Much more research needs to be done before natural alternatives to estrogen can be conclusively labeled as either harmful or beneficial for certain conditions and organ systems, a new literature review finds.

The study, published in the British Journal of Pharmacology, focused specifically on phytoestrogens, plant-based estrogen alternatives commonly found in soy, soy products, and other legumes. Several factors may play a part in determining whether phytoestrogens can definitively affect health either way -- and those factors are simply not understood well enough at the moment.

"This [study] implies that a definite conclusion on the health effects of phytoestrogens, positive or negative, cannot be made," the lead study author, Ivonne Rietjens, PhD, professor in toxicology at Wageningen University in The Netherlands, said in a statement. "It may be that the question of whether phytoestrogens are beneficial or harmful has different answers dependent on individuals' age, health status, and even the presence or absence of specific gut bacteria."

The study, a systematic overview of current research, examined the effect of phytoestrogens on menopausal symptoms, cardiovascular disease, obesity and diabetes, breast cancer, other forms of cancer, thyroid function, and brain function. In no area did researchers find that the potential benefits clearly outweighed the risks or were supported by enough evidence to justify wider clinical implementation.



"Reported benefits include a lowered risk of menopausal symptoms, cardiovascular disease, breast cancer, other forms of cancer including prostate cancer, bowel cancer, uterine cancer, and other cancers, and brain function disorders," Rietjens and colleagues wrote.

"On the other hand, phytoestrogens are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects such as infertility and increased risks on cancer of estrogen-sensitive organs. ... Consequently, the question of whether phytoestrogens are beneficial or harmful to human health remains of importance. The present overview reveals that the answer is rather complex."

That complexity is perhaps best encapsulated in the research review regarding plant-based estrogen's effects on menopausal women -- one of the most widely touted and discussed of phytoestrogens' many potential applications.

Rietjens and colleagues found conflicting and inconclusive studies regarding whether phytoestrogens can reduce the frequency or severity of hot flashes. The same held true when covering the role of these estrogen alternatives in changes in bone mineral density. The investigators pointed out that the European Food Safety Authority evaluated 14 long-term intervention studies on the effects of soy isoflavones on bone mineral density in postmenopausal women, and of those, only two reported an effect on bone mineral density at doses of 54 mg/day. The remaining 12 studies, testing phytoestrogen doses of up to 200 mg/day, showed no effects of soy isoflavones on bone mineral density or markers of bone formation or resorption.

Similarly inconclusive findings appeared in the case of cardiovascular health, where Rietjens and colleagues found that "the current evidence [for phytoestrogens] appears poor compared to that available for estrogens."

At the same time, there are areas where phytoestrogens do show promise, the team emphasized. For example, in breast cancer, a 2013 analysis of 40 randomized controlled trials, 11 uncontrolled trials, and 80 observational studies led to the conclusion that soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality.

Even in this case, however, the authors indicated that there is not enough evidence to confirm the safety of using soy isoflavones in doses that are high enough (generally >100 mg/day) to obtain the anti-cancer benefits.

Conversely, some of the more widely discussed harmful effects of phytoestrogens also remain unproven. Rietjens and colleagues highlighted a 1997 study in which the soy isoflavones daidzein and genistein were found to inhibit thyroid peroxidase, but no other adverse effects on thyroid functions had been observed.

Human trials on soy isoflavones and thyroid function are entirely inconclusive, Rietjens and colleagues found.