Bone density in men with disorders of androgen action

A clinical model of androgen effects on bone tissue is represented by the cohort of men undergoing therapeutic orchiectomy for the treatment of prostate cancer or sexual delinquency. In 12 men of the latter group, bone mineral density of the lumbar spine decreased after bilateral orchiectomy (Stepan etal. 1989). Corresponding effects were seen in men treated with surgical or chemical castration for prostate cancer; as a consequence, osteoporotic fractures were significantly increased in comparison to controls (14% vs. 1%) (Daniell 1997; 2000). This has been recently confirmed by a study involving 429 men who underwent bilateral orchiectomy for treatment of prostate cancer. Fractures were ascertained from medical records and compared with expected numbers based on local incidence rates; this demonstrated a three-fold increase of fractures accounted for by moderate trauma of the hip, spine and distal forearm, locations traditionally linked with osteoporosis (Melton etal. 2003). The administration of long-acting GnRH agonists, which has been used for treatment of benign prostate hyperplasia has similar effects (Goldray et al. 1993). Inhibition of 5a-reductase by finasteride for benign prostate hyperplasia led to significantly decreased levels of dihydrotestosterone, but did not result in any changes of bone metabolism or density (Tollin et al. 1996). Also the inhibition of both 5a-reductase isoforms, which is not effected by finasteride but the new substance dutasteride, has no consequence on bone tissue (but an elevated incidence of impotence, decreased libido, ejaculation disorders and gynaecomas-tia were observed in large, randomized, double-blind clinical trials involving 5655 men) (Andriole and Kirby 2003). This points out that testosterone and its metabolite estradiol are sufficient for maintenance of bone tissue, but not the 5a-reduction metabolite dihydrotestosterone.

In patients with androgen insensitivity, the effects observed in ARKO mice (see above) are confirmed. In patients with this rare condition, cortical bone mineral density is markedly lower than in normal male controls but similar to that of age-matched women (Bertelloni et al. 1998; Marcus et al. 2000; Zachman et al. 1986).

The majority of men with defective androgen action, however, present with other diagnoses: with primary hypogonadism due to Klinefelter syndrome or a condition after testicular tumors and men with secondary hypogonadism due to Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, pituitary disorders of various kinds or late-onset hypogonadism (Behre etal. 2000). A marked decrease in bone density in comparison to controls is seen all these patient groups, but especially in those men with secondary hypogonadism as demonstrated by a large study involving 156 newly diagnosed untreated hypogonadal men (62 men with primary and 94 men with secondary hypogonadism) and 224 healthy controls aged 18 to 91 years. This is due to those men within a group of secondary hypogonadal patients with a congenital disorder ofgonadotropin secretion causing impaired bone maturation during puberty (Zitzmann etal. 2002). An earlier report in a smaller cohort showed similar results (Behre et al. 1997). Bone density declines with decreasing total testosterone concentrations in a non-linear fashion, with a four to five-fold larger reduction for each nanomole-per-liter decrement in total testosterone in the hypogonadal range (<12 nmol/L) compared with the eugonadal range (Zitzmann et al. 2002). This is expressed in the non-linear association model demonstrated by Fig. 7.2 and suggests that hypogonadism does not present a uniform condition, but that androgen effects on bone tissue are still distinctly measurable depending on the androgen concentration, albeit below the eugonadal range. This is corroborated by findings of treatment effects which strongly depend on initial testosterone concentrations (see below).

Vanish Man Boobs

Vanish Man Boobs

Say goodbye to embarrassing man boobs forever. Thats right. Im going to share all of the research I collected and the cures I found with you. It is entirely possible to cure your man boobs forever without the use of drugs or surgery. Im going to show you how.

Get My Free Ebook

Post a comment