Does finasteride have negative effects on bone mineralization or metabolism?/nBackground: A 76-year

Fråga: Does finasteride have negative effects on bone mineralization or metabolism?

Background: A 76-year-old patient has been treated with finasteride (Proscar) for benign prostatic hyperplasia for over 2 years. Patient has suffered from backache in the lumbar region and compression fractures in Th7, 9, 11 and L1-2, and lumbar spondylosis and arthrosis have been recently diagnosed. According to the radiologist, these changes are probably not recent and not malignant.

Sammanfattning: Finasteride is not known to affect bone mineralization or metabolism.

A few cases of adverse bone effects have, however, been reported.

Svar: Finasteride is a specific inhibitor of the 5-alpha-reductase enzyme and thus blocks the conversion of testosterone to dihydrotestosterone (DHT). DHT is a potent androgen believed to play a major role in the pathogenesis of benign prostatic hyperplasia (BPH). The potential of finasteride in the treatment of BPH has recently been reviewed (1).

The most typical adverse drug reactions of finasteride are related to sexual dysfunction. Decreased libido, ejaculation disorders and impotence have been reported in 2.2-3.4 per cent of patients but total withdrawal rates have been essentially similar for the active- and placebo-treated groups in clinical studies performed (1). Finasteride has a rapid and pronounced effect on plasma DHT levels with little or no effects on plasma testosterone. A 10 per cent increase in circulating testosterone levels was, however, observed in the phase III trials.

In Medline, we could not find any data suggesting negative effects on bone and mineral metabolism. In 23 men who received finasteride 1 or 5 mg/day for one year, no effects on bone density or biochemical indices of bone and mineral metabolism were observed (2). Interestingly, bone mineral density was measured at the lumbar spine in this study. However, it is not quite clear whether testosterone or DHT is the most active androgen in the bone and whether 5-alpha-reductase activity is important in the bone. Animal data suggests that also DHT may stimulate bone formation and suppress resorption (3).

In the Swedish Adverse Drug Reactions Advisory Committee (SADRAC), there were no cases of adverse skeletal effects associated with the use of finasteride (4). In the WHO database, two cases of osteoporosis, one case of a pathological fracture and nine cases of back pain have, however, been described (5). The available information of these cases is very limited.

Finasteride treatment must be considered as an unlikely cause of your patients symptoms. If other reasons (malignancy?) for your patients fractures are not found, we recommend, however, to report this case to the regional center of the SADRAC. 1 Peters DH, Sorkin EM: Finasteride. A review of its potential in the treatment of benign prostatic hyperplasia. Drugs 1993; 46: 177-208 2 Matzkin H, Chen J, Weisman Y, Goldray D, Pappass F et al: Prolonged treatment with finasteride (1 5-alpha-reductase inhibitor) does not affect bone density and metabolism. Clin Endocrinol 1992; 37: 432-436 (enclosed) 3 Tobias JH, Gallagher A, Chambers TJ. 5 alpha-dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats. Am J Physiol 1994; 267: E953-959 4 Swedis 5 WHO INTDIS, Uppsala