infant, juvenile, and adult monkeys were measured by a radioimmunoassay (RIA) and by an in vivo bioassay that utilized luteinizing hormone (LH) secretion in estrogen- and progesterone-treated ovariectomized rats. The results of the bioassay provided no evidence to suggest that hypothalamic GnRH content in juvenile monkeys (mean = 83 ng/hypothalamus; n = 3) was less than that in infants (mean = 54 ng/hypothalamus; n = 4) and adults (mean = 36 ng/hypothalamus; n = 3). A similar developmental pattern in hypothalamic GnRH content was also observed when the decapeptide was measured by RIA. In striking contrast to the maintenance of hypothalamic GnRH content throughout postnatal development, pituitary gonadotropin contents and serum gonadotropin concentrations were markedly reduced in juvenile monkeys.     

Social and reproductive conditions modulate urinary cortisol excretion in black tufted-ear marmosets (Callithrix kuhli)

The links between psychosocial stress, social status, reproductive function, and urinary cortisol were assessed in social groups of black tufted-ear marmosets (Callithrix kuhli). Urinary cortisol excretion was monitored in cases of intrafamily conflict (“sibling fights”) and in daughters in four distinct social contexts: in the family group, while housed singly or in same-sex pairs, and while paired with a male pairmate. Cortisol excretion was elevated in participants in intra-family conflict on the day of and the day following the conflict, relative to concentrations a week prior to or following the conflict. Daughters in natal family groups had concentrations of cortisol that did not differ from reproductively active adult females. This finding held for daughters who were either anovulatory or undergoing ovulatory cycles while in the natal family group. Natal family members and male pairmates exerted buffering effects on levels of activity in the hypothalamic pituitary adrenal axis (HPA) in female C. kuhli. Placing females in solitary housing led to significantly increased cortisol excretion. In the 2 months subsequent to pairing with a male partner, excreted cortisol concentrations in females declined significantly. Daughters removed from their natal family group and housed with a sister did not exhibit increased cortisol levels. These data reveal that activity in the (HPA) axis in marmosets is sensitive to psychosocial stressors, and that urinary cortisol can provide a useful quantitative measure of HPA reactivity. As in other callitrichids, delayed breeding in daughters and reproductive anomalies in C. kuhli appear to be mediated by mechanisms other than elevated HPA activity. Am. J. Primatol. 42:253–267, 1997. © 1997 Wiley-Liss, Inc.