What do you know about hormonal therapy?
Prostate cancer is the most common cancer
diagnosed in Canadian men and the second
most common cause of cancer deaths. Hormonal
therapy is often used to treat men with
advanced prostate cancer. Despite this, most
men know very little about hormonal therapy.
Can you answer the following questions?
1. What is the most important male hormone
stimulating prostate cancer?
a) testosterone
b) thyroid hormone
C) estrogen
2. The male hormone testosterone is mainly
produced in the...
a) prostate
b) thyroid
c) testicles
d) brain
3. Hormonal treatment of prostate cancer usually
results in a cure...
a) yes
b) no
4. Benign prostatic hyperplasia (BPH) is a cancer...
a) yes
b) no
5. Hormonal treatment often results in a sharp
decline in sexual desire (libido)...
a) yes
b) no
6. Hormonal therapy will lead to a favourable
response in the majority of patients...
a) yes
b) no
7. Medical or surgical castration may result
in...
a) hot flashes
b) breast tenderness
c) impotence
d) all of the above
Try answering again after you read this booklet.
Answers can be found on the inside of the
back cover.
What is hormonal therapy?
Prostate cancer is a hormonedependent cancer,
that is, it requires male hormones (called
androgens), for its initiation and continued
growth. Testosterone, which comes mainly
from the testicles, is the most important androgen
in the body. Hormonal therapy stops the
production of testosterone or blocks its action
and is commonly used in the treatment of
advanced prostate cancer. This booklet will
explain how hormonal therapy works, when itis
used, and the different types of hormonal
therapy that are available.
How is testosterone related to the prostate?
Aftcr puberty, the prostate grows under the
influence of testosterone which is produced
mainly by specialized cells in the testicles. The
prostate usually increases in size as men age
(benign prostatic hyperplasia, BPH) and interferes
with urination.
When cancer cells develop, they too require
testosterone for continued growth. Removal of
testosterone from the body, for example by
surgical castration (removal of the testicles),
leads to destruction of many cancer cells, and
thus to a decrease in the size of the prostate
cancer. In other words, if testosterone is
removed from the body's circulation, prostate
cancer cells are either unable to survive and
may disappear, or are forced into a dormant
state. Today it is also possible to use medical
(non-surgical) means to deprive the prostate of
testosterone.
Testosterone, the most important androgen, comes from
the testicles and its release is controlled by a hormone in
the brain called luteinizing hormone (LH). The adrenal
glands produce androgens which are less important.
What regulates the production
of male hormones (androgens)?
The production of testosterone comes mainly
from the testicles and is controlled by other
hormones which come from the brain. There
are also some androgens produced by the adrenal
glands, which are small glands located just
above the kidneys. The androgens produced by
the adrenal glands have a lesser role in stimulating
the growth of prostate cancer.
Who needs hormonal therapy?
The most common therapy is to treat metastatic
prostate cancer. That is, when the cancer
has spread outside the prostate gland, most
often to the bones and/or lymph nodes. Hormonal
therapy will lead to a favourable
response in the majority of patients. For example,
patients with bone pain usually have relief
within days or weeks. Such responses can last
anywhere from 6 months to several years,
although the average is 24 months.
Hormonal therapy may also be used in patients
with earlier stages of disease. For example,
men who are not fit enough because of age or
other medical conditions to tolerate radiation
or surgical treatment may sometimes receive
hormonal therapy even when their cancer has
not spread.
Hormonal therapy may also be used for short
periods of time prior to surgery (radical prostatectomy)
or radiation therapy in order to
decrease the size of the prostate cancer. This is
called "neoadjuvant hormonal therapy". This
may allow the surgeon to remove the tumor
more effectively and completely and would
also decrease the size of the radiation field
required. This approach has shown some positive
results for radiation treatments, but has to
be studied for a longer period of time before
being considered standard recommended therapy
before radical prostatectomy. Remember
that even though the prostate-specific antigen
(PSA) level might become very low after this
hormonal treatment, the cancer has not necessarily
disappeared, and surgery or radiation
must still be carried out.
Finally, hormones are often started when other
forms of treatment are not successful.
