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Effects of Omega-3 Polyunsaturated Fatty Acids Intake on Vasomotor Symptoms, Sleep Quality and Depression in Postmenopausal Women: A Systematic Review

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01 September 2023

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04 September 2023

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Abstract
The menopausal transition often accompanies distressing manifestations, including vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 fatty acids have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of omega-3 supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic search focusing on randomized control trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 studies, 9 studies met the inclusion criteria and were incorporated into this review. Four studies suggested potential benefits of omega-3 intake for improving hot flashes and night sweats. Sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, the review found inconclusive evidence on omega-3's impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of omega-3 fatty acids in improving vasomotor symptoms, sleep quality, and depression. Further well-designed RCTs with larger participant groups are crucial to validate and generalize these results.
Keywords: 
Subject: Medicine and Pharmacology  -   Dietetics and Nutrition

1. Introduction

Menopause, a phase marked by complex physiological changes in women, significantly impacts their well-being [1]. Defined as a cessation of menstruation for approximately one year after the last menstrual cycle, menopause spans 40 to 60 years, with an average age of 52 [2]. Vasomotor symptoms (VMS), encompassing hot flashes (HF), and night sweats, alongside various other manifestations such as sleep disturbances, anxiety, depression, vaginal dryness, muscular discomfort, and sexual dysfunction, collectively impair the quality of life during this period [3,4]. HF and major depressive disorder (MDD) emerge as prominent symptoms, with HF occurring in up to 80% of cases and MDD affecting over 20% of menopausal women. Consequently, more than 1/3rd of women obtain medical assistance due to the discomfort induced by HF [5]. Menopause-related depression needing medication has a substantial age of onset; it is more prevalent (10-15%) when symptoms begin before 45, but less common (5-6%) when symptoms begin at 48 or later [6].
The etiology of HF remains incompletely understood, hypothesized to stem from disturbances in temperature regulation due to factors including estrogen fluctuations and neurotransmitter perturbations [7,8]. Declining estrogen levels disrupt the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic systems, triggering VMS characterized by HF and night sweats. These symptoms, in turn, disturb sleep patterns through stress-induced cortisol elevation and serotonin dysregulation. The interplay between hormonal changes, particularly reduced estrogen, and disrupted sleep contributes to depressive symptoms [9,10]. Hormone therapy (HT) remains the prevailing strategy for mitigating VMS, yet it harbors a spectrum of associated risks and potential adverse outcomes [11].
Omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), represent essential dietary components with multiple double bonds [12]. Renowned for their therapeutic potential, these long-chain omega-3 supplements find utilization in treating diverse medical conditions such as cardiovascular disease, depression, and cognitive disorders [13,14]. Their efficacy in addressing menopausal symptoms and MDD in perimenopausal and postmenopausal women has also been investigated [15,16,17]. Human and animal investigations elucidating the mechanistic underpinnings of omega-3 indicate their engagement in the regulation of serotonergic and dopaminergic neurotransmitter systems. However, the definitive favorable impact of omega-3- 3 on menopausal transition-associated HF, depression, and cognitive symptoms remains inconclusive [18,19,20].
In a clinical investigation, the supplementation of ethyl eicosapentaenoic acid, an omega-3 derivative, resulted in reduced HF and improved hot flash scores compared to a placebo [21]. However, another study failed to observe alterations in VMS and sleep quality when compared to a placebo [22]. A comprehensive review of 32 studies underscored the vulnerability of menopausal women to depression and anxiety [23]. Exploring the interplay of HF, sleep patterns, and depression in women undergoing menopause induced by a Gonadotropin-releasing hormone (GnRH) agonist medication, a study revealed significant associations between increased sleep interruptions, nocturnal HF, and heightened depression scores [24]. Although certain studies propose the potential of omega-3 fatty acids in mitigating depression and HF [25,26], discrepant evidence arises from studies that found no support for the influence of omega-3 on depression scores, as assessed through diverse rating scales [22].
Presently, the precise impact of omega-3 supplementation on VMS remains elusive. Convergent research in both animal and human subjects suggests that omega-3 may modulate neurotransmitter levels, including serotonin and dopamine, within the brain by elevating levels of these fatty acids [19,27]. Consequently, the definitive impact of omega-3 supplements on VMS, sleep quality, and depression scores lacks empirical validation. As such, this systematic review endeavors to synthesize existing evidence to elucidate the efficacy of omega-3 supplementation in ameliorating VMS, enhancing sleep quality, and reducing depression scores in the context of postmenopausal women.

2. Materials and Methods

2.1. Study Participants

The study focused on women at both menopausal and post-menopausal stages, who were experiencing VMS and depression due to menopause, or women undergoing surgical menopause who were also experiencing VMS and depression.

