A previous article in this column (No. 205/206 August-September, 2000) examined an Italian pilot study that claimed to demonstrate licorice consumption lowered testosterone in men and asserted that licorice should be avoided by men with low libido. (1) During the period of licorice administration (0.5 g of glycyrrhizin, around 10 g of licorice root) there was a substantial (around 35%) and significant drop in the men's serum testosterone and a (smaller) significant increase in 17-hydroxyprogesterone (p<0.001). Serum androstenedione was also raised, but the difference did not achieve statistical significance, possibly because of the small size of the experimental group. (2)
The authors concluded their results demonstrated that licorice inhibits the enzymes involved in the production of testosterone, namely 17[less than or equal to]-hydroxysteroid dehydrogenase and 17,20-lyase. They suggested that men with decreased libido or other sexual dysfunction, as well as those with hypertension, should be questioned about their intake of licorice confectionery.
Attempts at replicating the results of this trial were tried twice by a different research team using the same dosage of glycyrrhizin. An insignificant decrease in testosterone, as measured in saliva, was observed in both studies. The authors therefore disagreed with the above recommendation that men with low libido should avoid licorice consumption. (3) Normal values of salivary testosterone during licorice ingestion were found, but as a result the trial methodology may not have been suitably accurate. (4)
The Italian research group subsequently demonstrated that licorice decreased plasma testosterone in healthy women (22-26 years old) during the luteal phase of the menstrual cycle. The women received licorice containing 250 mg of glycyrrhizin daily for 2 cycles. At pretreatment the mean plasma testosterone was 27.8 ng/dL, which reduced to 19 ng/dL after the first cycle and 17.5 ng/dL after the second cycle, and returned to the pretreatment value one month after discontinuation of licorice. The reduction at both cycles was statistically significant (p<0.05). (4) This finding could certainly justify the current use of licorice in PCOS (polycystic ovarian syndrome).
Now, new findings have reopened the licorice and testosterone debate for men. (5) In the new research, a team from Iran investigated the effect of licorice root extract in 20 healthy male volunteers. The group took 1.3 g of dried extract (containing around 400-500 mg glycyrrhizin) daily for 10 days. Blood samples were collected before the study and then for 20 days to measure testosterone levels.
A significant (p<0.05) decrease in serum testosterone levels of around 35% after 10 days of licorice consumption was observed. The effect on testosterone was believed to relate to interference of the active agent glycyrrhizin with 17[less than or equal to]-hydroxysteroid dehydrogenase, the enzyme that catalyzes conversion of androstenedione to testosterone.
Commentary
Both the Italian and Iranian studies used relatively high doses of licorice over a short period of time. A daily dose of around 500 mg of glycyrrhizin corresponds to at least 10 g of licorice root. The long-term use of such doses would invariably result in the well-known side effects of licorice, namely potassium loss, hypertension and eventually fluid retention. Normal therapeutic doses of licorice root (between the equivalent of 2 to 3 g per day) are likely to cause only a modest reduction in serum testosterone in men, which is probably not clinically significant. However, women have considerably lower serum testosterone levels than men, and it is quite possible that therapeutic doses of licorice could reduce normal testosterone levels in women, albeit to a minor extent (around 10 to 20%). The clinical significance of such a decrease is uncertain.
References
1. Bone K. Townsend Letter 2000; 205/206: 160
2. Armanini D, Bonanni G, Palermo M. N Engl J Med 1999; 341(15): 1158
3. Josephs RA, Guinn JS, Harper ML et al. Lancet 2001; 358(9293): 1613-1614
4. Armanini D, Mattarello MJ, Fiore C et al. Steroids 2004; 69(11-12): 763-766
5. Mosaddegh M, Naghibi F, Abbasi PR et al. J Pharm Pharmacol 2003; 55(Suppl): 87-88