Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression.

Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile of metabolites in mood disorders is advancing, further research, maintaining consistent methodology, is necessary to reach a consensus. Therefore, the objective of the present study was to carry out an exploratory analysis of the plasma polar metabolites of pre- and postmenopausal women to explore whether the profile is affected by depression. The plasma analysis of 50 polar metabolites was carried out in a total of 67 postmenopausal women, aged between 50 and 65 years, either without depression (n = 25) or with depression symptoms (n = 42), which had spontaneous onset of menopause and were not in use of hormone replacement therapy, insulin, or antidepressants; and in 42 healthy premenopausal women (21 without depression and 21 with depression symptoms), aged between 40 and 50 years and who were not in use of contraceptives, insulin, or antidepressants. Ten metabolites were significantly affected by depression symptoms postmenopause, including adenosine (FDR = 3.778 × 10-14), guanosine (FDR = 3.001 × 10-14), proline (FDR = 1.430 × 10-6), citrulline (FDR = 0.0001), lysine (FDR = 0.0004), and carnitine (FDR = 0.0331), which were down-regulated, and dimethylglycine (FDR = 0.0022), glutathione (FDR = 0.0048), creatine (FDR = 0.0286), and methionine (FDR = 0.0484) that were up-regulated. In premenopausal women with depression, oxidized glutathione (FDR = 0.0137) was down-regulated, and dimethylglycine (FDR = 0.0406) and 4-hydroxyproline (FDR = 0.0433) were up-regulated. The present study provided new data concerning the consequences of depression on plasma polar metabolites before and after the establishment of menopause. The results demonstrated that the postmenopausal condition presented more alterations than the premenopausal period and may indicate future measures to treat the disturbances involved in both menopause and depression.

Insomnia Symptoms and Menstrual Health: Is There a Link in Women During Reproductive Phase of Life?

OBJECTIVES: To investigate the association between insomnia severity symptoms and menstrual health, fatigue and anxiety symptoms in women at reproductive age. METHOD: We used data from EPISONO (2007), an epidemiological study from the city of São Paulo, Brazil. Women completed the Insomnia Severity Index (ISI), the Chalder Fatigue Scale (CFS), and the Beck Anxiety Inventory (BAI) to obtain information about insomnia, fatigue, and anxiety symptoms. For menstrual health, we collected information using our Institutional Women's Questionnaire about menstrual flow and duration, the presence of pain during menstruation and menstrual cycle regularity. The statistical analysis was performed using ordinal logistic regression, considering p < .05. RESULTS: Of the 1,042 participants, only 282 women met the inclusion criteria to participate in this study. The mean age was 34.4 years (SD ± 8.36), and the body mass index (BMI) was 25.7 (SD ± 5.39). According to the model, a 1-unit higher CFS score increased the odds of having more insomnia symptoms in the ISI (OR = 1.170; 95% CI=[1.073; 1.279]; p < .001). In the same way, a 1-unit higher BAI score increased the chance of presenting insomnia symptoms, according to the ISI (OR = 1.072; 95% CI=[1.042; 1.104]; p < .001). The menstrual variables did not represent statistical significance in the model. CONCLUSIONS: Fatigue and anxiety symptoms were associated with insomnia symptoms; however, no association was observed between menstrual health and insomnia. The need to examine sleep when there are sleep complaints is essential to provide an accurate diagnosis that facilitates appropriate treatment and to provide better sleep quality for women.

How do phases of the menstrual cycle affect sleep? A polysomnographic study of the EPISONO database.

PURPOSE: Our study aimed to evaluate the impact of the menstrual cycle stages, especially menses, on sleep, inflammatory mediators, fatigue, anxiety, depression, and quality of life. METHODS: We used data from the EPISONO study cohort, selecting 96 women who had undergone one-night polysomnography. The women were distributed in three groups according to the time point of the menstrual cycle on the polysomnography night: menses, mid/late follicular phase, and luteal phase. The volunteers completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were collected to analyze interleukin 6, tumor necrosis factor-alpha, and C-reactive protein. RESULTS: Sleep efficiency was statistically higher in women in the mid/late follicular group (89.9% ± 9.6) compared to menstrual (83.0% ± 10.8) and luteal (83.7% ± 12.7) groups. The mid/late follicular group presented a statistically significant reduction in sleep onset latency (7.1 ± 7.1 min) compared to the menstrual (22.3 ± 32.4 min) and luteal groups (15.9 ± 14.7 min). No statistical differences among the three groups were observed in other polysomnographic parameters, inflammatory mediators, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. CONCLUSIONS: Our findings demonstrate that the mid/late follicular phase might be beneficial for women's sleep, although there were no statistically changes in inflammatory mediators among the groups.

