Reduction of Serum Testosterone in Men by Licorice
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 11(beta)-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 17(beta)-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 1).
These results demonstrate that licorice inhibits both
17(beta)-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
References
1. Farese RV Jr, Biglieri EG, Shackleton CHL, Irony I, Gomez-Fontes R.
Licorice-induced hypermineralocorticoidism. N Engl J Med 1991;325:1223-7.
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2. Armanini D, Lewicka S, Pratesi C, et al. Further studies on the
mechanism of the mineralocorticoid action of licorice in humans. J
Endocrinol Invest 1996;19:624-9.
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3. Sakamoto K, Wakabayashi K. Inhibitory effect of glycyrrhetinic acid
on testosterone production in rat gonads. Endocrinol Jpn 1988;35:333-42.