When the brain turns on with sexual desire: fMRI findings, issues, and future directions.

INTRODUCTION: More than 2 decades of neuroimaging research has sought to uncover the neurologic basis of sexual desire. However, the lack of a clear conceptual distinction between sexual desire and sexual arousal or even a broadly accepted definition of sexual desire has led to confusion in the literature regarding brain areas uniquely associated with sexual desire. OBJECTIVES: (1) To critically review the neuroimaging literature that seeks to identify brain areas and networks involved in sexual desire; (2) to identify and discuss those brain areas and potential networks that are most promising for providing insights to sexual desire; and (3) to offer recommendations for future studies. METHODS: Existing meta-analyses were used as a starting point to identify relevant neuroimaging studies on sexual desire, arousal, and love. This base was then expanded via Google Scholar and forward citation tracking of already identified studies. RESULTS: Brain areas that are commonly associated with sexual desire and arousal include the amygdala, hypothalamus, dorsal and ventral striatum, anterior cingulate, insula, and prefrontal and orbitofrontal cortex. However, because the same basic paradigm has been used to study sexual desire and arousal, unambiguous conclusions regarding areas uniquely involved in sexual desire cannot be drawn. Moreover, the lack of connectivity analyses and a failure to acknowledge negative BOLD (blood-oxygen level dependent) significantly limit conclusions on the neural basis of sexual desire. CONCLUSION: Five recommendations are made. First, stimulus types (ie, erotic vs sexually explicit) should be selected by the meaningful theoretical conceptualization of the constructs of interest. Second, participants should be provided with definitions of sexual desire, mental sexual arousal, and perceived genital sexual arousal, so they can choose which terms best describe their experience. Third, event-related designs should be used with caution when investigating sexual desire. Fourth, time series analyses should be used to identify both positive and negative BOLD. Fifth, connectivity analyses should be performed to identify brain networks.

Menstrual cycle-driven vs noncyclical daily changes in sexual desire.

BACKGROUND: Past research on the association between sexual desire and the menstrual cycle has provided inconclusive results and has not considered the potential influence of psychological and physical changes that are frequently associated with the menstrual cycle. AIM: To test the strength of association between the menstrual cycle (and associated symptoms) and changes in sexual desire. METHODS: Prospective daily reports across 2 full menstrual cycles (2 months) from a sample of female university students (n = 213), were analysed. Analyses tested for average effects of the menstrual cycle on sexual desire, individual differences in these effects, and cyclical and noncyclical associations between sexual desire and the 9 menstrual cycle-related changes. Note that data presented in the current article come from a larger study from which other reports have been published. OUTCOMES: Target variables were (1) daily change in sexual desire and (2) daily reports of 5 psychological changes and 4 physical changes that are commonly associated with the menstrual cycle. RESULTS: Results showed that when considering average effects across participants, the menstrual cycle was associated with a small midcycle increase in sexual desire. However, multilevel analyses showed large individual differences in how the menstrual cycle influences sexual desire. Specifically, some participants showed a midcycle increase, others a perimenstrual increase, and others no change across the menstrual cycle. Moreover, results demonstrated that psychological changes were more important for predicting sexual desire as compared with physical changes. CLINICAL IMPLICATIONS: These results suggest that daily measurement of sexual desire across multiple menstrual cycles may be an important tool in the assessment of sexual desire among some females. STRENGTHS AND LIMITATIONS: Strengths of this study are the daily assessment of sexual desire and all symptoms for 2 menstrual cycles and multilevel analyses that allow the study of individual differences. Limitations include limited measurement of sexual desire based on only 2 questions and the lack of measures of relationship status and sexual orientation. CONCLUSION: Emphasis is placed on the need to apply more rigorous research methods and to abandon simplistic average-effects models that are based on outdated theories and stereotypes.

Sexual Desire in Women: Paradoxical and Nonlinear Associations with Anxiety and Depressed Mood.

