Effect of Testosterone Treatment on Bone Mineral Density in Men Over 65 Years of Age¹

Abstract

As men age, their serum testosterone concentrations decrease, as do their bone densities. Because bone density is also low in hypogonadal men, we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities. We randomized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months. We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment. Ninety-six men completed the entire 36-month protocol. The mean serum testosterone concentration in the men treated with testosterone increased from 367 +/- 79 ng/dL (+/-SD; 12.7 +/- 2.7 nmol/L) before treatment to 625 +/- 249 ng/dL (21.7 +/- 8.6 nmol/L; P < 0.001) at 6 months of treatment and remained at that level for the duration of the study. The mean bone mineral density of the lumbar spine increased (P < 0.001) in both the placebo-treated (2.5 +/- 0.6%) and testosterone-treated (4.2 +/- 0.8%) groups, but the mean changes did not differ between the groups. Linear regression analysis, however, demonstrated that the lower the pretreatment serum testosterone concentration, the greater the effect of testosterone treatment on lumbar spine bone density from 0-36 months (P = 0.02). This analysis showed a minimal effect (0.9 +/- 1.0%) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL (13.9 nmol/L), but an increase of 5.9 +/- 2.2% for a pretreatment testosterone concentration of 200 ng/dL (6.9 nmol/L). Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall, but did increase it in those men with low pretreatment serum testosterone concentrations.

Androgen Replacement Therapy in the Aging Male—A Critical Evaluation

“…However, neither Orwoll and Klein (14) nor Sih et al (108) could observe any effect of T supplementation on biochemical parameters of bone turnover. Snyder et al (115), in a study involving 108 elderly subjects, observed that HRT increased BMD of the lumbar spine, but not of the hip, in patients with clearly subnormal T levels, but not in the whole elderly population studied, which included, all subjects with a T level below 16.5 nmol/L (475 ng/dL), a value which certainly is not in the hypogonadal range. On the other hand, it is evident that morbidity of osteoporosis relates essentially to hip fractures!…”

The treatment of late-onset hypogonadism

“…[40] TRT sonrası etkinliğin değerlendirildiği plasebo kontrollü bir çalışmada; başlangıç total testosteron ortalama değeri 12,8 nmol/L olan yaşlı erkeklerde 3 yıllık TRT'nin kemik dansitesine etkisinin olmadığı, ancak başlangıçta total testosteronu 10 nmol/L'nin altında olan hastalarda spinal kemik dansitesinde anlamlı iyileşmeler sağladığı bildirilmiştir. [41] Daha sonra yapılan bir çalışmada ise düşük-orta testosteron seviyesi olan hastalarda tedavinin kemik dansitesine etkisinin olmadığı gösterilmiştir. [42] Bu konuda sonuçları tutarsız olan iki meta-analiz bulunmaktadır ve bu tutarsızlığın sebebi olarak farklı preparatların kullanımı gösterilmektedir.…”

“…Yaşlanan erkektetestosteron replasman tedavisi ve olası faydaları [28] yapısındaki bu olumlu etkiye karşın TRT'nin kas gücüne etkisi tartışmalıdır. [4,41] Randomize plasebo kontrollü iki yeni çalışmada da benzer olarak; orta veya zayıf güçte, hareket kısıtlığı olan yaşlı erkelerde testosteron tedavisinin iyileşme sağladığı gösterilmiştir. [45,46] 36 ve 6 aylık testosteron tedavilerin uygulandığı plasebo kontrollü çalışmalarda ise sağlıklı yaşlı erkeklerde testosteron tedavisinin kas gücünde iyileşmeyi sağlamadığı ortaya çıkmıştır.…”

Le traitement substitutif par testostérone oral dans l’hypogonadisme lié à l’âge: bénéfices et tolérance (données d’un essai randomisé contre placebo)

“…Il n'existe pas plus d'effet versus placebo s'il existe également une supplémentation en calcium-vitamine D [2]. l'effet sur l'os est surtout démontré dans des études présentant un suivi sur le long terme, utilisant notamment des esters de testostérone par voie intramusculaire à des doses supraphysiologiques [3].…”