Julian H. Barth (Department of Clinical Biochemistry and Immunology, General Infirmary at Leeds, Leeds LS1 3EX, UK) As printed in: The Lancet, Vol 355, January, 2000, pp. 161-162.

At the turn of the 19th century, baldness in men was thought to be due to the wearing of hats and steel helmets. It was only in 1942 that James Hamilton clearly established, in a series of experiments in which he treated castrated men with testosterone, that androgens were essential for the development of baldness. The testosterone induced or aggravated baldness. The converse, treatment of baldness with anti-androgens, has not been throughly explored in men because of unacceptable side-effects, but it is effective for alleviating baldness in women.

The androgen effects involves the uptake of circulating testosterone by scalp hair-follicle cells, where it is converted by the enzyme steroid 5 -reductase (5 R) to dihydrotestosterone (DHT). DHT binds to the nuclear androgen receptor and activates androgen-response genes. 5 R has long been regarded as an important part of the mechanism because it provides local amplification of testosterone by converting it to DHT, which binds to the androgen receptor with greater affinity than does testosterone. Hair follicles in areas prone to male-pattern balding are better equipped to enhance the androgen effect than non-balding areas because they have more 5 R and androgen receptors are better equipped to enhance the androgen effect than non-balding areas because they have more 5 R and androgen receptors and less aromatase, which removes testosterone by converting the hormone to oestradiol. There are two forms of 5 R, both of which exist on the human hair follicle. The exact molecular relation between androgens and balding remains obscure since patients with congenital absence of 5 R type II do not become bald despite the presence of 5 R type I, and second, a woman who has no endogenous androgens has become bald.

Finasteride, a selective inhibitor of 5 R type II, was developed for the treatment of benign prostatic hyperplasia. It has been licensed in the USA for the treatment of male-pattern alopecia since 1997, and many developed countries have since done so too. Its efficacy has been reported in two large placebo controlled studies. K. D. Kaufman and colleagues report a double -blind study of the effects of 1 mg finasteride daily in 1553 subjects. After 12 months of therapy the number of hairs at the front of the balding scalp had increased by 11% in the treated group, where there was a loss of 2-7% in the untreated group. Not all patients responded; at 12 months, 14% of treated individuals had had an absolute reduction in hair numbers , compared with 58% of untreated men. Janet Roberts and colleagues did a placebo-controlled study at a higher dose of finasteride 5mg daily, and also a placebo -controlled dose-ranging study of 0.01, 0.1, and 1 mg/day. These studies show that a maximum effect on hair count is obtained at a daily dose of 1 mg/day. Neither study reported any side effects.

Despite improvements in global hair scores by investigators and independently scored photographs, not all the men were impressed by the treatment. Men were asked their views of the cosmetic value of treatment-i.e., size of bald spot, appearance of hair, growth of hair, slowing of hair loss, and satisfaction with hair; most of the men who received 1 mg/day were positive about the effects, but the scores for their responses ranged from 29 to 68%, compared with 17-45% for scores from the untreated group. Whether the strong response in the untreated group is a placebo response or a reflection of the cyclical manner in which balding progresses, it dilutes the apparent effect of treatment.

The data for finasteride and minoxidil are encouraging in that they show that balding is a reversible process. However, neither agent is capable of growing hair in a bare scalp. Finasteride seems to be more effective than minoxidil, but its place is likely to be for early balding and therapy has to be long term. For established balding, the most effective cosmetic therapy is hair autotransplantation, by an experienced surgeon, of multiple small punch grafts from the occipital region. Such surgery is expensive and carries the risk of complications. There is, however, a glimmer of hope. A. J. Reynolds and colleagues have recently reported that hairs can be transplanted into immunologically unrelated recipients. ŒThey grafted the sheath of scalp hair follicles into non-hairy areas of an immunologically unrelated recipient and grew pigmented terminal hair shafts.'

Many men will want to use finasteride because it has clearly shown to be able to stabilize hair loss and to produce a small reversal in the balding process. Whether it will change the natural history of hair loss or whether it will be useful in the prevention of balding is not known. Until then, men should still be encouraged to come to terms with their hair loss.