Analyzing the atypical - Methods for studying the menstrual cycle in adolescents.

BACKGROUND: The female pubertal transition is characterized by a rapidly changing hormone milieu, which is heavily influenced by the first menstrual cycle - menarche. The first year following menarche is associated with menstrual cycles that are irregular and anovulatory. Peripuberty also marks the beginning of a female-biased risk for suicidality and depression, suggesting some influence by the menstrual cycle and ovarian hormone fluctuations. However, there are limited methods and guidelines for studying the menstrual cycle and related affective symptoms in this developmental window. Thus, this study's objective was to identify the most accurate methods for detecting ovulation in irregular cycles (Part 1) and develop guidelines based on these methods for determining menstrual cycle phases. These methods were applied to investigate hormones and affective symptoms based on cycle phase and ovulation status in a sample of peripubertal females (Part 2). METHODS: Thirty-two peripubertal females (ages 11-14) provided daily urine samples of estrogen (E1G) and progesterone (PdG) metabolites and luteinizing hormone (LH), and ratings of affective symptoms for one menstrual cycle. Ten literature-derived methods for determining the presence of an LH-peak or PdG rise were compared, focusing on their feasibility for psychological research. RESULTS: Methods by Sun et al. (2019) and Park et al. (2007) most accurately detected PdG rises and LH peaks in this sample, identifying 40.6% of cycles as ovulatory. As expected, ovulatory participants showed greater LH in the periovulatory phase (p = .001), greater PdG in the mid-luteal phase (p < .0001), and greater E1G in the periovulatory phase (p = .001) compared with anovulatory participants. Exemplary methods to compare psychological symptoms between both groups are provided. CONCLUSIONS: Recommendations and guidelines for studying the menstrual cycle in irregular cycling adolescents are offered. Novel methods for ovulation detection identified phase-specific hormonal patterns in anovulatory and ovulatory adolescent cycles.

Biobehavioral mechanisms underlying testosterone and mood relationships in peripubertal female adolescents.

The pubertal transition is characterized by pronounced sex hormone fluctuation, refinement of affective neural circuitry, and an increased risk of depression in female adolescents. Sex hormones, including testosterone, exert modulatory effects on frontal-limbic brain networks and are associated with emotion dysregulation and depressive symptoms. Weekly changes in hormones predict affective symptoms in peripubertal female adolescents, particularly in the context of stress; however, the biobehavioral mechanisms underlying hormone change and mood relationships during the pubertal transition have yet to be determined and was the objective of the present study. Forty-three peripubertal female adolescents (ages 11-14) collected 8-weekly salivary hormone (estrone, testosterone) samples and mood assessments to evaluate hormone-mood relationships, followed by a biobehavioral testing session with psychosocial stress and EEG. Within-person correlations between weekly hormone changes and corresponding mood were performed to determine individual differences in mood sensitivity to weekly hormone change. Increased frontal theta activity indexing emotion reactivity, reduced cortisol reactivity, and reduced vagal efficiency predicted the strength of the relationship between testosterone and mood. Further, testosterone-sensitivity strength was associated with the enhancement of negative affect following stress testing. Results identify divergent frontal theta and stress responses as potential biobehavioral mechanisms underlying mood sensitivity to peripubertal testosterone fluctuation.

Life stress influences the relationship between sex hormone fluctuation and affective symptoms in peripubertal female adolescents.

Female adolescents have a greatly increased risk of depression starting at puberty, which continues throughout the reproductive lifespan. Sex hormone fluctuation has been highlighted as a key proximal precipitating factor in the development of mood disorders tied to reproductive events; however, hormone-induced affective state change is poorly understood in the pubertal transition. The present study investigated the impact of recent stressful life events on the relationship between sex hormone change and affective symptoms in peripubertal female participants. Thirty-five peripubertal participants (ages 11-14, premenarchal, or within 1 year of menarche) completed an assessment of stressful life events, and provided weekly salivary hormone collections [estrone, testosterone, dehydroepiandrosterone (DHEA)] and mood assessments for 8 weeks. Linear mixed models tested whether stressful life events provided a context in which within-person changes in hormones predicted weekly affective symptoms. Results indicated that exposure to stressful life events proximal to the pubertal transition influenced the directional effects of hormone change on affective symptoms. Specifically, greater affective symptoms were associated with increases in hormones in a high stress context and decreases in hormones in a low stress context. These findings provide support for stress-related hormone sensitivity as a diathesis for precipitating affective symptoms in the presence of pronounced peripubertal hormone flux.

Methods for characterizing ovarian and adrenal hormone variability and mood relationships in peripubertal females.

Peripubertal females are at elevated risk for developing affective illness compared to males, yet biological mechanisms underlying this sex disparity are poorly understood. Female risk for depression remains elevated across a woman's reproductive lifespan, implicating reproductive hormones. A sensitivity to normal hormone variability during reproductive transition events (e.g., perimenopause) precipitates affective disturbances in susceptible women; however, the extent of hormone variability during the female pubertal transition and whether vulnerability to peripubertal hormone flux impacts affective state change in peripubertal females has not been studied. 52 healthy peripubertal females (ages 11-14) provided 8 weekly salivary samples and mood ratings. 10 salivary ovarian and adrenal hormones (e.g., estrone, testosterone, dehydroepiandrosterone (DHEA)) were analyzed weekly for 8 weeks using an ultrasensitive assay to characterize the female peripubertal hormone environment and its association with affective state. Hormone variability indices, including standard deviation, mean squared and absolute successive differences of the 8 weekly measurements were analyzed by menarche status. Within-person partial correlations were computed to determine the strength of the relationship between weekly change in hormone level and corresponding mood rating for each participant. As expected, results indicated that hormone variability was greater for post- relative to pre-menarchal females and with advancing pubertal development, yet pregnenolone-sulfate and aldosterone did not differ by menarche status. Mood sensitivity to changes in estrone was exhibited by 57% of participants, whereas 37% were sensitive to testosterone and 6% were sensitive to DHEA changes. The present results offer novel evidence that a substantial proportion of peripubertal females appear to be mood sensitive to hormone changes and may inform future investigations on the biological mechanisms underlying hormone-induced affect dysregulation in peripubertal females.