Estrogens in the Treatment of Advanced Prostate Cancer
Introduction | DES in treatment of advanced prostate cancer | The use of other estrogens
The administration of estrogens (female hormones) to a man has a series
of complex effects on that man's hormonal system. One is an effect on
the hypothalamus which reduces release of luteinizing hormone releasing
hormone (LHRH), with a consequent suppression of production of
luteinizing hormone (LH). Suppression of LH production has the resulting
effect of suppressing production of testosterone. An appropriate dose of
estrogens can reduce a man's testosterone to castrate levels; in other
words, it will have the same effect as a surgical orchiectomy. Although
a whole series of different estrogens can be used to induce this effect,
the compound most commonly used in diethylstilbestrol (DES).
DES in treatment of advanced prostate cancer
Worldwide, DES is still one of the most commonly used agents for the
hormonal treatment of advanced prostate cancer for one reason if no
other -- it is very low in price. The critical disadvantage of this
pharmaceutical is that it has been associated with a relatively high
risk for cardiovascular side effects at higher dosages. These severe
side effects can include death due to induction of cardiovascular
problems, including heart attacks, strokes, and pulmonary embolisms.
Specialists in the treatment of prostate cancer would now be very
careful to avoid the use of DES in patients who were already at any risk
of heart or circulatory disorders. As a consequence, DES is now clearly
contraindicated for patients with any signs of cardiovascular disorder.
However, even in the US, a small number of physicians continue to treat
carefully selected patients who have advanced prostate cancer but no
signs of cardiovascular disease with 1, 2, or 3 mg of DES per day.
Doses of less than 1 mg/d DES do not appear to have any appreciable
effect on testosterone levels and are now considered to be ineffective.
For some patients, but not others, doses of 1 mg/d can lower
testosterone levels to castrate levels. It is for this reason that
different patients may require doses of DES that are higher than 1
Apart from the cardiovascular risks, the other common side effects of
DES include loss of libido, impotence, gynecomastia, fluid retention,
and hot flashes.
The use of other estrogens
Because of the cardiovascular side effects of DES, there have been many
attempts over the years to find other estrogens which would have a
similar impact on testosterone levels but without the risks associated
with DES therapy. Unfortunately, these attempts have all proven
unsuccessful so far.