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Correspondence

Reduction of Serum Testosterone in Men by Licorice

N Engl J Med 1999; 341:1158October 7, 1999DOI: 10.1056/NEJM199910073411515

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

3 References

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