2.2. Type of Intervention and Control

Included studies evaluated the omega-3 fatty acid supplementation in any dosage, frequency, and form (capsule, oil, powder) compared to placebo or other control groups. Studies involving fish consumption, use of antidepressants, hormone replacement therapy, use of anticoagulants, and those lacking placebo or adequate control groups, were excluded from consideration.

2.3. Study Search and Selection

A comprehensive search strategy was executed to identify pertinent studies for this systematic review. Multiple databases including the Cochrane Library, Web of Science, PubMed, Embase, CINAHL, and SCOPUS were utilized. The search employed both free text and Medical Subject Headings (MeSH) terms, such as "omega-3," "fish oils," "PUFA," "menopause," "hot flashes," "night sweats," "vasomotor," "sleep quality," "insomnia," and "depression." Supplementary sources, such as Google Scholar and ClinicalTrials.gov, were also consulted to identify ongoing or unpublished research. The search encompassed studies published in English from inception to the present, without imposing restrictions on publication time or status. The study’s registration in PROSPERO was completed under registration number CRD42023421922.
The systematic review adhered to the following inclusion criteria: (1) randomized controlled trials (RCTs) determine the effect of omega-3 fatty acid supplements on postmenopausal symptoms in women; (2) studies encompassing both naturally postmenopausal and surgically postmenopausal women; (3) studies reporting outcomes pertinent to postmenopausal symptoms such as HF, night sweats, mood swings, sleep quality, and depression; (4) studies comparing omega-3 fatty acid intake with a placebo or control group. Exclusion criteria encompassed: (1) studies lacking relevant outcome reporting, and (2) studies published in languages other than English.

2.4. Outcome Measures

The primary outcomes targeted VMS, including the frequency and intensity of HF and night sweats, which were assessed through patient-maintained diaries or measured using scales such as the Hot Flash-Related Daily Interference Score Kupermann index, and menopause rating scale. Additional primary outcomes included sleep quality and depression, measured using established scales including the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Beck’s Depression Inventory, Montgomery-Asberg Depression Rating Scale, Generalized Anxiety Disorder Questionnaire, and Physician’s Health Questionnaire depression domains. Secondary outcomes encompass menopause-specific quality of life scores and the monitoring of adverse events.

2.5. Data Extraction

The initial screening involved the assessment of titles and abstracts in the first stage, with disagreements resolved by a third reviewer. In the subsequent stage, all papers extracted from the previous phase were individually evaluated by two reviewers. An initial subset of nine papers was chosen to establish reviewer consistency.

3. Results

3.1. Selected Studies

Figure 1 depicts the results of the screening process. The database searches yielded a total of 163 studies; after eliminating 58 duplicate entries, 107 publications were reviewed. After selection based on the title and abstract, 44 publications were selected. Finally, this systematic review identified nine relevant papers that contained randomized controlled trials (RCTs) with sample sizes ranging from 60 to 546 people. These studies evaluated how omega-3 supplements affected menopausal symptoms, sleep quality, and depression in menopausal women. The participants in the RCTs were given varying amounts of EPA and DHA, the omega-3 fatty acids of interest. Depending on the trial design, the placebo groups got soybean oil, sunflower oil, or olive oil. Furthermore, some research used interventions other than the aforementioned placebos, extending the types of interventions used.

3.2. The effect of omega-3 fatty acids on vasomotor symptoms

The studies evaluating the impact of omega-3 supplementation on menopausal symptoms are summarized in Table 1. Two randomized control trials outlined no significant difference in the frequency of vasomotor symptoms (VMS) with omega-3 supplementation [22,28], whereas others found a decrease in both VMS and HF frequency and intensity [21,29,30]. Moreover, a separate study found a decrease in HF frequency but no effect on the intensity [31]. Overall, the systematic review indicates that omega-3 supplementation may have a variable impact on menopausal symptoms, with some studies showing a decrease in symptoms and others reporting no significant change.

3.2. The effect of omega-3 fatty acids on sleep quality

Three studies examining how postmenopausal women’s sleep quality is affected by omega-3 supplementation were included in the review. They were all evaluated using the PSQI and ISI measures. The study by Reed et al. found that omega-3 supplementation had no influence on the sleep quality among 355 menopausal women compared to the placebo group [28]. Similar to this, a double-blind, randomized clinical trial by Cohen et al. found no effect in menopausal women taking 615 mg of omega-3 daily for 12 weeks [22]. Moreover, an increased daily intake of 1.8 g of omega-3 fatty acids also had no impact on sleep quality, according to research by Guthrie et al. According to a thorough study of the research, omega-3 supplements do not appear to have a substantial impact on postmenopausal women’s sleep quality [33]. Based on the existing research, the comprehensive review concludes that omega-3 supplementation does not appear to have a substantial impact on sleep quality in postmenopausal women.

