Question: Why are adrenal glands so important to HRPC and the secondary hormonal treatments?
Answer: Other than the testicles, the human body makes androgens or male hormones in the adrenal glands (one of which sits on top of each kidney). The actual metabolic products that come from the adrenal gland hormones are known as “adrenal androgens,” or “androgen building blocks,” or “precursors” because they are used to make testosterone. Adrenal gland androgens include dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione. They all have the potential to continue to stimulate prostate cancer growth. Even if a patient has castrate levels of testosterone, it is known that adrenal gland androgens can at least weakly stimulate the androgen receptor (AR).
Thus, dietary supplements that should NOT be used when taking a secondary hormonal therapy include DHEA, DHEA-S, Tribulus Terrestis (which may have some DHEA-resembling compound in it), androstenedione, or any other supplement that claims to increase male hormone (testosterone) levels. Androstenedione is no longer sold over the counter, but there are still ways it can be obtained.
The problem with these supplements or compounds is that they can offset the impact of some of the secondary hormonal therapies as the treatments work better when the body has lower levels of these compounds. For example, new studies have shown better responses to anti-androgen drugs in individuals with lower DHEA blood levels. Therefore, be watchful for those compounds in supplements, and be sure always to check with your physician before taking a supplement.
CORTICOSTEROIDS
Corticosteroids are not considered to be true “secondary hormonal treatments” like the other drugs listed in this chapter. However, they are often given in conjunction with these drugs as well as a number of other HRPC treatments, so some information is being offered on them here.
Also known as glucocorticoids (generally); examples include: dexamethasone, hydrocortisone, prednisone, prednisolone, and methylprednisolone.
How is it taken? Usually as a pill, but can also be given by injection or intravenously (IV).
Dosage There is a variety of drugs and doses. It is not unusual to see patients taking 30 to 40 mg of hydrocortisone, or 10 mg or less of prednisone, or less than 1 mg of dexamethasone. Doctors are careful about the potency of these drugs.
Steroid Medication Review
Hydrocortisone—least potent
Prednisone—4 times more potent than hydrocortisone
Prednisolone—5 times more potent than hydrocortisone
Methylprednisolone—5 times more potent than hydrocortisone
Dexamethasone—most potent, 30 times more than hydrocortisone
Advantages These drugs are simple to take and have a good safety record.
The catch These drugs serve largely to reduce the side effects of some secondary hormonal drugs (ketoconazole or abiraterone) and chemotherapy drugs. They also suppress the immune system.
What else do I need to know? These medications have at least some anti-prostate cancer effect, probably by lowering adrenal androgen production. They have not received a lot of attention compared to the other secondary hormone therapies because they do not appear to be as effective or have an impact that lasts as long as the other therapies. Regardless, it is important to know that they at least have some impact. There does not seem to be an advantage to using one specific corticosteroid drug or dosage as compared to another, but check with your doctor on the latest research.
ESTROGEN
Also known as DES, estradiol, or by multiple generic names.
How is it taken? pill, patch, or injection.
Dosage Various doses based on the drug and situation.
Advantage Usually inexpensive, and it also has a role in reducing hot flashes and preventing bone loss in very small dosages.
The catch It increases the risk of several cardiovascular problems, particularly blood clots, so the drug is usually given with a prescription blood thinner. It also can cause breast pain and enlargement and fluid retention. The higher the dosage, the higher the risk of serious side effects.
What else do I need to know? The “female” hormone estrogen has been used for more than 50 years to treat prostate cancer. In some countries, it is still used to lower testosterone levels and function as an androgen deprivation treatment (ADT) instead of LHRH therapy. However, in most countries, LHRH drugs replaced estrogen many years ago because estrogen has serious cardiovascular toxicity (blood clots, edema, high blood pressure) in higher doses, especially as an oral drug.
Some doctors still use estrogen for two purposes in treating prostate cancer. First, as mentioned above, it can be used to treat side effects of ADT, such as hot flashes, bone loss, and perhaps even cognitive changes. Secondly, research has shown that estrogen can reduce adrenal androgens, and it also may directly kill some HRPC cells. Lower doses of estrogen seem to cause fewer side effects, and there are now several drugs to reduce these side effects if they still occur. For example, there are blood pressure medications, diuretic drugs, and blood thinners that can reduce the risk of most of estrogen’s side effects.
Newer delivery systems make it easier for some patients to use estrogen, and they may also reduce side effects. For example, some patients use an estrogen patch (estradiol transdermal patch) to reduce hot flashes. The patch appears to reduce the risk of blood clots by bypassing the liver’s ability to increase the clotting production that usually occurs when exposed to oral estrogen.
However, overall, the oral form of estrogen is still very popular as a secondary hormone treatment. One of the most popular is diethylstilbestrol or DES. This drug is quite inexpensive and is prescribed in a range of doses (less than 1 mg to 2 or 3 mg/day). Most doctors prefer patients to be on a prescription blood thinner, such as Coumadin (warfarin), to counteract the blood clotting concerns.
Other notable side effects of estrogen are breast pain (mastalgia) and breast enlargement (gynecomastia). These conditions can mostly be prevented by taking an oral (pill) dose of tamoxifen daily, or more simply by getting a dose of radiation to each breast (just once, taking seconds). Some studies suggest that oral tamoxifen daily is a little more effective at preventing breast pain and enlargement as compared to radiation, but radiation works with just a single treatment. Regardless, there are many issues to consider if you and your doctor decide that estrogen is an option for you in preventing ADT side effects or as a secondary hormonal treatment.
There are also other estrogen-derived treatments that you may hear about, and they are just as effective as DES for cancer treatment or for treating side effects. Several common ones are listed below:
• EMCYT (pill, also known as estramustine phosphate)
• Ethinyl estradiol (pill)
• Estradurin (injectable, also known as polyestradiol phosphate)
• Fosfestrol (pill)
• Vivelle-Dot and others (patch)
FIVE-ALPHA REDUCTASE INHIBITORS (5AR INHIBITORS)
Also known as 5AR inhibitors, finasteride, and dutasteride (brand name Avodart).
How is it taken? pill.
Dosage A single pill, taken daily. There are two options, namely finasteride (dosage 5 mg per day) and dutasteride (dosage 0.5 mg