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PROGESTERONE FOR PROSTATE HEALTH

By James South, M.A.

For middle-aged and older men, especially those over age 50, prostate problems are an unpleasant fact of life. It is estimated that half of men in the 50-plus age group suffer from benign prostatic hyperplasia (BPH), an abnormal enlargement of the prostate gland.1
This swelling of the prostate usually manifests as urinary problems: urinary frequency, urinary hesitation, reduced urinary flow, etc. The prostate gland is also the most common site for cancer to develop, with over 300,000 new cases in the U.S. in 1996.1 The medical establishment places the blame for these prostate problems on the male hormones testosterone (T) and dihydrotestosterone (DHT), yet this belief generates an obvious paradox. The highest levels of T/DHT occur in young men, and T/DHT levels drop with aging. Yet prostate problems are almost non-existent in young men, while they increase with age, affecting 90 percent of all men by age 85, when T/DHT levels are extremely low.2


The Estrogen Connection

An important determinant of male hormonal health is the testosterone/estrogen balance (T/E). Healthy male physiology depends on a high T:E ratio. Although testosterone is the “male hormone,” men naturally produce small amounts of estrogen from testosterone.3 With aging, the T:E ratio drops, often dramatically. An enzyme called “aromatase,” especially prevalent in fat cells, converts testosterone to estrogen.4 Since most men lose muscle and gain fat as they age, aromatase activity increases, reducing testosterone even as it increases estrogen. Many scientists have commented on the importance of estrogen and the T:E ratio in promoting prostate problems. M. Krieg and colleagues note “…numerous experiments indicate that estrogens might also be involved in the abnormal growth of the human prostate.”5 “The data in this communication show a clear-cut, direct biochemical effect of estrogens on the human prostate and provide a cellular mechanism by which estrogens may affect prostatic physiology [negatively].”2
In a review on benign prostatic hyperplasia (BPH) and estrogen, W. Farnsworth reports that “…the induction of BPH is shown to be determined by the androgen [T+DHT]/estrogen ratio….”6 S. Boehm and coworkers conclude that “… estrogen suppression may be considered an efficient pharmacotherapeutic strategy in the medical treatment of uncomplicated benign prostatic hyperplasia.”7


Progesterone to the Rescue

Most people think of progesterone as a “female hormone.” Yet men normally produce progesterone as well, in both their adrenal and testicular tissue.8 Unfortunately, male progesterone levels drop with aging, just as do male testosterone levels.4 Severe, prolonged stress also depletes progesterone, since the “state-of-siege” stress hormone cortisol is made from progesterone, as are testosterone, estrogen, aldosterone and other steroid hormones.8
And as researcher Ray Peat emphasizes, one of the most important roles for progesterone is to oppose the many toxic effects of excess estrogen.9 Progesterone expert Dr. John Lee noted multiple roles for progesterone in antagonizing estrogen and promoting prostate health.
Progesterone inhibits the conversion of testosterone to DHT.4 DHT is a weaker androgen than testosterone, and thus lowers the androgen/estrogen ratio in favor of estrogen. In addition, DHT is a far more potent stimulant of prostate cell growth than testosterone.4  Both testosterone and progesterone stimulate the activity of a protective gene called “p53.”4 The products of this gene activation are anti-cancer, and promote healthy apoptosis.10 Apoptosis is a “programmed cell suicide” that plays a key role in preventing cellular overgrowth (e.g., BPH) and cancer.10 Estrogen, on the other hand, activates a gene called “bcl2.”4 Bcl2 products inhibit healthy apoptosis.10
Progesterone may even help with prostate cancer. V. Petrow et al reported results of their study with rats and prostate cancer in 1984. “Growth of the Dunning R 3327-H prostatic adenocarcinoma, implanted in the rat, is inhibited by 6-methylene progesterone. This compound is a potent inhibitor of rat prostatic 5-alpha-reductase [as is progesterone; 5-alpha-reductase is the enzyme that converts testosterone to DHT] and in-vivo produced marked involution [shrinkage] of the prostate. Thus, this tumor requires dihydrotestosterone and not testosterone for growth.”11 Andrews and colleagues also
note: “Another steroid hormone that interacts with the androgen receptor in LNCaP [prostate cancer] cells (progesterone) also promotes apoptosis of these cells.”12