The aim of the present study was to expand previous findings regarding paradoxical effects of negative mood on sexual desire. This was done by considering the full range of depressed mood and anxiety symptoms and using methods that are unaffected by recall bias and that don't require participants to infer causal associations between their mood and sexual desire. A convenience sample of 213 university students completed daily questionnaires for approximately two months. Multilevel random-effects models were used to estimate average effects for the entire sample and to test for variability across participants in the associations between negative mood and sexual desire, controlling also for potential influences of the menstrual cycle. Previous findings showing that some women report decreased sexual desire and others increased sexual desire when depressed or anxious were confirmed. More importantly, for both depressed mood and anxiety, results demonstrated the presence of within-person paradoxical associations, whereby there were some women for whom both low and high levels of negative mood were associated with the same change (an increase or a decrease) in sexual desire. Related to these diverse response patterns, paradoxical associations between negative mood and sexual desire were also present at low levels of negative mood. The discussion underlines the importance of considering individual variability and multifactorial nonlinear models when studying sexual desire.

Affective Risk Associated With Menstrual Cycle Symptom Change.

In the present study we test whether cyclical changes in affective symptoms of the menstrual cycle are associated with higher mean levels of those same symptoms. Using prospective daily reports across two full menstrual cycles, from two samples of female University students (n = 213; n = 163), we applied both quartic polynomial regressions and cosine regressions to model cyclical change in symptoms, and to test for mean-level differences in symptoms across the resulting trajectory patterns. Counter to prior findings, but consistent with theoretical expectations, these results show that females who experience menstrual cycle-related changes in affect (whether a perimenstrual or mid-cycle increase) are at risk for higher average levels of affective symptoms. These results suggest that the mid-cycle group should be recognized as a target for future research that is associated with increased risk for chronic negative affective symptoms.

How to study the menstrual cycle: Practical tools and recommendations.

Despite decades of research on the physiological and psychological effects of the menstrual cycle, studies have not sufficiently adopted consistent methods for operationalizing the menstrual cycle. This has resulted in substantial confusion in the literature and limited possibilities to conduct systematic reviews and meta-analyses. In order to facilitate more rapid accumulation of knowledge on cycle effects, the present paper offers a set of integrative guidelines and standardized tools for studying the menstrual cycle as an independent variable. We begin with (1) an overview of the menstrual cycle and (2) premenstrual disorders, followed by (3) recommendations and tools regarding data collection in cycle studies. These recommendations address selecting the appropriate study design and sampling strategy, managing demand characteristics, identifying a sample of naturally-cycling individuals, and measuring menstrual bleeding dates, ovarian hormones, and ovulation. We proceed with suggestions for (4) data preparation and coding of cycle day and phases, as well as (5) data visualization, statistical modeling, and interpretation of menstrual cycle associations. We also provide (6) recommendations for using menses start day and ovulation testing to schedule visits in laboratory studies and end with a (7) comprehensive summary and conclusion. Regardless of whether the influence of the menstrual cycle is of central interest in a study or should be controlled to accurately assess the effects of another variable, the use of these recommendations and tools will help make study results more meaningful and replicable.

Evolution, the Menstrual Cycle, and Theoretical Overreach.

A considerable amount of recent psychological research has attributed a variety of menstrual-cycle-related changes in social behavior to evolutionarily adaptive functions. Although these studies often draw interesting and unusual conclusions about female emotion and behavior within evolutionary theory, their significant limitations have not yet been addressed. In this article, we outline several methodological and conceptual issues related to the menstrual cycle that constitute threats to the internal validity and theoretical integrity of these studies. We recommend specific guidelines to address these issues and emphasize the need to apply more comprehensive and sophisticated theoretical structures when considering menstrual-cycle-related changes in emotion and behavior.

Menstrual Cycle Changes in Vagally-Mediated Heart Rate Variability are Associated with Progesterone: Evidence from Two Within-Person Studies.

A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), or both are responsible for HRV fluctuations. We present the first studies to use repeated measures of E2, P4, and HRV across the cycle to model both the unique and interactive effects of person-centered E2 and P4 on HRV in multilevel models. In study one, 40 naturally-cycling participants were assessed weekly across four weeks, and were blind to the cycle focus of the study. In study two, 50 naturally-cycling participants were examined in three precisely defined cycle phases via ovulation testing. Both studies revealed that only P4 was correlated with HRV, such that higher-than-usual P4 significantly predicted lower-than-usual HRV within a given participant. In line with this, cycle phase comparisons revealed lower HRV in the mid-luteal phase (characterized by elevated P4) than in other phases. No significant main or interactive effects of E2 on HRV were found. Future female health studies should investigate individual differences in these effects and potential consequences of cyclical HRV changes on daily functioning.

