Post by Allen on Jul 29, 2014 22:21:44 GMT -8
SERMs (Selective Estrogen Receptor Modulators)
The role of estrogen and estrogen receptors in prostate cancer is very complex. Estrogen is an old therapy and is sometimes still used as a second-line therapy because it acts in the brain to inhibit the production of androgens, called negative feedback. However, estrogen receptor beta (ERβ) is highly expressed in prostate cells, and when activated, it seems to have anti-proliferative properties. ERα may have an opposite effect, so the trick is to activate ERβ without activating ERα, hence the selective ER modulators. The estrogen story is even more complex: a person may have damaged estrogen receptors that are unresponsive to ERβ stimulation, or the receptors may disappear -- estrogen receptors diminish as the cancer progresses (the opposite of the androgen receptor). Therefore, it makes sense to use this earlier rather than later in the progression.
Gamma and delta-tocotrienols are thought to enhance ERβ activity. It is available as a pure annatto extract from health food stores and on the internet. It’s important not to try to obtain it from other mixed Vitamin E extracts – even small amounts of alpha-tocopherol seem to suppress absorption of tocotrienols.
Clomiphene is a relatively cheap and effective SERM that may be worth trying. It selectively blocks ERα. Also, soy isoflavones stimulate ERβ, so taking the two together may be a good one-two punch.
(I'll address tocotrienols and soy isoflavones in a thread on supplements.)
I should add about clomiphene that it would not make sense to take it while on Lupron, and could be dangerous with it. Clomiphene blocks the ERα receptor, which in turn controls the negative feedback between steroids and GnRH in the brain. Therefore taking Clomiphene with a GnRH agonist (like Lupron) may cause a runaway super-flare of testosterone production. It should work fine, however, with a GnRH antagonist like Firmagon, or with Casodex plus a 5-ARI.
There is a drug in clinical trials now called Capesaris that could potentially be used instead of Lupron. It does the opposite of what clomiphene does in the brain -- it is ERα receptor agonist. (See Capesaris thread)
Here are some references:
• Estrogen action and prostate cancer and summary table
• Current concepts and significance of estrogen receptor β in prostate cancer.
Safety:
• Estrogen (e.g., DES, estradiol, etc.), taken as pills, has been used for many years for PC. It’s side effects may include blood clots, stroke, liver toxicity, gynecomastia, and fat accumulation. The new patches and skin creams reduce the levels of side effects.
• Tocotrienols seem to be quite safe. It is thought that one reason for the increase in PC with Vitamin E is because it blocks absorption of tocotrienols.
• Clomiphene (Clomid) has been used for many years as a fertility drug in women, and, off-label, to increase sperm production in men. Unless there is hepatic impairment, it seems to be safe.
The role of estrogen and estrogen receptors in prostate cancer is very complex. Estrogen is an old therapy and is sometimes still used as a second-line therapy because it acts in the brain to inhibit the production of androgens, called negative feedback. However, estrogen receptor beta (ERβ) is highly expressed in prostate cells, and when activated, it seems to have anti-proliferative properties. ERα may have an opposite effect, so the trick is to activate ERβ without activating ERα, hence the selective ER modulators. The estrogen story is even more complex: a person may have damaged estrogen receptors that are unresponsive to ERβ stimulation, or the receptors may disappear -- estrogen receptors diminish as the cancer progresses (the opposite of the androgen receptor). Therefore, it makes sense to use this earlier rather than later in the progression.
Gamma and delta-tocotrienols are thought to enhance ERβ activity. It is available as a pure annatto extract from health food stores and on the internet. It’s important not to try to obtain it from other mixed Vitamin E extracts – even small amounts of alpha-tocopherol seem to suppress absorption of tocotrienols.
Clomiphene is a relatively cheap and effective SERM that may be worth trying. It selectively blocks ERα. Also, soy isoflavones stimulate ERβ, so taking the two together may be a good one-two punch.
(I'll address tocotrienols and soy isoflavones in a thread on supplements.)
I should add about clomiphene that it would not make sense to take it while on Lupron, and could be dangerous with it. Clomiphene blocks the ERα receptor, which in turn controls the negative feedback between steroids and GnRH in the brain. Therefore taking Clomiphene with a GnRH agonist (like Lupron) may cause a runaway super-flare of testosterone production. It should work fine, however, with a GnRH antagonist like Firmagon, or with Casodex plus a 5-ARI.
There is a drug in clinical trials now called Capesaris that could potentially be used instead of Lupron. It does the opposite of what clomiphene does in the brain -- it is ERα receptor agonist. (See Capesaris thread)
Here are some references:
• Estrogen action and prostate cancer and summary table
• Current concepts and significance of estrogen receptor β in prostate cancer.
Safety:
• Estrogen (e.g., DES, estradiol, etc.), taken as pills, has been used for many years for PC. It’s side effects may include blood clots, stroke, liver toxicity, gynecomastia, and fat accumulation. The new patches and skin creams reduce the levels of side effects.
• Tocotrienols seem to be quite safe. It is thought that one reason for the increase in PC with Vitamin E is because it blocks absorption of tocotrienols.
• Clomiphene (Clomid) has been used for many years as a fertility drug in women, and, off-label, to increase sperm production in men. Unless there is hepatic impairment, it seems to be safe.