Progesterone for Men

Dr. John Lee has recommended a dose of approximately 4 to 6 mg once or twice daily for men in their late forties or older.4,13 Approximately 6 mg can be achieved with one-eighth level teaspoon of a cream containing 900 to 1,000 mg progesterone per 2 ounces. The cream should be rubbed onto thin skin areas such as inner forearm, chest, neck or scrotum morning and/or evening. Do not exceed the recommended dose.
Progesterone therapy is especially relevant for obese men; those with a family history of prostate cancer; those with proven low androgen/low progesterone/high estrogen levels. Progesterone may reduce fertility in men, and it is to be avoided by men with nonalcoholic liver cirrhosis.
References
1. Wright, J. and Lenard, L. Maximize Your Vitality and Potency, Petaluma, CA: SMART Publications™, 1999: 158.
2. Nakhla, A. et al. “Estradiol causes the rapid accumulation of cAMP in human prostate.” Proc Natl Acad Sci USA 1994, 91: 5402-05.
3. Kutsky, R. Handbook of Vitamins, Minerals and Hormones, NYC: Van Nostrand Reinhold, 1981: 418-19.
4. Lee, J. “Prostate disease and hormones.” The John R. Lee, M.D. Medical Letter Feb. 2002.
5. Krieg, M. et al. “Effect of aging on endogenous level of 5 a-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate.” J Clin Endocrinol Metab 1993, 77: 375-81.
6. Farnsworth, W. “Estrogen in the etiopathogenesis of BPH.” Prostate, 1999, 41: 263-74.
7. Boehm, S. et al. “Estrogen suppression as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia: evidence for its efficacy from studies with mepartricin.” Wien Klin Wochenschr 1998, 110: 817-23.
8. Kutsky, op. cit. 427-28.
9. Peat, R. Progesterone in Orthomolecular Medicine Eugene, OR, 1993: 4-6.
10. Hetts, S. “To die or not to die: an overview of apoptosis and its role in disease.” JAMA 1998, 279: 300-07.
11. Petrow, V. “Endocrine dependence of prostatic cancer upon dihydrotestosterone and not upon testosterone.” J Pharmacol 1984, 36: 352-3.
12. Andrews, P. et al. “Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells.” Cancer Chemother Pharmacol 2002, 49: 179-86.
13. Mercola, J. “Progesterone cream can help prostate cancer.” 1998. www.mercola.com/fcgi/pf/1998/ archive/natural_progesterone2.htm.
14. deLarminat, M. and Blaquier, J. “Effect of in vivo administration of 5 alpha reductase inhibitors on epididymal function.” Acta Physiol Lat Am 1979, 29:1-6.
15. Farthing, M. et al. “Progesterone, prolactin, and gynecomastia in men with liver disease.” Gut 1982, 23: 276-79..

THE JOHN R. LEE, M.D. MEDICAL LETTER (MARCH 2002)

PROSTATE DISEASE AND HORMONES

The solutions are straightforward when you understand the problem

If you know a man over the age of 50 who’s not sleeping well, chances are good it’s because he’s got prostate problems that require visits to the bathroom a couple of times a night. It’s estimated that benign prostate disease affects over 40 percent of American men by age 50 and over 70 percent by age 60. The most common symptom is trouble with urination. Such men may have urinary frequency (hence getting up at night), their urine flow may be decreased in force or rate, they may have urinary urgency, and they may feel that they haven’t emptied the bladder (a sign of urinary retention), especially after drinking coffee. Urinary retention also makes them more susceptible to urinary tract infections.

When such men consult with their doctor, he will usually examine the prostate gland through the rectum (a digital exam) and diagnose the problem as BPH, an acronym meaning benign prostate hypertrophy (enlarged cells in the prostate gland) or hyperplasia (enlarged by an increase in the number of cells in the gland). The two meanings of BPH are used interchangeably. BPH, like most conditions, varies in how it manifests itself. In some men, the obstruction of urine flow is due to prostate tissue overgrowth and the gland will be definitely enlarged. In others, however, the obstruction is due to smooth muscle contraction of the urinary sphincters in the prostate gland, causing the same urinary problems without much prostate enlargement. In some men, the problem is mixed.

Conventional Medicines for the Prostate

The doctor may prescribe the drug terazosin (Hytrin) to relax urinary sphincter muscles, or the drug finasteride (Proscar) which inhibits the enzyme 5 alpha reductase, which converts testosterone into dihydrotestosterone (DHT, a compound believed to stimulate prostate cell growth, or hyperplasia). Or, he may recommend transurethral resection of the prostate (TURP), the surgical coring out of the urine passageway through the prostate, quite often resulting in undesirable dribbling problems.