3.4. The effect of omega-3 fatty acids on depression

The systematic review included four studies investigating the effects of omega-3 supplementation on depression in menopausal women. Masoumi et al.’s triple-blind, randomized controlled trial demonstrated that menopausal women who received a combination of 20 mg citalopram and 1g of omega-3 showed a decrease in depression as measured by the BDI-II [32]. However, The double-blind, randomized clinical trial conducted by Cohen et al. and Reed et al. observed no statistically significant alterations in depression levels, as evaluated through the PHQ-8 and GAD-7 scales, following a 12-week regimen of 1.8 g/day omega 3 supplementation (425 mg of EPA, 100 mg DHA and 90 mg of other omega-3s, 3 pills/day) [22,28]. In contrast, the double-blind, placebo-controlled study conducted by Lucas et al. revealed a reduction in depression scores (measured using PGWB, HSCL-D-20, and HAM-D-21) among menopausal women administered with 500 mg omega-3 capsules (350 mg EPA and 50 mg DHA) thrice daily over 8 weeks [25]. Overall, the comprehensive review reveals that omega-3 supplementation may improve depressive symptoms in menopausal women, as indicated by several of the included studies, but not all studies showed meaningful changes.

3.5. Other Outcomes

Out of the nine studies, the majority of the studies found no adverse effects associated with omega-3 supplementation [21,22,29,30,31]. In addition, as indicated by the Menopause-specific quality of life score (MENQOL), two studies found increases in quality of life specifically related to menopause, suggesting a potential positive impact of omega-3 supplementation [21,28]. These findings highlight the safety and potential benefits of omega-3 supplementation for menopausal women.

4. Discussion

The study aimed to evaluate the impact of omega-3 fatty acid supplementation on menopausal symptoms in postmenopausal women. The review encompassed nine pertinent randomized controlled trials (RCTs) that exhibited diversity in terms of sample sizes and treatment approaches. The trials were comprehensive in investigating a range of menopause-related issues, including VMS, sleep quality, depression, and various indicators of quality of life.
The menopausal transition signifies a profound period of transformation for women. This natural progression involves a decline in estrogen levels, potentially leading to modifications in brain neurochemicals and instability within the hypothalamus – the brain region responsible for regulating body temperature. These changes are often attributed to the emergence of VMS, encompassing HF and night sweats [34]. The ingestion of a diet rich in omega-3 fatty acids exhibited a capacity to diminish VMS, suggesting the potential utility of omega-3 fatty acids in addressing such symptoms [35]. Within the scope of this study, the trials included demonstrated a heterogeneous nature, with certain trials indicating a decrease in VMS (including HF and night sweats) following omega-3 intervention, while others did not exhibit such effects. For example, Lucas et al. documented a reduction in both frequency and intensity of HF and night sweats in menopausal women who consumed omega-3 capsules [21]. In contrast, Cohen et al. and Reed et al. did not observe substantial effects on VMS through omega-3 treatment. The divergent outcomes might potentially be attributed to variations in dosages, treatment durations, and participant characteristics [28,36].
Sleep disturbances frequently afflict postmenopausal women, often linked to the presence of HF and night sweats [37]. Several studies have revealed a graduated correlation between the frequency and severity of HF and the intensity of insomnia symptoms, accompanied by quantifiable measures of disrupted sleep patterns [38,39]. An intriguing randomized controlled trial (RCT) displayed noteworthy results: when Omega-3 PUFA supplementation was employed alongside conventional medication, it led to improved outcomes spanning depression symptoms, anxiety, sleep dimensions, and emotional self-regulation, surpassing placebo effects [40]. However, our comprehensive systematic analysis did not yield robust evidence supporting the notion that omega-3 supplementation significantly enhances sleep quality in postmenopausal women. In line with this, Guthrie et al., Cohen et al., and Reed et al. all concurred by reporting no substantial impact on sleep quality through diverse sleep assessment scales, including the PSQI and ISI [28,33,36]. Despite the common occurrence of sleep issues in menopausal women, it appears that omega-3 supplementation does not offer discernible efficacy in augmenting sleep quality within this cohort. In contrast, a distinct study highlighted that DHA/EPA supplementation did enhance sleep quality in middle-aged and elderly individuals, even at the lower doses employed in earlier investigations [41]. These disparities in outcomes could potentially be attributed to suboptimal omega-3 doses or an imbalance in the optimal quantities of individual components needed for a comprehensive effect.
Depression, characterized by persistent low mood and reduced interest in daily activities for more than two weeks, is notably more prevalent among females, with 1.5 to 3 times higher incidence rates compared to males [42,43]. In seeking relief from depressive symptoms, individuals often turn to antidepressants, particularly selective serotonergic reuptake inhibitors (SSRIs), despite potential side effects such as sexual dysfunction and weight gain if used over extended periods [44,45]. In contrast, emerging research has spotlighted the polyunsaturated fatty acids role, including omega-3s, in mitigating depression symptoms [46,47,48]. An intriguing study underscored the clinical efficacy of endocannabinoids derived from ω–3 polyunsaturated fatty acids in the treatment of major depressive disorder (MDD), opening avenues for innovative therapeutic approaches [49]. However, the impact of omega-3 supplementation on depression among postmenopausal women remains equivocal. Masoumi et al. demonstrated reduced depression scores through combined citalopram and omega-3 supplementation [32]. In contrast, Cohen et al. and Reed et al. did not observe significant changes in depression scores with omega-3 supplementation alone [22,28]. Lucas et al., on the other hand, reported lowered depression scores in women who received omega-3 capsules, suggesting potential benefits in alleviating depressive symptoms [25]. Notably, due to the diverse range of outcomes, prudence is necessary when drawing definitive conclusions about the antidepressant effects of omega-3 supplementation in menopausal women.
Vasomotor symptoms, which can significantly compromise women’s quality of life, have often been linked to the menopausal transition. Although prior epidemiological studies have primarily associated this transition with somatic symptoms, the connection to other areas of quality of life remains unclear [50]. A study within this review demonstrated improvements in the MENQOL score among the omega-3-supplemented group, indicating a potential positive impact on overall well-being during menopause [21]. Additionally, our comprehensive analysis affirms the general safety of omega-3 supplementation in menopausal women, as adverse effects were not prominently noted.