Are there temporal subtypes of premenstrual dysphoric disorder?: using group-based trajectory modeling to identify individual differences in symptom change.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnosis characterized by the cyclical emergence of emotional and physical symptoms in the luteal phase of the menstrual cycle, with symptom remission in the follicular phase. Converging evidence highlights the possibility of distinct subtypes of PMDD with unique pathophysiologies, but temporal subgroups have yet to be explored in a systematic way. METHODS: In the current work, we use group-based trajectory modeling to identify unique trajectory subgroups of core emotional and total PMDD symptoms across the perimenstrual frame (days -14 to +9, where day 0 is menstrual onset) in a sample of 74 individuals prospectively diagnosed with DSM-5 PMDD. RESULTS: For the total daily symptom score, the best-fitting model was comprised of three groups: a group demonstrating moderate symptoms only in the premenstrual week (65%), a group demonstrating severe symptoms across the full 2 weeks of the luteal phase (17.5%), and a group demonstrating severe symptoms in the premenstrual week that were slow to resolve in the follicular phase (17.5%). CONCLUSIONS: These trajectory groups are discussed in the context of the latest work on the pathophysiology of PMDD. Experimental work is needed to test for the presence of possible pathophysiologic differences in trajectory groups, and whether unique treatment approaches are needed.

Assay validation of hair androgens across the menstrual cycle.

INTRODUCTION: Saliva is a common noninvasive biofluid for measuring stress and sex hormones, yet one pressing limitation is that salivary hormones fluctuate momentarily, daily, and (for girls) across the menstrual cycle. Hair steroid assays are thought to provide a cumulative index which collapses across hormonal variability, potentially eliminating the confound of daily and menstrual cyclicity and thereby reflecting individual differences in average hormone levels. Here we seek to validate a hair bioassay methodology and test whether hair androgens accurately measure long-term, stable androgen levels in emerging adult women across two menstrual cycles. METHODS: Hair samples were collected at the end of each menstrual cycle for two cycles, and saliva samples were collected in the morning once per week across two menstrual cycles (N = 11 women). Hair samples were segmented by 1 cm for the first 4 cm to reflect the hormone levels of the past four serial months. Hair samples were assayed using commercially-available enzyme-immuno-assays for testosterone and DHEA. RESULTS: Hair androgen concentrations were significantly correlated with averaged saliva hormone levels (DHEA: r = .75, p < .05; Testosterone: r = .67, p < .05). With respect to hair hormone stability, there were significant correlations for almost all the pairs of two 1 cm hair segments collected in two months that corresponded to the same time period. Hair androgens in one segment were significantly correlated with those in next segment. Regarding salivary androgen stability, the intra-class correlation across the weekly saliva samples indicated that for DHEA 59% of the total variance was within person and 41% was between person; and for testosterone 91% of the total variance was between person, and only 9% within person. DISCUSSION: Results suggest that a one-time measure of hair provides a valid and reliable estimate of average steroid levels across two months. Moreover, whereas saliva measures of androgen levels capture week-to-week fluctuations in steroids, hair samples provide information on individual differences in average exposure to steroids, across long periods of time, such as months. Results are encouraging that hair DHEA and testosterone reflects the cumulative hormonal concentration and can be used as a stable hormonal index. Results also indicate that it is feasible to collect the first 3-4 centimeters of hair for studies of stable hormone levels.

The Menstrual Cycle-Response and Developmental Affective-Risk Model: A multilevel and integrative model of influence.

