Yonsei Med J.  2013 Nov;54(6):1331-1335. 10.3349/ymj.2013.54.6.1331.

Effect of Testosterone Replacement Therapy on Bone Mineral Density in Patients with Klinefelter Syndrome

• Jo DG
• Lee HS
• Joo YM
• Seo JT

• KMID: 1798127
• DOI: http://doi.org/10.3349/ymj.2013.54.6.1331

Abstract

PURPOSE
Klinefelter syndrome (KS) is related to testicular insufficiency, which causes low testosterone levels in serum. Generally, sex hormone levels and bone mineral density (BMD) are lower in patients with KS than normal. We investigated the effects of testosterone replacement on serum testosterone levels and BMD in KS patients.
MATERIALS AND METHODS
From December 2005 to March 2008, 18 KS patients with a 47, XXY karyotype were treated with initial intramuscular injections of long-acting testosterone undecanoate (Nebido(R), 1000 mg/4 mL) at baseline and second injections after six weeks. An additional four injections were administered at intervals of 12 weeks after the second injection. BMD was measured at the lumbar spine (L2-4), the left femoral neck and Ward's triangle, using dual energy X-ray absorptiometry. Medical histories, physical examinations and prostate specific antigen, hematology and serum chemistry were conducted for each patient. In addition, total testosterone and sex hormone-binding globulin levels were measured.
RESULTS
Following testosterone replacement, mean serum total testosterone increased significantly from baseline (0.90 vs. 4.51 ng/mL, p<0.001), and total testosterone rose to normal levels after replacement in all patients. The mean BMD of the lumbar spine increased significantly (0.91 vs. 0.97 g/cm2, p<0.001). Similar increases of BMD were also observed at the femoral neck, but this increase was not significant.
CONCLUSION
These findings suggest that testosterone replacement therapy may be effective in treating BMD deficiency in men with testosterone deficiency, especially those with Klinefelter syndrome.

Keyword

Bone mineral density; Klinefelter syndrome; testosterone

MeSH Terms

Adult
Bone Density/*drug effects
Female
Hormone Replacement Therapy/*methods
Humans
Klinefelter Syndrome/*drug therapy
Male
Testosterone/*therapeutic use
Testosterone

Figure

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  Fig. 1 Testosterone injection schedule. TU, testosterone undecanoate.

Reference

1. Seeman E. During aging, men lose less bone than women because they gain more periosteal bone, not because they resorb less endosteal bone. Calcif Tissue Int. 2001; 69:205–208.

2. Klinefelter HF. Background of the recognition of Klinefelter's syndrome as a distinct pathologic entity. Am J Obstet Gynecol. 1973; 116:436–437.

3. Seeman E, Melton LJ 3rd, O'Fallon WM, Riggs BL. Risk factors for spinal osteoporosis in men. Am J Med. 1983; 75:977–983.

4. van den Bergh JP, Hermus AR, Spruyt AI, Sweep CG, Corstens FH, Smals AG. Bone mineral density and quantitative ultrasound parameters in patients with Klinefelter's syndrome after long-term testosterone substitution. Osteoporos Int. 2001; 12:55–62.

5. Orwoll ES, Klein RF. Osteoporosis in men. Endocr Rev. 1995; 16:87–116.

6. Horowitz M, Wishart JM, O'Loughlin PD, Morris HA, Need AG, Nordin BE. Osteoporosis and Klinefelter's syndrome. Clin Endocrinol (Oxf). 1992; 36:113–118.

7. Seo JT, Lee JS, Oh TH, Joo KJ. The clinical significance of bone mineral density and testosterone levels in Korean men with non-mosaic Klinefelter's syndrome. BJU Int. 2007; 99:141–146.

8. Choi HR, Lim SK, Lee MS. Site-specific effect of testosterone on bone mineral density in male hypogonadism. J Korean Med Sci. 1995; 10:431–435.

9. De Rosa M, Paesano L, Nuzzo V, Zarrilli S, Del Puente A, Oriente P, et al. Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment. J Endocrinol Invest. 2001; 24:246–252.

10. Stepan JJ, Burckhardt P, Hána V. The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter's syndrome: the influence of vitamin D deficiency and hormonal status. Bone. 2003; 33:589–596.

11. Wang C, Swerdloff RS. Androgen replacement therapy. Curr Ther Endocrinol Metab. 1997; 6:331–337.

12. Wong FH, Pun KK, Wang C. Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement. Osteoporos Int. 1993; 3:3–7.

13. Aminorroaya A, Kelleher S, Conway AJ, Ly LP, Handelsman DJ. Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men. Eur J Endocrinol. 2005; 152:881–886.

14. Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005; 63:280–293.

15. Smith DA, Walker MS. Changes in plasma steroids and bone density in Klinefelter's syndrome. Calcif Tissue Res. 1977; 22:Suppl. 225–228.

16. Schubert M, Minnemann T, Hübler D, Rouskova D, Christoph A, Oettel M, et al. Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism. J Clin Endocrinol Metab. 2004; 89:5429–5434.

17. von Eckardstein S, Nieschlag E. Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: a phase II study. J Androl. 2002; 23:419–425.