International Research Journal of Pharmacy: Benign Prostatic Hyperplasia: Updated Review
International Research Journal of Pharmacy: Benign Prostatic Hyperplasia: Updated Review
International Research Journal of Pharmacy: Benign Prostatic Hyperplasia: Updated Review
2013, 4 (8)
www.irjponline.com
Review Article
INTRODUCTION
Benign prostatic hyperplasia (BPH) is one of the most
common conditions affecting the elderly males1, as the
elderly constitute the major proportion of the population.
This result in a major impact on the medical practice
nowadays.2 The enlargement of the prostate can produce
voiding symptoms, which can lead to pathological changes in
the urinary bladder and the kidney. Management of BPH has
also changed significantly with a considerable advance in the
understanding of the demographics and natural history of the
disease.3 The pharmacotherapy of BPH comprises of alpha-1
receptor antagonists, 5-alpha reductase inhibitors,
phytotherapy, Gonadotropin releasing hormone analogues
and androgen receptor blockers.
Prevalence of BPH
Previously, the prevalence of BPH used to be determined
only from autopsy studies only. Approximately half of the
men in the sixth decade of life exhibited histological evidence
of BPH. Almost 90 % of men developed histology BPH by
the ninth decade of life. A review of the literature provides
compelling evidence that the prevalence of histology BPH is
similar throughout the world.5 The specific factors that
initiate and promote the proliferative process are unknown.
The development of histology BPH requires both ageing and
androgens.6,7 Dihydrotestosterone (DHT) is the specific
androgen mediating prostate for its development and growth.
Testosterone is converted to DHT by the enzyme 5-alpha
reductase (5AR). There are two subtypes of 5AR, type 1 and
type 2. The primary subtype in the prostate is Type 2. Males
with the 5AR deficiency syndrome do not convert
intraprostatic testosterone to DHT. 8 Interestingly, males with
this syndrome have rudimentary prostates as adults and do
not develop BPH.5 Long-term treatment with the 5-alpha
reductase inhibitors (5ARIs) dutasteride9 and finasteride10 not
only causes some reduction of prostate volume but also
prevents further growth of the prostate. The primary
advantage of dutasteride is that it inhibits both 5alphareductase type 1 and type 2 subtypes, which results in a
more complete suppression of DHT production. All of these
observations demonstrate a pivotal role for androgens in the
development of the prostate and BPH. The observation that
the growth of the prostate does not directly correlate with
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Complementary Medicine
Interest in alternative treatments for BPH increased after
epidemiologic studies showed a lower incidence of BPH and
prostate cancer in Asians compared with persons from
Western countries.37 One postulated explanation is the higher
soy content of the typical Asian diet. Genistein, a major
isoflavone ingredient of tofu, has been found to decrease the
growth of hyperplastic prostate tissue in histoculture.38
Because natural soy food products are not readily available or
accepted worldwide, a standardized isoflavone product
containing genistein may be tried.39 Initial short term studies
showed rapid relief of BPH symptoms. However, long-term
and independent studies are not available. Saw palmetto
(Seren a repens) is a popular complementary treatment for
BPH.40Although it has been shown to inhibit the enzyme 5alpha reductase, this has not been confirmed clinically.41 In
patients with BPH and saw palmetto has been shown to be as
effective as finasteride but not as effective as other medical
treatments like alpha blockers. In an analysis of 18 studies,
40
saw palmetto had fewer side effects than traditional
medications, and serial ultrasound examinations showed that
treatment with this medicinal herb decreased prostate size
without changing serum PSA levels. The usual dosage of saw
palmetto is 160 mg twice daily. Side effects are rare
(incidence of less than 3 percent) and usually consist of mild
headaches or gastrointestinal upset.41 Throughout the world,
other herbal or complementary medicines are used to treat
BPH.41 However, many of these medicines are not
standardized or have not been well studied for efficacy.
Commonly used agents include African plum, South African
star grass, stinging nettle, and rye pollen.41
Medical Treatments
Nonselective Alpha-1 Blockers
Doxazosin, prazosin, and terazosin reduce prostatic smooth
muscle tone and, thus, have an immediate effect on urinary
flow. Although these medications quickly improve BPH
symptoms, International prostate symptom scores improve
less than with surgery.34 Side effects occur such as dizziness,
postural hypotension, fatigue, asthenia and retrograde
ejaculation.42 Side effects can be minimized by bedtime
administration and slow titration of the dosage. Alpha
blockers can be used with other therapies as needed. Prazosin
has the cost advantage of generic availability.43
Selective Alpha-1 Blocker
Tamsulosin is a highly selective alpha-1 adrenergic
antagonist that was developed to avoid the side effects of non
selective agents. Some patients who do not respond to non
selective alpha blockers may respond to tamsulosin and,
because of the selectivity, may have fewer side effects,
including hypotension. Tamsulosin is initiated in a dosage of
0.4 mg once daily2, with a maximum dosage of 0.8 mg per
day. Tamsulosin has no antihypertensive effect and is more
expensive than non selective alpha blockers.
5-Alpha Reductase Inhibitors
Finasteride slowly induces a 50 percent reduction in the
serum dihydrotestosterone level.23 As a result, prostatic
volume decreases by about 19 percent over three to six
months of treatment.23 The treatment with finasteride led to
significant improvements in urinary symptoms and flow
rates. However, in the Prospect study, the improvements with
finasteride were significantly less than those with any alpha
blocker or surgery.34 Studies suggest that finasteride may
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