Propecia Prescription Online

The initial observation that the prostate could convert
testosterone to dihydrotestosterone (DHT) (1), e.g. contained
5
-reductase activity, was the first of a long succession of
pieces of evidence thatDHTmight be important in the pathogenesis
of benign prostatic hyperplasia (BPH). In 1980 it was
hypothesized that: “Treatment directed at inhibiting 5
-
reductase activity (and consequently dihydrotestosterone
formation). . . might inhibit further prostatic growth and/or
induce regression of the prostate without causing impotence
or other manifestations of hypogonadism” (2). This hypothesis
was consistent with observations in a group of patients
with a genetic deficiency of 5
-reductase who had, among
other phenotypic abnormalities, small prostates (3). A few
years later it was demonstrated that the oral administration
of a 5
-reductase inhibitor prevented the testosteronemotivated
increase in prostate size and weight in castrated
dogs (4). Although BPH in dogs is an imperfect model for
BPH in humans, it is probable that this proof of principle
served as the impetus for human studies, which demonstrated
the convincing efficacy of this drug for BPH (5, 6) and
led to its (finasteride 5 mg, Proscar) approval for use by the
Federal Drug Administration.
Two years after (1994) the approval of Proscar for BPH, a
trial began to determine whether it could decrease the incidence
of prostate cancer; the subjects were men 55 yr of age
and older. The major result of the trial, a decrease in the
incidence of low-grade prostate cancers accompanied by an
absolute and relative increase in high-grade prostate cancers
(Table 1), was surprising and led to discontinuation of the
trial before its planned ending (7). The New England Journal
of Medicine (NEJM) believed the results of the study to be of
sufficient import to release them weeks before they appeared
in print and to warrant the publication of both an accompanying
editorial (8) and a perspective (9). The accompanying
editorial by Scardino (8) concluded that Proscar probably
should not be used for the prevention of prostate cancer, but that, based on his view of its risk to benefit ratio, it remained
reasonable to use it for the treatment of BPH. Unlike
Scardino, the authors of the article refrained from making
specific recommendations on the use or nonuse of the drug.
For a variety of reasons, the interpretation of the data is
moderately contentious, as attested to by a series of letters in
the NEJM (10 –16) in October 2003, and a “News” article in
the Journal of the National Cancer Institute (JNCI) (17) that
swiftly followed the release of the results of the study.
Although the issue of using Proscar to treat BPH has been
addressed, there remains the question of how to advise patients
who take Propecia (finasteride, 1 mg) for the treatment
of baldness. This concern was not raised in the article itself,
in the NEJM editorial, in the discussion in the JNCI, or in the
correspondence in the October issue of the NEJM. This is a
most significant oversight because the effects of 1 and 5 mg
of finasteride result in more or less equal changes in serum
DHT and testosterone (Refs. 18 and 19 and Fig. 1A), prostatic
DHT and testosterone (Ref. 19 Fig. 1B), and scalp DHT (Refs.
18 and 20 and Fig. 1C). A subsequent study (21) confirmed
the lack of difference in blood, but found a significantly
greater fall in prostate DHT for the 5-mg than the 1-mg dose
(placebo, 18.6 nmol/kg; 1 mg, 3.8 nmol/kg; 5 mg, 1.0 nmol/
kg; P
0.049 between the two doses of finasteride) after 6–8
wk of treatment. It is important to recall that these hormonal
surrogates for clinical efficacy formed the most important
basis for the early dose-ranging studies of this drug, which,
in turn, led to the choice of the doses to be used in the large
clinical trials addressing efficacy. The defining large trial (5)
assessed efficacy in almost 900 men given placebo or 1 or 5
mg finasteride. At the end of 1 yr, 5 mg finasteride improved
total urinary-symptom scores compared with placebo,
whereas 1 mg did not. However, there was no difference
between the doses in their effect on either prostate size or
maximum urinary flow rate. Both were equally better than
placebo. Thus, at least for purposes of this discussion, it is
both conservative and reasonable to presume that the long-term effects of 1 and 5 mg finasteride, in regard to prostate
cancer, will not differ.
The biology of the relationship between testosterone,
DHT, and the etiology of prostate cancer was—and is—less
clear than the relationship between these steroids and BPH.
Although the steroidal surrogates correctly predicted the
efficacy of Proscar in BPH, its action on the prevention of
prostate cancer appears mixed. This issue is now unsettled

but raises concern for those in whom finasteride is used for
a cosmetic rather than a moderately severe medical problem
(BPH). This predicament resolves itself into two separate but
related questions. First, is the observed decrease in low-grade
prostate cancer worth the tradeoff for an increased risk of
high-grade cancers in patients with BPH? Unfortunately, the
data do not furnish an unambiguous answer to this question;
furthermore, it is not an issue that has escaped the attention

of the medical community. For the moment anyway, it appears
that the benefits of therapy with finasteride for BPH are
probably worth the risk. Second, and more problematic, is
the fact that there has been no open discussion of the potential
danger in the long-term use of Propecia.
We need to think seriously about the large group of men,
younger by far than those with prostate disease, who use
finasteride for hair loss and not for symptoms arising from
BPH. Bear in mind that the treatment of alopecia with finasteride
is a lifelong commitment and that “lifelong’” means
a long time for young men. Will these patients be protected
from prostate cancer, or are they at greater risk of serious
disease? Whatever the answer, because of the prospect of
many years of use, there should be a sense of urgency in
sorting out this dilemma. In the interim, physicians and their
patients should at least be aware of the potential risks and
together should evaluate the use of Propecia for baldness. For
mypart, I will stay with the tried and true, “first do no harm.”