Does hormonal therapy cure prostate cancer?
Hormonal therapy is an effective means of
controlling, not curing prostate cancer. For
many men, hormonal therapy offers years of
good quality of life. In some cases, the cancer
is particularly aggressive or not dependent on
testosterone for growth or the cancer may only
show a transient and partial response (fortunately
these are the minority). Your physician
cannot predict whether or not, nor for how
long, you will respond to hormonal therapy. If
you are a candidate for treatment, try it and if it
works, you will have your answer.
Are there side effects from hormonal therapy?
A fter removal of testosterone, it is not unusual
for a man to have symptoms similar to female
menopause, such as hot flashes. Should these
symptoms be serious enough to affect quality
of life, there are medications available which
control these side effects. Men often notice a
sharp decline in sexual desire (libido) and frequently
become impotent (unable to obtain an
erection). However, they do not usually notice
any significant change in other "maleness"
characteristics such as hair patterns and voice.
Depending upon the drugs which are used,
there may be other side effects such as breast
tenderness or swelling. You will be made
aware of the potential side effects by your doctor.
What types of hormonal therapy are available?
Testosterone can be reduced to very low levels
by removing the testicles surgically (surgical
castration). Alternatively, certain drugs called
LHRH agonists can prevent the testicles from
producing testosterone (medical castration).
Finally, other drugs can be used which work
within the prostate cancer cells and block the
action of testosterone and other androgens.
These drugs are called antiandrogens.
What is surgical castration?
Surgical castration (orchidectomy or orchiectomy)
is the standard against which all forms
of hormonal treatments are compared. Testosterone
in the blood drops rapidly to very low
levels and will remain there without having to
take pills or injections. The operation to
remove the testicles is quite straight forward
and well tolerated. It can be done under a local
anesthetic, spinal anesthetic or general anesthetic.
The operation is performed through a
small incision in the scrotum and the testicles
removed. When the scrotum is healed, the
space where the testicles had been shrinks
somewhat and the individual may feel small
lumps which are actually scars at the end of the
cut spermatic cords. Surgical castration has
very few complications. Postoperative pain,
swelling or bleeding is usually minimal. Infection
in the incision can occur, as with any type
of surgery, but responds to antibiotics. After
routine surgical castration, most patients go
home the same day, or the next day, and can
resume most activities within 2-3 weeks.
Are there alternatives to surgical castration?
Some men find the concept of surgical castration
difficult to accept. There are however,
good alternatives available. These alternatives
to surgery are known as medical castration.
These include drugs called
LHRH agonists
which are usually given by injection and which
stop the production of testosterone by the testicles.
Another alternative is the use of drugs
called
antiandrogens
, which are usually taken
by mouth and which block the action of testosterone.
What are LHRH agonists?
LHRH agonists prevent the testicles from producing
testosterone. These include leuprolide,
goserelin, and buserelin. Originally, these
drugs had to be administered by daily injection,
but now they are available in a depot form
that can be injected into the muscle or under
the skin either once a month or every three
months.
LHRH agonists prevent release of LH, and testosterone
levels fall (i.e., medical castration). Surgical castration
removes the source of testosterone. Antiandrogens
block the effects of androgens within the prostate and
some also work within the brain to prevent the release of
LH and therefore testosterone.
When treatment is first started, there is a transient
rise in serum testosterone which may
cause a transient worsening of the disease.
This testosterone surge or "flare" may be
blocked by administering an antiandrogen, at
least for the first month or two of therapy. The
side effects of LHRH agonists are identical to
those of surgical castration, i.e., decreased
libido, impotence and hot flashes. The advantage
of LHRH agonists is that there is no Surgery.
The disadvantage is that they must be
given continually for the rest of one's life and
are expensive.
What are antiandrogens?
Antiandrogens are drugs that block the effect
of testosterone on prostate cancer cells. One
type of antiandrogen is related to the female
sex hormone, progesterone and is usually
referred to as a steroidal antiandrogen. There
are two antiandrogens of this type, megestrol
acetate and cyproterone acetate.
