Does Licorice increase estrogen levels? I am frequently asked this question – and if you don’t know me, I am a health coach for people going through breast cancer.

One of my favorite subjects is herbal medicine because, well, I’ve been involved with herbal medicine for over 20 years. It is a passion of mine.

So many herbs have anticancer, and immune stimulating or modulating properties and can offer very real benefits for those going through a cancer healing journey.

But here’s why I’m writing this article – there are any number of blogs and articles out there in internet-land warning women with hormone driven breast cancer not to take licorice because of its estrogenic properties. Is this true?

Easy question to ask, not so easy to answer!

For one thing, we are lacking in clinical trials with actual humans, so we mainly have to rely on cell studies and animal studies. But the studies that do exist have turned up some interesting things, which I’ll share with you.

I found studies that said licorice had an estrogenic effect AND studies that said it had an anti-estrogenic effect. So we need to really dig deep and understand how licorice works.

Licorice or Liquorice – the herb, not the candy – has been used as a medicinal plant for over 5,000 years in China and India to treat respiratory and liver diseases.

Licorice is one powerful herb. It is the root of the plant that is utilized in herbal medicine and though there are over thirty different licorice plants, only three are most commonly used in herbal preparations – Glycyrrhiza glabra (which I will call GG hereinafter), Glycyrrhiza inflata (GI) and Glycyrrhiza uralensis (GU).

GG is native to the Mediterranean and parts of southwestern Asia. GI is found mainly in China, and GU grows in China and other parts of Asia.

Studies on the properties and therapeutic benefits of the phytochemicals (plant-based compounds) in licorice root have shown that it contains more than 20 triterpenes, 300 flavonoids, and 73 bioactive compounds. 91 potential targets for its therapeutic action have been identified. [1]

Some of the phytochemicals in licorice have been shown to have effects on estrogen receptors on cells, that is true. But are they the sort of estrogenic properties that lead to uncontrolled growth in breast cells, or do they have protective properties?

Let’s dive into the research. I’ll endeavor to make it clearer for you. It’s a complex issue.

A number of the phytochemicals in licorice appear to have estrogenic properties, with some being stronger than others. Also, different varieties of licorice vary in their estrogenic effects. Licorice has been studied for its estrogenic properties since 1950 [2].

Until very recently much was still not known about how the phytochemicals in licorice actually work and whether they have the same activity or a different mode of activity from that of the body’s own estrogen.

Another issue is that we were not sure (and still are not entirely sure) whether any of the phytochemicals with estrogenic properties present in licorice extracts were of sufficient strength that they would be any kind of problem at the doses typically taken in herbal supplements.

To complicate matters further, the estrogenic effects between licorice subtypes appear to vary. One 2013 study [3] investigated the estrogenic effects of each of GG, GI and GU and found that GU had the most estrogenic effects, followed by GI, and the least estrogenic was GG. This study found that liquiritigenin, the principal phytoestrogen in each licorice species, selectively binds with estrogen receptor beta. Researchers concluded “These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of botanical supplements.”

So what is meant by estrogen receptor beta? I’ll explain.

Cells have receptors inside the cell or sitting on their surfaces and these receptors help things like hormones, neurotransmitters and enzymes dock with that cell and communicate with it or activate it to do something.

Phytoestrogens (plant-based estrogens) interact with the two known estrogen receptors – estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta).

ER-alpha has been shown to promote cellular proliferation (rapid growth) in estrogen responsive tissues. Studies point to the potential increased risk of hormone–dependent cancers when ER-alpha is stimulated. On the other hand, ER-beta activity has been found to be anti-proliferative (reducing rapid growth), and counterbalances or suppresses the effects of ER-alpha. In short, ER-beta is deemed to be the more protective of the two estrogen receptors when promoted, especially insofar as estrogen receptor positive breast cancer is concerned. [4]

A 2014 review of medical studies [5] tells us “The alpha subtype has a more prominent role on the mammary gland and uterus, as well as on the preservation of skeletal homeostasis and the regulation of metabolism. The beta subtype seems to have a more profound effect on the central nervous and immune systems, and it generally counteracts the ERa-promoted cell hyperproliferation in tissues such as breast and uterus.”

Several studies have revealed that ER-beta is associated with anticancer properties in that when promoted it inhibited the rapid growth of human breast cancer cells and formation of tumors. I have listed just two of those studies at [6] and [7].

In one 2020 cell study [7] researchers showed that GI did have some docking affinity with ER-alpha but had greater functional efficacy docking with ER-beta.

A 2016 study [8] looked at nine different phytochemicals in licorice to evaluate which or both of the estrogen receptors they had an affinity to dock with. Researchers found that of these nine phytochemicals, all except for two bound with approximately equal affinity to ER-alpha and ER-beta. Those two that didn’t bind with ER-alpha had a greater than 10-fold preference for ER-beta. Interestingly, all of the licorice root components had binding affinities for estrogen receptors at least one thousand times lower than that of estrodiol, the body’s own estrogen.

So what that last study [8] means to me is that when estrodiol is present, those licorice phytochemicals are one thousand times less likely to bind with estrogen receptors than the body’s own estrogen. That sounds to me like they are pretty weak estrogenic substances.

