Hormones and Behavior: An emergent journal.

Hormones and Behavior was founded in 1969 by Frank A. Beach and members of his laboratory. Prior to the founding there was no journal specifically devoted to hormones and behavior. This paper explores how the editorship of the journal has developed over the first 50 years, going from the initial three male editors to the current female editor-in-chief, five associate editors (four men and one women), and a 98 member editorial board consisting of 46 men and 52 women. Early concerns that a specialty journal of hormones and behavior might ghettoize the field did not come to pass and the visibility and impact of the journal has helped to expand the spread of the field, now called Behavioral Neuroendocrinology. This growth accelerated with the creation of the Society for Behavioral Neuroendocrinology in 1996 and the adoption of Hormones and Behavior as the Society's official journal. The growth has been striking with total annual citations going from 1321 per year in 1997 to the current 10,874 annual citations. The journal's impact factor (JIF), 1.42 in 1997, has increased to the current (2018) JIF of 3.95. Over the 50 years of Hormones and Behavior's existence it has emerged as a principle voice of the Hormones and Behavior community. It will be intriguing to see what the next 50 years reveals.

Effects of sex and prenatal androgen manipulations on Onuf's nucleus of rhesus macaques.

The role of gonadal steroids in sexual differentiation of the central nervous system (CNS) is well established in rodents, but no study to date has manipulated androgens prenatally and examined their effects on any CNS structure in a primate. Onuf's nucleus is a column of motoneurons in the sacral spinal cord that innervates the striated perineal muscles. This cell group is larger in males than in females of many species, due to androgens acting during a sensitive perinatal period. Here, we examined Onuf's nucleus in 21 adult rhesus monkeys, including control males and females, as well as males whose mothers had been treated with an anti-androgen or testosterone during gestation. We found a robust sex difference, with more motoneurons in control males than in females. The soma size of Onuf's nucleus motoneurons was also marginally larger in males. Treatment with the anti-androgen flutamide for 35-40 days during early gestation partially blocked masculinization of Onuf's nucleus: motoneuron number in flutamide-treated males was decreased relative to control and testosterone-treated males, but remained greater than in females, with no effect on cell size. A control motor nucleus that innervates foot muscles (Pes9) showed no difference in motoneuron number or size between control males and females. Prenatal testosterone treatment of males did not alter Onuf's nucleus motoneuron number, but did increase the size of both Onuf's and Pes9 motoneurons. Thus, prenatal androgen manipulations cause cellular-level changes in the primate CNS, which may underlie previously observed effects of these manipulations on behavior.

Correction to: Women's Experience of Orgasm During Intercourse: Question Semantics Affect Women's Reports and Men's Estimates of Orgasm Occurrence.

The name of coauthor Kaytlin J. Renfro has been corrected since this article was originally published.

Women's Experience of Orgasm During Intercourse: Question Semantics Affect Women's Reports and Men's Estimates of Orgasm Occurrence.

Most women report reliably experiencing orgasm from masturbation, but a smaller proportion of women report regularly experiencing orgasm from intercourse. Research suggests that concurrent clitoral stimulation during intercourse increases the likelihood of orgasm, yet most surveys of orgasm during intercourse leave unspecified whether vaginal intercourse does or does not include concurrent clitoral stimulation (assisted intercourse or unassisted intercourse, respectively). Using an online sample of 1569 men and 1478 women, we tested whether phrasing of questions about the occurrence of orgasm in intercourse modulates women's reported frequency and men's estimates of women's frequency of orgasm in intercourse. Participants provided estimates of orgasm when asked explicitly about intercourse with stimulation unspecified, assisted intercourse, and unassisted intercourse. Women's reports of orgasm occurrence were highest in response to assisted intercourse (51-60%), second highest in response to intercourse with clitoral stimulation unspecified (31-40%), and lowest in response to unassisted intercourse (21-30%). Men's estimates of women's orgasms were highest in response to assisted intercourse (61-70%), and lowest in response to unassisted intercourse (41-50%); in both conditions, men's estimates were significantly higher than women's reports. When clitoral stimulation was unspecified, women interpreted "orgasm in intercourse" in three ways: as from intercourse alone, as including concurrent clitoral stimulation though it was unspecified, or as an average of assisted and unassisted intercourse. Taken together, these results demonstrate that the phrasing of questions about women's orgasm produces markedly different orgasm estimates, and suggest that concurrent clitoral stimulation increases the likelihood of women experiencing orgasm in intercourse.

Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens.

Both estradiol and testosterone have been implicated as the steroid critical for modulating women's sexual desire. By contrast, in all other female mammals only estradiol has been shown to be critical for female sexual motivation and behavior. Pharmaceutical companies have invested heavily in the development of androgen therapies for female sexual desire disorders, but today there are still no FDA approved androgen therapies for women. Nonetheless, testosterone is currently, and frequently, prescribed off-label for the treatment of low sexual desire in women, and the idea of testosterone as a possible cure-all for female sexual dysfunction remains popular. This paper places the ongoing debate concerning the hormonal modulation of women's sexual desire within a historical context, and reviews controlled trials of estrogen and/or androgen therapies for low sexual desire in postmenopausal women. These studies demonstrate that estrogen-only therapies that produce periovulatory levels of circulating estradiol increase sexual desire in postmenopausal women. Testosterone at supraphysiological, but not at physiological, levels enhances the effectiveness of low-dose estrogen therapies at increasing women's sexual desire; however, the mechanism by which supraphysiological testosterone increases women's sexual desire in combination with an estrogen remains unknown. Because effective therapies require supraphysiological amounts of testosterone, it remains unclear whether endogenous testosterone contributes to the modulation of women's sexual desire. The likelihood that an androgen-only clinical treatment will meaningfully increase women's sexual desire is minimal, and the focus of pharmaceutical companies on the development of androgen therapies for the treatment of female sexual desire disorders is likely misplaced.

Neonatal amygdala lesions lead to increased activity of brain CRF systems and hypothalamic-pituitary-adrenal axis of juvenile rhesus monkeys.

The current study examined the long-term effects of neonatal amygdala (Neo-A) lesions on brain corticotropin-releasing factor (CRF) systems and hypothalamic-pituitary-adrenal (HPA) axis function of male and female prepubertal rhesus monkeys. At 12-months-old, CSF levels of CRF were measured and HPA axis activity was characterized by examining diurnal cortisol rhythm and response to pharmacological challenges. Compared with controls, Neo-A animals showed higher cortisol secretion throughout the day, and Neo-A females also showed higher CRF levels. Hypersecretion of basal cortisol, in conjunction with blunted pituitary-adrenal responses to CRF challenge, suggest HPA axis hyperactivity caused by increased CRF hypothalamic drive leading to downregulation of pituitary CRF receptors in Neo-A animals. This interpretation is supported by the increased CRF CSF levels, suggesting that Neo-A damage resulted in central CRF systems overactivity. Neo-A animals also exhibited enhanced glucocorticoid negative feedback, as reflected by an exaggerated cortisol suppression following dexamethasone administration, indicating an additional effect on glucocorticoid receptor (GR) function. Together these data demonstrate that early amygdala damage alters the typical development of the primate HPA axis resulting in increased rather than decreased activity, presumably via alterations in central CRF and GR systems in neural structures that control its activity. Thus, in contrast to evidence that the amygdala stimulates both CRF and HPA axis systems in the adult, our data suggest an opposite, inhibitory role of the amygdala on the HPA axis during early development, which fits with emerging literature on "developmental switches" in amygdala function and connectivity with other brain areas.

Early adolescent Depo-Provera exposure increases stillbirths in adult sooty mangabeys.

The 3-month injectable contraceptive medroxyprogesterone acetate (MPA; Depo-Provera) is a synthetic progestin that protects against pregnancy by suppressing ovulation. Studies have focused on the resumption of ovulation after MPA-treatment cessation but neglected potential long-term effects of MPA exposure on future successful reproduction. MPA is frequently administered to adolescent girls; however, long-term fertility effects of adolescent MPA exposure have not been explored. We investigated fertility after extended MPA exposure in a species of old world primate, the sooty mangabey (Cercocebus atys). Female sooty mangabeys (n=31) received chronic MPA-treatment for 4-8 years. At MPA-treatment onset, subjects were either parous adults (n=14) or nulliparous adolescents (n=17), with adolescent-treated subjects being further divided into those who had reached first ovulation (n=10) and those who had not (n=7). After MPA-treatment cessation, adolescent-treated females had a significantly higher incidence of stillbirth than did age-matched and parity-matched controls, whereas adult-treated females did not differ from their matched controls. Females placed on MPA-treatment prior to first ovulation had a significantly higher incidence of stillbirth post-treatment than did females placed on MPA-treatment after first ovulation. Diabetic females had an increased incidence of stillbirth as compared to nondiabetic females; however, when controlling for diabetes, MPA exposure prior to first ovulation was still a significant positive predictor of stillbirth. These findings suggest that the post-treatment fertility effects of chronic MPA exposure vary with the developmental timing of treatment onset and raise concern about the use of MPA as a contraceptive for adolescent girls.

