Glycyrrhiza: Licorice root and testosterone

by Paul Bergner

Medical Herbalism 11(3):11-12

Large doses of licorice extract, usually in the form of candy or chewing gum, may cause hypertension and electrolyte imbalances through a well-defined mechanism (de Klerk et al). This effect was seen in an adult female with administration of a simple decoction of licorice root over three months (Bergner). Researchers have recently demonstrated that doses of licorice root extract, delivering the constituent glycyrrhizin in amounts similar to that contained in standard medical doses of the root, rapidly and significantly lowered levels of circulating testosterone in males (Armanini et al.). This effect appears to occur much more rapidly than the previously observed mineral corticoid effects. Similar effects of licorice on testosterone had been suggested previously in animal trials (Sakamoto and Wakabayashi; Takeuchi et al.) and in female subjects with polycystic ovarian syndrome (PCOS) (Takahashi et al; Yaginuma et al).

In the Armanini trial, seven men aged 22-27 years old were given 7 grams daily of a commercial preparation of licorice tablets for a week. The daily dose contained about 0.5 grams (7.14%) of glycyrrhizin, as determined by gas chromatography-mass spectrometry. The tablets appear to be crude licorice root, which reportedly contains between 6-15% glycyrrhizin (Budavari), rather than a concentrate. Table 1 shows the changes is several hormones during an eleven-day period. Testosterone levels fell by about 40% within four days of licorice administration, returning to normal four days after its withdrawal.

Table 1

Ng/dl                  Day 0         Day 4         Day 7         Day 11

Testosterone             740 +/-216     414 +/-43     484 +/-191     704+/-42

Androstenedione        159 +/-35     140+/-29     177+/-30     170+/-20

17-hydroxy-progesterone     189+/-36     216+/-31     229+/-36     193+/-55

            (Licorice administration was stopped at day 7)

In a 1982 trial, eight anovulatory infertile women with elevated testosterone were investigated for lowering serum testosterone levels and inducing regular ovulation by a formula containing equal parts of peony root (Paeonia lactiflora) and licorice root (Glycyrrhiza glabra). Serum testosterone levels were significantly lowered in seven patients by doses of 5-10 grams of the combination daily for 2-8 weeks. Six of seven patients ovulated regularly and two of six patients conceived (Yaginuma et al.) In a similar trial in 1988, a significant reduction of circulating testosterone occurred in 18 of 20 female subjects with PCOS (Takahashi et al.). Five of the 18 became pregnant. In the above trials, it was not established which plant or plant constituents altered the testosterone levels. In 1991, researchers performed in vitro tests of the effects of several plant constituents from peony and licorice on rat ovary cells, and suggested that glycyrrhetic acid, a metabolite of glycyrrhizin in humans, inhibits the conversion of androstenedione to testosterone. Armanini et al. suggested that glycyrrhizin, or its metabolites, act on the enzymes that convert 17-hydroxy-progesterone to androstenedione, effectively lowering testosterone.

Glycyrrhiza glabra samples reportedly contain approximately 6-15% glycyrrhizin (Budavari). Therefore the 500 mg daily dose of glycyrrhizin in the trial represents about 3.0 to 8.0 grams of crude plant material. A significant dose of this constituent would be difficult to deliver with standard tincture doses of less than one teaspoon per day. As ô00ö capsules containing about 400 mg of licorice root each, about 8-20 capsules would be expected to deliver a dose of glycyrrhizin comparable to that used in the trial. This would be the equivalent of two-six teaspoons of the powder. Doses of glycyrrhizin on the same order of magnitude as those in the trial could be expected to be delivered from a standard decoction. The standard daily dose in Chinese medicine is 3-12 grams/day, usually as a decoction. This could also result in a dose of glycyrrhizin similar to that in the trial. The German Commission E monograph on licorice prescribes a dose of 5-15 grams of the root per day, which would deliver a dose of 200-600 mg of glycyrrhizin (Blumenthal). (This monograph defines the glycyrrhizin content of licorice at 4% instead of the 6-15% described in the Merck Index.) According to the Merck data, this dose of crude material could deliver 0.3 to 2.3 grams of glycyrrhizin, up to over four times the dose used in the trial.

 The Commission E monograph assertion that daily doses of licorice as a flavoring agent delivering less than 100 mg of glycyrrhizin are safe should be reconsidered until it is demonstrated that such a dose does not affect testosterone levels. Most reported adverse mineral corticoid effects to licorice are due to consumption or concentrated licorice extracts in candy or in medicines. Such preparations might also present the greatest public risk from testosterone lowering effects.

The above data indicate both potential adverse and therapeutically beneficial effects of licorice. In cases of reproductive dysfunction in males, screening for licorice intake and avoidance of licorice administration may be appropriate. On the other hand, in situations where it would be desirable to lower testosterone levels, such as prostate cancer or male pattern baldness, licorice might be useful. In females, the testosterone-lowering effects of licorice appear to have been helpful in the treatment of PCOS, and might be useful for other expressions of androgenization, such as alopecia, hirsutism, or other effects, including those following menopause. This research reinforces the traditional contraindication of licorice in pregnancy or possible pregnancy, where normal testosterone levels in the male fetus are essential for sexual differentiation and maturation. The recent availability of simple salivary hormone tests for testosterone invites simple investigations on the clinical effects of licorice on various clinical conditions.

References

Armanini D, Bonanni G, Palermo M. Reduction of serum testosterone in men by licorice. N Engl J Med 1999 Oct 7;341(15):1158

Bergner P. Adverse effects anecdotes. Medical Herbalism. 1998:10(4):15

Blumenthal, M [editor] The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Texas: American Botanical Council, 1998

Budavari, S. [editor]. The Merck Index. Eleventh Edition. Rahway, New Jersey, 1989

De Klerk, G.J., Nieuwenhuis M.G., Beutler J.J. Hypokalemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ 1997;314:731 (8 March)

Sakamoto K, Wakabayashi K Inhibitory effect of glycyrrhetinic acid on testosterone production in rat gonads. Endocrinol Jpn 1988 Apr;35(2):333-42

Takahashi K, Yoshino K, Shirai T, Nishigaki A, Araki Y, Kitao M. Effect of a traditional herbal medicine (shakuyaku-kanzo-to) on testosterone secretion in patients with polycystic ovary syndrome detected by ultrasound. Nippon Sanka Fujinka Gakkai Zasshi 1988 Jun;40(6):789-92

Takeuchi T, Nishii O, Okamura T, Yaginuma T. Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production. Am J Chin Med 1991;19(1):73-8

Werbach M, and Murray M. Botanical Influences in Illness: A Sourcebook of Clinical Research. Tarzana, California: Third Line Press, 2000

Yaginuma T, Izumi R, Yasui H, Arai T, Kawabata M Effect of traditional herbal medicine on serum testosterone levels and its induction of regular ovulation in hyperandrogenic and oligomenorrheic women [Article in Japanese]. Nippon Sanka Fujinka Gakkai Zasshi 1982 Jul;34(7):939-44
  Copyright 2001 Paul Bergner 


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