5. Conclusions

In summary, the outcomes of our investigation indicate that the impact of omega-3 supplementation on menopausal symptoms in postmenopausal women is varied. While certain studies highlight benefits for vasomotor symptoms (VMS) and mood disturbances, others do not corroborate these effects. The data suggesting a positive influence of omega-3 supplementation on sleep quality in menopausal women is limited. Nonetheless, the safety profile of such supplementation remains promising. Therefore, we propose that future research should entail extended follow-up periods, encompass larger cohorts, and explore combined therapeutic approaches with other medications aimed at enhancing the management of menopausal symptoms.

Author Contributions

The authors’ responsibilities were as follows: Conceptualization, A.Z.I, S.D.L; methodology, A.Z.I, S.D.L; investigation, A.Z.I, S.D.L, SK; writing-original draft preparation, A.Z.I, S.D.L; writing-review and editing, A.Z.I, S.D.L. SK, HZ, W.C.L, and K.P.S; supervision, S.D.L., and K.P.S. The manuscript’s published version has been read and approved by all authors.

Funding

This study received no outside funding.

Institutional Review Board Statement

Not applicable

Informed Consent Statement

Not applicable

Data Availability Statement

Not applicable.

Acknowledgment

None

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. Dalal, P.K.; Agarwal, M. Postmenopausal syndrome. Indian J. Psychiatry 2015, 57, S222. [Google Scholar] [CrossRef] [PubMed]
  2. Gold, E.B. The timing of the age at which natural menopause occurs. Obstetrics and Gynecology Clinics 2011, 38, 425–440. [Google Scholar] [CrossRef] [PubMed]
  3. Nelson, H.D.; Haney, E.M.; Humphrey, L.; Miller, J.; Nedrow, A.; Nicolaidis, C.; Vesco, K.K.; Walker, M.; Bougatsos, C.; Nygren, P. Management of menopause-related symptoms. Agency for Healthcare Research and Quality Publication 2005. [Google Scholar]
  4. Noll, P.R.E.S.; Nascimento, M.G.; Bayer, L.H.C.M.; Zangirolami-Raimundo, J.; Turri, J.A.O.; Noll, M.; Baracat, E.C.; Soares Junior, J.M.; Sorpreso, I.C.E. Changes in Food Consumption in Postmenopausal Women during the COVID-19 Pandemic: A Longitudinal Study. Nutrients 2023, 15, 3494. [Google Scholar] [CrossRef] [PubMed]
  5. Kessler, R.C. Epidemiology of women and depression. J. Affect. Disord. 2003, 74, 5–13. [Google Scholar] [CrossRef]
  6. Kułak-Bejda, A.; Krajewska-Ferishah, K.; Szyszko-Perłowska, A.; Waszkiewicz, N. Risk Assessment of Depression amongst Women during Menopause before and during the COVID-19 Pandemic. Int. J. Environ. Res. Public Health 2022, 20. [Google Scholar] [CrossRef]
  7. O’Neill, S.; Eden, J. The pathophysiology of menopausal symptoms. Obstetrics, Gynaecology & Reproductive Medicine 2017, 27, 303–310. [Google Scholar]
  8. Clayton, A.H.; Ninan, P.T. Depression or menopause? Presentation and management of major depressive disorder in perimenopausal and postmenopausal women. Prim. Care Companion J. Clin. Psychiatry 2010, 12, PCC–08r00747. [Google Scholar] [CrossRef]
  9. Giannini, A.; Caretto, M.; Genazzani, A.R.; Simoncini, T. Neuroendocrine Changes during Menopausal Transition. Endocrines 2021, 2, 405–416. [Google Scholar] [CrossRef]
  10. Weber, M.T.; Maki, P.M.; McDermott, M.P. Cognition and mood in perimenopause: A systematic review and meta-analysis. The Journal of Steroid Biochemistry and Molecular Biology 2014, 142, 90–98. [Google Scholar] [CrossRef]
  11. Mehta, J.; Kling, J.M.; Manson, J.E. Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts. Front. Endocrinol. (Lausanne) 2021, 12, 564781. [Google Scholar] [CrossRef] [PubMed]