An integrative developmental model is presented in which menstrual cycle-related symptoms are hypothesized to result in a cascade of developmental challenges that contribute to increased affective symptoms among adolescent girls, and to long-term developmental sequelae. To provide the basis for this model a broad foundation is developed considering (a) psychological symptoms and disorders associated with reproductive events across the life span, and (b) the many and complicated effects that female reproductive steroids (estrogen & progesterone) have which trigger a variety of physical and psychological changes that are commonly associated with the menstrual cycle. The Menstrual Cycle-Response and Developmental Affective-Risk Model is driven by 3 central concepts: (a) individual differences in response to steroids are very large and thus require analysis of individual response, rather than group-level tendencies; (b) the menstrual cycle itself represents an important and complex set of biological, physical, psychological, behavioral, and social changes, and should not be studied exclusively as changing steroid levels; and (c) the effects of the menstrual cycle during adolescence and early adulthood may have long-term developmental consequences. This model integrates specific effects of the menstrual cycle with contextual and social developmental variables, and with past theoretical models. (PsycINFO Database Record

Individual differences in self-reported difficulty sleeping across the menstrual cycle.

The effect of menstrual cycle phase on sleep has been studied for decades; however, individual differences in the associations between sleep and menstrual phase have not been well studied. In addition, the associations between changes in sleep and other physiological and psychological factors that vary as a function of menstrual phase have not been thoroughly assessed. This study explored individual differences in daily self-reports of difficulty sleeping across the menstrual cycle, as well as associations between daily changes in difficulty sleeping and psychological/vegetative and somatic symptoms. Participants (n = 213 females, mean age = 21.29 ± 4.01 years) completed daily online questionnaires assessing` sleep, psychological and physical symptoms for two menstrual cycles. Two patterns of menstrual cycle-related self-reported difficulty sleeping emerged in addition to women who showed no cyclical change in self-reported difficulty sleeping: a perimenstrual increase and a mid-cycle increase. All psychological/vegetative symptoms and some of the somatic symptoms showed significant associations with self-reported difficulty sleeping. These findings highlight the importance of examining individual differences in sleep across the menstrual cycle and the significant contribution of a wide range of menstrual cycle-related psychological/vegetative and somatic symptoms.

The impact of menstrual cycle-related physical symptoms on daily activities and psychological wellness among adolescent girls.

Associations between perimenstrual physical and psychological symptoms have not been adequately studied among adolescent girls. The purpose of the present study was to test a mediation hypothesis postulating that perimenstrual disengagement from daily activities would mediate the association between physical symptoms and psychological symptoms. A non-clinical sample of N = 208 Italian adolescent girls (age M = 16.68 years) completed a 95-item online retrospective questionnaire regarding perimenstrual symptoms, and how these symptoms affect their daily activities. Structural Equation Modeling was used to test the mediation hypothesis. Results showed that physical and psychological symptoms were strongly associated. More importantly, results supported the hypothesis that perimenstrual disengagement from daily activities mediates the association between physical symptoms and psychological symptoms, but only for depressed mood and cognitive symptoms. This study provides support for a novel theoretical framework linking diverse aspects of menstrual cycle change. Longitudinal research is needed to replicate these findings.

A lack of consistent evidence for cortisol dysregulation in premenstrual syndrome/premenstrual dysphoric disorder.

Although decades of research has examined the association between cortisol regulation and premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD), no review exists to provide a general set of conclusions from the extant research. In the present review we summarize and interpret research that has tested for associations between PMS/PMDD and cortisol levels and reactivity (n=38 original research articles). Three types of studies are examined: correlational studies, environmental-challenge studies, and pharmacological-challenge studies. Overall, there was very little evidence that women with and without PMS/PMDD demonstrate systematic and predictable mean-level differences in cortisol, or differences in cortisol response/reactivity to challenges. Methodological differences in sample size, the types of symptoms used for diagnosis (physical and psychological vs. only affective), or the type of cortisol measure used (serum vs. salivary), did not account for differences between studies that did and did not find significant effects. Caution is recommended before accepting the conclusion of null effects, and recommendations are made that more rigorous research be conducted, considering symptom-specificity, within-person analyses, and multiple parameters of cortisol regulation, before final conclusions are drawn.

Mid-cycle headaches and their relationship to different patterns of premenstrual stress symptoms.