The success rate of the two drugs listed above is not uniform or consistent. Both drugs were tested in an interesting study in the New England Journal of Medicine (NEJM) in 1996. It was found that finasteride (the hyperplasia inhibitor) helped men with considerable prostate gland enlargement, but not those with more normal sized prostate glands. Interestingly, saw palmetto berry and nettle root similarly inhibit 5alpha reductase, and are just as effective as finasteride. Though often beneficial in BPH, neither saw palmetto berry nor finasteride prevent prostate cancer.

Terazosin (the smooth muscle relaxer) helped men with less gland enlargement, but not men with larger prostate glands. None of these treatments recognize the true importance of sex hormones that underlie the cause of BPH.

The Role of Sex Hormones

Conventional medicine is beginning to recognize the true role of sex hormones in prostate disease. For example, like a woman, a man’s body fat will convert male hormones into estrogen. Some physicians advocate using aromatase inhibiting drugs (such as Arimidex) that inhibit the conversion of adrenalgenerated androstenedione (a male hormone) into estrone (an estrogen) in body fat. Estrone is then available to be converted to estradiol. The rationale for this treatment is the understanding that estrogen is a growth stimulating hormone in prostate tissue. This leads us to the hypothesis that the balance of estradiol to progesterone and/or to testosterone is an important factor in prostate disease.

As men age, prostate levels of estradiol gradually rise, and levels of progesterone and testosterone decline. The decline in testosterone and progesterone levels is greater than the rise of estradiol. The ratio of testosterone to estradiol MEA for instance, is dramatically lower in men over 60 than it is at age 40. Studies in the U.S., Germany and Japan have reached similar conclusions: not only is the T/E2 ratio lower in men after age 40, but also those men with the lowest T/E2 ratio are the ones most likely to develop BPH. Conventional medicine, stuck in the outdated and unfounded paradigm that claims testosterone is dangerous, opts to attack and destroy estrogen production rather than supplement testosterone in their effort to raise the T/E2 ratio and protect men against prostate disease. Why not raise the low testosterone levels by supplementing physiological doses of testosterone to restore the ratio of T/E2 to that of younger men? There is no evidence that the high levels of testosterone in young men puts them at any risk of BPH. Or of prostate cancer, for that matter.

Progesterone’s Role

Progesterone plays several roles in the protection against prostate disease. Progesterone, like finasteride and saw the conversion of testosterone to DHT. In this manner, progesterone helps raise testosterone levels, and helps lower the level of the more growth stimulating DHT. Progesterone, like testosterone, is an anabolic hormone, meaning that it helps burn fat for energy. Thus, it helps keep men from becoming obese. With less body fat, there is less endogenous (within the body) estrone production. Further, both progesterone and testosterone stimulate gene p53, the product of which protects us from the oncogene (cancer causing) Bcl 2, and stimulates healthy apoptosis (normal cell death). Estradiol, on the other hand, stimulates Bcl 2 production, which increases the risk of cancer. These are all good reasons to restore the same progesterone and testosterone levels that younger men have.

Restoring Hormone Balance

Restoring proper hormone levels is not difficult. The best place to begin is with a saliva hormone test, so that you have clinical evidence of a hormone imbalance. Saliva hormone testing reflects the total blood levels of non protein bound (“free”) sex hormones. The free hormone is bioavailable and filters into saliva, whereas the protein bound (non bioavailable) hormones do not. Conventional blood serum tests of estradiol, for example, are essentially irrelevant since they do not distinguish between free and protein bound estradiol. I usually recommend ZRT Lab in Oregon; you can order a kit through their Web site www.salivatest. com, or you can call them at (503) 466 2445. You do not need a doctor’s prescription to get a saliva hormone test, although I do recommend that you work with a qualified health professional to help interpret the results.

The ratio of saliva progesterone to estradiol in healthy young men is usually greater than 200: 1. Similarly, the ratio of saliva testosterone to estradiol is also about 200 to 300: 1. These ratios can be used as a guideline for the transdermal supplementation of progesterone and testosterone in older men with E2 dominance and low P/E2 and T/E2 ratios. From experience, we have found that just 6 to 8 mg per day of progesterone (in a cream) will raise low saliva progesterone levels to normal healthy levels. In a two ounce jar or tube of cream containing 960 mg of progesterone, this would be a bit less than 1/8 tsp of cream daily, and it would last for about 140 days, or about four and a half months.

