New methods to decipher how natural substances affect the body’s hormone balance

A team of researchers from Vienna has developed methods of deciphering precisely how plants and medicinal substances affect the body’s own hormone balance. Initial analyses show that in high doses some natural substances promote the growth of breast cancer cells.

As current research has shown, the isoflavones found in soy plants have a marked impact on the hormonal balance of women. Source: PookieFugglestein / CC0

The number of cancer cases has been rising in Austria for many years, one of the reasons being that people are living longer lives. The chances of surviving cancer have also increased, which means there is a greater number of people living with cancer. In women, breast cancer is still the most common diagnosis. According to Statistik Austria, 5,355 women were affected by malignant breast tumours in 2017, which is 28 per cent of new cases and 17 per cent of all cancer deaths. Worldwide, one in eight women will develop breast cancer during their lifetime.

Just as in the case of uterine and ovarian cancer, the growth of these tumours is promoted by oestrogens. As many tumours develop during menopause and postmenopause in women, the treatment of menopausal symptoms—such as hot flushes, sleep disorders and depression—with oestrogens is now known to be associated with too high a risk. For this reason, women increasingly resort to natural alternatives to alleviate their complaints, which may often last for years. Popular substitutes are phytoestrogens such as those found in soy, red clover or black cohosh (Cimicifuga racemosa), which are readily available as food supplements. We still hardly know, however, how these natural substances affect the growth of tumours and the hormonal balance of women when used over a longer period of time.

Research develops special methods

A research project led by the pharmacist Walter Jäger of the University of Vienna is now investigating for the first time the influence of phytoestrogens and other natural substances, which are often advertised as “miracle cures”, on the metabolism of oestrogens and the hormonal balance in general. To this end, the project funded by the Austrian Science Fund FWF involved an examination of breast tumour cells obtained from patients in various stages of development. Using state-of-the-art molecular biological methods, the team at the University of Vienna’s Division of Clinical Pharmacy and Diagnostics characterized cell lines in the presence and absence of phytoestrogens.

Risky interaction with isoflavones

We examined both resveratrol, which is found in grapes and is considered to be cancer-inhibiting, and soy components.”

Walter Jäger, pharmacist, University of Vienna

The researchers were particularly interested in whether there was any evidence that menopausal women suffering from cancer should refrain from taking certain food supplements. The first results have cleared resveratrol. According to Jäger, very high concentrations would have to be taken in order for interactions to occur. According to the scientist, the products available in Austria do not pose a risk with regard to their dosage, but it should be noted that products with high dosages are easily available via the Internet. From other studies, for example, it is known that an amount of 500 mg resveratrol, taken over a longer period of time, does have an impact on hormone levels in healthy women.

In the case of soy, however, the research team was able to show a clear interaction with endogenous oestrogens. For the soy ingredients genistein and daidzein, so-called isoflavones, molecular biological analyses showed a marked influence on the metabolism of these oestrogens in breast cancer cells , i.e. these compounds inhibited their biotransformation. In the case of hormone-dependent breast cancer, Walter Jäger therefore advises against isoflavone-containing food supplements. “It might even be that the growth of tumour cells could be stimulated in a woman who has breast cancer and eats tofu twice a day,” explains the pharmacist. As a next step in the project that will run until spring 2020, in cooperation with the University of Ljubljana in Slovenia, the research teams will test the active ingredients of black cohosh, which is a popular treatment for menopausal symptoms administered in the form of tablets or capsules.

Hormone analyses increase therapy chances

The analytical methods developed in Vienna can also be used to test drugs and their effects on hormonal balance. Jäger’s team has, for instance, tested ovarian tumour cells, a type of cancer that is often diagnosed late and has an aggressive progression, for frequently used drugs (cytostatics). The tumours often develop resistance to these standard drugs. “We have seen for the first time that resistant tumour cells suddenly metabolize less well, which means we can tell which are resistant and which are not,” explains Jäger. The expert regrets that such methods for hormone analysis are not yet fully developed in clinics. While they are complex and therefore cost-intensive, these tests are also effective.

Apart from exploring how active substances from plants interfere with hormonal levels, the researchers are also interested in providing more insight into other metabolic processes. This means finding out, for example, how the concentrations of various endogenous substances in a tissue, or in body fluids such as urine or blood, change when someone takes natural substances or drugs. This information is still missing for drugs and food supplements currently on the market. “We would like to have a much closer look at endogenous metabolic processes, which would require well developed analytical methods,” says Jäger. These insights could help not only to identify undesirable side effects at an early stage, but also to find new drugs that act specifically on specific metabolic pathways.