Duration of oral contraceptive use predicts women's initial and subsequent subjective responses to sexual stimuli.

Recent work suggests that a woman's hormonal state when first exposed to visual sexual stimuli (VSS) modulates her initial and subsequent responses to VSS. The present study investigated whether women's initial hormonal state was related to their subjective ratings of VSS, and whether this relationship differed with VSS content. We reanalyzed previously collected data from 14 naturally cycling (NC) women and 14 women taking oral contraceptives (OCs), who subjectively rated VSS at three hormonal time-points. NC women's ratings of 216 unique sexual images were collected during the menstrual, periovulatory, and luteal phases of their menstrual cycles, and OC women's ratings were collected at comparable time-points across their pill-cycles. NC women's initial hormonal state was not related to their ratings of VSS. OC women's initial hormonal state predicted their ratings of VSS with minimal contextual information and of images depicting female-to-male oral sex. Specifically, women who entered the study in the third week of their pill-cycle (OC-3 women) rated such images as less attractive at all testing sessions than did all other women. OC-3 women were also the only women to rate decontextualized VSS as unattractive at all testing sessions. These results corroborate previous studies in which women's initial hormonal state was found to predict subsequent interest in sexual stimuli. Future work, with larger samples, should more directly investigate whether OC-3 women's negative assessment of specific types of VSS reflects a reaction to the laboratory environment or a broader mechanism, wherein OC women's sexual interests decrease late in their pill-cycle.

Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls.

Variation in orgasm occurrence by sexual orientation in a sample of U.S. singles.

INTRODUCTION: Despite recent advances in understanding orgasm variation, little is known about ways in which sexual orientation is associated with men's and women's orgasm occurrence. AIM: To assess orgasm occurrence during sexual activity across sexual orientation categories. METHODS: Data were collected by Internet questionnaire from 6,151 men and women (ages 21-65+ years) as part of a nationally representative sample of single individuals in the United States. Analyses were restricted to a subsample of 2,850 singles (1,497 men, 1,353 women) who had experienced sexual activity in the past 12 months. MAIN OUTCOME MEASURES: Participants reported their sex/gender, self-identified sexual orientation (heterosexual, gay/lesbian, bisexual), and what percentage of the time they experience orgasm when having sex with a familiar partner. RESULTS: Mean occurrence rate for experiencing orgasm during sexual activity with a familiar partner was 62.9% among single women and 85.1% among single men, which was significantly different (F1,2848 = 370.6, P < 0.001, η(2) = 0.12). For men, mean occurrence rate of orgasm did not vary by sexual orientation: heterosexual men 85.5%, gay men 84.7%, bisexual men 77.6% (F2,1494 = 2.67, P = 0.07, η(2) = 0.004). For women, however, mean occurrence rate of orgasm varied significantly by sexual orientation: heterosexual women 61.6%, lesbian women 74.7%, bisexual women 58.0% (F2,1350 = 10.95, P < 0.001, η(2) = 0.02). Lesbian women had a significantly higher probability of orgasm than did either heterosexual or bisexual women (P < 0.05). CONCLUSIONS: Findings from this large dataset of U.S. singles suggest that women, regardless of sexual orientation, have less predictable, more varied orgasm experiences than do men and that for women, but not men, the likelihood of orgasm varies with sexual orientation. These findings demonstrate the need for further investigations into the comparative sexual experiences and sexual health outcomes of sexual minorities.

Mother recognition and preference after neonatal amygdala lesions in rhesus macaques (Macaca mulatta) raised in a semi-naturalistic environment.