Testosterone, being a stronger hormone, usually requires just I to 2 mg per day by transdermal cream to raise low levels to healthy normal levels. Creams with the proper testosterone content are not readily available, so a patient with BPH should ask his doctor to write a prescription for the cream, then take it to a compounding pharmacist. It is essential that the pharmacist use real testosterone, and not one of the synthetic versions such as methyltestosterone.

I have seen remarkable benefits and no side effects in men who use hormones this way. The low doses used attest to the excellent absorption of these hormones when applied transdermally. As an interesting aside, in a recent study of women with low free testosterone levels (in women after removal of their ovaries), the researchers found that the optimal dose of transdermal testosterone for them was just 0.25 mg per day.

Defense Against Prostate Cancer

Research has shown that BPH is not a risk factor for prostate cancer. Nevertheless, defense against prostate cancer follows the same precepts. Men with aggressive prostate cancer have higher numbers of progesterone receptors (PRs), relative to men with less aggressive cancer. This does not mean that progesterone increases the aggressiveness of prostate cancer. Progesterone receptors are made only by estrogen. An increase of PRs in prostate tissue is a sign of estradiol dominance (relative progesterone deficiency). In other studies it is found that prostate cancer incidence is greater in men with lower T/E2 ratios (lower testosterone and higher E2 levels) than in men with higher T/E2 ratios.

Conventional medicine’s fear of testosterone is unfounded. In clinics that routinely treat men with even higher doses of testosterone, the incidence of prostate cancer is usually less than in men without supplemental testosterone. While it is true that, in 19 4 1, Dr. Huggins claimed to have demonstrated that castration (removal of testes) in men with prostate cancer delayed death (a bit) from their cancer, it does not mean that testosterone reduction was the cause of this observed benefit. Dr. Huggins forgot that the testes also supply estrogen. It is far more likely that the estrogen reduction was the source of the benefit. Since that time, it is now clear that total androgen blockade does not enhance longevity compared to men without total androgen blockade. It is time to recognize that progesterone and testosterone are important hormones in men, and that normal physiological levels of these hormones do not increase the risk of prostate cancer but, on the other hand, may help prevent prostate cancer.

Some research indicates that BPH and prostate cancer correlate with higher levels of sex hormone binding globulin (SHBG). As a result, some have hypothesized that SHBG may play a role in the cause of BPH and of prostate cancer. SHBG is the binding hormone for estradiol. Excessive levels of estradiol activate the liver to make more SHBG. Thus, it is likely that the elevated SHBG is merely a marker for excessive estradiol. Observations are one thing, but the conclusions that one draws from them are quite something else. Conclusions often follow underlying assumptions that may be erroneous, and are subject to observer bias.

Xenoestrogen (petrochemical toxins often used as pesticides, etc.) exposure during embryo life may damage gonadal and prostate tissue, making these tissues more susceptible to carcinogens later in life. Although one can’t change these circumstances, one can take preventive steps to reduce estrogen levels and maintain hormone balance. Our new book, What Your Doctor May Not Tell You About Breast Cancer, goes into some detail about how to avoid xenoestrogens.

Some Non Drug Treatments for BPH

Certain botanicals have been found to be of benefit in treating prostate disease though their mechanisms of action are still unclear. These botanicals, and a few others like them, deserve further research. Many products for the prostate found at health food stores contain various combinations of these ingredients.

” ” Saw Palmetto berry extract, according to Jonathan Wright, M.D., not only inhibits 5alpha reductase but also blocks DHT binding to prostatic androgen receptors, reduces prostatic edema (swelling), inhibits estradiol and antagonizes alpha adrenergic receptors.
” ” Nettle root (may inhibit aromatase, reducing conversion of androgens to estrogen).
” ” Antioxidants, such as vitamin E, lycopene (found in cooked tomatoes), and vitan An C.
” ” Polyphenols (e.g., catechins, found in green tea.)
” ” Ellagic acid (found in nuts and raspberries) may trigger beneficial apoptosis.
” ” Zinc (low zinc levels correlate with increased prostate disease). Be sure to get extra copper if you’re taking zinc for longer than a few weeks.