That seems to be borne out across the studies I’ve read about phytoestrogens – that they appear to exert much less of an effect than the body’s own estrogen, which hardly makes them a threat. In fact, many phytoestrogens, for instance flaxseed, are known to be extremely PROTECTIVE against breast cancer.

Let me just state that again. While phytoestrogens do exert an effect on cells with estrogen receptors, it appears to be a profoundly more mild influence. That makes them protective, rather than dangerous to someone with hormone receptor positive breast cancer.

At least, that’s the way I’m reading the research. I could be wrong. Be sure to read all the way to the bottom of this article.

Other Benefits of Licorice

All the Important Anti’s

Licorice is well known to herbalists for its anti-stress benefits due to the fact that it is an adaptogen, meaning it helps the body to adapt to stressors. In addition it is anti-inflammatory, antimicrobial, antioxidant, antispasmodic, antiviral, and anti-constipation!

Digestive Complaints

Because of its anti-inflammatory, antispasmodic, and demulcent properties and ability to soothe and restore the mucosal lining of the digestive tract, licorice has been found to be helpful for acid reflux, indigestion, Gastroesophageal Reflux Disease (GERD), Inflammatory Bowel Disorder (IBD) and other digestive system disorders. It may also act as a prebiotic (a food for beneficial gut bacteria). [9]-[13] Licorice extracts have also been found to be helpful for those suffering from ulcers. [14]-[16]

Antiviral

Licorice extracts have been shown to prevent a virus from entering cells, and directly killing viruses through a variety of mechanisms including stopping replication, inhibiting growth, and stimulating the immune system to attack the virus.

A 2019 review of medical studies [17] stated that glycyrrhizic acid “can significantly inhibit the proliferation of HIV, showing an immune activation.”

A 2021 review of medical studies [18] investigated GG for its pharmacological actions including modulation of the immune system, inhibition of virus growth, anti-inflammatory activity, and ability to inactivate viruses. They also included information on the role of licorice in managing respiratory infections caused by viruses and bacteria.

Two 2021 studies [19] [20] evaluated licorice for its benefits in helping to ameliorate the symptoms of COVID-19. Because of its anti-viral, anti-inflammatory, antioxidant, immunomodulatory and expectorant effects, licorice may very well be wonderful for COVID-19 patients.

Liver Protective

Herbalists have long been using licorice root for its ability to protect the liver by inhibiting injury from toxic compounds. It has proven to be beneficial for chronic hepatitis and cirrhosis, and it also works synergistically with other herbs. [21]-[23]

Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a condition that affects a woman’s hormone levels wherein the ovaries enlarge and cysts form on the outside edge. Naturopaths have been using licorice for quite some time to assist their patients with this disorder and it seems that science is catching up. A 2020 study [24] of mice with PCOS found that licorice had protective effects and appeared to decrease the incidence of ovarian cysts in these animals and eased PCOS. I found two more interesting studies on licorice and PCOS. [25]-[26]

May Be Helpful in Cancer

Licorice may indeed have anticancer effects. A 2018 animal study [27] investigated two varieties of licorice – GG and GI. The objective of the study was to determine the distribution of the phytochemicals in licorice, how they were metabolised, and a few other parameters I couldn’t get my head around, not being a research scientist. They also evaluated the effects of licorice extracts on CYP1A1, a gene that is a biomarker exhibiting cancer-preventive properties. When CYP1A1 is upregulated (activated), it helps with the breakdown of steroidal hormones, including estrogen. The licorice extracts also had an effect on CYP1B1, a gene that is a biomarker for carcinogenesis (cancer development). When CYP1B1 is down-regulated (inhibited) or deficient, carcinogenic pathways are avoided (if I understand that correctly). The researchers in this study found that in mammary tissue, GI increased CYP1A1 and decreased CYP1B1, whereas GG just increased CYP1A1. Either way, this equals some very interesting cancer-preventive benefits.

Several preliminary studies have found that licorice may have benefits for those with breast cancer. Whether this is borne out with actual human beings in clinical trials has not been investigated yet to my knowledge.

A 2009 animal study [28] found that the flavonoid isoliquiritigenin from licorice had anti-aromatase activity. Aromatase is an enzyme required for the synthesis of estrogen. Isoliquiritigenin also significantly deterred tumor growth in ER+ PR+ metastatic breast cancer cells that were overexpressing aromatase.

A 2014 study [29] of isoliquiritigenin derived from GG found that it had anticancer activity in ER+ PR+ metastatic breast cancer cells.

In a 2017 cell study [30] one of the phytochemicals, Licochalcone A, from GI reduced proliferation (rapid growth) and promoted apoptosis (planned cell death, absent in cancer cells) in ER positive, PR positive AND triple negative breast cancer cells.

A 2021 cell study [31] evaluated the phenols in licorice and found that quite a few of them were cytotoxic (toxic to cancer cells) in three different cancer cells lines, including ER positive, PR positive metastatic breast cancer cells.

