phytoestrogens and Anxiety-Disorders

Phytoestrogens, such as daidzein and genistein, may be used to treat various hormone-dependent disorders. Daidzein can be metabolized by intestinal microbes to S-equol. However, not all individuals possess bacteria producing this metabolite, resulting in categorization of equol vs nonequol producers. Past human and rodent studies have suggested that supplementation of this compound might yield beneficial metabolic and behavioral effects. We hypothesized that administration of S-equol to diet-induced obese male and female mice would mitigate potential diet-induced metabolic and comorbid neurobehavioral disorders. To test this possibility, we placed 5-week-old C57 mice on a high-fat diet (HFD) to mimic the diet currently consumed by many Western adults. Animals were randomly assigned to S-equol supplementation (10 mg/kg body weight) or vehicle control group. After 4 weeks on HFD with or without S-equol supplementation, metabolic and behavioral phenotyping was performed. Although the initial hypothesis proposed that S-equol treatment would improve metabolic and neurobehavioral outcomes, this supplementation instead exacerbated aspects of HFD-induced metabolic disease, as indicated by suppressed physical activity in treated individuals, reduced energy expenditure in treated males, and serum chemistry changes (hyperglycemia in treated individuals; hyperinsulinemia and hypoleptinemia in treated males). Conversely, S-equol individuals exhibited less anxiety-like and depressive-like behaviors, as evidenced by increased exploratory time in the elevated plus maze by treated males and increased time spent mobile in the tail suspension test for treated individuals. In summary, S-equol may be beneficial in mitigating depression and anxiety disorders in individuals, but for indeterminate reasons, supplementation may worsen facets of metabolic disorders in obese individuals.

Topics: Animals; Anxiety; Anxiety Disorders; Behavior, Animal; Blood Glucose; Depression; Depressive Disorder; Dietary Supplements; Equol; Female; Hindlimb Suspension; Insulin; Isoflavones; Leptin; Male; Maze Learning; Metabolic Diseases; Metabolic Syndrome; Mice, Inbred C57BL; Phytoestrogens; Sex Factors

Context • Psychoneurological symptoms are present in nearly all women in the perimenopausal period. Key elements of care in the period may include hormone replacement therapy (HRT). Alternatively, phytoestrogens, antidepressant pharmacotherapy, or a combination of hormonal and antidepressant therapies may be recommended. Objective • The study intended to verify whether women who are menopausal believe that a reduction in their symptoms of anxiety and depression depends on the type of pharmacotherapy used. Design • The study was designed as a multicenter study, conducted in public and private, gynecological, outpatient clinics. Setting • The study took place in public and private, gynecological, outpatient clinics in 3 regions of Poland: northwestern, central, and northern. Participants • Potential participants were 1239 women of menopausal age who visited gynecologists at the clinics. Outcome Measures • Participants were divided into 3 subgroups using the divisions of menopause defined by the World Health Organization, either premenopausal, perimenopausal, or postmenopausal. The study evaluated the severity of participants' menopausal symptoms using the Kupperman Index and the severity of their depression and anxiety disorders using the Hospital Anxiety and Depression Scale. A general mental health assessment was performed using a visual analogue scale, whereas the drugs used were evaluated using a Likert scale. Results • The study found statistically significant differences between the menopausal period and the severity of the menopausal symptoms. The highest efficacy in terms of relief from menopausal symptoms, such as shortness of breath, flushing, or sweating, was observed for a combined HRT and selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor antidepressant therapy. Nevertheless, phytoestrogen therapy was also highly effective. Conclusions • The best method of treatment with the smallest risk of adverse effects together with a high level of patient satisfaction was found to be the phytoestrogen therapy. The women themselves believed that the therapies were effective and largely helped them to stay mentally fit.

Topics: Anxiety; Anxiety Disorders; Depression; Female; Humans; Menopause; Outcome Assessment, Health Care; Patient Satisfaction; Phytoestrogens; Prevalence; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Women's Health