US Pharm. 2008;33(3)(suppl):8-11.
By the age of 70, nearly 80% of men have
benign prostatic hyperplasia (BPH), a prostate condition that can cause a
variety of bothersome urinary symptoms.1 Two other common prostate
disorders are prostatitis and prostate cancer. Men with prostate disorders may
self-administer OTC products, vitamins, herbs, or supplements for their
condition. One survey reported that 27% of men with prostate cancer used some
form of alternative medicine.2 Another retrospective analysis found
that 73% of men diagnosed with prostate cancer were using some type of dietary
supplement.3 Many men utilize these alternative therapies without
knowledge of their efficacy and risks, and they commonly do not inform their
physicians about their use. The pharmacist is well positioned to answer
patients' queries about prostate health and OTC treatments for prostate
disease. This article will discuss some common nonprescription therapies that
are used for prostate health.
Prostate cancer is prevalent
among men. The male hormone testosterone can stimulate the growth of
hormone-dependent prostate cancer cells. Known risks for prostate cancer
include age, family history, African-American ethnicity, certain dietary
factors, and obesity.4 Evidence suggests that men who eat a diet
high in animal fat or red meat may be at increased risk for prostate cancer
and that those who eat a diet rich in fruits and vegetables may have a lower
Products commonly taken for prostate cancer
include vitamin E, selenium, and saw palmetto (discussion following). Selenium
is a trace element that plays an important role as an antioxidant defense
mechanism in the body. Vitamin E is a fat-soluble vitamin that also is an
antioxidant. There has been some debate as to whether supplementation with
selenium or vitamin E may have a protective effect and decrease the likelihood
of prostate cancer development.3,4
Low selenium levels have been statistically
correlated with prostate cancer, and supplementation with it can inhibit the
growth of prostate carcinoma cells in vitro.5 Selenium is an
essential component of the antioxidant enzyme glutathione peroxidase, which
helps protect cells from oxidative damage. One proposed mechanism of action
for selenium in improving prostate health is its effect on the endocrine
system; it influences testosterone production, thereby evidencing a possible
link to the pituitary-adrenal-gonadal axis.6
One large-scale, randomized, double-blind,
placebo-controlled trial published by Clark et al in 1996 investigated the
role of selenium in oncogenesis.5 The patients (N=1,312), all with
a history of skin cancer, were studied to determine the incidence of cancer
recurrence and of secondary endpoints, including all-cause cancer mortality.
After randomization, patients received either 200 mcg of selenium or placebo
daily for an average of 4.5 years. Selenium treatment did not protect against
development of basal- or squamous-cell carcinoma, but the study was terminated
early due to a statistically significant improvement in overall cancer
mortality and other secondary endpoints such as lung, colon, and prostate
cancer. The highest prostate cancer prevention rate was found in patients with
the lowest baseline selenium levels. This study has been questioned, however,
since its primary endpoint was to determine selenium's possible protective
effects on skin cancer. The secondary endpoints (e.g., prostate cancer
development) were not added until 1990, even though trial enrollment began in
1983. Thus, while the findings were intriguing, the authors suggested that
selenium's effects be confirmed in a separate, appropriately designed trial
before new recommendations regarding supplementation with it be made.
Another study, published by Yoshizawa et al
(N=51,000), found a strong correlation between selenium levels and prostate
cancer risk.7 Based on toenail selenium concentration, patients in
the highest quartile of concentration had approximately half the risk of
developing prostate cancer compared with the lowest quartile. After
influencing factors such as family history, diet, and geographical region were
controlled for, the difference was significant. A similar but smaller study
conducted by Hardell et al found that serum selenium concentrations were
significantly lower in men with prostate cancer than in those without it.8
A nested case-control study was performed by
Peters et al within the screening arm of the Prostate, Lung,
Colorectal, and Ovarian Cancer Screening Trial.9 Serum
selenium concentrations were compared prospectively among 724 subjects with
prostate cancer and 879 subjects without the disease; subjects were followed
for up to eight years. Serum selenium was not associated with a significant
decrease in prostate cancer risk overall. Higher serum selenium,
however, was associated with significantly lower risks in subjects
reporting a high vitamin E intake and in multivitamin users, indicating that
combination therapy may decrease the risk of prostate cancer.