Effect of a lavender essential oil and sleep hygiene protocol on insomnia in postmenopausal women: A pilot randomized clinical trial.

INTRODUCTION: Insomnia and vasomotor symptoms are frequently experienced during the menopausal transition and in postmenopause, worsening sleep maintenance and quality of life. Our study evaluated the use of lavender essential oil and sleep hygiene guidance on quality of life, sleep patterns and self-reported hot flashes in postmenopausal women with insomnia diagnosis. METHODS: This study is part of a larger experimental, double-blind, randomized controlled trial. We included 35 postmenopausal women with a diagnosis of insomnia who were distributed in two groups: A Placebo group (sunflower oil) and an Aroma group (Lavandula angustifolia essential oil); both inhaled the oils before bedtime for 29 days. The groups received sleep hygiene guidelines and weekly follow-up. Validated questionnaires were used to assess the effect of the intervention, and a sleep diary was used to assess sleep onset latency (SOL), total sleep time (TST), and sleep efficiency (SE) daily. Participants who complained of vasomotor symptoms at baseline kept a daily record of their frequency and intensity. RESULTS: All participants benefited in almost all domains of quality of life and in the self-assessed TST and SE. The Aroma group achieved a significant improvement in their overall quality of life score over time. No differences were observed in respect of the hot flashes record and daytime sleepiness. CONCLUSIONS: The aromatherapy intervention was effective in improving the overall quality of life in the Aroma group. Moreover, the sleep diary and sleep hygiene instructions helped all participants to, respectively, self-assess and improve their sleep patterns.

Efficacy of methenamine with methylthioninium in the treatment of dysuria: a randomized clinical study.

INTRODUCTION AND HYPOTHESIS: Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional symptomatic treatment. This study evaluated the combination of methenamine 250 mg and methylthioninium chloride 20 mg in the treatment of dysuria versus phenazopyridine. METHODS: This was a multicenter, single-blind, randomized, superiority clinical trial, including individuals over 18 with dysuria and a score ≥ 5 points on the pre-treatment categorical scale for pain. The primary outcome was the proportion of participants presenting excellent clinical response within 24 h after treatment. Improvement up to 72 h, time to reach improvement, sustained healing, investigators' opinion, and safety were also evaluated. RESULTS: Three hundred and fifteen participants were evaluated. Demographic characteristics and symptoms of dysuria were comparable between groups at baseline. The difference in the excellent response rate between treatments within 24 h was 12.7% (95% CI 6.16, 19.21) for pain, 9.4% (95% CI 3.32, 15.39) for burning, and 12.7% (95% CI 6.37, 18.99) for burning on urination, all in favor of the test drug, which was also superior from 36 to 48 h. Treatments were similar concerning time to reach the absence of symptoms and in the percentage of participants with sustained healing after 72 h. CONCLUSIONS: The association of methenamine with methylthioninium is superior to phenazopyridine in the treatment of dysuria.

Insomnia is associated with symptoms of central sensitization in patients with painful temporomandibular disorders.

BACKGROUND: Central sensitization (CS) and temporomandibular disorder (TMD) are both associated with insomnia. Therefore, the authors aimed to investigate whether insomnia was associated with more symptoms of CS in patients with TMD. METHODS: In 82 volunteers with TMD, insomnia was clinically assessed, allowing sample stratification according to its presence. The Central Sensitization Inventory questionnaire was self-applied to assess the clinical symptoms of CS. RESULTS: Participants with insomnia had significantly higher mean (SD) scores of CS according to the Central Sensitization Inventory than participants without insomnia (43.10 [12.57] vs 26.59 [13.66]; P = < .001). CONCLUSIONS: Insomnia was associated with higher scores of CS symptoms in patients with TMD. PRACTICAL IMPLICATIONS: Insomnia influences TMD as well as its relationship with CS, and, therefore, it is critical to the clinical management of TMD.

Association between night pain and quality of life in women: A general population sleep study.

