The influence of sex hormones on human behavior and psychological functioning has increasingly become the focus of scientific interest. Differences in various psychological domains are traced back to different hormonal profiles between the sexes. These hormones have an influence on developmental processes and have a formative effect on brain structure and function. Even before birth, sex hormones contribute significantly to the differentiation between the sexes. Sex hormones not only channel the developmental process, the acute levels and fluctuations in the release of these hormones have a significant effect on emotional and cognitive processes in adulthood. Of note, fluctuations in estradiol and progesterone levels play an important role in the pathogenesis of common mental disorders. Women are significantly more affected by anxiety and depression, yet this difference only occurs after puberty and gonadal maturation. Borderline personality disorder, also diagnosed more frequently in women, has been associated with increased basal testosterone. In this symposium, we will present current research findings from basic research and clinical practice. Yasaman Rafiee will present data on the moderating role of sex and gender role self-concepts on sex hormones and cortisol reactivity to social stress, Christian Deuter about effects of estradiol and progesterone administration on fear extinction in healthy women, Eugenia Kulakova about the role of testosterone in women with borderline personality disorder, Serenay Sarıkaya about effects of antiestrogen therapy on brain structure, mood, and well-being in women with breast cancer and Kim Hoffmann about the relationship between menstrual cycle, stress and cortisol in women with PMDD.

The stress response is a regulatory process involving both psychological and biological mechanisms. Previous research has demonstrated sex differences in salivary cortisol levels following the Trier Social Stress Test (TSST), potentially influenced by sex hormone levels, though this relationship remains understudied.

This exploratory analysis is part of a larger study currently under publication. Here, we aimed to investigate the association between sex hormones (estradiol and testosterone) and cortisol reactivity to the TSST in a sample of 175 healthy individuals (98 females). Additionally, we examined whether gender role self-concepts, specifically agency and communion, moderated the relationship between sex hormones and cortisol reactivity, assessing the extent to which observed sex differences align with stereotypical gender roles.

Participants underwent the TSST, and saliva samples were collected at five time points via passive drooling. Cortisol levels were measured at all five time points, while estradiol and testosterone were assessed at T1 and T5.

We found no significant association between estradiol or testosterone (measured at T1) and cortisol levels (log-transformed). Additionally, a weak interaction effect between estradiol and communion on cortisol levels was observed, indicating that higher estradiol levels were associated with lower cortisol levels in individuals with a high communion. This suggests that the relationship between estradiol and cortisol might be influenced by individuals' gender role self-concept. Although exploratory, these findings provide a basis for future research examining the interplay between sex hormones, gender roles, and cortisol reactivity to social stress.

Fear conditioning and extinction learning are discussed as important etiologic features in anxiety disorders. The risk of anxiety disorders is increased in women, and fear conditioning has been shown to be influenced by the phase of the menstrual cycle and circulating sex hormones. The aim of our study was to investigate the effects of separate and combined administration of estradiol and progesterone on fear extinction in healthy women. We investigated these relationships in a placebo-controlled, randomized trial of 116 healthy women (mean age 25.7 ± 6.0 years) who completed a fear conditioning paradigm, with acquisition (fear learning), extinction and retrieval on three consecutive days. Skin conductance responses (SCR) served as the main outcome variable. Two hours before testing on day 2, participants received estradiol, progesterone, a combination of both or placebo. During acquisition, participants responded stronger to CS+ compared to CS- across groups, indicating successful fear learning. In the subsequent extinction phase, estradiol administration produced a lack of differentiation between the CS. At retrieval on day 3, the estradiol groups showed stronger SCR to the previously extinguished CS- while progesterone had no effect. We conclude that exogenous estradiol administration influenced the extinction of the conditioned fear response, which subsequently led to a stronger return of fear.

Theoretical Background: Elevated baseline levels of the sex hormone testosterone have repeatedly been observed in biologically female patients with Borderline Personality Disorder (BPD). Furthermore, the increased prevalence of polycystic ovary syndrome in this population suggests a hyperandrogenic phenotype. The possible causes and consequences of higher testosterone levels in this population remain underexplored.

