Search Results (26)

Approximately 4% of women of reproductive age are estimated to suffer from premenstrual dysphoric disorder (PMDD), a condition likely underdiagnosed due to various biases, suggesting that actual prevalence may be higher. Addressing this, a novel electrochemical sensor was developed using a screen-printed electrode of reduced graphene oxide modified with a Cu(II) triazole complex, Cu(L^NO2)₂/rGO/SPCE. This sensor aims to determine levels of serotonin and 17β-estradiol rapidly, and simultaneously, key analytes implicated in PMDD. The method demonstrated high sensitivity for both analytes, achieving sensitivity levels of 0.064 μA/μmol L⁻¹ for serotonin and 0.055 μA/μmol L⁻¹ for 17β-estradiol, with a linear detection range of 2 to 42 μmol L⁻¹. Detection limits were 42 nmol L⁻¹ for serotonin and 53 nmol L⁻¹ for estrogen. The sensor also exhibited high stability and selectivity against common interferents found in biological fluids. It was successfully used to measure serotonin and 17β-estradiol in human serum and urine, with recovery percentages within the expected ranges. This demonstrates that the sensor proposed in this work holds significant potential to contribute not only to the accurate diagnosis of such disorders but also to their treatment. We hope that this research will pave the way for the development of devices that have a positive impact on the quality of life of women suffering from multisystem diseases caused by hormonal malfunctions. Full article

Premenstrual Syndrome (PMS) is a disorder between gynecology and psychiatry which includes cognitive, affective, and somatic symptoms from mild to severe. The most severe form of PMS is premenstrual dysphoric disorder (PMDD) and it is considered a form of depressive disorder. An association between diet composition and the occurrence of PMS and its severity have been suggested. As such, this manuscript discusses the relationships between diet composition, dietary patterns and eating behaviors, and PMS. PubMed, Embase, Cochrane, and Web of Science databases were searched for related studies up to 18 January 2024. A text search with the following keywords singly or in combination was conducted: “Premenstrual syndrome”, “Nutrition”, “Diet composition”, “Dietary patterns”, and “Eating behaviors”. Studies published so far showed that low intake of simple carbohydrates, fats, salt, and alcohol, and high of fresh, unprocessed foods rich in B vitamins, vitamin D, zinc, calcium, and omega-3 fatty acids may help prevent the onset of PMS and reduce the severity of its symptoms. However, further studies are needed to formulate definitive recommendations for the use of vitamins, micronutrients and other dietary ingredients supplementation in women with PMS to improve functioning, overall well-being, and physical health. Large, randomized, double-blind clinical trials across diverse populations are necessary to formulate clear recommendations for supplementation in women with PMS. Full article

Premenstrual Dysphoric Disorder (PMDD) is a psychiatric condition characterized by debilitating affective symptomatology in the luteal phase of the menstrual cycle. Based on the previous reports that PMDD may be related to GABAergic cellular dysfunction(s), we assessed whether cation–chloride cotransporter (CCC) gene expression across the menstrual cycle is altered in PMDD. As there are limitations in accessing the human CNS to study CCC-encoding genes, we utilized peripheral blood mononuclear cells (PBMCs) as an alternative model. We first sought to replicate previous reports characterizing CCC gene expression patterns in PBMCs of reproductive age women. We subsequently investigated potential distinct CCC mRNA expression patterns in women with PMDD. We collected blood samples across 8 menstrual cycle visits for PBMC separation/RNA extraction to study mRNA expression of four KCCs (KCC1, KCC2, KCC3, KCC4) and two NKCCs (NKCC1, NKCC2) cotransporters. We mostly replicated the earlier gene expression pattern findings, and found that the expression levels of KCC1 were significantly downregulated during the mid-follicular and periovulatory subphases of the menstrual cycle in women with PMDD. The present study shows that PBMCs is a valid model for studying GABAergic mechanisms underlying PMDD. Full article

Background/Objectives: Premenstrual dysphoric disorder (PMDD) is an understudied psychiatric condition affecting reproductive-age women who experience negative mood in the luteal phase of the menstrual cycle. Cognitive functions in PMDD are not well understood as patients have been tested in the luteal phase. This may confound study results due to noted emotional interferences, as well as the potential opposing effects of the sex hormones estradiol and progesterone. In the present study, we evaluated visuospatial function in the follicular phase in women with PMDD and healthy controls, and further examined the effect of estradiol as research into the hormonal mediation of visuospatial function in reproductive-age women has produced mixed results. Methods: To this end, we analyzed estradiol concentrations using the gold standard mass spectrometry. Serum samples were collected in the early follicular and mid/late follicular subphases when estradiol is low and high, respectively, while progesterone is low and steady. We assessed visuospatial function using the classic mental rotation task. Results: Women with PMDD had a higher mental rotation total score (t = 2.17; p < 0.05). The addition of six demographic, biological, and anthropomorphic variables in a hierarchical fashion accounted for 45.3% of the total variance in the final model with diagnosis remaining statistically significant (t = 4.36; p < 0.001). Estradiol did not mediate the group difference and was not significantly associated with visuospatial function. Conclusions: The present results provide support for new research directions into the potential biological mechanisms that underlie the pathophysiology of PMDD, represented as enhanced visuospatial ability in women with PMDD in the follicular phase. We review the theory that PMDD is a disorder of the enhanced excitation-to-inhibition ratio, with a focus on findings to date from brain imaging research. Full article