BACKGROUND: Women with pain present decreased sleep duration and quality of life, but little is known about the consequences of nighttime pain on overall health. Our goal was to compare levels of anxiety, depression and fatigue in women with pain during the night with those without pain. We hypothesized that pain perception is associated with the worsening of fatigue and mood. METHODS: In total, 244 women aged 20-80 years who took part in the Epidemiologic Sleep Study (EPISONO) met the inclusion criteria, 85 in the self-reported pain group and 171 in the control group. Participants were assigned to the pain group if they both responded (i) they generally had pain, according to Pre-Sleep Questionnaire (PSQ) and (ii) their pain generally interfered with their sleep 3 or more times a week, according to Pittsburg Sleep Quality Index (PSQI). Those who answered negatively to both questions were allocated to the control group. All participants underwent a full night laboratory polysomnography, and completed questionnaires related to fatigue, depression, anxiety and quality of life. RESULTS: Pain group participants had a significantly lower perception of quality of life, and significantly higher levels of fatigue (5.4 times), anxiety and depression. Pain perception was also correlated to levels of anxiety and depression in the psychological (rs  = -0.463, -0.607, respectively) and social (rs  = -0.423, -0.438, respectively) quality of life domains. CONCLUSIONS: Nighttime pain in women was associated with decreased quality of life, worsening mood and fatigue. Our data shows the importance of investigating pain and its deleterious effects on women's health. SIGNIFICANCE: Our study highlights that women experiencing nighttime pain also reported worse mood outcomes and decreased quality of life, regardless of the level and type of pain. Our data, based on association analysis and not investigating causality, suggest it is important to consider nighttime pain in clinical care to improve quality of life and general health.

The effects of hormonal contraceptive use on sleep in women: A systematic review and meta-analysis.

Hormonal contraceptives are some of the most widely used medications worldwide, but studies on their effects on sleep are contradictory, with some reporting a sleep-promoting effect, while others a sleep-inhibiting effect. Our objective was, therefore, to undertake a systematic review and meta-analysis of the literature on this subject to try to clarify their effects. A search was conducted in three databases (PubMed, Scopus and Web of Science). Only studies evaluating hormonal contraception use were considered eligible, and both objective and subjective sleep-related outcomes were considered. Individual effect size was calculated for each article, and meta-analyses were performed using a DerSimonian and Laird random effects method. The initial search identified 2076 articles, of which 13 met the criteria for the study after full text evaluation. A total of 33 meta-analyses were performed, three of them related to subjective measures and 30 considering data from polysomnography. The only statistically significant result between contraceptive users and non-contraceptive users was observed in respect of wake after sleep onset, which was 7 min shorter among contraceptive users (-7.12 [-12.80; -1.44]; I2  = 65%; p = 0.01). In conclusion, hormonal contraceptives are not associated with clinically relevant changes in sleep patterns in women.

Sleep During Menopause.

Postmenopause is defined retrospectively after 12 consecutive months of amenorrhea. It represents the end of the reproductive period and ovarian failure. A decrease in estrogen leads to several changes in the short and long term. Among the early changes, vasomotor symptoms (hot flashes) are particularly common, occurring in about 70% of women. In addition, there are changes in mood, anxiety, depression, and insomnia. Insomnia occurs in almost 60% of postmenopausal women. Psychosocial aspects may also affect sleep. Proper diagnosis may lead to adequate treatment of sleep disturbances during menopause. Hormonal or other complementary therapies can improve sleep quality.

Dysmenorrhea and Sleep: A Review.

This review encompasses the clinical features and relevance to investigate sleep in women with dysmenorrhea. Dysmenorrhea is a prevalent gynecologic dysfunction that affects the social and professional lives of women. It can occur at every menstrual cycle, depending on the cause and psychologic factors. Studies have reported poor sleep and insomnia symptoms in dysmenorrhea condition, which may intensify the dysmenorrhea manifestation and interfere negatively to its treatment. There is an urgent need to identify the main cause of this dysfunction and provide efficient treatments to minimize the detrimental effects of dysmenorrhea in quality of life of these women.

The Effects of Hormonal Contraceptives on the Sleep of Women of Reproductive Age.

Research about the effects of hormonal contraceptives on sleep has been performed but is subjected to important levels of methodological heterogeneity. Hormonal contraceptives impact sleep, but the direction of this association is not clear. Most studies describe a negative sleep profile among contraceptive users, including increased sleepiness, insomnia symptoms, decreased sleep efficiency, and a reduced overall sleep quality. Hormonal intrauterine contraceptives are associated with less negative effects. More research on the field, especially randomized controlled trials, is needed to increase the level and certainty of evidence about the effects of hormonal contraceptives on sleep.

Depression and obesity, but not mild obstructive sleep apnea, are associated factors for female sexual dysfunction.

