The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. The main known endocrine effect of licorice consumption is its mineralocorticoid-like effect, resulting in pseudohyperaldosteronism and arterial hypertension through the inhibition of 11 beta-hydroxysteroid dehydrogenase (11ßHSD) type 2 enzyme. However, it seems that this is not the only endocrine effect produced by licorice, and a role in the reproductive system has been proposed. In fact, preclinical studies showed that licorice displays antiandrogen and estrogen-like properties. Several bioactive licorice compounds, such as glycyrrhetinic acid and glycyrrhizin, lower androgen secretion mostly via enzyme inhibition. Licorice consumption seems to be associated with a slight reduction in testosterone levels in males, although existing data are poor and conflicting. Because of the antiandrogenic properties, a fascinating effect of licorice in the treatment of polycystic ovary syndrome (PCOS) and a potential fertility-promoting role has been proposed, but data are scarce. Extreme caution is needed when using herbal remedies. Notwithstanding, licorice has shown great promise. Hence, it may be beneficial to conduct an observational study to confirm its benefits on reproductive system and safety, particularly in fertility-affecting diseases. In this context, the aim of this study is to evaluate the antiandrogenic effects and cardiovascular safety of licorice administration in healthy female and males. The primary endpoint is to evaluate the change of total testosterone levels (measured by liquid chromatography-tandem mass spectrometry- LCMS / MS) in males and pre-menopausal female healthy volunteers, highlighting the need of studies that take into account sex-differences.
Historically, in medicine the majority of clinical trials have been evaluated primarily in men; however, there is a fascinating and emergent approach of medicine ("gender medicine") aimed at recognizing and analyzing the differences arising from gender in several aspects. Clinicians and scientists must take care of this approach. While the antiandrogen proposed effect of licoricet can be effective in women suffering from hyperandrogenism due to PCOS, a disease affecting between 5 and 10% of women of reproductive-age, this antiandrogen effect can be detrimental in men. We therefore need to clarify with high sensitivity and specificity the physiological effects of licorice on steroidogenesis, focusing on sex-differences. In the last years, steroid hormones measurement was completely changed showing that immunoassays were not as reliable as believed and the use of LC-MS/MS is always needed to produce reliable results. My Department makes such an approach possible, in fact in this study steroid hormone will be analyze using LC/MS-MS (under my tutor supervision). For the first time, studying the effects on sex hormones and reproductive system we will also monitor the eventual side effects of the supplementation, in particular arterial hypertension, taking advantage of the use of a 24-hour pressure holter (model TM 2440) available at Department of Experimental Medicine. Moreover, the interpretation of the results of the existing studies on the topic is complicated by the huge disparity in herbal extraction processes, resulting in extreme variability in the chemical profiles of licorice products. To avoid this, we can product a pill containing only 3.5 g of licorice (250 mg of glycyrrhizic acid). Accurate studies are indispensable to confirm the antiandrogen and estrogen-like effects of licorice, its possible benefits, and safety.