Dysregulated food craving is a complex weight-related behavior. To identify novel targets for enhancing the efficacy of weight loss interventions, we examined whether food craving varies across the menstrual cycle according to the abdominal obesity type and premenstrual dysphoric disorder (PMDD) diagnosis, and, if so, whether it is related to affective symptomatology. Reproductive-age women were classified into one of the four study groups according to whether they have abdominal obesity (AO) or are abdominally lean (AL), and the presence of PMDD: (1) AO:PMDD+ (n = 13), (2) AL:PMDD+ (n = 14), (3) AO:PMDD− (n = 15), and (4) AL:PMDD− (n = 16). Self-report measures as well as urinary luteinizing hormone (LH) tests were provided by the participants across 2–3 menstrual cycles. The ratings of food cravings were similar across the menstrual cycle, except the last, late luteal subphase as the AO:PMDD+ participants had the highest food craving rating. Irritability and depression were correlated with food cravings, but not in a distinctive manner across the menstrual cycle by group. Our study found that women with abdominal obesity and PMDD display a temporal vulnerability to a food-related behavior. The possibility of shared neurobiology between the two conditions is discussed and should be examined in future studies. Full article

Most women who menstruate experience various physical, psychological, and behavioral changes during the period between ovulation and menstruation. This study focuses on defining and diagnosing premenstrual disorders, distinguishing between premenstrual symptoms (PS), PMS, and premenstrual dysphoric disorder (PMDD). It highlights the prevalence of these conditions and their impact on women’s quality of life, including social, occupational, and psychological aspects. Furthermore, the study examines the role of physical activity, particularly aerobic exercise, in managing premenstrual symptoms. Several systematic reviews are cited, suggesting that regular physical activity can effectively reduce both physical and psychological symptoms associated with PMS. In conclusion, the management of PMS involves a multifaceted approach, with exercises, dietary modifications, stress management, cognitive-behavioral therapy, and medications all playing roles. Physical activity, especially aerobic exercise, has been found to be an effective non-pharmacological therapy for alleviating PMS symptoms and improving overall well-being. However, more research is needed to determine the optimal type and dosage of exercise for individual women with PMS. Full article

Previously, we reported that a reduction in β-Arrestin1 protein levels in peripheral blood mononuclear leukocytes (PBMC) significantly correlated with the severity of depression symptoms in women with premenstrual dysphoric disorder (PMDD). This study aimed to determine whether the reduced premenstrual β-Arrestin1 protein levels were associated with changes in the regulator for late luteal phase progesterone secretion. The study participants (n = 25) were non-pregnant women between 18 and 42 years of age not taking any antidepressants or receiving therapy and experiencing the luteal phase of menstruation. ELISA determined the β-Arrestin1 protein in PBMC; testosterone and prolactin levels from the plasma were determined by radioimmunoassay. Reduced levels of β-Arrestin1 protein in women with Hamilton Rating Scale for Depression (HAM-D) scores above 19 were observed alongside significantly higher plasma testosterone and prolactin concentrations. Understanding the mechanism underlying the initiation of PMDD will allow for identification of a key perturbed metabolic enzyme that can serve as a target for drug development to ensure the alleviation of PMDD, which has been suggested earlier as a risk factor for developing major depressive disorders. Full article

FSH, estrogen and progesterone testing are widely utilized in clinical practice. Lateral flow assays (LFAs) are cost-effective tools used for diagnosing infectious diseases, pregnancy, and substance testing. The focus of this narrative review is the potential for the wider utilization of listed hormone LFAs. A search was conducted with PubMed, Google Scholar and Wiley online libraries using keywords without any limitation on the publication date; animal studies were excluded. Clinical guidelines for the related conditions were included. According to published data, E3G and PdG are used to determine ovulatory cycles and can be utilized for research purposes to establish the normal range of menstrual cycles, as there is currently disagreement among guidelines. FSH measurement in blood samples is utilized to predict oocyte yield in assisted cycles and to differentiate women with premature ovarian insufficiency from hypothalamic amenorrhea, and can be replaced with more convenient urine testing. PdG was tested to assess the risk of pregnancy complications, specifically miscarriage and ectopic pregnancy, and might become a screening tool for miscarriage in the future. PMS, PMDD and ovarian carcinogenesis could be extensively studied using LFAs to gain a better understanding of the biology behind these conditions. Before implementing these LFAs into clinical practice, the reproducibility of progesterone assays should be evaluated. The results are critical for treatment decisions, and universally recognized standards for estradiol measurement should be developed. Full article