PURPOSE: Mild obstructive sleep apnea (OSA) is more prevalent than moderate and severe OSA and is more frequent in men than women. The association between OSA and female sexual dysfunction (FSD) is still poorly explored in published studies. Our aim was to investigate the prevalence of FSD in women with mild OSA and assess the impact of OSA on FSD, as well as to determine the predictors for FSD risk. METHODS: The sample comprised 70 women aged 26-65 years: a control group (N = 28) with no sleep complaints, and a group with mild OSA (an apnea-hypopnea index of 5 or more and less than 15 events/hour, N = 42), who had been diagnosed using polysomnography performed in the sleep laboratory of a sleep research institute. All participants volunteered to take part in the study and completed the female sexual function index (FSFI), the Beck depression index (BDI), the Kupperman menopausal index (KMI), and the Epworth sleepiness scale (ESS). Their socioeconomic group was assessed using the Brazilian Economic Classification Criterion. Polysomnography and serum levels of free testosterone and total testosterone were analyzed. RESULTS: We found low FSFI scores (< 26.55) in the mild OSA (18.1) and control (21.7) groups (p = 0.97). There was no statistically significant difference between the mild OSA group and the control group. However, a higher BMI (p = 0.04), a higher BDI (p = 0.02), and being sexuality inactive (p = 0.001) were risk factors for FSD. CONCLUSION: There was a high prevalence of FSD in the entire sample. The presence of mild OSA did not affect sexual function in this sample. Depressive symptoms and a high BMI were associated risk factors for FSD. Being sexually active may protect female sexual function.

Effects of Mindfulness-Based Relapse Prevention on the Chronic use of Hypnotics in Treatment-Seeking Women with Insomnia: a Randomized Controlled Trial.

BACKGROUND: Hypnotics are one of the most frequently prescribed drugs worldwide, especially for women, and their chronic use may lead to tolerance, dosage escalation, dependence, withdrawal syndrome, and cognitive impairments, representing a significant public health problem. Consistent evidence from previous studies shows benefits of mindfulness-based interventions (MBIs) for substance use disorders (SUD) and insomnia. However, to date, there is a lack of research about effects of MBIs on reduction/cessation of chronic hypnotic use among women with insomnia. METHOD: The present randomized trial evaluated the efficacy of the 8-week group-delivered mindfulness-based relapse prevention (MBRP) program in an intervention group (IG, n = 34) compared with weekly phone monitoring only in the control group (CG, n = 36) in reducing hypnotic use and insomnia severity over a 6-month follow-up period. RESULTS: There were significant differences between groups at baseline regarding hypnotic use but not insomnia. Group effects on hypnotic use were found immediately after the intervention (bT1 = 2.01, p < 0.001) and at the 2-month follow-up (bT2 = 2.21, p < 0.001), favoring the IG. The IG also had a greater reduction from baseline levels than the control group in insomnia severity at the 4-month (bT3 = 0.21, p = 0.045) and 6-month (bT4 = 0.32, p = 0.002) follow-ups. CONCLUSIONS: The findings provide preliminary evidence of benefits of MBRP for reducing insomnia severity and potentially chronic hypnotic use. However, IG effects on chronic hypnotic use may have resulted from IG and control group differences in chronic hypnotic use at baseline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02127411.

Hot flashes, insomnia, and the reproductive stages: a cross-sectional observation of women from the EPISONO study.

STUDY OBJECTIVES: To investigate the association of hot flashes and insomnia in women in premenopause and postmenopause. METHODS: The study was performed using data from the São Paulo Epidemiological Sleep Study. Women in premenopause were classified as having regular menstrual cycles, being anovulatory, or using hormonal contraceptives. Women in menopause were classified as being in perimenopause, early postmenopause, or late postmenopause. Women reporting frequent insomnia symptoms and relevant daytime complaints were classified as having insomnia disorder. Polysomnography alterations suggestive of insomnia were also identified. RESULTS: The frequency of hot flashes was 42% among women in postmenopause (mainly in early postmenopause) and 9% among women in premenopause (mainly anovulatory; P < .01). Approximately 18.7% had insomnia disorder, 48% had isolated insomnia symptoms, and 32.4% had polysomnography alterations. Comparing women in menopause with those in premenopause, the diagnosis of insomnia was similar (premenopause: 18.9% vs menopause: 17.5%), but women in menopause had more frequent isolated insomnia symptoms (premenopause: 43.9% vs menopause: 55.9%; P = .02) and polysomnography correlates of insomnia (premenopause: 26.5% vs menopause: 42.6%; P < .01). Hot flashes were more frequent among women with insomnia disorders (25.5%) and with isolated insomnia symptoms (23.0%) when compared with good sleepers (12.6%) in the entire sample (P = .01). Among women in late menopause, the prevalence of hot flashes was higher in both women with insomnia disorders (42.1%) and with isolated insomnia symptoms (37.5%) when compared with women who were good sleepers (14.3%; P = .05). CONCLUSIONS: Hot flashes are associated with insomnia and polysomnography alterations suggestive of insomnia. The prevalence of hot flashes among women with insomnia disorder is especially high among women in late postmenopause. CITATION: Hachul H, Castro LS, Bezerra AG, et al. Hot flashes, insomnia, and the reproductive stages: a cross-sectional observation of women from the EPISONO study. J Clin Sleep Med. 2021;17(11):2257-2267.