A large, randomized, double-blind study
currently in progress, the Selenium and Vitamin E Cancer Prevention Trial
(SELECT) is evaluating whether selenium and vitamin E reduce the risk of
prostate cancer.10 A total of 32,400 healthy subjects will be
randomized into four groups: vitamin E and selenium (200 mcg), vitamin E and
placebo, selenium (200 mcg) and placebo, and placebo and placebo. Treatment
will be given for seven to 12 years. Final results, expected in 2013, will
clarify the relationship between these supplements and prevention of prostate
In summary, current evidence suggests that
certain men may benefit from OTC selenium supplementation (200 mcg daily) to
reduce the risk of prostate cancer. Men with a baseline selenium concentration
below 122 ng/mL and a prostate-specific antigen (PSA) level less than 4 ng/mL
appear to receive the greatest benefit from daily selenium supplementation.
5,11 However, results from the SELECT study are necessary to confirm
that supplementation with 200 mcg of selenium is safe and effective in
reducing the risk of prostate cancer among healthy men. Most of the research
on selenium supplements has focused on prostate cancer prevention. At this
time, it is unclear whether OTC selenium supplements should be used for the
treatment of prostate cancer. The most recent evidence does not support the
use of vitamin E in preventing prostate cancer.12
In BPH, the prostate gland
becomes enlarged and may push against the urethra, causing various urinary
symptoms, although not all men with an enlarged prostate experience symptoms.
BPH occurs as men age, possibly due to an increased ratio of estrogen to
testosterone in the bloodstream. BPH is not associated with an increased risk
of cancer, although the two may occur simultaneously. Symptoms of BPH include
a weak or slow urinary stream, inability to urinate or difficulty starting
urination, frequent urination, urinary urgency, nocturia, and sensations of
incomplete emptying after urination. Treatment is unnecessary for asymptomatic
men; however, once pain or difficulty urinating is involved, treatment may be
The most common nonprescription agent used
to alleviate symptoms of BPH is saw palmetto (Serenoa repens).
13 Extracted from the berry of the saw palmetto shrub, this substance is
thought to inhibit 5-alpha reductase (5-AR), thus blocking the conversion of
testosterone to dihydrotestosterone, which is responsible for stimulating
growth of the prostate gland. Saw palmetto is generally well tolerated; side
effects are infrequent, but include headache and gastrointestinal upset. No
known drug interactions are associated with use of this herb.
Some studies found that saw palmetto led to
an increase in urine flow rate in men with BPH compared to placebo, with
effects comparable to finasteride.13,14 More recently, Bent et al
conducted a randomized, double-blind, placebo-controlled study of 225 men with
BPH who took standardized saw palmetto extract 160 mg or placebo twice daily
for one year.15 Men with prostate cancer or urinary bladder
problems were excluded. Subjects could participate if they had stopped taking
alpha-blockers, 5-AR inhibitors, or saw palmetto for a specified length of
time prior to the study. There was no significant difference between the saw
palmetto and placebo groups in standardized objective urinary symptom scores
(e.g., maximal urinary flow rate), prostate size, residual volume after
voiding, quality of life, or serum PSA levels. The incidence of side effects
was similar in the two groups. This study has cast considerable doubt on the
effectiveness of saw palmetto for the treatment of BPH.