  12. Zailani, H.; Satyanarayanan, S.K.; Liao, W.C.; Liao, H.F.; Huang, S.Y.; Gałecki, P.; Su, K.P.; Chang, J.P. Omega-3 Polyunsaturated Fatty Acids in Managing Comorbid Mood Disorders in Chronic Obstructive Pulmonary Disease (COPD): A Review. J Clin Med 2023, 12. [Google Scholar] [CrossRef] [PubMed]
  13. Hooper, L.; Thompson, R.L.; Harrison, R.A.; Summerbell, C.D.; Ness, A.R.; Moore, H.J.; Worthington, H.V.; Durrington, P.N.; Higgins, J.P.; Capps, N.E. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 2006, 332, 752–760. [Google Scholar] [CrossRef] [PubMed]
  14. Wu, S.-K.; Chen, W.-J.; Chang, J.P.-C.; Guu, T.-W.; Hsin, M.-C.; Huang, C.-K.; Mischoulon, D.; Capuron, L.; Su, K.-P. Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients. Journal of Personalized Medicine 2023, 13, 1003. [Google Scholar] [CrossRef]
  15. Barnes, P.M.; Bloom, B.; Nahin, R.L. Complementary and alternative medicine use among adults and children: United States, 2007. 2008.
  16. Appleton, K.M.; Hayward, R.C.; Gunnell, D.; Peters, T.J.; Rogers, P.J.; Kessler, D.; Ness, A.R. Effects of n–3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. The American journal of clinical nutrition 2006, 84, 1308–1316. [Google Scholar] [CrossRef]
  17. Chae, M.; Park, K. Association between dietary omega-3 fatty acid intake and depression in postmenopausal women. Nutr. Res. Pract. 2021, 15, 468. [Google Scholar] [CrossRef]
  18. Hibbeln, J.R.; Linnoila, M.; Umhau, J.C.; Rawlings, R.; George, D.T.; Salem Jr, N. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early-and late-onset alcoholics. Biol. Psychiatry 1998, 44, 235–242. [Google Scholar] [CrossRef]
  19. Carlezon Jr, W.A.; Mague, S.D.; Parow, A.M.; Stoll, A.L.; Cohen, B.M.; Renshaw, P.F. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol. Psychiatry 2005, 57, 343–350. [Google Scholar] [CrossRef]
  20. Ciappolino, V.; Mazzocchi, A.; Enrico, P.; Syrén, M.-L.; Delvecchio, G.; Agostoni, C.; Brambilla, P. N-3 Polyunsatured Fatty Acids in Menopausal Transition: A Systematic Review of Depressive and Cognitive Disorders with Accompanying Vasomotor Symptoms. Int. J. Mol. Sci. 2018, 19, 1849. [Google Scholar] [CrossRef]
  21. Lucas, M.; Asselin, G.; Mérette, C.; Poulin, M.-J.; Dodin, S. Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause 2009, 16, 357–366. [Google Scholar] [CrossRef]
  22. Cohen, L.S.; Joffe, H.; Guthrie, K.A.; Ensrud, K.E.; Freeman, M.; Carpenter, J.S.; Learman, L.A.; Newton, K.M.; Reed, S.D.; Manson, J.E.; et al. Efficacy of omega-3 for vasomotor symptoms treatment: a randomized controlled trial. Menopause (New York, N.Y.) 2014, 21, 347–354. [Google Scholar] [CrossRef] [PubMed]
  23. Grigolon, R.B.; Ceolin, G.; Deng, Y.; Bambokian, A.; Koning, E.; Fabe, J.; Lima, M.; Gerchman, F.; Soares, C.N.; Brietzke, E.; et al. Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression. Menopause 2023, 30, 95–107. [Google Scholar] [CrossRef] [PubMed]
  24. Joffe, H.; Crawford, S.L.; Freeman, M.P.; White, D.P.; Bianchi, M.T.; Kim, S.; Economou, N.; Camuso, J.; Hall, J.E.; Cohen, L.S. Independent Contributions of Nocturnal Hot Flashes and Sleep Disturbance to Depression in Estrogen-Deprived Women. J Clin Endocrinol Metab 2016, 101, 3847–3855. [Google Scholar] [CrossRef] [PubMed]
  25. Lucas, M.; Asselin, G.; Mérette, C.; Poulin, M.-J.; Dodin, S. Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial2. The American Journal of Clinical Nutrition 2009, 89, 641–651. [Google Scholar] [CrossRef]
