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Premenstrual syndrome (PMS), a recurrent and moderate disorder that occurs during the luteal phase of the menstrual cycle and quickly resolves after menstruation, is characterized by somatic and emotional discomfort that can be severe enough to impair daily activities. Current therapeutic drugs for PMS such as selective serotonin reuptake inhibitors are not very satisfying. As a critical pineal hormone, melatonin has increasingly been suggested to modulate PMS symptoms. In this review, we update the latest progress on PMS-induced sleep disturbance, mood changes, and cognitive impairment and provide possible pathways by which melatonin attenuates these symptoms. Moreover, we focus on the role of melatonin in PMS molecular mechanisms. Herein, we show that melatonin can regulate ovarian estrogen and progesterone, of which cyclic fluctuations contribute to PMS pathogenesis. Melatonin also modulates gamma-aminobutyric acid and the brain-derived neurotrophic factor system in PMS. Interpreting the role of melatonin in PMS is not only informative to clarify PMS etiology but also instructive to melatonin and its receptor agonist application to promote female health. As a safe interaction, melatonin treatment can be effective in alleviating symptoms of PMS. However, symptoms such as sleep disturbance, depressive mood, cognitive impairment are not specific and can be easily misdiagnosed. Connections between melatonin receptor, ovarian steroid dysfunction, and PMS are not consistent among past studies. Before final conclusions are drawn, more well-organized and rigorous studies are recommended. [ABSTRACT FROM AUTHOR]

Study Question: Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)?Summary Answer: We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors.What Is Known Already: Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown.Study Design, Size, Duration: A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants.Participants/materials, Setting, Methods: AYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry.Main Results and the Role Of Chance: The median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures.Limitations, Reasons For Caution: Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress.Wider Implications Of the Findings: The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans.Study Funding/competing Interest(s): NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Problem Tumor necrosis factor-like weak inducer of apoptosis ( TWEAK)/fibroblast growth factor-inducible 14 (Fn14) interactions affect the regulation of cytotoxic/immunotrophic pathways that are themselves under control of IL-18. The effect of Fn14 on regulation of endometrium IL-18 expression, however, remains unclear. Method and study The aim was to determine the mode of ovarian steroid action in regulating Fn14 expression by goat endometrial epithelial cells ( EECs) in the presence and absence of endometrial stromal cells ( ESCs). The possible role of Fn14 on the expression of IL-18 by EECs was also evaluated. Results Opposite effects of E2 and/or P4 on the regulation of both Fn14 mRNA and protein expression by EECs were observed in the presence and absence of ESCs. Fn14 knockdown by blocking antibody or siRNA resulted in a decrease of IL-18 mRNA and protein levels in EECs cocultured with ESCs, and no significant difference of the IL-18 mRNA and protein levels in the EECs was observed between steroid treatment group and control group. Conclusion These findings confirm the importance of steroids in controlling Fn14 expression in goat EECs. Furthermore, Fn14 appears as a novel modulator of the steroid-related IL-18 expression in EECs in the presence of ESCs. [ABSTRACT FROM AUTHOR]