Effects of chronic administration of Stevia rebaudiana on fertility in rats

Abstract

A study conducted on prepubertal male rats showed that chronic administration (60 days) of a Stevia rebaudiana aqueous extract produced a decrease in final weight of testis, seminal vesicle and cauda epididymidis. In addition, the fructose content of the accessory sex glands and the epididymal sperm concentration are decreased. Stevia treatment tended to decrease the plasma testosterone level, probably by a putative affinity of glycosides of extract for a certain androgen receptor, and no alteration occurred in luteinizing hormone level. These data are consistent with the possibility that Stevia extracts may decrease the fertility of male rats.

Introduction

Glycosides of Stevia rebaudiana (Bert.) Bertoni (Asteraceae) leaves, as stevioside, are powerful sweetening agents. They have been used for the last 15 years by Brazilian people for this purpose.

Physiological and pharmacological experiments have suggested that stevioside and S. rebaudiana extracts promote effects on some physiological systems, such as cardiovascular (Haebisch, 1992, Melis, 1992a) and renal (Melis and Sainati, 1991, Melis, 1992b). Haebisch (1992) have studied the effects of Stevia extract on cardiovascular parameters in humans and reported that this extract induce hypotension and marked decrease in heart rate. This finding was confirmed by another author following stevioside administration in rats (Melis, 1992a). In addition, stevioside and Stevia extracts are able to induce diuresis, natriuresis and kaliuresis (Melis, 1992b, Melis, 1995). The hypoglycemic effect reported by some authors has been observed exclusively with total extracts of S. rebaudiana and not with purified stevioside (Curi et al., 1986).

Planas and Kuc (1968) reported that female rats fed a 5% aqueous extract of S. rebaudiana displayed reduced fertility, an effect apparently not reversible following drug withdrawal. Similar results were reported later by Portella Nunes and Pereira (1988) for female mice. However, results of others cited by Kinghorn and Soejarto (1991) did not confirm the antifertility effect. On the other hand, a previous report described an anti-androgenic activity of dihydroisosteviol, diterpenoid acid derived from S. rebaudiana (Dorfman and Nes, 1960). Dihydroisosteviol, when administered to the chick’s comb at a dose of 3.0 mg/comb, inhibited the action of testosterone. Purified stevioside was shown in vitro to displace 5α-dihydrotestosterone specifically bound to prostate androgen receptors (Uehara et al., 1982). This finding was confirmed with the synthetic androgen, methyltrienolone (R 1881), a specific ligand of androgen receptors (Uehara et al., 1983). However, later studies carried out in male rats showed that chronic administration of Stevia extract did not alter the number of binding sites for androgens (Oliveira-Filho et al., 1989). These results are likely due to the relatively small amount of active principles reaching the cell biophase when the Stevia principles are administered in vivo.

The present experiment was undertaken to examine the possibility that S. rebaudiana extract may induce changes (i) in male accessory sex glands and (ii) in androgenic levels in rats. The results may provide important information about the level of inhibition of androgens in male rats treated with Stevia extract and help in the interpretation of subsequent experiments on reproductive function.