  26. Freeman, M.P.; Hibbeln, J.R.; Silver, M.; Hirschberg, A.M.; Wang, B.; Yule, A.M.; Petrillo, L.F.; Pascuillo, E.; Economou, N.I.; Joffe, H.; et al. Omega-3 fatty acids for major depressive disorder associated with the menopausal transition: a preliminary open trial. Menopause 2011, 18, 279–284. [Google Scholar] [CrossRef]
  27. Patrick, R.P.; Ames, B.N. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. The FASEB Journal 2015, 29, 2207–2222. [Google Scholar] [CrossRef]
  28. Reed, S.D.; Guthrie, K.A.; Newton, K.M.; Anderson, G.L.; Booth-LaForce, C.; Caan, B.; Carpenter, J.S.; Cohen, L.S.; Dunn, A.L.; Ensrud, K.E.; et al. Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements. Am. J. Obstet. Gynecol. 2014, 210, 244.e241-211. [Google Scholar] [CrossRef]
  29. Palacios, S.; Lilue, M.; Mejia, A.; Menendez, C. Omega-3 versus isoflavones in the control of vasomotor symptoms in postmenopausal women. Gynecol. Endocrinol. 2017, 33, 951–957. [Google Scholar] [CrossRef]
  30. Purzand, B.; Rokhgireh, S.; Shabani Zanjani, M.; Eshraghi, N.; Mohamadianamiri, M.; Esmailzadeh, A.; Alkatout, I.; Gitas, G.; Allahqoli, L. The comparison of the effect of soybean and fish oil on supplementation on menopausal symptoms in postmenopausal women: A randomized, double-blind, placebo-controlled trial. Complement. Ther. Clin. Pract. 2020, 41, 101239. [Google Scholar] [CrossRef]
  31. G. Ozgoli, R.M., B.Molaei, M. Hajifaraji, H. Soori, S.Najafi. Effect of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) Supplementation on Hot Flashes in Menopausal Women: A Randomized, Double - Blind, Placebo- Controlled Clinical Trial. New York Science Journal 2014, 7, 37–42. [Google Scholar]
  32. Masoumi, S.Z.; Kazemi, F.; Tavakolian, S.; Rahimi, A.; Oshvandi, K.; Soltanian, A.; Shobeiri, F. Effect of citalopram in combination with omega-3 on depression in post-menopausal women: A triple blind randomized controlled trial. Journal of Clinical and Diagnostic Research 2016, 10, QC01–QC05. [Google Scholar] [CrossRef] [PubMed]
  33. Guthrie, K.A.; Larson, J.C.; Ensrud, K.E.; Anderson, G.L.; Carpenter, J.S.; Freeman, E.W.; Joffe, H.; LaCroix, A.Z.; Manson, J.E.; Morin, C.M.; et al. Effects of Pharmacologic and Nonpharmacologic Interventions on Insomnia Symptoms and Self-reported Sleep Quality in Women With Hot Flashes: A Pooled Analysis of Individual Participant Data From Four MsFLASH Trials. Sleep 2018, 41. [Google Scholar] [CrossRef] [PubMed]
  34. Freedman, R.R.; Norton, D.; Woodward, S.; Cornélissen, G. Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab 1995, 80, 2354–2358. [Google Scholar] [CrossRef] [PubMed]
  35. Rotolo, O.; Zinzi, I.; Veronese, N.; Cisternino, A.M.; Reddavide, R.; Inguaggiato, R.; Leandro, G.; Notarnicola, M.; Tutino, V.; De Nunzio, V.; et al. Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial. Endocr. Metab. Immune Disord. Drug Targets 2019, 19, 1232–1239. [Google Scholar] [CrossRef]
  36. Cohen, L.S.; Joffe, H.; Guthrie, K.A.; Ensrud, K.E.; Freeman, M.; Carpenter, J.S.; Learman, L.A.; Newton, K.M.; Reed, S.D.; Manson, J.E.; et al. Efficacy of omega-3 for vasomotor symptoms treatment: A randomized controlled trial. Menopause 2014, 21, 347–354. [Google Scholar] [CrossRef]
  37. Shaver, J.L.; Woods, N.F. Sleep and menopause: a narrative review. Menopause 2015, 22, 899–915. [Google Scholar] [CrossRef]
  38. Ensrud, K.E.; Stone, K.L.; Blackwell, T.L.; Sawaya, G.F.; Tagliaferri, M.; Diem, S.J.; Grady, D. Frequency and severity of hot flashes and sleep disturbance in postmenopausal women with hot flashes. Menopause 2009, 16, 286–292. [Google Scholar] [CrossRef]