They are taken orally on a daily basis and may
be given along with very low doses of another
female hormone, estrogen, which enhances
their activity. Using these drugs, the effects of
surgical castration can be mimicked quite
closely and rapidly. However, these drugs too
have side effects. The most prominent are
impotence and loss of libido, shortness of
breath on exertion, generalized fatigue, depression,
nipple tenderness and slight breast swelling
and a risk, though low, of blood clots and
heart disease.
The second type of antiandrogen acts within
the prostate cancer cells to directly block the
cells' ability to be stimulated by androgens.
These are called non-steroidal antiandrogens.
Examples of drugs in this class are flutamide,
bicalutamide and nilutamide. These drugs are
usually given in combination with other forms
of hormonal therapy such as surgical castration
or a LHRH agonist as they are usually inadequate
if given alone. The main side effects
include breast enlargement, hot flashes, diarrhea,
nausea and vomiting.
What is maximal androgen blockade?
Some have suggested that the combination of
surgical or medical castration with antiandrogen
drugs, known as maximal androgen blockade
(MAB) may be more effective than
castration alone. The rationale is that by adding
antiandrogen, this will block the effect of
the androgens that come from the adrenal
glands. This issue has been studied extensively
in many centres around the world. Although
some investigators have shown some advantage
to MAB, generally the difference has been
small and variable.
What is hormone-resistant prostate cancer?
Hormonal therapy does not cure prostate cancer.
The reasons for this are under investigation.
It is possible that, in the absence of male
sex hormone, some cancer cells die while others
go into a dormant state. The dormant cells,
and perhaps some cancer cells which were
never dependent on serum testosterone, learn
to grow in the absence of testosterone stimulation.
These cells arc known as hormone-resistant
cancer cells. The ideal method of
controlling such cells is not yet known, but is
under intensive investigation.
What is intermittent therapy?
An innovative approach to hormonal therapy
for prostate cancer involves a technique called
intermittent therapy. Intermittent hormonal
therapy or "cycling therapy remains under
investigation at this time. The principle is the
following: Once the patient has been on drug
treatment for 6-8 months, his PSA has stabilized,
and he is without symptoms, the drug is
stopped to allow the serum testosterone level
to return to normal, usually allowing him to
recover sexual function. If all goes well, his
prostate cancer should respond again to repeat
hormonal therapy which would be reinstituted
when the cancer shows signs of reactivation. It
is important to keep in mind that intermittent
therapy is still considered "experimental" and
that only time and ongoing patients studies
will determine how this form of therapy compares
to the more standard approach of continuous
therapy.
Which of these treatments is best?
There is no best treatment. The choice of
which treatment is more suitable for you
depends upon the stage of your disease and
other medical problems. Of course, if the treatment
is to be temporary, i.e., prior to radical
prostatectomy or radiation therapy of the prostate,
then surgical castration would not be an
option.
After reading this booklet, you can discuss the
options with your doctor. He or she will help
you with your decision, but ultimately, the
decision is yours.
Glossary
The following is a list of words and terms that
you may hear during the course of your diagnosis
and treatment. We have customized these
explanations for the purposes of explaining
prostate cancer. We have left some blank space
at the end of our list. You can use it to fill in
words you might hear and don't understand so
that they can be discussed with your doctor.
Adrenal
(AD - REE - NALL): A gland that
sits above each kidney and secretes several
hormones.
Androgen
(ANN - DROW - JEN): A male
hormone.
Antiandrogen
(AN - TEE - ANN - DROW -
JEN): A substance that blocks the action of testosterone.
Benign prostatic hyperplasia
(BEE -
NINE - HI - PER - PLAY - ZEE - AH):
Enlargement of the prostate gland that is a natural
course of aging and is not due to cancerous
growth.
Biopsy
(BYE - OP - SEE): Taking a sample
of tissue from the body in order to examine it
more closely (usually under a microscope).
Bone scan
: A technique that allows doctors
to see the bones in much detail. A bone scan is
more sensitive in detecting abnormal bone
activity than is an X-ray. You are given an
injection that makes all of your bones appear
illuminated on the black background. It is usually
painless and gives your doctor much information.
Once you begin treatment for your
prostate cancer, your doctor may send you for
repeated bone scans.
