Glycyrrhizin and Serum Testosterone Concentrations in Male Patients With Type 2 Diabetes

Extracts of licorice root are widely used in many countries as flavoring agents, breath fresheners, and candy. Licorice consumption had been reported to decrease serum testosterone concentrations (1). An explanation for this result was that glycyrrhizic acid, the active component of licorice, interfered with 17β-hydroxysteroid dehydrogenase, which catalyzes the conversion of androstenedione to testosterone. We were very interested in the effects of glycyrrhizic acid to decrease serum testosterone concentrations. Glycyrrhizin, which is extracted from the roots of the plant Glycyrrhiza glabra (licorice), is widely used for the treatment of chronic hepatitis in Japan and reportedly reduces the progression of liver disease to hepatocellular carcinoma. The efficacy of glycyrrhizin treatment is currently under investigation in Europe (2). There are few data available on the effects of glycyrrhizin on serum testosterone concentrations (3). We have recently reported that reduced serum testosterone concentrations could cause insulin resistance (4) and atherosclerosis (5) in male patients with type 2 diabetes. Therefore, we attempted to determine the effects of glycyrrhizin on serum testosterone concentrations in male patients with type 2 diabetes and chronic hepatitis.

This study included 18 male patients with type 2 diabetes and chronic hepatitis who were given weekly glycyrrhizin, which contained 240–525 mg glycyrrhizic acid, for >1 year and 21 male patients not given glycyrrhizin. We measured serum concentrations of total and free testosterone (normal range 2.7–10.7 ng/ml and 14–40 pg/ml, respectively) and performed carotid ultrasonography (5), which is used increasingly in clinical research concerning pathophysiology of atherosclerosis, in those patients.

Clinical characteristics of patients treated with (n = 18) and without (n = 21) glycyrrhizin are as follows: mean age (66.9 ± 7.1 vs. 66.8 ± 6.7 years), duration of diabetes (13.7 ± 7.3 vs. 12.6 ± 10.3 years), BMI (23.0 ± 2.3 vs. 22.7 ± 1.8 kg/m²), levels of HbA_1c (7.4 ± 1.5 vs. 7.0 ± 0.9%), presence of hypertension (77.8 vs. 66.7%), presence of hyperlipidemia (33.4 vs. 38.1%), and history of cigarette smoking (61.1 vs. 57.1%) were not significantly different between groups. Serum concentrations of total and free testosterone were significantly lower in patients given glycyrrhizin than those in patients not given glycyrrhizin (4.3 ± 2.2 vs. 5.9 ± 1.7 ng/ml, P = 0.0113; 6.7 ± 3.8 vs. 11.1 ± 3.8 pg/ml, P = 0.0009, respectively). Mean intima-media thickness and plaque score by carotid ultrasonography were significantly greater in patients given glycyrrhizin than in patients not given glycyrrhizin (1.12 ± 0.29 vs. 0.89 ± 0.23 mm, P = 0.0385; 6.8 ± 3.1 vs. 3.7 ± 3.3, P = 0.0326, respectively). Glycyrrhizin treatment was an independent risk factor (β = 0.464, P = 0.0433) for atherosclerosis (plaque score) after adjustment for age, hypertension, hyperlipidemia, smoking history, and glycemic control (HbA_1c).

Despite a major limitation of small sample size, this study suggests that glycyrrhizin decreased serum testosterone concentrations in male patients with type 2 diabetes and chronic hepatitis. Reduced serum testosterone concentrations may cause insulin resistance and atherosclerosis, as well as sexual dysfunction and decreased libido in men. Special attention should be directed at serum testosterone concentrations in male patients with type 2 diabetes and chronic hepatitis treated with glycyrrhizin.