Reviewed: Fattah A. Effect of phytoestrogen on depression and anxiety in menopausal women: A systematic review. J Menopausal Med. December 2017;23(3):160-165. doi: 10.6118/jmm.2017.23.3.
Symptoms of menopause may include mood disturbances such as mood swings, irritability, anxiety, and depression.* Conventional treatments for menopausal symptoms include hormone therapy (HT), which is associated with an increased risk of cardiovascular events and breast cancer, and antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs), which can cause adverse effects such as sleep disturbances, weight gain, diarrhea, and sexual dysfunction.
The author of this review conducted a systematic search of MEDLINE (1966-March 2017), Scopus (1990-March 2017), and the Cochrane Library (Cochrane Central Register of Controlled Trials; 2017) using various keywords related to anxiety, depression, and commonly used herbal treatments for symptoms of menopause. There were no language restrictions, and references were hand-searched. Included studies were randomized, controlled, parallel or crossover trials that included perimenopausal or postmenopausal women with depression or anxiety. The Consolidated Standards of Reporting Trials (CONSORT) checklist was used to evaluate study quality.
A total of 1,786 studies were identified, and nine met the inclusion criteria. The studies evaluated four herbs, including soy (Glycine max, Fabaceae), hops (Humulus lupulus, Cannabaceae), kava (Piper methysticum, Piperaceae), and red clover (Trifolium pratense, Fabaceae).
Three studies evaluated the effects of soy on symptoms of depression and/or anxiety. The first was a small study that compared the effects of soy flour (100 mg isoflavones) (n = 7) with a placebo of wheat (Triticum spp., Poaceae) grain cereal (n = 12) for 24 weeks. Neither group experienced a significant improvement in depression compared with baseline. The second study compared 12-week treatment with soy protein (n = 44; dose not reported) to placebo (n = 50). The soy group experienced a 25% improvement in depression scores from baseline, compared with no change in the placebo group (P value not reported). There was no difference between groups in the anxiety score post-treatment. The third study evaluated soymilk (n = 15; dose not reported), soymilk plus exercise (n = 12), or placebo (n = 10) for 12 weeks; there was no significant difference in depression or anxiety among groups. “To sum up, soy slightly improved anxiety and depression,” wrote the author of the review. However, this conclusion may not be warranted considering the small sample size of two of the included trials, the differences in soy products, and that only one of the three trials found an improvement in depression only.
One study evaluated the effects of hops on depression and anxiety using the Greene Climacteric Scale, a questionnaire that assesses various mental, physical, and vasomotor symptoms of menopause. Patients received placebo (n = 60) or 500 mg/day of powdered hops corymbs (flower clusters) (n = 60) for 12 weeks. Hops significantly decreased anxiety and depression compared with placebo at two, four, eight, and 12 weeks (P < 0.001 for all).
One study evaluated the effect of kava on depression and anxiety. For 12 weeks, patients took 100 mg/day kava rhizome extract (containing 55% kavain; Natural Bradel; Milan, Italy) plus 1 g/day calcium (n = 15), 200 mg/day kava plus 1 g/day calcium (n = 19), or 1 g/day calcium only (n = 34). There was a significant decrease in depression at three months in the 200 mg/day kava group compared with baseline (P value not reported) but not compared to the calcium-only group. Compared with baseline, there was a significant decrease in anxiety at three months in the 100 mg/day and 200 mg/day kava groups but not the calcium-only group (P values not reported). This study did not report a placebo group.
Four studies evaluated the effects of red clover on depression and anxiety. One of these treated patients with red clover extract (n = 50; dose not reported; described in the original paper as “MF11RCE,” containing 80 mg red clover isoflavones) or placebo (n = 59) for 12 weeks. On the Zung Self-Rating Depression Scale, the red clover group experienced a significant improvement compared with both baseline and placebo (P < 0.001 for both). In a separate 12-week study, patients were assigned to one of three groups: placebo (n = 85), Promensil (PharmaCare Laboratories; Warriewood, NSW, Australia; n = 85), or Rimostil (Novogen Ltd.; Plédran, France; n = 83). Promensil and Rimostil are dietary supplements that each provide 82 mg of red clover isoflavones. Anxiety and depression scores did not differ significantly among the groups after 12 weeks. Another study evaluated 80 mg red clover or placebo for 12 weeks in a crossover study (n = 53) with a one-week washout period. The red clover groups exhibited a significant improvement in depression and nervousness (P = 0.05 for both). In the fourth study, participants who received an ethanolic extract of red clover aerial parts (standardized to 120 mg/day isoflavones) (n = 22**) for 12 months experienced significantly reduced Greene anxiety scores at the end of the study, compared to placebo (n = 17) (P = 0.04) in a double-blind trial. The anxiety score was a secondary outcome; primary outcome measures were the reduction of occurrence and intensity of hot flashes and night sweats.
The quality ratings for the individual trials are not clearly indicated. The author of the review reported that “the random sequence generation, allocation concealment and blinding of outcome assessment was either not performed or not reported in sufficient detail in most of [the] studies. The overall methodological quality was moderate to high.”
The author concluded that soy may have a beneficial effect on anxiety and depression, red clover findings are inconclusive, and 200 mg/day of kava and 500 mg/day of hops may be beneficial for anxiety and depression. However, the author cautioned that, in general, “beneficial effects still remain indeterminate due to poor methodology, limited RCTs and small sample size.”
Limitations of this review article include: incomplete literature searches (several eligible trials were not included), inaccurate or incomplete reporting of results, unfounded conclusions regarding soy and kava, unreported doses and/or manufacturers of some herbal products, grammatical and typographical errors, and a misleading title (some of the included botanicals do not contain phytoestrogens). Also, the standardization of the products was not described. Therefore, it is difficult to make any conclusions from the reported studies becuase the analyzed botanical products could vary widely in chemical composition and thus in biological activity.
—Heather S. Oliff, PhD
* Some scientists contest that depression is a symptom of menopause. It may be coincidental to menopause and more due to cultural values favoring youth as women are getting older, secondary to sleep problems due to menopause, and other factors — but not menopause itself.
** The review article incorrectly reported the number as 14; the original study publication reports n = 22.