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Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair.
Nandralone and Hair Loss Benefits
TST in hypogonadal men results in elevated levels of free serum testosterone and, in turn, DHT. This occurs due to conversion of testosterone to DHT via 5AR inhibitors (5ARi) (19,20). Androgenic alopecia, or male pattern hair loss, typically occurs in 20% of 20-year-old men and then increases by approximately 10% every 10 years (21). A critical role for DHT in hair growth can be seen in the case study of men with Imperato-McGinley syndrome. This condition results from a mutation in the gene for type II 5AR that prevents the expression of the enzyme. As a consequence, men with this condition never become bald (22).
Androgen dependent miniaturization of scalp hair follicles by DHT is implicated as the primary cause of alopecia (23). Controlled clinical trials demonstrated that use of finasteride resulted in decreased accumulation of DHT and improvements in both subjective and objective assessments of hair growth and density (23).
Indeed, the most established management paradigm for the treatment of alopecia in the male is finasteride (24). First approved in 1992 in the treatment of benign prostatic hypertrophy, finasteride was approved for the treatment of alopecia in 1997 at a dose of 1 mg daily (propecia®) (24). In men on TST, finasteride at 1 mg is used as a means of preventing the excess exogenously administered testosterone from converting to DHT. By decreasing the amount of DHT, less is available to act on the hair follicles stabilizing the amount of hair loss.
The theory underlying the possible use of nandrolone in the context of alopecia results from the fact that it does not convert to DHT but instead gets transformed into 5α-dihydro-19-nortestosterone, a molecularly distinct compound (15,25). It is thus possible that in hypogonadal males nandrolone, in addition to or in replacement for testosterone, could alleviate concerns for the development of androgenic alopecia.
There are several lines of evidence that make this hypothesis particularly appealing. In experimental animal models, nandrolone is synthesized endogenously through a mechanism distinct from DHT (25). Furthermore, the metabolism of nandrolone in animal models yields compounds completely unrelated to DHT (15,26). It has also been proven that the actions of 5AR on nandrolone produce a compound that has decreased affinity and activity at the androgen receptor (15). Given that nandrolone is not converted to DHT it seems logical to assume that it would have less effect on hair loss than exogenous testosterone (with its subsequent conversion to DHT). Thus, nandrolone may be beneficial in treating hypogonadal men concerned about alopecia in the setting of TST.
Another aspect of this discussion also involves consideration for the possible existence of persistent sexual side effects and anxiety/depressive symptoms reported with the use of 5ARis like finasteride (27,28). Some symptoms of which have been shown to last for months to years (29). Therefore, by utilizing an agent with less direct effects on hair loss, nandrolone may represent a viable option for men in the treatment of hypogonadism. Altered levels of neuroactive steroids related to depressive symptoms have been identified in men with a history of finasteride use, even when the drug has been discontinued (30). The use of nandrolone would obviate these concerns.
Nandrolone and Joint Healing
Recent studies in animal models have identified a potential role for nandrolone in joint pain, particularly post rotator cuff tears (31,32). In one such study by Gerber et al. (31), 20 New Zealand white rabbits had their supraspinatus tendon released with musculotendinous retraction and observed over 6 weeks. Rabbits were organized into groups treated with placebo as well as local and systemic administration of nandrolone (31). Nandrolone, given in the phase after tendon release, was found to inhibit fatty infiltration of the supraspinatus muscle and reduced functional impairment of the rotator cuff (31).
An earlier 2010 study by Papaspiliopoulos et al. (32) examined 48 male rabbits that underwent rotator cuff incision and reconstruction after stratification into groups based on local nandrolone administration and immobilization. In this study, local administration of nandrolone proved detrimental to wound healing however, systemic administration was not studied (32). Other limitations include the fact that anabolic steroids affect the tensile strength of tendons that may then cause failure with less elongation (33). Local administration of nandrolone may impair the healing of acute tendon injuries and the perceived benefits to retracted muscle may be outweighed by its effects on tendon healing (34).
Interestingly, Internet and discussion group anecdotal data suggests that nandrolone is effective in decreasing joint pain in bodybuilders. These athletes lift large amounts of weights putting extreme pressure on their joints while reporting improvement and lowered pain with the use of nandrolone. While limited data is available, and dosages are unknown, further investigations are needed to determine the effects of nandrolone on joints in general, and the rotator cuff in particular.
Nandrolone and Muscle Growth
Nandrolone has long been known to have significant stimulatory effects on muscle growth. As described above, nandrolone displays a greater myotrophic:androgenic ratio compared to testosterone (15). When compared to testosterone, the high levels of 5AR in androgenic tissues (i.e., the prostate) convert nandrolone to a less active metabolite (versus DHT that is highly active). Furthermore, the lack of 5AR in skeletal muscle allows nandrolone to produce a primarily anabolic/myotrophic (i.e., muscle growing) effect (15). The ability of nandrolone to preferentially stimulate muscle growth formed the basis of its use in the treatment of anorexia and cachexia in patients with chronic medical disorders such as chronic renal failure and HIV (8,35). In these patients, administration of nandrolone has been shown to increase lean body mass as well as muscle mass and strength (8,35).
Hypogonadism has been shown to be associated with dyslipidemia, atherosclerosis, cardiovascular disease, metabolic syndrome, and diabetes (36). Testosterone supplementation in hypogonadal men improves these risk factors leading, in some patients, to complete resolution of their metabolic syndrome (36-38). Indeed, an increase in lean body mass and muscle mass with the systemic administration of nandrolone could improve body composition and augment testosterone’s effects in preventing (39) and reversing metabolic syndrome and the risk of type 2 diabetes in hypogonadal men