Licorice may lower sex hormone production, reduce fertility

Licorice root has been hailed for its possible anticancer properties, and is sometimes marketed for the relief of hot flashes and other menopausal symptoms. But according to a new study, licorice may have negative implications for women's fertility.

Published in the journal Reproductive Toxicology, the study found that exposure to the licorice compound isoliquiritigenin reduced expression of genes related to the production of sex hormones, causing a decrease in estrogen production.

Study leader Jodi Flaws, of the University of Illinois, and colleagues did not show how the reduction in sex hormones affected reproductive health, but they say a similar reduction in humans could have serious implications for fertility.

Licorice is a perennial plant native to parts of Europe and Asia. It is often referred to as "sweet root," as its root contains a compound that is around 50 times sweeter than sugar.

While best known in the form of chewy candy, licorice has been used in medicine for centuries. Studies have shown it may help stave off peptic ulcers, treat coughs and colds, relieve indigestion, reduce menopausal hot flashes, and even reduce the risk of some cancers.

The licorice compound isoliquiritigenin is added to herbal supplements and teas; it is also used as a flavoring agent in some forms of tobacco.

According to Flaws and colleagues, previous studies in animal models have shown that some botanical compounds may interfere with the production of the sex hormone estrogen.

For their study, the researchers wanted to determine whether isoliquiritigenin might have a similar effect.

Isoliquiritigenin exposure halved aromatase gene expression

The team exposed antral follicles of female mice to various concentrations of isoliquiritigenin or a control compound for 48-96 hours. Antral follicles are situated in the ovaries, and express genes involved in the production of estrogen and other hormones.

When the antral follicles were exposed to high levels of isoliquiritigenin, the researchers noticed a reduced expression of genes related to sex hormone production.

Specifically, they identified a minimum 50 percent reduction in expression of a gene for aromatase - an enzyme responsible for turning testosterone into estrogen.

The researchers stress that their findings are preliminary and studies in live animals are needed. However, the team believes these early results suggest isoliquiritigenin has the potential to promote reproductive problems and other health issues.

"In general, when you start to have lower hormone levels, you could start to have problems with reproduction. And because estrogen is also important for healthy brains, healthy bones, a healthy cardiovascular system, if the levels are depleted for too long, you could have problems with those systems. We haven't shown that to be the case. That's just a possibility.

I would say, though, that a 50-plus percent drop in aromatase in humans would be a serious problem for fertility and for other things."

Jodi Flaws

Supporting this theory, Flaws points out that aromatase inhibitors are used in cancer therapy to halt tumor growth, but one side effect of these drugs is reduced fertility. As such, she hypothesizes isoliquiritigenin may have the same effects.

"This could lead to a good outcome in certain tissues, depending on dose and timing of exposure," Flaws adds. "In the ovary, though, if you reduce aromatase, you're also reducing estrogen, so you could be interfering with fertility."

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    Effects of isoliquiritigenin on ovarian antral follicle growth and steroidogenesis, Jodi Flaws et al., Reproductive Toxicology, doi: http://dx.doi.org/10.1016/j.reprotox.2016.10.004, published online 20 October 2016, abstract.

    University of Illinois at Urbana-Champaign news release, accessed 10 November 2016 via EurekAlert.

    Additional source: University of Maryland Medical Center, Licorice, accessed 10 November 2016.