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5α-Dihydrotestosterone in Adults

Testosterone can be converted into 5α-dihydrotestosterone, a form that binds with even more affinity to the testosterone receptor. In fetuses, 5α-dihydrotestosterone (DHT) causes the development of the prostate gland and the descent of the scrotum. In adults, DHT is still producing phenotypic effects. It is thought that both prostate growth and male pattern baldness may be due to increased production of DHT.

Recently, finasteride (sold as Propecia and Proscar) has been utilized to block the major steroid 5α steroid reductase enzyme that converts testosterone to DHT. This selective action allows the drug to block only the effects of DHT and not the effects of testosterone. In the adult, DHT appears to be especially important in mediating the testosterone effect in the prostate and the hair follicles. Thus, finasteride is active in these regions. (But since testosterone can act in other tissues without being converted to DHT, this drug does not block other characteristics such as libido, potency, sperm production, musculature, or voice.

Proscar has been on the market since 1992 as an alternative to surgery in benign prosatic hyperplasia (BPH). It does not appear to work on all men with BPH, but in some men, it can reduce DHT levels in the prostate by about 90 percent. As a result, the prostate shrinks. On average, it takes about a year to reduce the size of the gland 25%, and it does not usually shrink more than that. Long-term medical therapy with finasteride can reduce clinically significant endpoints such as acute urinary retention or surgery (Bartsch et al., 2000). However, these improvement are not seen in a majority of the cases (Harvard Men’s Medical Watch, 2000) and to achieve these benefits, men with BPH and enlarged prostates have to take Proscar daily, an expensive situation.

Propecia is sold in a lower dose than Proscar (each tablet containing 1 mg finasteride rather than the 5 mg of Proscar). This dose does not control prostate growth, but it can affect the hair follicles—at least to some degree. The drug appears to be able to thicken the hair in young men who have moderate pattern baldness (Roberts et al., 1999). Since Proscar does not grow hair in older men who are bald, Propecia is not expected to revive hair follicles that are inactive (Harvard Men’s Health Watch, 2000).

As expected from its mode of action, a male fetus within a woman taking finasteride might have the same phenotype as a male fetus lacking the 5α steroid reductase enzyme. Studies of finasteride on fetal development in rhesus monkeys (Prahalada et al., 1997) suggests that this drug does cross the placenta and causes the infant monkeys to be born with undescended scrota and small penises. (The dosage was much higher than that expected for a person taking the drug). Since finasteride is being used by some women to regrow thinning hair (something that does not have much support—at least in postmenopausal women—see Whiting et al., 1999), the manufacturers of these drugs warn women not to use it if they are of childbearing age.

Another drug marketed for male pattern baldness is minoxidil (sold as Rogaine). Rogaine does not affect testosterone or DHT, but it does seem to stimulate hair follicles. Its mode of action is not yet clear, although it may work by increasing blood flow to the scalp where it is applied (Kurbel et al., 1999). Like Propecia, Rogaine works only on active hair follicles; it’s only partially effective, and its benefits persist only while it is used daily.

Literature Cited

Bartsch, G., Rittmaster, R. S., and Klocker, H. 2000. Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Eur Urol. 2000:367-380.

Harvard Men’s Health Watch 2000. Finasteride revisited: proscar for the prostate and propecia for the pate. 4: 1-4.

Kurbel, S., Kurbel, B., Zanic-Matanic, D. 1999. Minoxidil and male-pattern alopecia: a potential role for a local regulator of sebum secretion with vasoconstrictive effects? Med Hypotheses. 53: 402-406.

Prahalada S, and twelve others. 1997. Effects of finasteride, a type 2 5-alpha reductase inhibitor, on fetal development in the rhesus monkey (Macaca mulatta). Teratology 55:119-131.

Roberts J. L., and 23 others. 1999. Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss. J Am Acad Dermatol. 41: 555-563.

Whiting, D.A., Waldstreicher, J., Sanchez, M., and Kaufman, K. D. 1999. Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women. J Investig Dermatol Symp Proc. 4: 282-284.

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