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Jewish World Review Dec. 23, 2003 / 28 Kislev, 5764
By Robert A. Wascher, M.D., F.A.C.S.
http://www.NewsAndOpinion.com |
As men age, their prostate glands gradually enlarge under the year-to-year
influence of the male sex hormones. The prostate gland is a walnut-sized
organ that is situated at the base of the bladder. Since the urethra passes
through the prostate gland, significant enlargement of the prostate gland
can prevent the bladder from emptying properly. When benign prostatic
hypertrophy (BPH) is sufficiently advanced, urinating can become very
difficult. The bladder then becomes distended with urine, causing
discomfort, as well as an increased risk of infection, bladder stones and
kidney damage.
Based upon previous autopsy studies, BPH occurs in about 50% of men in their
60s, rising to more than 90% among men 85 years of age and older. Symptoms
of BPH occur in approximately 14% of men in their 40s, 24% of men in their
50s, and in more than 40% of men in their 60s. In the US, an estimated 15
million men experience symptoms of BPH. At the present time, most experts
believe that there is no significant link between BPH and prostate cancer,
although both diseases arise due to, at least in part, the lifelong effects
of exposure to male sex hormones.
There are several medications that have been shown to improve the urinary
symptoms of BPH. In general, two classes of medications have been used most
frequently: alpha-adrenergic blockers and 5-alpha reductase inhibitors.
The former class of medications relax the muscle fibers at the base of the
bladder, and within the urethra, to improve urine flow. The latter class of
BPH medications inhibit the actions of male sex hormones in the prostate
gland, as well as in other cells of the body that respond to testosterone
and related androgenic hormones. This androgen hormone blockade results in
gradual shrinkage of the enlarged prostate gland. Various other
non-prescribed remedies have also been touted for BPH, most of them herbal
in origin. These include saw palmetto fruit, South African star grass
roots, African plum tree bark, stinging nettle roots, rye pollen and pumpkin
seeds. Among these, saw palmetto has, arguably, the largest following.
Unfortunately, there has been little scientific evidence to support the use
of these alternative therapies for the treatment of BPH.
Two interesting studies that were reported this week may be helpful to men
with symptomatic BPH. The first, in the New England Journal of Medicine,
looked at the effects of combining the alpha-adrenergic blocker doxazosin
with the 5-alpha reductase inhibitor finasteride as combined therapy for
symptomatic BPH. This was a double-blind placebo-controlled study, where
neither patients nor their doctors knew if the study volunteers were
receiving one of the BPH drugs, both of them, or just sugar pills. A total
of 3,047 men were followed for an average of almost 5 years during this
study. The study found that the men who took doxazosin alone experienced a
39% reduction in the severity of their BPH symptoms, while those who took
finasteride alone experienced a 34% reduction in symptoms (both results were
relative to the symptom severity reported by the men who received only
placebo pills). The men who received both BPH medications during the study
reported a rather dramatic 66% reduction in the severity of their symptoms,
however. This is a rather unusual case where the combination of two
different classes of drug therapy prove to be completely additive in their
benefit when compared to each drug given alone. In most cases, combined
therapies for virtually all human diseases may be somewhat more effective
than each individual drug given by itself, but the additive effect of the
two drugs are rarely on the order of the sum of their individual beneficial
effects. An interesting side note from this study: patients who received
doxazosin alone experienced fewer symptoms of BPH, but did not experience a
lower risk of acute episodes of urinary tract obstruction or the need for
surgical intervention when compared to placebo. However, finasteride,
whether given alone or in combination with doxazosin, did significantly
reduce the incidence of these events.
This study, therefore, strongly supports the combined use of both 5-alpha
reductase inhibitors and alpha-adrenergic blockers to treat symptomatic BPH,
and may offer a non-surgical alternative to many men now contemplating
surgery to relieve their BPH symptoms.
