The safety of application and the benefits of isoflavones for postmenopausal women were the focus of a symposium organised by the CRN (Council for Responsible Nutrition), which took place on the 13th and 14th of May 2009 in Milan (Italy) under active participation of the EFSA (European Food Safety Authority).
Recent hypotheses on the aetiology of menopausal hot flushes
Next to the hypotheses regarding safety of application of isoflavones the BfR had postulated a lack of effects against menopausal complaints, and therefore concluded on a negative benefit-risk ratio (Anon. 2007). One block of topics of the Milan soy symposium was therefore dedicated to the effects of isoflavones in menopause.
Dr. Maria Andrikoula of the Ioannina Medical School (Ioannina, Greece) introduced the topic of hot flushes (Andrikoula 2009). Menopausal complaints are characterized by hot flushes, profuse sweating, depression, sleep disorder and headache. The prevalence of these complaints shows noticeable differences in different world regions. Whereas 74 % of European women complain about hot flushes, only 5 % of the Japanese women indicate the same problem (Nagata et al. 1999). Hot flushes are by no means restricted to the duration of menopause: the symptoms may occur until far into postmenopause.
The occurrence of hot flushes may be favoured by various factors such as smoking, caffeine, adiposity, strong climatic temperature shifts or stress. As hot flushes usually react well to the application of hormones, a relation between the regulatory mechanism of body temperature and hormone turnover is suspected (Sturdee 2008). The exact mechanism of hot flushes is, however, not known. Estrogen deficiency alone is obviously not sufficient to trigger the symptoms. It still occurs paradoxical that overweight women having a higher endogenous menopausal estrogen production through biosynthesis in the fat tissue suffer from more instead of fewer hot flushes (Thurston et al. 2008).
A recent hypothesis is about a narrowing of the so-called thermoneutral zone, the range of body temperatures where the organism does not react to temperature changes with shivering or sweating (Sturdee 2008). When the upper limit of the thermoneutral zone is lowered, the organism will try to get rid of the apparently excessive body temperature by inducing hot flushes and sweating. This mechanism seems to be triggered by the decrease of estrogens, which is paralleled by a decrease of endorphin concentrations in the hypothalamus. Subsequently the neurotransmitters serotonin and norepinephrin are excreted, which causes a lowering of the limits of the thermoneutral zone. Other hypotheses discuss an excess of serotonin in the hypothalamus, or changes in the vascular reactivity (Sturdee 2008). Independent of the exact knowledge of the mechanism hot flushes are a severe impairment of the quality of life which requires a therapeutic intervention – despite of all risks the hormones are still considered the most efficacious option, although recent studies have shown some mild response to soy (Shen et al. 2009).
Hot flushes: Isoflavones better than placebo
The clinical realities must not be overlooked in the debate of theoretically possible adverse effects of isoflavones. This essential practical aspect was presented by Dr. Gordana Prelevic of the Royal Free Hospital in London (Prevelic 2009). According to her estimate 70-80 % of menopausal women suffer from vasomotor symptoms such as hot flushes or profuse sweating until approximately 5 years after the beginning of menopause. In 65 % of these women the complaints are severe. In 29 % of cases the complaints even persist after this period, and may continue until the end of life (Bachmann 1999; Huang et al. 2008; Santoro 2008).
Estrogen therapy is considered the gold standard in the treatment of menopausal complaints (Shen et al. 2009) – although it is not in all cases efficacious. The rate of success is about 90 % - however, most women declined a long-term hormonal intervention already before the risks become known: 40-50 % terminated the use of hormones within one year, 65-75 % within two years. Since the publication of the results of the WHI study regarding the negative consequences of hormonal therapy (increase of the incidence rate of breast cancer, apoplexy, thromboembolism and cardiac infarction) (Rossouw et al. 2002) the prescriptions of estrogen preparations against menopausal complaints have crashed world-wide. Whereas in the year 2000 approximately 22 % of all women in the age above 50 years were still treated with hormones, this was only the case in 11.8 % of women of the same age group in the year 2008. Australia alone reported a reduction of the use of hormones by 50 %.
The complaints of the women do, however, persist, and the women are actively searching for alternatives for their relief. Already prior to the publication of the WHI study 22 % of women were using “natural therapies” to control their hot flushes and sweating. Meanwhile the fraction of such users is at 25 %. Among the most cited alternative treatments are isoflavone-containing preparations (Anon. 2004; Nelson 2008). Their efficacy may not be in the same magnitude as that of hormone therapy, but the achievable reduction of complaints by 50 % is considered a great relief by the women. From the practical point of view the use of isoflavones is an option which can be recommended together with changes of life style, quitting smoking, more physical activity and reduction of body weight.
Further reports from the Milan 2009 Soy Safety Symposium:
2. Facts Related to Bioavailability
3. Lack of relevance of animal models for an extrapolation of risks of isoflavones
4. Isoflavones protect „menopausal” mice from breast cancer
5. Breast cancer risk is increased by synthetic gestagens
6. Breast tissue density remains unaltered with soy
7. Clinical studies demonstrate safety of soy in the breast
8. Study in more than 5,000 breast cancer patients: First positive tendencies with soy!
9. No effects of isoflavones on the endometrium
10. Isoflavones also safe at the thyroid gland
11. Backgrounds on Menopausal Hot Flushes
12. Clinical safety of isoflavone-containing preparations
13. Clinical effects of isoflavones against menopausal hot flushes
References
Anon. (2007). Isolierte Isoflavone in Nahrungsergänzungsmitteln und bilanzierten Diäten. Gesundheitliche Bewertung des BfR vom 30 11 2007.
Andrikoula M (2009). Current understanding of the etiology of menopause-related hot flushes and prevalence of menopausal symptoms among European women. Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.
Nelson HD (2008). Menopause. Lancet 371(9614):760-770.
Prevelic G (2009). Perspectives on the need for non-pharmacological options for the treatment of hot flushes. Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.
Santoro N (2008). Symptoms of menopause: hot flushes. Clin Obstet Gynecol 51(3):539-548.
Sturdee DW (2008). The menopausal hot flush--anything new? Maturitas 60(1):42-49.
Clinical effects 