Fluctuating hormone levels during the menstrual cycle and major reproductive cycle stages have been linked to mood changes, mental health conditions, and an increased likelihood of psychotic episodes. This knowledge could potentially be used for the predictive modeling of exacerbations and mood deterioration through the collection and analysis of data from wearables and apps. A literature search for a narrative review has been conducted using selected keywords in Pubmed, Embase and Google Scholar. Based on published data, it can be seen that hormonal changes affect the severity of symptoms in several mental health conditions, including depression, PMDD, PTSD, bipolar disorder and schizophrenia. The influence of FSH, LH, testosterone, and other hormone precursors has also been investigated, but there is less information available regarding their impact. E2 levels have been measured as a treatment–response biomarker and have demonstrated significant predictive ability for treatment responder groups. On the other hand, FSH has been demonstrated to be helpful in predicting treatment non-responder groups in schizophrenia. Monitoring reproductive hormones in combination with wearables or digital solutions has the potential to predict mood changes more effectively. Precise and frequent hormone measurements might prove to be more effective than relying on absolute threshold levels. Further research is needed to validate the utility and precision of hormone use in the field of mental health. Full article

Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1β2γ2L and α4β3δ GABA-A receptor subtypes. In this study, we also investigated whether ISO could antagonize the estrus cycle-dependent aggressive behaviors in female Wistar rats using a resident–intruder test. Our results confirmed previous reports of estrus cycle-dependent behaviors in that 42% of the tested rats showed higher levels of irritability/aggression at diestrus compared to those at estrus. Furthermore, we found that, during the treatment with ISO, the aggressive behavior at diestrus was alleviated to a level comparable to that of estrus. We noticed an 89% reduction in the increase in aggressive behavior at diestrus compared to that at estrus. Vehicle treatment in the same animals showed a minimal effect on the diestrus-related aggressive behavior. In conclusion, we showed that ISO can antagonize Steroid-PAM both in α1β2γ2L and α4β3δ GABA-A receptor subtypes and inhibit estrus cycle-dependent aggressive behavior. Full article

It is not clear whether progesterone and estradiol associate with premenstrual food cravings, which significantly contribute to cardiometabolic adverse effects associated with obesity. We sought to investigate this question in the present study based on the prior literature showing a protective effect of progesterone on drug craving and extensive neurobiological overlaps between food and drug cravings. We enrolled 37 non-illicit drug- or medication-using women in the study to provide daily ratings of premenstrual food cravings and other symptoms across two-three menstrual cycles, based on which we classified them as premenstrual dysphoric disorder (PMDD) or control participants. In addition, the participants provided blood samples at eight clinic visits across the menstrual cycle. We aligned their mid-luteal progesterone and estradiol using a validated method which relies upon the peak serum luteinizing hormone and analyzed estradiol and progesterone using ultraperformance liquid chromatography tandem mass spectrometry. Hierarchical modeling, adjusted for BMI, showed a significant inverse effect of progesterone (p = 0.038) but no effect of estradiol on premenstrual food cravings. The association was not unique to PMDD or control participants. Results of research to date in humans and rodents showing that progesterone has dampening effects on the salience of the reinforcer translate to premenstrual food cravings. Full article

Human survival and wellbeing require appropriate responses to stress, including a highly coordinated and efficient nervous system control of the heart rhythm. During stress, a greater disinhibition of the vagal nerve is reflective of poor stress adaptability, which may be relevant in premenstrual dysphoric disorder (PMDD)—a debilitating affective condition thought to be marked by dysregulated stress processing and sensitivity to allopregnanolone. In the present study, women with PMDD (n = 17) and healthy controls (n = 18), who did not take medication, smoke, or consume illicit drugs, and who were free of other psychiatric conditions, participated in the Trier Social Stress Test, during which we measured the high frequency of the heart rate (HF-HRV) and allopregnanolone using ultra-performance liquid chromatography tandem mass spectrometry. Relative to their baseline, women who have PMDD, but not the healthy controls, experienced a reduction in HF-HRV during stress anticipation (p ≤ 0.05) and stress (p ≤ 0.01). Their recovery from stress was significantly delayed (p ≤ 0.05). Absolute peak HF-HRV change from baseline was significantly predicted by baseline allopregnanolone only in the PMDD group (p ≤ 0.01). The present study shows how an interaction between stress and allopregnanolone—which have both been separately implicated in PMDD—underlies PMDD expression. Full article

