Quality of life of patients undergoing androgen deprivation is
an issue that has received limited attention in the past but is
currently being actively evaluated in clinical trials. This issue
becomes more important as patients with longer life expectancy
and no metastatic disease are treated for longer durations.
The type and extent of potential long-term androgen deprivation-related
side effects, such as osteoporosis and effects on muscle mass,
heart, and lipids, are not clear. However, the association of
impotence and hot flashes with the two leading modalities of androgen
deprivation--bilateral orchiectomy and luteinizing hormone-re-
leasing hormone (LHRH) agonists--is better documented. These side
effects seem to be the most bothersome from the patient's perspective.
While not a serious adverse effect, hot flashes, when severe,
are annoying and interfere with quality of life, although they
rarely warrant discontinuation of therapy.
Dr. Smith provides a fair assessment of hot flashes and their
management in patients undergoing androgen deprivation. The cause
of vasomotor hot flashes is not entirely clear, but Dr. Smith
discusses potential physiologic mechanisms.
Therapy of hot flashes is not always necessary and is dictated
by the severity of symptoms. As outlined in the article, various
therapeutic interventions, both hormonal and nonhormonal, are
available. However, therapy must be individualized, weighing the
risks vs benefits of such treatment.
Of the available remedies, hormonal agents, such as estrogens,
lowdose megestrol acetate, and cyproterone acetate, are reported
to be the most effective. Estrogens are associated with cardiovascular
adverse effects, gynecomastia, and breast tenderness, however,
and cyproterone acetate is not commercially available in this
country. Low-dose megestrol acetate could be offered as an effective
treatment of hot flashes, although the possible effects of long-term,
low-dose therapy with this agent on the course of prostate cancer
and other biologic systems are unknown.
In general, nonhormonal agents are not very effective. In hormonally
treated breast cancer patients, the palliation of hot flashes
has not been limited to prescribed medications but also includes
agents that might be viewed as "natural" remedies, such
as vitamin E, ginseng, and garlic tablets. Anecdotally, these
substances seem to afford some symptomatic relief in certain hormonally
treated prostate cancer patients.
Intermittent Androgen Deprivation?
Recent interest in improving the efficacy of hormone therapy while
enhancing quality of life has led to the clinical investigation
of intermittent androgen deprivation. This involves, on average,
8 to 10 months of treatment with an LHRH agonist plus an antiandrogen
to ensure a sustained suppression of prostate-specific antigen
(PSA) to a nadir below the normal range, followed by an off-therapy
period. The off-therapy period will last as long as the PSA does
not rise above an arbitrarily determined level of 10 to 20 ng/mL.
The cycle is then repeated.
Preclinical data suggest a therapeutic advantage of intermittent
androgen deprivation over continuous therapy. The potential for
full recovery from medical castration makes this approach feasible,
as is suggested by the preliminary clinical data. Serum testosterone
returns to the normal range within 8 weeks on average. This
generally results in an improvement in patients' sense of well-being
in addition to a marked reduction in or elimination of hot flashes.
The efficacy of intermittent androgen suppression relative to
the continuous approach is currently being investigated in patients
with newly diagnosed metastatic prostate cancer in a phase III
randomized intergroup trial (INT-0162 ). The intermittent approach
is a very promising alternative to continuous androgen deprivation,
particularly when long-term therapy is entertained, as it appears
to minimize such side effects as hot flashes. However, patients
must be counseled about its investigational nature.
1. Loprinzi CL, Michalak JC, Quella SK, et al: Megestrol acetate
for the prevention of hot flashes. N Engl J Med 331:347-352, 1994.
2. Goldenberg SL, Bruchovsky N, Gleave ME, et al: Intermittent
androgen suppression in the treatment of prostate cancer: A preliminary
report. Urology 45:839-845, 1995.