Attachment to the caregiver, typically the biological mother, is crucial to young mammals' socio-emotional development. Although studies in nonprimate species suggest that the amygdala regulates social preference and attachment development, its role in primate filial attachment development has been little investigated and has produced mixed results. This study assessed the effects of neonatal amygdala- (Neo-A, N = 16) and sham- (Neo-C, N = 12) lesions on mother recognition and discrimination in macaques raised in species-typical social groups. Neonatal amygdalectomy did not affect social discriminative abilities and mother preference at 3 and 6 months of age, strongly suggesting that the amygdala is not involved in the cognitive processes underlying the development of filial attachment at least when the amygdala damage occurred after the third to fourth weeks of age. Nevertheless, as compared to sham-operated controls, amygdalectomized infants initiated physical contact with their mothers less frequently. The findings are discussed in relation to the known contribution of the amygdala to filial attachment in both rodents and humans.

Neonatal amygdala lesions alter mother-infant interactions in rhesus monkeys living in a species-typical social environment.

The current study examined the effects of neonatal amygdala lesions on mother-infant interactions in rhesus monkeys reared in large species-typical social groups. Focal observations of mother-infant interactions were collected in their social group for the first 12 months postpartum on infants that had received amygdala lesions (Neo-A) at 24-25 days of age and control infants. Early amygdala lesions resulted in subtle behavioral alterations. Neo-A females exhibited earlier emergence of independence from the mother than did control females, spending more time away from their mother, whereas Neo-A males did not. Also, a set of behaviors, including coo vocalizations, time in contact, and time away from the mother, accurately discriminated Neo-A females from control females, but not Neo-A and control males. Data suggest that neonatal amygdalectomy either reduced fear, therefore increasing exploration in females, or reduced the positive reward value of maternal contact. Unlike females, neonatal amygdala lesions had little measurable effects on male mother-infant interactions. The source of this sex difference is unknown.

Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates.

This article is part of a Special Issue "Puberty and Adolescence". Puberty is the developmental period when the hypothalamic-pituitary-gonadal (HPG) axis is activated, following a juvenile quiescent period, and reproductive capacity matures. Although pubertal events occur in a consistent sequence, there is considerable variation between individuals in the onset and timing of pubertal events, with puberty onset occurring earlier in girls than in boys. Evidence in humans demonstrates that social and environmental context influences the timing of puberty onset and may account for some of the observed variation. This review analyzes the nonhuman primate literature, focusing primarily on rhesus macaques (Macaca mulatta), to examine the social and environmental influences on puberty onset, how these factors influence puberty in males and females, and to review the relationship between puberty onset of adult neuroendocrine function and sexual behavior. Social and environmental factors influence the timing of puberty onset and pubertal events in nonhuman primates, as in humans, and the influences of these factors differ for males and females. In nonhuman primates, gonadal hormones are not required for sexual behavior, but modulate the frequency of occurrence of behavior, with social context influencing the relationship between gonadal hormones and sexual behavior. Thus, the onset of sexual behavior is independent of neuroendocrine changes at puberty; however, there are distinct behavioral changes that occur at puberty, which are modulated by social context. Puberty is possibly the developmental period when hormonal modulation of sexual behavior is organized, and thus, when social context interacts with hormonal state to strongly influence the expression of sexual behavior.

Sex-dependent role of the amygdala in the development of emotional and neuroendocrine reactivity to threatening stimuli in infant and juvenile rhesus monkeys.

Amygdala dysfunction and abnormal fear and stress reactivity are common features of several developmental neuropsychiatric disorders. Yet, little is known about the exact role the amygdala plays in the development of threat detection and emotional modulation. The current study examined the effects of neonatal amygdala lesions on defensive, emotional, and neuroendocrine reactivity of infant rhesus monkeys reared with their mothers in large species-typical social groups. Monkeys received either bilateral MRI-guided ibotenic acid amygdala (Neo-A; n = 16) or sham (Neo-C; n = 12) lesions at 24.8 ± 1.2 days of age, or served as behavioral control (Neo-BC; n = 3). Defensive and emotional responses were assessed using the Human Intruder paradigm as infants and as juveniles (2.5 and 12 months of age, respectively), whereas neuroendocrine reactivity was only examined during the juvenile period. As infants, Neo-A animals expressed similar levels of freezing and hostile behaviors as compared to controls, whereas during the juvenile period Neo-A animals expressed significantly less freezing compared to controls. Interestingly, the sex of the infant modulated the behavioral effects of neonatal amygdalectomy, leading to different patterns of behavior depending on the sex and lesion status of the infant. Unlike controls, Neo-A infants did not modulate their behavioral responses based on the salience of the threat. The impact of neonatal amygdalectomy increased with age, such that Neo-A juveniles exhibited fewer emotional behaviors and increased cortisol response to the stressor as compared to controls. These data indicate that the amygdala plays a critical role in the development of both emotional and neuroendocrine reactivity as well as the expression of sexually dimorphic emotional expression.

