Randomized Placebo-Controlled Trial of Androgen Effects on Muscle and Bone in Men Requiring Long-Term Systemic Glucocorticoid Treatment

Abstract

Long-term glucocorticoid therapy in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone. We tested the effect of two androgens, testosterone and its minimally aromatizable analog nandrolone, on muscle mass (dual x-ray absorptiometry), muscle strength (knee flexion and extension by isokinetic dynamometry), bone mineral density (BMD), and quality of life (Qualeffo-41 questionnaire) in 51 men on a mean daily prednisone dose of 12.6 +/- 2.2 mg. Men were randomized, double blind, to testosterone (200 mg mixed esters), nandrolone decanoate (200 mg), or placebo given every fortnight by im injection for 12 months. At 12 months, both androgens increased muscle mass (mean change from baseline +3.5%, +5.8%, and -0.9% in testosterone, nandrolone, and placebo groups, respectively, P < 0.0001) and muscle strength (P < 0.05). Lumbar spine BMD increased significantly only in men treated with testosterone (4.7 +/- 1.1%, P < 0.01). There was no significant change in hip or total body BMD. Testosterone, but not nandrolone or placebo, improved overall quality of life (P < 0.001). These results suggest that androgen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for androgen action on bone but not on muscle.

Guidelines for the diagnosis, prevention and management of osteoporosis

“…Hormone replacement therapy: glucocorticoids reduce the production of sex hormones. As such, it appears rationale to replace sex hormones in women with amenorrhea and estrogen deficiency (hypothalamic amenorrhea or primary ovarian insufficiency) or in men with proven hypogonadism (31,32). While estrogen therapy is no longer considered a first line therapy for the prevention of postmenopausal osteoporosis, it appears reasonable -in the absence of contraindications -to consider hormone replacement therapy in premenopausal women with estrogen deficiency or in men with hypogonadism treated with glucocorticoids, even if controlled studies on the incidence of fractures are lacking (Grade A recommendation).…”

Androgen regulation of satellite cell function

“…Glucocorticoid receptor Glucocorticoid hormones have profound effects on metabolism and cellular proliferation. In skeletal muscle glucocorticoids have catabolic effects on muscle (Crawford et al 2003). The actions of glucocorticoids on muscle are mediated through the glucocorticoid receptor (GR) (Chen et al 1997).…”

“…In humans, androgen treatment increased muscle mass in men with muscle wasting due to long-term glucocorticoid therapy (Crawford et al 2003). Androgen therapy in COPD patients who are on glucocorticoid treatment can partly reverse muscle wasting (Creutzberg & Schols 1999, Creutzberg et al 2003.…”

Therapeutic Dilemmas for Androgen Deficiency in Aging Males

“…In fact, a long-term study, performed over 3 years and providing physiologic testosterone levels, did not reveal any difference in respiratory disturbance index compared with the placebo-treated group [90]. Other studies have demonstrated no change in upper airway caliber with high-dose testosterone [58], no development of OSA symtomatology with TRT versus placebo [91], and no effect of testosterone blockade on nocturnal breathing or chemosensitivity in OSA patients [92]. Santamarie and colleagues even demonstrated that low testosterone levels may be associated with OSA [93].…”