Research Question: It remains an open question whether testosterone levels are related to specific psychiatric symptoms in females with BPD. Based on the assumption that testosterone promotes aggressive, dominant, and status-seeking behaviour, we investigated whether elevated testosterone levels in females with BPD were associated with externalizing (aggressive or impulsive) symptoms.

Method: Baseline testosterone levels in saliva were measured in a sample of 98 patients with BPD. The relationship between testosterone levels and the severity of self-reported depressive and BPD symptoms was examined using the Borderline Symptom List (BSL-23) and the Beck Depression Inventory (BDI-II).

Results: Positive associations were found between testosterone levels and the overall severity of psychiatric symptoms. Further analysis of individual questionnaire items revealed that testosterone was particularly associated with heightened feelings of self-dislike, senselessness, pessimism, and the feeling of being a failure.

Conclusion: Our analyses confirm that baseline testosterone concentration is a relevant correlate of BPD symptomatology. However, elevated testosterone levels were linked to internalising and depressive symptoms rather than externalising ones. Possible explanations for the observed association and their implications are discussed.

Breast cancer is the most common cancer in women worldwide. While lifesaving, treatment can significantly affect physical health, mood, and brain architecture. Antiestrogen therapy is a type of breast cancer treatment that inhibits estrogen production and its effects. Given the role of estrogen in brain structure and mental health, we hypothesize that its reduction will negatively affect both mood and brain structure. Specifically, we expect that, compared to baseline, women with breast cancer will show decreased gray and white matter volume in the amygdala and hippocampus, along with increased negative mood and anxiety three weeks after starting antiestrogen therapy.

Women with breast cancer were recruited from the University Women's Hospital in Tübingen, Germany, and underwent MRI scans on a 3T PRISMA scanner. In addition to MRI scans, participants completed several questionnaires assessing mood, depression, and state anxiety. Neuroimaging data were preprocessed using SPM-CAT12, with the Neuromorphometrics Atlas used for regional brain volume analysis. Statistical analyses were performed using SPSS and R.

Preliminary results from 12 women with breast cancer showed a trend toward decreased right amygdala and left hippocampal volume. Additionally, a trend indicated an increase in negative affective states, depression, and anxiety at the second time point. While the findings suggest possible effects of antiestrogen therapy on brain structure and mental health, the limited sample size (n=12) may account for the lack of statistical significance. Recruitment is ongoing, and additional data will be presented to provide a more comprehensive analysis.

Introduction: Studies suggest there are alterations in the cortisol awakening response (CAR) in patients with premenstrual dysphoric disorder (PMDD), as exemplified by delayed cortisol peaks and flatter diurnal cortisol slopes compared to healthy controls. While inconsistent, previous research associates CAR alterations with prefrontal serotonin transporter (5-HTT) binding and severity of depressive symptoms. The CAR in relation to 5-HTT binding and depressive symptoms in patients with PMDD across the menstrual cycle has not been investigated yet.

Methods: 30 females with PMDD and 29 healthy controls self-collected three saliva samples (awakening, +30min, +60min) to assess the CAR and five more samples (9am, 12pm, 3pm, 6pm, 9pm) to assess the diurnal cortisol slope once during the periovulatory and once during the premenstrual phase. [¹¹C]DASB positron emission tomography scans were performed to measure 5-HTT non-displaceable binding potential (BP_ND). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D).

Results: A significant interaction between group and cycle phase was found on cortisol peak (β = 0.78, p = 0.05, d = 0.62, 95% CI = [0.01;1.56], corrected for awakening cortisol: β = 0.89, p = 0.03, d = 0.76, 95% CI = [0.13;1.64]). During the premenstrual phase, cortisol peak concentration correlated negatively with midbrain 5-HTT BP_ND (r = -0.35, p < 0.01, R² = 0.12) and HAM-D scores (r = -0.30, p = 0.02, R² = -0.09).

Conclusion: Patients with PMDD demonstrated attenuated cortisol peaks compared to healthy controls, with underlying associations to the serotonergic system and the severity of depressive symptoms.