Stress susceptibility could play a role in developing premenstrual anxiety due to abnormalities in the hypothalamus–pituitary–adrenal (HPA) axis and impairments in the GABAA receptors’ benzodiazepine (BDZ) site. Hence, we studied the stress-vulnerable Wistar Kyoto rat strain (WKY) to evaluate progesterone withdrawal (PW) effects on anxiety, HPA axis response, and to explore indicators of GABAA functionality in the BDZ site. For five days, ovariectomized WKY rats were administered 2.0 mg/kg of progesterone. Twenty-four hours after the last administration, rats were tested in the anxiety-like burying behavior test (BBT) or elevated plus maze test (EPM), and corticosterone was determined. [3H]Flunitrazepam binding autoradiography served as the BDZ binding site index of the GABAA receptor in amygdala nuclei and hippocampus’s dentate gyrus (DG). Finally, different doses of diazepam in PW-WKY rats were tested in the BBT. PW induced anxiety-like behaviors in both BBT and EPM compared with No-PW rats. PW increased corticosterone, but was blunted when combined with PW and BBT. PW increased [3H]Flunitrazepam binding in the DG and central amygdala compared with No-PW rats. Diazepam at a low dose induced an anxiogenic-like response in PW rats, suggesting a paradoxical response to benzodiazepines. Overall, PW induced anxiety-like behavior, a blunted HPA axis response, and higher GABAAR/BZD binding site sensitivity in a stress-vulnerable rat strain. These findings demonstrate the role of stress-susceptibility in GABAAR functionality in a preclinical approximation of PMDD. Full article

Objective: Cognitive and somatic symptoms were vital factors in developing personalized treatment of depressive disorder. The study aimed to evaluate the following: (1) the cognitive and somatic symptoms of premenstrual dysphoric disorder (PMDD) in the early luteal (EL) and later luteal (LL) phase; and (2) their association with depression and functional impairment of PMDD. Methods: We prospectively evaluated executive function, emotion regulation, cognitive and somatic symptoms, and depression in the EL and LL phases in women with PMDD. Sixty-three women with PMDD and 53 healthy controls completed Simon’s task and questionnaire to assess emotion regulation, inattention, fatigue, insomnia, and depression. Results: Women with PMDD had a poor performance in Simon’s task during the LL phase. They were less likely to exercise cognitive reappraisal during EL and LL phases. Their cognitive reappraisal positively correlated with executive function and negatively associated with depression. In the LL phase, they also experience higher inattention, insomnia, and fatigue, which correlate with the depression and functional impairment of PMDD. Inattention is the most associated factor of PMDD and functional impairment in controlling depression. Conclusion: Executive function was impaired in women with PMDD during the LL phase. Its performance correlated positively with emotion regulation and negatively with depression. The association between inattention and PMDD functional impairment indicates that evaluation and intervention for cognitive impairment were essential in treating women with PMDD. Further studies were required to elucidate the possible etiology underlying these associations. Full article

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) encompass a variety of symptoms that occur during the luteal phase of the menstrual cycle and impair daily life activities and relationships. Depending on the type and severity of physical, emotional or behavioral symptoms, women of reproductive age followed for at least two prospective menstrual cycles may receive one of the two diagnoses. PMDD is the most severe form of PMS, predominantly characterized by emotional and behavioral symptoms not due to another psychiatric disorder. PMS and PMDD are common neuro-hormonal gynecological disorders with a multifaceted etiology. Gonadal steroid hormones and their metabolites influence a plethora of biological systems involved in the occurrence of specific symptoms, but there is no doubt that PMS/PMDD are centrally based disorders. A more sensitive neuroendocrine threshold to cyclical variations of estrogens and progesterone under physiological and hormonal therapies is present. Moreover, altered brain sensitivity to allopregnanolone, a metabolite of progesterone produced after ovulation potentiating GABA activity, along with an impairment of opioid and serotoninergic systems, may justify the occurrence of emotional and behavioral symptoms. Even neuro-inflammation expressed via the GABAergic system is under investigation as an etiological factor of PMS/PMDD. Pharmacological management aims to stabilize hormonal fluctuations and to restore the neuroendocrine balance. The rationale of suppressing ovulation supports prescription of combined hormonal contraception (CHC). Its effect on mood is highly variable and depends on biochemical characteristics of exogenous steroids and on type and severity of symptoms. Hormonal regimens reducing the estrogen-free interval or suppressing menstruation seem better choices. Psychoactive agents, such as serotonin reuptake inhibitors (SSRIs), are effective in reducing the symptoms of PMS/PMDD and may be prescribed continuously or only during the luteal phase. Novel therapeutic approaches include inhibition of progesterone receptors in the brain, i.e., with ulipristal acetate, reduced conversion of progesterone with dutasteride, and modulation of the action of allopregnanolone on the brain GABAergic system with sepranolone. Full article