BACKGROUND: Recent research has shown that affective changes associated with the menstrual cycle may follow diverse patterns, including a classic premenstrual syndrome pattern, as well as the mirror opposite pattern, referred to as a mid-cycle pattern. OBJECTIVE: Test for the presence of a mid-cycle pattern of headaches, in addition to a menstrual pattern and a noncyclic pattern; test for an association between experiencing a specific pattern of headaches and a specific (previously identified) pattern of depression/anxiety; and test for mean-level differences, across headache pattern groups, in average headache index and depression/anxiety scores (averaged across 2 menstrual cycles for each participant). METHODS: A sample of 213 female university students completed daily questionnaires regarding symptoms of headaches and depression/anxiety for 2 menstrual cycles. Hierarchical linear modeling, polynomial multiple regression, analyses of variance, and chi-square analyses were used to test the hypotheses. RESULTS: Confirmed the existence of a mid-cycle pattern of headaches (16%), in addition to a menstrual pattern (51%), and a noncyclic pattern of headaches (33%). Patterns of headaches and affective change were significantly associated (χ(2) = 21.33, P = .0003; 54% correspondence), as were the average headache index and depression/anxiety scores (r = .49; P < .0001). No significant mean-level differences were found between the headache pattern groups on the average headache index scores or depression/anxiety scores. CONCLUSIONS: A significant number of women experience a mid-cycle pattern of headaches during the menstrual cycle. Moreover, women often, but not always, demonstrate the same pattern of headaches and depression/anxiety symptoms.

Affective response to the menstrual cycle as a predictor of self-reported affective response to alcohol and alcohol use.

Past research suggests that women with premenstrual syndrome (PMS) have higher levels of alcohol use/abuse. The present study was conducted to test the hypothesis that women with diverse patterns of affective response to the menstrual cycle (PMS pattern, mid-cycle pattern, and noncyclical pattern) would show mean-level differences on measures of self-reported affective response to alcohol, alcohol use, and sleep changes following alcohol use. All participants from an initial study of n = 213 college-aged women who had prospectively completed daily questionnaires for two full menstrual cycles were asked to complete a one-time retrospective questionnaire regarding their alcohol use and typical affective response when consuming alcohol. From that original study, n = 161 also participated in the present study. Results showed significant differences, in the expected direction, on three out of five measures (hard alcohol use, negative affective response to alcohol, and change in sleep following alcohol use). Women in the PMS pattern group reported (retrospectively) higher levels of hard alcohol use, a less negative affective response associated with alcohol use, and lower levels of sleep changes in relation to alcohol use, as compared to the mid-cycle group. The discussion considers potential mechanisms that may be responsible for these associations (i.e., GABA(A) modulation).

Developmental associations between adolescent change in depressive symptoms and menstrual-cycle-phase-specific negative affect during early adulthood.

The causal factors associated with increases in depressive symptoms among adolescent girls remain an area of theoretical debate, and the limited research considering a hormonal influence has provided mixed results. The goal of the present study was to test a set of longitudinal associations, that, if found, would provide support for a hormonal contribution to these changes. Specifically, this study tested the hypotheses that changes in depressive symptoms among adolescent girls would be associated with phase-specific symptoms of the menstrual cycle during early adulthood; that these associations would differ across three phases of the menstrual cycle; and that the pattern of associations would differ for changes in depressive symptoms during early- and late-adolescence. The sample consisted of 47 women with longitudinal data from 12 to 21 years old (approximately 91% European Canadian, 4% Middle Eastern Canadian, 2% Haitian Canadian, and 2% Asian Canadian). Consistent with expectations, results showed that early-adolescent increases in depressive symptoms were negatively associated with menstrual-phase negative affect, and positively associated with mid-cycle negative affect, but not associated with premenstrual negative affect; whereas late-adolescent change in depressive symptoms was only associated with depressive symptoms at 20-21 years. Thus, early-adolescent changes in depressive symptoms are longitudinally associated with later mood change across the menstrual cycle, suggesting a common underlying cause, which is hypothesized to be hormonal. Moreover, results suggest that, with respect to variables that are involved in affective development, important differences exist between early- and late-adolescence. The discussion considers menstrual-cycle-related symptoms (e.g., dysmenorrhea) during adolescence, and the need to study their effects on development. It is suggested that focused intervention and prevention efforts may be indicated to interrupt negative developmental outcomes.

A short-term longitudinal analysis of friendship selection on early adolescent substance use.