  39. Ohayon, M.M. Severe hot flashes are associated with chronic insomnia. Arch. Intern. Med. 2006, 166, 1262–1268. [Google Scholar] [CrossRef]
  40. Jahangard, L.; Sadeghi, A.; Ahmadpanah, M.; Holsboer-Trachsler, E.; Sadeghi Bahmani, D.; Haghighi, M.; Brand, S. Influence of adjuvant omega-3-polyunsaturated fatty acids on depression, sleep, and emotion regulation among outpatients with major depressive disorders - Results from a double-blind, randomized and placebo-controlled clinical trial. J. Psychiatr. Res. 2018, 107, 48–56. [Google Scholar] [CrossRef]
  41. Yokoi-Shimizu, K.; Yanagimoto, K.; Hayamizu, K. Effect of Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation on Sleep Quality in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial. Nutrients 2022, 14. [Google Scholar] [CrossRef]
  42. Kessler, R.C.; McGonagle, K.A.; Swartz, M.; Blazer, D.G.; Nelson, C.B. Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J. Affect. Disord. 1993, 29, 85–96. [Google Scholar] [CrossRef] [PubMed]
  43. Judd, F.K.; Hickey, M.; Bryant, C. Depression and midlife: are we overpathologising the menopause? J. Affect. Disord. 2012, 136, 199–211. [Google Scholar] [CrossRef] [PubMed]
  44. Su, K.P. Nutrition, psychoneuroimmunology and depression: the therapeutic implications of omega-3 fatty acids in interferon-α-induced depression. Biomedicine (Taipei) 2015, 5, 21. [Google Scholar] [CrossRef] [PubMed]
  45. Hirschfeld, R.M. Long-term side effects of SSRIs: sexual dysfunction and weight gain. J. Clin. Psychiatry 2003, 64 Suppl 18, 20–24. [Google Scholar]
  46. Nemets, B.; Stahl, Z.; Belmaker, R.H. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am. J. Psychiatry 2002, 159, 477–479. [Google Scholar] [CrossRef]
  47. Peet, M.; Horrobin, D.F. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch. Gen. Psychiatry 2002, 59, 913–919. [Google Scholar] [CrossRef]
  48. Su, K.P.; Huang, S.Y.; Chiu, C.C.; Shen, W.W. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur. Neuropsychopharmacol. 2003, 13, 267–271. [Google Scholar] [CrossRef]
  49. Yang, B.; Lin, L.; Bazinet, Richard P. ; Chien, Y.-C.; Chang, Jane P.-C.; Satyanarayanan, Senthil K.; Su, H.; Su, K.-P. Clinical Efficacy and Biological Regulations of ω–3 PUFA-Derived Endocannabinoids in Major Depressive Disorder. Psychother. Psychosom. 2019, 88, 215–224. [Google Scholar] [CrossRef]
  50. Matthews, K.A.; Bromberger, J.T. Does the menopausal transition affect health-related quality of life? Am. J. Med. 2005, 118 Suppl 12B, 25–36. [Google Scholar] [CrossRef]
Preprints 83931 g001
Figure 1. Flowchart for study search and screening.
Figure 1. Flowchart for study search and screening.
Preprints 83931 g001
Table 1. The main characteristics of nine included studies evaluating the effect of omega-3 PUFA intake on vasomotor symptoms, sleep quality, and depression in postmenopausal women.
Table 1. The main characteristics of nine included studies evaluating the effect of omega-3 PUFA intake on vasomotor symptoms, sleep quality, and depression in postmenopausal women.
Authors & Year Study Design Participants, No. Intervention Duration Vasomotor Symptoms Sleep Quality Depression Other Outcomes
[32] Triple-Blind Randomized Controlled Trial Menopause women, n=60;
Intervention group, n=30;
Control group, n=30		 Intervention group:
20 mg citalopram and 1g of omega-3 PUFAs per day
Placebo group:
20 mg citalopram along with a placebo per day		 4 weeks -------- -------- BDI-II
(p < 0.001)		 ------
[33] Double-blind placebo-controlled, RCT Postmenopausal women, n=188
Intervention group, n=; 95
