Equally contributed as first author.
7α-methyl-19-nortestosterone vs. testosterone implants for hypogonadal osteoporosis: a preclinical study in the aged male orchidectomized rat model
Article first published online: 26 JUL 2011
© 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology
International Journal of Andrology
Volume 34, Issue 6pt2, pages e601–e611, December 2011
How to Cite
Sinnesael, M., Callewaert, F., Morreels, M., Kumar, N., Sitruk-Ware, R., Van Proeyen, K., Hespel, P., Boonen, S., Claessens, F. and Vanderschueren, D. (2011), 7α-methyl-19-nortestosterone vs. testosterone implants for hypogonadal osteoporosis: a preclinical study in the aged male orchidectomized rat model. International Journal of Andrology, 34: e601–e611. doi: 10.1111/j.1365-2605.2011.01198.x
- Issue published online: 17 NOV 2011
- Article first published online: 26 JUL 2011
- Received 10 November 2010; revised 28 April 2011; accepted 4 May 2011
- hypogonadal osteoporosis;
Overt male hypogonadism induces not only osteoporosis but also unfavourable changes in body composition, which can be prevented by testosterone (T) replacement. In this preclinical study, the potential of synthetic androgen 7α-methyl-19-nortestosterone (MENT) as alternative treatment for male hypogonadism was evaluated in comparison with T. Eleven-month-old male rats were orchidectomized (orch) and left untreated for 2-months. Subsequently, the effects of 4-month MENT (12 μg/day) and T (72 μg/day) treatment on bone, muscle and fat were analysed using microcomputed tomography, dual-energy X-ray absorptiometry, dynamic bone histomorphometry and muscle fibre typing. At the onset of treatment, orch rats were clearly hypogonadal. This was evidenced by significant reductions of androgen-sensitive organ weight, lean mass, cortical thickness and trabecular bone volume compared with sham-operated aged-matched controls (sham). MENT and T restored weight of androgen-sensitive organs to a similar extent, with a superior anabolic action of MENT on levator ani muscle. Both androgens not only fully rescued hypogonadal loss of lean mass but also restored muscle fibre type composition and trabecular bone volume. Cortical bone loss was similarly prevented by MENT and T, but without full recovery to sham. Both androgens stimulated periosteal bone formation, but with a stronger effect of T. By contrast, MENT more strongly suppressed endocortical bone formation and bone turnover rate and reduced fat mass and serum leptin to a greater extent than T. MENT and T are both effective replacement therapies to stimulate bone and muscle in hypogonadal rats, with stronger lipolytic action of MENT.