There is a strong empirical connection between individual and peer substance use during adolescence. The determination of whether this level of covariation reflects influence or selection is obscured by both the design and measurement strategies used. This present study utilizes a short-term longitudinal design with bi-monthly assessments to address the following two hypotheses: a) Adolescents select friends on the basis of their substance use, and b) New friend substance use predicts changes in future use. French Canadian adolescents (n = 143) were interviewed on their friendship networks and substance use behaviors (e.g., tobacco, alcohol and marijuana) four times during a school year. Cross-lag panel models revealed that adolescents who use substances tend to select new friends who use. Moreover, once in the network, these new friends also contribute to changes in the adolescents' substance use. These findings are relevant to understanding the multiple functions of adolescent substance use.

One woman's low is another woman's high: Paradoxical effects of the menstrual cycle.

Although past research on affective changes associated with the menstrual cycle has focussed on a specific pattern commonly referred to as Premenstrual Syndrome, there are compelling reasons to hypothesize that an opposite pattern, with a mid-cycle increase and a premenstrual low in symptoms, may also exist. Focusing on depression and anxiety, the present study tested whether this mid-cycle pattern of symptoms could be identified, using a sample of 213 female university students, who completed daily questionnaires for two menstrual cycles. Results confirmed the existence of a group of women who demonstrate the mid-cycle pattern of symptom changes (13%), in addition to the classic PMS pattern (61%), and individuals demonstrating no cyclical pattern of symptoms (26%). Moreover, women with a strong PMS pattern showed lower average levels of depression/anxiety than women with no cyclical changes. These findings require that current conceptions of menstrual-cycle related psychological changes be redefined to include the mid-cycle pattern, and suggest that women with strong PMS symptoms may actually benefit from a mid-cycle sense of wellness.

Adolescent Substance Use with Friends: Moderating and Mediating Effects of Parental Monitoring and Peer Activity Contexts.

The influence of using substances with friends on future individual use was examined in the context of parental monitoring rules and the ecology of peer activities. A one-year longitudinal study design included a combined sample of North Italian and French Canadian adolescents (N = 285, 53% girls, M = 14.25 years). Data analyses were conducted using structural equation modeling and multiple regression analyses. As expected, the covariation between parental monitoring and adolescent substance use was mediated by "co-use" with friends. Moreover, the relation between substance use with friends and individual substance use was moderated by parental monitoring rules and the peer activity context. Specifically, the relation between substance co-use with friends and individual substance use was stronger when the level of parental monitoring rules was low and when friends spent their time together primarily in unstructured contexts such as on the street or in park settings. These findings underline the importance of adults' use of rules to monitor adolescents prone to substance use, and the role of context in facilitating or reducing peer influence.

Day-to-day co-variations of psychological and physical symptoms of the menstrual cycle: insights to individual differences in steroid reactivity.

The associations between physical and psychological symptoms of the menstrual cycle have not been carefully studied in past research, but may lead to a better understanding of the underlying mechanisms of these symptoms. The present study examines the day-to-day co-variations among physical and psychological symptoms of the menstrual cycle. These symptoms were evaluated on a daily basis across one entire menstrual cycle, with a non-clinical sample of 92 university students. Results showed that headaches, gastrointestinal problems, lower abdominal bloating, skin changes, and breast changes, were all significantly associated with higher levels of psychological symptoms; whereas back and joint pain, lower abdominal cramps, cervical mucous, and menstrual flow, were not associated with psychological symptoms. However, significant differences in these associations were observed across individuals for back and joint pain, headaches, lower abdominal cramps, skin changes, and menstrual flow: Whereas some women demonstrated higher levels of psychological symptoms associated with these physical symptoms, other women demonstrated lower levels of psychological symptoms. Finally, correlations among the associations between physical and psychological symptoms (slopes) demonstrated clear differences across the different physical symptoms. These results indicate that, although higher levels of some physical symptoms are associated with higher levels of psychological symptoms, there are significant differences in the magnitude and direction of these relations across individuals. Further consideration of physical symptoms may provide useful information for understanding individual differences in symptom profiles and response to steroid fluctuations, and for improving differential diagnosis and treatment planning and evaluation.