Correspondence

Reduction of Serum Testosterone in Men by Licorice

N Engl J Med 1999; 341:1158October 7, 1999

Article

To the Editor:

Extracts of licorice root are widely used in many countries as flavoring agents, breath fresheners, or candy. The active component of licorice is glycyrrhizic acid, which is hydrolyzed in vivo to glycyrrhetinic acid. The well-known mineralocorticoid-like effect of licorice results from the inhibition of 11β-hydroxysteroid dehydrogenase, the enzyme that catalyzes the conversion of cortisol to cortisone, thereby minimizing the binding of cortisol to mineralocorticoid receptors.1 Licorice may also directly activate mineralocorticoid receptors.2 In vitro, licorice can block 17β-hydroxysteroid dehydrogenase, which catalyzes the conversion of androstenedione to testosterone.3

We evaluated the effect of licorice on gonadal function in seven normal men, 22 to 24 years of age. The men were given 7 g daily of a commercial preparation of licorice in the form of tablets (Saila, Bologna, Italy) containing 0.5 g of glycyrrhizic acid, as determined by gas chromatography–mass spectrometry; the effect on the metabolism of mineralocorticoids in these men was reported previously.2 Serum testosterone, androstenedione, and 17-hydroxyprogesterone were measured by radioimmunoassay before and after four and seven days of administration of licorice and four days after it was discontinued. During the period of licorice administration, the men's serum testosterone concentrations decreased and their serum 17-hydroxyprogesterone concentrations increased (Table 1Table 1Serum Hormone Concentrations in Seven Men Given Licorice for Seven Days.).

These results demonstrate that licorice inhibits both 17β-hydroxysteroid dehydrogenase and 17,20-lyase, which catalyzes the conversion of 17-hydroxyprogesterone to androstenedione. The amounts of licorice given to these men are eaten by many people. Thus, men with decreased libido or other sexual dysfunction, as well as those with hypertension, should be questioned about licorice ingestion.

Decio Armanini, M.D.
Guglielmo Bonanni, M.D.
University of Padua, 35100 Padua, Italy

Mario Palermo, M.D.
University of Sassari, 07100 Sassari, Italy

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Citing Articles (23)

Citing Articles

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   E.A.S. Al-Dujaili, C.J. Kenyon, M.R. Nicol, J.I. Mason. (2011) Liquorice and glycyrrhetinic acid increase DHEA and deoxycorticosterone levels in vivo and in vitro by inhibiting adrenal SULT2A1 activity. Molecular and Cellular Endocrinology 336:1-2, 102-109
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   Salvador F. Sena. 2010. Licorice and Laboratory Tests. , 255-272.
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   Farzaneh Zamansoltani, Marjan Nassiri-Asl, Mohammad-Reza Sarookhani, Hassan Jahani-Hashemi, Amir-Abdollah Zangivand. (2009) Antiandrogenic activities of Glycyrrhiza glabra in male rats. International Journal of Andrology 32:4, 417-422
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   Marjan Nassiri Asl, Hossein Hosseinzadeh. (2008) Review of Pharmacological Effects ofGlycyrrhiza sp. and its Bioactive Compounds. Phytotherapy Research 22:6, 709-724
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   R ISBRUCKER, G BURDOCK. (2006) Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regulatory Toxicology and Pharmacology 46:3, 167-192
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   Mee Jung Mattarello, Stefano Benedini, Cristina Fiore, Valentina Camozzi, Paola Sartorato, Giovanni Luisetto, Decio Armanini. (2006) Effect of licorice on PTH levels in healthy women. Steroids 71:5, 403-408
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   Helga Agusta Sigurjonsdottir, Magnus Axelson, Gudmundur Johannsson, Karin Manhem, Ernst Nyström, Sven Wallerstedt. (2006) Liquorice in Moderate Doses Does Not Affect Sex Steroid Hormones of Biological Importance although the Effect Differs between the Genders. Hormone Research 65:2, 106-110
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   Kevin M Comar, Donald F Kirby. (2005) Herbal Remedies in Gastroenterology. Journal of Clinical Gastroenterology 39:6, 457-468
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   D. Deluca, A. Krazeisen, R. Breitling, C. Prehn, G. Möller, J. Adamski. (2005) Inhibition of 17beta-hydroxysteroid dehydrogenases by phytoestrogens: Comparison with other steroid metabolizing enzymes. The Journal of Steroid Biochemistry and Molecular Biology 93:2-5, 285-292
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    Decio Armanini, Mee Jung Mattarello, Cristina Fiore, Guglielmo Bonanni, Carla Scaroni, Paola Sartorato, Mario Palermo. (2004) Licorice reduces serum testosterone in healthy women. Steroids 69:11-12, 763-766
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    Yue Fu, Tze-chen Hsieh, Junqiao Guo, Jan Kunicki, Marietta Y.W.T. Lee, Zbigniew Darzynkiewicz, Joseph M. Wu. (2004) Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells. Biochemical and Biophysical Research Communications 322:1, 263-270
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    Sérgio F. Cabrita, Raquel silva, Miguel P. Correia. (2003) Allergic contact dermatitis due to glycyrrhizic acid as an ingredient of a hair restorer. Contact Dermatitis 49:1, 46-46
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    Monte S. Willis, Frank H. Wians. (2003) The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances. Clinica Chimica Acta 330:1-2, 57-83
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    Eric A. Jackson. (2003) RESOURCES FOR INFORMATION ON HERBAL MEDICINALS AND DIETARY SUPPLEMENTS. Journal of Herbal Pharmacotherapy 3:3, 51-57
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    WenChieh Chen, Diane Thiboutot, Christos C Zouboulis. (2002) Cutaneous Androgen Metabolism: Basic Research and Clinical Perspectives. Journal of Investigative Dermatology 119:5, 992-1007
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    Mark A Moyad. (2002) Lifestyle/dietary supplement partial androgen suppression and/or estrogen manipulation. Urologic Clinics of North America 29:1, 115-124
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    James M. Dabbs, Anthony E. Karpas, Natalia Dyomina, Jennifer Juechter, Amanda Roberts. (2002) EXPERIMENTAL RAISING OR LOWERING OF TESTOSTERONE LEVEL AFFECTS MOOD IN NORMAL MEN AND WOMEN. Social Behavior and Personality: an international journal 30:8, 795-806
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