The second study, as reported in the Journal of Urology, compared saw
palmetto and finasteride as individual therapies for BPH in men with
symptomatic prostate gland enlargement. Study volunteers were randomized to
receive either saw palmetto (325 mg per day) or finasteride (5 mg per day)
for a period of 1 year. The patients then had their BPH-related symptoms
reassessed at 3 months, 6 months and 12 months. At 12 months, 56 of the
original 64 patients continued to participate in this study. The results of
this study were consistent with other similar recent studies. The group
assigned to take saw palmetto experienced no improvement in their BPH
symptoms when compared to placebo pills, while the group of men who received
finasteride did experience considerable improvement in symptoms. This is a
rather small study, but it adds to other studies that call into question the
use of saw palmetto as a treatment for BPH.
EFFECTS OF DISCONTINUATION OF HRT FOLLOWING THE DIAGNOSIS OF BREAST CANCER
Hormone replacement therapy (HRT) following menopause has declined
precipitously since last summer's release of the interim results from the
huge Womens' Health Initiative Study (WHIS), The study found a
significantly increased risk of breast cancer, colon cancer, heart disease
and dementia in women who had chronically taken combined HRT with estrogen
and progesterone tablets. These adverse effects were so significant that
this portion of the WHIS was prematurely terminated so that the women who
were taking combination HRT could be warned about the worrisome findings.
(Another subgroup of women who took only estrogen pills are still being
followed by the study.) While many women without a personal history of
breast cancer have subsequently opted to go back on their Prempro tablets
following the initial WHIS scare, another subgroup of women, women with
breast cancer, tend to be more ambivalent. Even so, many women who have
been diagnosed with breast cancer ultimately choose to resume HRT, although
usually against the recommendations of their doctors.
A new study reported in the journal Cancer looked at the impact on their
breast cancer tumors of discontinuing HRT after they were diagnosed with
breast cancer. A total of 140 women, all of whom had been taking HRT,
participated in the study after they were diagnosed with breast cancer with
a needle biopsy. Following an average subsequent duration of 17 days, the
women all underwent surgical removal of their breast tumors. Twenty-five of
the 140 women elected to continue HRT during the interval between their core
needle biopsies and the surgical removal of their breast cancers. An
additional 55 women who were not taking HRT at the time of their diagnosis
of breast cancer (also by core needle biopsy) were included in this study as
"controls."
In the 125 women who discontinued HRT following their needle biopsy, there
was a significant decrease in their breast tumors' expression of a protein,
Ki-67, that reflects how fast the cancer cells are dividing and growing.
This decrease in the so-called proliferation of breast cancer cells was
identified by comparing the levels of Ki-67 in tumor cells recovered from
the needle biopsy with the tumor cells subsequently removed by definitive
surgery. Further evidence that HRT was stimulating breast tumor cell growth
was the finding that the reduction in Ki-67 expression seen in the
surgically removed breast tumors taken from women who stopped HRT occurred
only in cancers that were chemically sensitive to the female hormone
estrogen. The estrogen receptor-negative tumor cells did not appreciably
differ in their expression of Ki-67 protein between the needle biopsy
specimens and the surgical excision specimens, even among the women who
stopped taking HRT after their initial needle biopsy. In addition to a
reduction in the levels of Ki-67 protein expressed in estrogen-sensitive
tumors following withdrawal of HRT, the scientists found that other proteins
linked with more aggressive growth of breast cancer cells declined after
discontinuing HRT in the women with estrogen-sensitive tumors. This result
is exactly what the majority of oncologists would have predicted, but this
innovative little study is the first to actually show a correlation between
HRT withdrawal and a subsequent biochemical improvement in the
aggressiveness of estrogen-sensitive breast cancers in living human beings.
The results of this study, while not proving or disproving that HRT
cessation reduces the risk of recurrent or second breast cancers, does add
powerful evidence to the growing awareness (among both patients and
physicians) that estrogen-sensitive breast cancers are likely to respond to
continued HRT by behaving more aggressively.
JWR contributor Dr. Robert Wascher is an oncologic surgeon, professor of surgery, oncology research scientist, and author. He lives in Honolulu with his wife and two daughters.
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Update on benign enlargement of the prostate; effects of discontinuation of hrt following the diagnosis of breast cancer
