Nandrolone and ED
[From: Pan MM, Kovac JR. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness. Translational Andrology and Urology 2016;5(2):213-9. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness ]
In spite of its potential beneficial uses described above, one major limitation to the use of nandrolone in hypogonadal males stems from the fact that a relationship may exist between the use of nandrolone and ED. Although the World Health Organization INCHEM database compiled by the International Program on Chemical Safety (http://www.who.int/ipcs/en) lists impotence under adverse effects of nandrolone; no consistent reports of ED associated with the use of nandrolone have been reported in the literature.
Anecdotal evidence from patients, as well as those men who have previously used nandrolone from “alternative” sources suggests a relationship with the use of nandrolone (alone, not in combination with testosterone) and ED. Indeed, nandrolone may contribute to the development of ED through two mechanisms: the suppression of testosterone/DHT via negative feedback and the buildup of estrogens.
Numerous studies have shown that DHT is the active androgen involved in maintenance of nitric oxide-mediated penile erections. Castrated rats treated with exogenous testosterone recovered erectile function but, when co-administered with a 5ARi to block DHT production, this recovery was lost (40,41). Moreover, administration of transdermal DHT in aging men resulted in improvement in early morning erections and the ability to maintain erections (42). In fact, one of the most common sexual side-effects of 5ARi’s (described above) is ED (43).
Nandrolone has also been shown to decrease LH, FSH, and endogenous testosterone levels in animal models, indicating a negative feedback loop to inhibit the hypothalamic-pituitary-gonadal (HPG) axis (44). In this context, nandrolone acts as an androgen receptor agonist that is not converted endogenously to DHT (15). As such, it provides negative feedback to the HPG axis to suppresses testosterone levels, further decreasing the available testosterone and DHT, compounding its negative effects on erectile function.
Imbalance in the testosterone to estrogen ratio has been associated with ED (45). Numerous subsets of patients with ED have elevated estradiol levels, indicating a relationship between estrogens and erectile function (45). Nandrolone and other members of the 19-nor-androgen families have been shown to undergo aromatase-mediated conversion to estrogens in animal models (17,18,46). Nandrolone itself shows significant binding affinity and full agonist activity with the alpha-estrogen receptor (47). Indeed, increased serum estrogen levels in men have been associated with development of gynecomastia, increased body fat mass, and unfavorable lipid profiles—all contributing factors to ED (48-51). As such, it can be theorized that nandrolone should be administered with testosterone to prevent ED with an eye towards regulation of a patients estradiol levels. However, specific in vivo studies examining the effects of nandrolone administration in humans has not been described.
[From: Pan MM, Kovac JR. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness. Translational Andrology and Urology 2016;5(2):213-9. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness ]
In spite of its potential beneficial uses described above, one major limitation to the use of nandrolone in hypogonadal males stems from the fact that a relationship may exist between the use of nandrolone and ED. Although the World Health Organization INCHEM database compiled by the International Program on Chemical Safety (http://www.who.int/ipcs/en) lists impotence under adverse effects of nandrolone; no consistent reports of ED associated with the use of nandrolone have been reported in the literature.
Anecdotal evidence from patients, as well as those men who have previously used nandrolone from “alternative” sources suggests a relationship with the use of nandrolone (alone, not in combination with testosterone) and ED. Indeed, nandrolone may contribute to the development of ED through two mechanisms: the suppression of testosterone/DHT via negative feedback and the buildup of estrogens.
Numerous studies have shown that DHT is the active androgen involved in maintenance of nitric oxide-mediated penile erections. Castrated rats treated with exogenous testosterone recovered erectile function but, when co-administered with a 5ARi to block DHT production, this recovery was lost (40,41). Moreover, administration of transdermal DHT in aging men resulted in improvement in early morning erections and the ability to maintain erections (42). In fact, one of the most common sexual side-effects of 5ARi’s (described above) is ED (43).
Nandrolone has also been shown to decrease LH, FSH, and endogenous testosterone levels in animal models, indicating a negative feedback loop to inhibit the hypothalamic-pituitary-gonadal (HPG) axis (44). In this context, nandrolone acts as an androgen receptor agonist that is not converted endogenously to DHT (15). As such, it provides negative feedback to the HPG axis to suppresses testosterone levels, further decreasing the available testosterone and DHT, compounding its negative effects on erectile function.
Imbalance in the testosterone to estrogen ratio has been associated with ED (45). Numerous subsets of patients with ED have elevated estradiol levels, indicating a relationship between estrogens and erectile function (45). Nandrolone and other members of the 19-nor-androgen families have been shown to undergo aromatase-mediated conversion to estrogens in animal models (17,18,46). Nandrolone itself shows significant binding affinity and full agonist activity with the alpha-estrogen receptor (47). Indeed, increased serum estrogen levels in men have been associated with development of gynecomastia, increased body fat mass, and unfavorable lipid profiles—all contributing factors to ED (48-51). As such, it can be theorized that nandrolone should be administered with testosterone to prevent ED with an eye towards regulation of a patients estradiol levels. However, specific in vivo studies examining the effects of nandrolone administration in humans has not been described.
