Nikander, E., Metsa-Heikkila, M., Ylikorkala, O., & Tiitinen, A. (2004). Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer. Journal of Clinical Endocrinology and Metabolism, 89, 1207–1212.

The study explored the effects of daily use of isoflavonoids on climacteric symptoms and QOL in postmenopausal women who had been treated for breast cancer.

Phytoestrogen tablets and similar-looking placebo tablets (six tablets per day) were taken every 12 hours with a glass of water. The participants were seen at the research center before and after each treatment period. Sixty-two postmenopausal, symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for three months; the treatment regimens were reversed after a 2-month washout period.

Six women discontinued the trial for various reasons during the first phase. Thus, 56 women completed the study. The mean age pf participants was 54 (± 6 years).

• Inclusion criteria: breast cancer survivors (none using tamoxifen) who reported incapacitating hot flashes and other climacteric symptoms after the onset of spontaneous menopause, as seen from their high circulating levels of FSH and LH. 
• Exclusion criteria: Use of sex steroids (including tamoxifen); use of natural products with possible estrogenic activity; use of drugs possibly affecting climacteric symptoms, metabolism, or absorption of phytoestrogens (e.g., antibiotics during the previous three months); and history of any thromboembolic or hepatic event.

This was a randomized placebo-controlled crossover trial of phytoestrogens in treatment of menopause in breast cancer participants.

At each visit, the participants were interviewed about hot flashes and other typical climacteric symptoms using the Kupperman index and Menopausal Visual Analogue scale. Blood levels of phytoestrogens, FSH, LH, estradiol, and sex hormone-binding globulin, liver enzymes, and creatinine levels were followed. Compliance with treatment was confirmed by diary records and by measurement of serum phytoestrogen levels.

The use of phytoestrogens led to significant rises in the levels of phytoestrogens, whereas the placebo regimen had no effect. Kupperman indexes at the end of treatment with phytoestrogen or placebo did not differ. Hot flashes and the other components of the Kupperman index were not relieved by the phytoestrogen regimen when evaluated separately.

Pure isoflavonoids at a dose of 114 mg for three months did not relieve hot flashes or other menopausal symptoms in participants with breast cancer

Potential limitations of the trial included:

1. Study period was of short duration (three months). 
2. Possibility that phytoestrogens may trigger changes in target organs in processes requiring more than three months. It would be valuable to have long-term data on the effects of phytoestrogens.
3. Were doses physiologically suitable? Doses appeared sufficiently large, given the elevations in phytoestrogen levels in participants.