Cancer
(CAN - SIR): The growth of cells at
an abnormal rate.
Computed Tomography Scan
(CAT
scan or CT scan): An imaging technique that
allows doctors to view organs on the inside of
your body. A CT scan takes images in crosssectional
planes through the body with painless
X-rays. By using many different planes
and different directions, the desired structures
can be viewed.
Hormone
(HOAR - MOAN): Chemicals in
the body that control growth, reproduction,
sexual characteristics, and metabolism. They
are carried to various places in the body in the
blood.
Imaging
(IMM - A - JING): Techniques that
allow the visualization of structures inside the
body.
Impotence
(IMM - PO - TENSE): The
inability to have an erection.
Lymph
(LIMF): A body fluid that is like
blood, but contains no red blood cells. It carries
white blood cells to body tissues, and carries
away waste. It moves through the body in
lymph vessels.
Lymph nodes
(LIMF - NO - DS): Small
structures that are connected by lymph vessels
and act as filters.
Lymph vessels
(LIMIT - VESS - ELS):
Like blood vessels (veins and arteries) carry
blood, so too do lymph vessels carry lymph.
Magnetic Resonance Imaging Scan
(MRI Scan): An imaging technique that allows
doctors to view organs on the inside of your
body. This technique uses a magnetic field that
is formed within a cylindrical hollow tube.
Metastasis
(ME - TA - STAY - SIS): The
medical term for the spread of cancer from the
site where it began to other parts of the body.
Oncology
(ON - CALL - 0 - GEE): The
study of cancer. An oncologist is a doctor who
specializes in the study of cancer.
Orchidectomy
(OR - KID - ECK - TO -
ME): Removal of one or both testicles. Same
as orchiectomy.
Orchiectomy
(OR - KEY - ECK - TO -
ME): Removal of one or both testicles. Same
as orchidectomy.
Pathology
(PATH - ALL - 0 - GEE): The
study of body tissues. Biopsies are usually sent
to pathology to be studied by a pathologist. A
pathologist is a doctor who specializes in the
study of samples of tissues.
Prognosis
(PROG - NO - SIS): An estimate
of whether the prostate cancer will be cured,
stay the same, or recur in the future.
Prostatectomy
(PROS - TA - TECK - TO -
ME): Surgery to remove part or all of the prostate
gland. Simple, radical, and nerve sparing
surgeries can be performed.
Prostate gland
(PROS - TATE gland often
incorrectly pronounced as PROS - TRAY -
TE): A chestnut-shaped structure that surrounds
the urethra. It produces components of
seminal fluid.
PSA
: An abbreviation for prostatespecific
antigen. This is a protein made solely by the
prostate gland.
PSA levels
: A PSA test measures the amount
of a protein, made only by the prostate, that
circulates in the blood. Both benign and malignant
prostate cells produce PSA.
Radiation therapy
(RAY - DEE - AY -
SHUN therapy): A form of energy that passes
into the body through a beam. It kills cancer
tissue, but may also damage healthy tissue.
Rectal examination
(RECK - TUL examination):
An examination that involves inserting
a finger into the rectum in order to feel the size
and shape of the prostate gland.
Stages of cancer
: Names to describe the
extent of cancer. The stages describe whether
the disease is limited to the prostate, extends
beyond the confines of the gland, or whether it
has metastasized.
Ultrasound
(ULL - TRA - SOUND): An
imaging technique that allows doctors to view
organs on the inside of your body. The process
of ultrasonography allows for the location,
measurement or delineation of deep structures
by measuring the reflection or transmission of
ultrasonic waves. These waves pass painlessly
through the body and yield an image on a monitor.
Urethra
(YER - EE - THRA): The tube that
urine passes through when it exits the body.
The prostate gland surrounds it.
Urinary incontinence
(IN - CON - TIN -
ENS): Weak or no bladder control at all.
Urology
(YER - ALL - 0 - GEE): The study
of the urinary and the male reproductive system.
A urologist is a doctor who specializes in
diseases of the male and female urinary system
and the male reproductive system.
Answers to quiz: 1a; 2e; 3b; 4b; 5a; 6a; 7d.
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