Control group,
n= 93		 Intervention group:
1.8 g omega-3 fatty acids per day
Placebo group:
3 capsules per day containing olive oil 		12 weeks -------- PSQ-I
(0.0933)
ISI = (0.729)
 ------ ------
[22] Double-Blind, Randomized Clinical Trial Menopause women, n=355;
Intervention group, n=177;
Placebo group, n=178		 Intervention group:
615 mg omega-3 PUFAs (EPA= 425 mg, DHA=100 mg) 3 capsules per day
Placebo group:
3 capsules per day containing olive oil 		12 weeks VMS frequency = (p=0.283) PSQ-I
(0.0933)
ISI = (0.729)
 PHQ-8 (0.097)
GAD-7 = (0.191
)		 No Adverse Effect
[25] Double-blind placebo-controlled, RCT Menopause women, n=120;
Intervention group, n=59;
Placebo group, n=61		 Intervention group:
500 mg omega-3 PUFAs (EPA= 350 mg and DHA= 50 mg in ethyl esters form) / day
Placebo group:
500 mg capsule containing sunflower oil per day
0.2% of regular fish oil (18% EPA/12% DHA) 3 times daily 		8 weeks ------- ----- PGWB
(p = 0.034)
HSCL-D-20 (p = 0.040)
HAM-D-21 (p = 0.030)		 ------
[21] Double-blind placebo-controlled, RCT Menopause women, n=120;
Intervention group, n=59;
Placebo group, n=61		 Intervention group:
500 mg omega-3 PUFAs (EPA= 350 mg and DHA= 50 mg in ethyl esters form) / day
Placebo group:
500 mg capsule containing sunflower oil per day
0.2% of regular fish oil (18% EPA/12% DHA) 3 times daily		 8 weeks HF and night sweats Frequency
(p= 0.005)
and Intensity (0.64)		 ------ ------- MENQOL (p=0.2)
No Adverse Effect
[28] Randomized control trial Menopause women, n=355;
Intervention group, n=177; Placebo group, n=178		 Intervention group:
Omega-3 supplement contained 425 mg ethyl EPA, 100 mg DHA acid per day
Placebo group:
90 mg placebo containing olive oil per day		 12 weeks VMS frequency = (p=0.06) PSQ-I
(0.0933)
ISI = (0.729)
PSS = (0.08)
 PHQ-8 (0.097)
GAD-7 = (0.191
)		 MENQOL = (0.12)
[29] Randomized, Prospective, Two-Arm Study Menopause women, n=76;
Omega-3 group, n=40;
Isoflavone group, n=36		 Intervention group:
omega-3 PUFAs (425 mg of omega-3/capsule), 2 capsules per day
Placebo group:
Soybean isoflavones (54.4 mg of isoflavones/ tablet), 2 tablets per day		 16 weeks VMS Frequency
and HF
(p < .001)		 ----- ------ No Adverse Effect
[30] Double-Blind, Placebo-Controlled, Randomized Clinical Trial Menopause women, n=180;
Soy group, n=60;
Omega-3 group, n=60;
Placebo group, n=60		 Intervention group:
1000 mg Omega-rex soft gel
Soygan 500 mg capsule
Placebo group:
placebo 		3 months MRS
(p = 0.03)		 ----- ----- No Adverse Effect
[31] Double-blind, randomized controlled clinical trial Menopause women, n=68; Omega-3 group, n=38;
Control, n=38		 Intervention group:
300 mg (contain EPA=120 mg and DHA= 180 mg) per day
Placebo group:
Placebo containing paraffin 		8 weeks HF frequency (p=0.003) but no intensity (p=0.2) ----- ------- No Adverse Effect
Abbreviations: PUFAs, Polyunsaturated Fatty Acids; BDI, Beck’s Depression Inventory; PSQI, Pittsburgh Sleep Quality Index; EPA, Eicosapentaenoic Acid; DHA, Docosahexaenoic acid; VMS, Vasomotor Symptoms; ISI, Insomnia Severity Index; PHQ-8, Physician’s Health Questionnaire depression domains; GAD-7, Generalized Anxiety Disorder questionnaire; PGWB, Psychological General Well-Being Schedule; HSCL-D-20, 20-item Hopkins Symptom Checklist Depression Scale; HAM-D- 21, 21-item Hamilton Depression Rating Scale; HF, Hot flashes; MENQOL, Menopause-specific quality of life score; MRS, Menopause Rating Score.
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Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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