Dose‐Dependent Effects and Reversibility of the Injuries Caused by Nandrolone Decanoate in Uterine Tissue and Fertility of Rats

Abstract

This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30-day recovery (2), and 60-day recovery (3). At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day). Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity. Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers. Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent. We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response.

Histopathological changes in androgenized ovaries are recovered by melatonin treatment

“…In this study, the final body weight of animals was not influenced by the treatments. Previous studies have shown no effect of synthetic steroids on the final body weight of rats, corroborating with our results . Mostafavi et al identified that melatonin as an adjunctive treatment has a buffering role on the side effects of several drugs on body weight.…”

“…Treatment with different doses of ND is capable of promoting oestrous acyclicity . In this study, the persistence of the dioestrus stage occurred even in androgenized groups that were treated with MLT.…”

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods

“…Thus, a previous study conducted in our laboratory (Belardin et al . ) showed that 60 days after last ND dose, the females were receptive to males as sperm was observed in vaginal smears, except to those females receiving the highest dose of ND (15 mg/kg). Only two females receiving 1.87 mg ND/kg became pregnant, and the rats receiving doses of 3.75 and 7.5 mg ND/kg probably did not ovulate because no uterine implantation and/or resorption site was found.…”

“…; Belardin et al . ). However, no study has evaluated the dose‐dependent effect of the ND on ovarian tissue and whether this effect can be reversed after discontinuing steroid treatment.…”

Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system

“…However, the misuse of these substances has increase among women (Elliot and Goldberg 2000). Therefore, because there is evidence that AAS alters the female reproductive physiology (Belardin et al 2014), other studies need to be conducted to elucidate the changes induced by AAS in females, particularly the changes associated with the cardiovascular system and its regulation.…”