Red clover isoflavones used to improve mood after menopause

Up to 70% of women experience mood symptoms, such as frequent crying and anxiety, during and after menopause.1 While hormone replacement therapy (HRT) effectively relieves mood symptoms,2 it is associated with numerous health risks and thus many women are reluctant to use it.3 For these women, recent evidence that red clover isoflavones, a natural alternative to HRT, can improve post-menopausal anxiety and mood swings is an important development.1

Menopause and psychological symptoms

Psychological symptoms such as an anxious mood are more common amongst women than men. Menopause is a stage of life when women are particularly likely to experience mood changes.¹ Hormonal and life changes (e.g. children leaving home) both contribute to the increased likelihood of psychological symptoms at this time of life, as do comorbid menopausal symptoms, in particular vasomotor symptoms.³

Mood swings are common in menopausal women, and can considerably disrupt a woman’s life and her relationships. HRT provides some relief of mood symptoms, but is contraindicated in some women. Others avoid HRT because of the associated health risks.⁴

New interest in natural therapies for menopausal mood symptoms

Due to the implications of menopausal symptoms on women’s quality of life and the health risks associated with HRT, there has been increasing interest in natural therapies to relieve menopausal symptoms. Phyto-oestrogens, including red clover isoflavones, have received considerable recent attention.¹

Phyto-oestrogens

Phyto-oestrogens, including the subgroup isoflavones, are plant-derived compounds with weak oestrogenic effects. They selectively bind with beta oestrogen receptors found in the brain, vagina and bone, and have a null effect on oestrogen receptors sites in the breast and endometrium. Thus they are expected to have a favourable long-term side-effect profile compared to HRT.¹

Recent evidence that red clover isoflavones relieve psychological symptoms

A recent randomised controlled trial by Lipovac et al.¹ provides evidence regarding the efficacy of red clover isoflavones. The study, in which women were randomised to receive either daily 80 mg doses of red clover isoflavones or placebo, used validated measures of psychological symptoms. It also included a crossover phase after a seven day washout period. Over 100 post-menopausal women were included in the trial, all of whom were experiencing moderate to severe menopausal symptoms (although they did not necessarily experience psychological symptoms).

Anxiety and other psychological scores significantly reduced three months from baseline in both groups. While the group treated with placebo experienced a 21.7% reduction in anxiety scores compared to baseline, the group treated with red clover isoflavones experienced a significantly greater reduction of 76.9%. No adverse events were experienced by patients during the trial.¹

Further research needed

The results of this trial support the results of a previous small trial which showed that 60 mg daily doses of red clover isoflavones were effective in relieving the psychological symptoms of menopause.² They suggest that red clover isoflavones may be a safe and effective treatment for menopausal symptoms.¹ However, evidence remains limited and there is a lack of data regarding the relative efficacy of phyto-oestrogens compared to HRT.²

In the current study, it is important to note that experiencing psychological symptoms was not an inclusion criterion. The participants may or may not have had disruptive mood symptoms at baseline.¹

Practitioners should also note that this study did not control for some factors which influence the likelihood of a woman experiencing menopausal psychological symptoms. Women in the treatment arm reported a significant reduction in menopausal hot flushes, which are known to exacerbate anxiety mood swings. It is therefore possible that psychological symptoms improved because comorbid symptoms reduced, rather than due to any direct effect of the medication.¹

In this study, women received two 40 mg daily doses of isoflavone.¹ In Australia, medications containing red clover isoflavones are sold in 40 mg and 80 mg doses.⁵

Safety

While there are no serious concerns with short-term administration of red clover isoflavones, long-term safety data is lacking.⁷ In one study, women at high risk for breast cancer were followed for three years while taking 40 mg daily doses of red clover isoflavones. It reported no increase in endometrial or breast risk and authors concluded that the study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women.⁶

Isoflavones promising

The new data reported by Lipovac et al. support the efficacy of red clover isoflavones for the treatment of menopausal psychological symptoms.¹ While this is promising news for symptomatic menopausal women, further high-quality research regarding efficacy¹ and long-term safety are warranted.⁷

In Australia, the only product that offers 80mg of red clover isoflavones is Promensil Menopause Double Strength. It is used to help reduce hot flushes and night sweats.⁸ Evidence from this study suggests that it may also offer an additional benefit in helping to reduce anxiety symptoms amongst menopausal women.

References

Lipovac M, Chedraui P, Gruenhut C, et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas. 2010;65(3):258-61. [Abstract | Full text]
Burbos N, Morris E. Menopausal symptoms. BMJ Clin Evid. 2010; 2: 804.
Abernethy K, Hillard A, Holloway D, et al. Complementary approaches to menopausal symptoms: RCN guidance for nurses, midwives and health visitors. London, UK: Royal College of Nursing; 2 October 2007 [cited 25 July 2010]. Available from: URL link
Bélisle S, Blake J, Basson R, et al. Canadian consensus conference on menopause, 2006 update. J Obstet Gynaecol Can. 2006;28(2 Suppl 1):S7-S94. [Abstract | Full text]
Promensil: A clinical summary. North Ryde, NSW: Novogen Consumer Healthcare; 12 August 2009. Available from: URL link
Powles TJ, Howell A, Evans DG, et al. Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int. 2008;14(1):6-12. [Abstract]
Panay N, Rees M. Alternatives to HRT for the management of symptoms of the menopause (SAC Opinion Paper 6) [online]. London: Royal College of Obstetricians and Gynaecologists; 1 May 2006 [cited 15 September 2010]. Available from: URL link
Promensil [online]. St Leonards, NSW: MIMS Online; 1 February 1999 [cited 16 August 2010]. Available from: URL link