Similar results were found in a study
undertaken by Marks et al.16 Patients with BPH (n=44) were treated
for six months with either saw palmetto or placebo. In this study, saw
palmetto did not produce a significant benefit in clinical parameters,
prostate volume, or PSA versus placebo. Additionally, a
meta-analysis published in 2002 suggested that saw palmetto may be effective
for alleviating symptoms of BPH only in the short term.17
A new study that may prove useful for
alternative-therapy recommendations is the Complementary and Alternative
Medicine for Urological Symptoms (CAMUS) trial.18 The primary
objective of this trial is to determine whether the phytotherapies S repens
and Pygeum africanum (discussion following) can delay or prevent the
progression of BPH. This randomized, double-blind, actively controlled
efficacy study, which began in 2005, has enrolled 2,860 patients and will be
completed in 2012. Participants are randomly assigned to one of four
treatments: extract of S repens, extract of P africanum,
tamsulosin, or placebo. Patients will have clinic visits every four months for
four years. The following assessments will be performed at clinic visits:
physical examination; digital rectal examination; medical follow-up (new
diagnoses, treatments, hospitalizations); urinalysis; vital signs; PSA;
uroflow measurement; and questionnaires related to prostate health, adverse
events, and medications. The CAMUS trial will provide a solid comparison
between some phytotherapies, placebo, and the currently recommended
prescription-treatment drug class.
P africanum is a tall evergreen that
grows in South and Central Africa. The powdered bark historically has been
used in tea form for the relief of a variety of urinary disorders.
Concentrated extracts of P africanum have been studied for its efficacy
for BPH.19 As is the case with saw palmetto, however, methodologic
problems such as short duration of follow-up, incomplete outcome assessment,
and lack of product standardization have been identified in clinical trials.
The risks of saw palmetto are not known,
although the herb is theorized to interact with 5-AR inhibitors based upon the
supposed mechanism of action; this may produce abnormal or unexpected results.
20 Pharmacists should engage patients in a risk-versus-benefit
discussion of saw palmetto. Men with new-onset obstructive urinary symptoms
should be discouraged from self-medicating with saw palmetto; rather, these
patients should be under medical supervision since the symptoms of BPH can
mimic other disorders, such as prostate cancer and prostatitis.
Prostatitis--inflammation of the
prostate gland--can be acute (bacterial) or chronic (bacterial or
nonbacterial). Some symptoms of prostatitis are pain, urination problems, and
fever. Recently, Kaplan et al published results of a one-year, randomized,
single-blind trial comparing saw palmetto with finasteride in the treatment of
prostatitis and chronic pelvic pain.21 Sixty-four men were
randomized equally to the two treatment arms. All patients had previously been
given antibiotics (nine to 93 weeks' duration), and 52 of them had been on
alpha-blockers. At 12 months, the mean total National Institutes of Health
Chronic Prostatitis Symptom Index score was significantly lower in the
finasteride group (23.9 to 18.1), but not the saw palmetto group. In the
finasteride arm, pain and quality of life were significantly improved at 12
months. The authors concluded that the patients who received saw palmetto had
no tangible long-term improvement and that patients who received finasteride
had significant, long-term improvement in all parameters except urination.
Diseases of the prostate gland normally produce
urinary symptoms but may also cause pain, especially in the case of acute
bacterial prostatitis and later stages of BPH. OTC analgesics such as
acetaminophen and NSAIDs can be recommended to relieve pain in prostate
disease. A working knowledge of the supplements utilized for prostate
disorders will help the pharmacist field patients' questions about their use.
In general, the pharmacist should refer patients who develop obstructive
urinary symptoms to a physician for management.
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3. Wiygul JB, Evans BR, Peterson BL, et al.
Supplement use among men with prostate cancer. Urology. 2005;66:161-166.
4. Diefenbach M, Hamrick N, Uzzo R, et al.
Clinical, demographic, and psychosocial correlates of complementary and
alternative medicine use by men diagnosed with localized prostate cancer. J
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of selenium supplementation for cancer prevention in patients with carcinoma
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6. Klein EA, Thompson IM, Lippman SM, et al.
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