My suggestion is that if you have hormone-driven breast cancer and are excessively worried about how licorice will affect you, just don’t take it. Having said that, I believe that in moderation, it could be beneficial – it has been shown to have great effects on inflammation (and cancer is an inflammatory disease), for docking with ER-beta, for its immunomodulatory function, and for being cytotoxic to breast cancer cells.

I would recommend taking GG if you can find it, since it appears to have the least estrogenic activity, but please do so with the guidance of a trained herbalist.

Because licorice root can interact with some pharmaceutical drugs, please check on herb-drug interactions. Web MD is a decent source of information on interactions, also drugs.com. People with edema and high blood pressure should avoid licorice because high doses of glycyrrhizin may increase blood presure and/or cause fluid imbalances. This will not apply to deglycyrrhizinated licorice (DGL) products. Licorice should not be taken when pregnant.

References:

[1] Licorice (Glycyrrhiza glabra) Extracts-Suitable Pharmacological Interventions for COVID-19? A Review – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708549/
[2] Estrogenic substances from plants; glycyrrhiza – https://onlinelibrary.wiley.com/doi/abs/10.1002/jps.3030390316
[3] Evaluation of Estrogenic Activity of Licorice Species in Comparison with Hops Used in Botanicals for Menopausal Symptoms – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709979/
[4] Development of subtype-selective oestrogen receptor-based therapeutics – https://pubmed.ncbi.nlm.nih.gov/21921919/
[5] Estrogen Receptors Alpha (ERa) and Beta (ERß): Subtype-Selective Ligands and Clinical Potential – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192010/
[6] Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest – https://pubmed.ncbi.nlm.nih.gov/14729654/
[7] SAR Study on Estrogen Receptor a/ß Activity of (Iso)Flavonoids: Importance of Prenylation, C-ring (Un)Saturation, and Hydroxyl Substituents – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294944/
[8] Licorice Root Components in Dietary Supplements are Selective Estrogen Receptor Modulators with a Spectrum of Estrogenic and Anti-Estrogenic Activities – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714869/
[9] An Extract of Glycyrrhiza glabra (GutGard) Alleviates Symptoms of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123991/
[10] Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615700/
[11] Prevention of symptoms of gastric irritation (GERD) using two herbal formulas: An observational study – https://search.informit.org/doi/10.3316/INFORMIT.950298610899394
[12] Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037654/
[13] Anti-inflammatory and Anti-oxidant Effects of Licorice Flavonoids on Ulcerative Colitis in Mouse Model – https://www.sciencedirect.com/science/article/abs/pii/S1674638417601163
[14] Antiulcer properties of Glycyrrhiza glabra L. extract on experimental models of gastric ulcer in mice – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673944/
[15] To evaluate of the effect of adding licorice to the standard treatment regimen of Helicobacter pylori – https://pubmed.ncbi.nlm.nih.gov/27614124/
[16] Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167813/
[17] Research Progress of Glycyrrhizic Acid on Antiviral Activity – https://pubmed.ncbi.nlm.nih.gov/30659537/
[18] Pharmacological Efficacy and Safety of Glycyrrhiza glabra in the treatment of respiratory tract infections – https://pubmed.ncbi.nlm.nih.gov/34579633/
[19] Licorice (Glycyrrhiza glabra) Extracts-Suitable Pharmacological Interventions for COVID-19? A Review – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708549/
[20] Licorice: A Potential Herb in Overcoming SARS-CoV-2 Infections – https://journals.sagepub.com/doi/full/10.1177/2515690X21996662
[21] Natural products in licorice for the therapy of liver diseases: Progress and future opportunities – https://pubmed.ncbi.nlm.nih.gov/31022523/
[22] The efficacy of licorice root extract in decreasing transaminase activities in non-alcoholic fatty liver disease: a randomized controlled clinical trial – https://pubmed.ncbi.nlm.nih.gov/22308054/
[23] Hepatoprotective and Antioxidant Effects of Licorice Extract against CCl4-Induced Oxidative Damage in Rats – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210994/
[24] Protective effects of licorice extract on ovarian morphology, oocyte maturation, and embryo development in PCOS-induced mice: An experimental study – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569710/
[25] Licorice reduces serum testosterone in healthy women – https://www.sciencedirect.com/science/article/abs/pii/S0039128X04001783
[26] Licorice: From Pseudohyperaldosteronism to Therapeutic Uses – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657287/
[27] Evidence for chemopreventive and resilience activity of licorice: Glycyrrhiza glabra and G. inflata extracts modulate estrogen metabolism in ACI rats – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435032/
[28] Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase – https://pubmed.ncbi.nlm.nih.gov/19065667/
[29] The licorice flavonoid isoliquiritigenin reduces DNA-binding activity of AhR in MCF-7 cells – https://pubmed.ncbi.nlm.nih.gov/25110319/
[30] Licochalcone A Suppresses Specificity Protein 1 as a Novel Target in Human Breast Cancer Cells – https://pubmed.ncbi.nlm.nih.gov/28498645/
[31] Biotransformation of the Phenolic Constituents from Licorice and Cytotoxicity Evaluation of Their Metabolites – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465054/