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.

Female sexual arousal: genital anatomy and orgasm in intercourse.

In men and women sexual arousal culminates in orgasm, with female orgasm solely from sexual intercourse often regarded as a unique feature of human sexuality. However, orgasm from sexual intercourse occurs more reliably in men than in women, likely reflecting the different types of physical stimulation men and women require for orgasm. In men, orgasms are under strong selective pressure as orgasms are coupled with ejaculation and thus contribute to male reproductive success. By contrast, women's orgasms in intercourse are highly variable and are under little selective pressure as they are not a reproductive necessity. The proximal mechanisms producing variability in women's orgasms are little understood. In 1924 Marie Bonaparte proposed that a shorter distance between a woman's clitoris and her urethral meatus (CUMD) increased her likelihood of experiencing orgasm in intercourse. She based this on her published data that were never statistically analyzed. In 1940 Landis and colleagues published similar data suggesting the same relationship, but these data too were never fully analyzed. We analyzed raw data from these two studies and found that both demonstrate a strong inverse relationship between CUMD and orgasm during intercourse. Unresolved is whether this increased likelihood of orgasm with shorter CUMD reflects increased penile-clitoral contact during sexual intercourse or increased penile stimulation of internal aspects of the clitoris. CUMD likely reflects prenatal androgen exposure, with higher androgen levels producing larger distances. Thus these results suggest that women exposed to lower levels of prenatal androgens are more likely to experience orgasm during sexual intercourse.

Sexual minority women's sexual motivation around the time of ovulation.

We investigated whether motivation for same-sex sexual contact was related to mid-cycle peaks in estrogen levels (typically associated with ovulation) among women with consistent versus inconsistent patterns of same-sex sexuality. Twenty women (M age = 30 years), all of whom have been providing data on their sexual behavior and identities since 1995, completed daily diaries assessing sexual motivation and provided 10 days of salivary estrogen samples. During the 3 consecutive days on which estrogen levels peaked, women who had consistently identified as lesbian since 1995 (n = 5) showed increased motivation for sexual contact with women. This change in same-sex motivation was significantly smaller among women who consistently identified as bisexual (n = 7) and women who had given up their lesbian or bisexual identities at some point since 1995 (n = 8). Women who ascribed a role for "choice" in their same-sex sexuality also showed smaller increases in same-sex motivation. The findings suggest that women with consistent versus inconsistent patterns of same-sex sexuality might be experiencing different types of same-sex desires influenced by different factors.

Women's interest in visual sexual stimuli varies with menstrual cycle phase at first exposure and predicts later interest.

This study investigated whether women's interest in visual sexual stimuli varied with their hormonal state. Viewing times of 30 women, 15 normal cycling (NC) and 15 oral contracepting (OC), to sexually explicit photos were measured at three different times. NC women were tested during their menstrual, periovulatory, and luteal phases, and OC women were tested at equivalent temporal intervals. Subjects viewed stimuli as long as desired, thus viewing time measured subject interest. Subjective ratings of stimulus sexual attractiveness were obtained on each test. There was no overall relationship between menstrual cycle phase and viewing time. However the participant's menstrual cycle phase during first exposure to sexual stimuli predicted subsequent interest in sexual stimuli during the next two tests. NC women who first viewed stimuli during their periovulatory phase looked longer at the sexual stimuli across all sessions than did women first tested in their luteal phase. OC women first exposed to the sexual stimuli during menstruation looked longer at the stimuli across all sessions than did OC women first exposed at other test phases. Neither current test phase nor initial cycle phase influenced subjective ratings. Women had increased interest in sexual stimuli across all sessions if first exposed to sexual stimuli when endogenous estrogens were most likely highest. These data suggest that women's interest in visual sexual stimuli is modulated by hormones such that the hormonal condition at first exposure possibly determines the stimuli's emotional valence, markedly affecting subsequent interest in sexual stimuli.