Andropause is also referred to as male menopause and has been the subject of increasing attention in the past few years in the medical community and media. Through several proposed mechanisms, aging men suffer from the dual effects of having too little testosterone and excess estrogen (estradiol). Aging men sometimes convert testosterone to estrogen. Testosterone receptor sites in cells throughout the body then take up the estrogen. When an estrogen molecule occupies a testosterone receptor site on a cell membrane, it blocks the ability of serum testosterone to induce a healthy hormonal signal. It does not matter how much serum free testosterone is available if excess estrogen is competing for the same site.
Testosterone is much more than a sex hormone. Other receptor sites of testosterone are the brain and heart. Testosterone improves oxygen uptake throughout the body, helps control blood sugar, regulate cholesterol and maintain immune function. The body requires testosterone to maintain youthful cardiac output and neurological function. Men suffering from depression often have lower levels of testosterone than control subjects.
Testosterone levels decline gradually in men, starting from approximately age 30, and this decline continues throughout life. On the average, a man’s testosterone levels begin to decline at a rate of about 1% per year after age 40.
SYMPTOMS OF HYPOGONADISM (DECREASED TESTOSTERONE):
ADAM (Androgen Deficiency in the Aging Male) Questionnaire:
Men answering YES to questions 1,7, or a combination of any 3 or more might be candidates for testosterone replacement therapy. Please consult a qualified healthcare practitioner for further testing via blood or saliva (see saliva testing) or urine.
Male hormone therapy has been shown to be dramatically effective in relieving symptoms of andropause and restoring drive, health, potency, and a renewed sense of renewed vitality. The treatment includes careful monitoring of testosterone and estrogens (estradiol), and supplemental therapy so that a healthy balance can be achieved. Remember, an imbalance can occur either because of decreases in testosterone levels, increases in estrogen levels, or a combination of both.
ORAL—This is an inefficient way of dosing because of the high first-pass effect, in which the liver converts most of the testosterone into inactive metabolites. Most researchers and experienced clinicians do not recommend oral dosing because doses as high as 400mg per day may be required to obtain physiologic levels. Note: methyltestosterone has greater bioavailability by the oral route, but is not preferred because of its adverse side effect profile and potential harm to the liver.
INTRAMUSCULAR INJECTION—This is probably the most common form of dosing, but it has a serious drawback in its uncontrolled release. Many men will experience high testosterone levels in the first week (typically dosed at 2 or 3-week intervals), with noticeable declining effects beyond that. Also, there is more possibility of increasing conversion to Estradiol as the body cannot properly store the excess. Instead of reaching a more positive testosterone-estrogen ratio, the opposite effect sometimes occurs with gynecomastia as an occasional outcome, as well as potential testicular shrinkage and thicker blood, which can decrease blood flow to the penis.
SUBLINGUAL OR BUCCAL—Given this way, testosterone is best given in 3-4 doses daily. Effective sublingual doses can range from 10-40mg per day. This must be done in a consistent daily dosage, not as needed and most men will find the multi dosing cumbersome and difficult to be compliant.
IMPLANTABLE PELLETS—This is an office procedure that is relatively simple and offers a major compliance advantage: effectiveness can last from 3-5 months from a procedure, eliminating the compliance issue.
TOPICAL—Currently, topical application seems to be the most effective way of dosing testosterone-creams, lotions, and gels have been used with good results. There are two good reasons that sex steroid hormones may be applied topically: they are potent, and they are highly lipid soluble. Thus, if 5-10mg of testosterone (out of, for example 150mg applied) penetrates the skin, therapeutic levels are achieved. When using testosterone gel a larger surface area compared with a more concentrated, smaller volume is an important factor in restoring testosterone levels and maintaining them in a consistent manner. Studies have shown that a once-a-day application can be sufficient to elevate and maintain levels.
Note: Since young men only make 4-7 mg/day, 50-100mg may only yield 5-10mg testosterone but the rest may turn into DHT in Estradiol and yield side effects. 14
The choice of application site is quite important. When the gel is applied to the trunk or axillary area, the resulting balance of testosterone, DHT, and estradiol (E2) will be very much in the normal physiologic range. However, if the gel is applied to the scrotum, the level of DHT becomes much higher because the prostate has a much higher level of the enzyme 5-alpha-reductase. DHT then becomes an important androgen player. This might be preferred for a man with higher levels of estradiol, because DHT cannot be converted into estradiol. Although some experts have voiced concern about excess DHT may be linked to increased prostate growth and possible prostatic hypertrophy, practical experience has not supported that theory. The incidence of prostate problems in those who wore scrotal patches was no greater than that in subjects given placebo.* Additional studies have indicated a 15% decrease in the size of the prostate in men treated with pure DHT gels, probably due to inhibition of the normal production of DHT and estradiol (E2) occurring in the prostate itself.** It does appear that DHT acts as a circulating androgen, and it is thought to be more potent than testosterone; however, it is much more tightly bound to SHBG and is therefore less bioavailable.**
*McClure D, Oses R, Ernest ML. Hypogonadal impotence treated by transdermal testosterone.Urology. 1991;37:224-228.
**DeLignieres B. Transdermal dihydrotestosterone treatment of andropause.Ann Med. 1993;25:235-241.
ZINC: The mineral zinc is important in many ways and plays an important role in andropause. It inhibits aromatase, the enzyme that converts testosterone to estradiol. A deficiency of zinc is associated with increased activity of the aromatase system, which results in a higher level of estradiol and a lower level of testosterone. Oral daily doses of 50-100mg of zinc can reduce the estradiol level and increase the level of testosterone until physiologic levels of zinc are restored. 1
VITAMIN C: Deficiencies in vitamin C are also associated with increased aromatase activity; doses of at least 1gm a day can be helpful in treating an elevated level of estrogen.2
CHRYSIN: Chrysin is a naturally occurring bioflavinoid that acts as an aromatase inhibitor. In controlled studies 3, chrysin was found to be similar in potency and effectiveness to a pharmaceutical aromatase inhibitor used clinically to treat patients with an estrogen-dependent carcinoma. Chrysin is poorly absorbed orally, so doses range from 1-3gm/day.4 Transdermally applied chrysin is effective at a much lower dose; the recommended dosage is from 100-300mg/day. In addition, chrysin may produce anti-anxiety effects similar to diazepam but without sedation and muscle relaxation. 5
PROGESTERONE: In men, progesterone has several important roles to play in the metabolism of testosterone, estradiol and DHT. Progesterone is an aromatase inhibitor; it prevents the excess production of estradiol. 6 It also is a 5 alpha reductase competitor that governs the conversion of testosterone to potent dihyrotestosterone(DHT). 7 According to one article, 7 the development of benign prostatic hypertrophy (BPH) occurs when the progesterone level declines as the patient ages, and this causes the levels of estradiol and DHT to increase. The suggested dosage of transdermally applied progesterone ranges from 2-5mg daily for men, and this dose may be applied to the anus for better absorption.
SAW PALMETTO: Saw Palmetto is a naturally occurring nonprescription plant product derived from the berries of Serenoa repens. According to a recently published article 8, saw palmetto may be safely used for BPH, and it causes no adverse effects. In this same article the mechanism of action of saw palmetto is discussed-inhibition of 5-alpha reductase enzyme, adrenergic receptor antagonism, and intraprostatic androgen receptor blockade. A randomized, placebo-controlled trial9 showed that a saw palmetto blend seems to be a safe, highly desirable choice for men with moderately symptomatic BPH. Suggested oral dose=160mg twice a day.
DIM in Men: A principal breakdown product of 13C called DIM helps to maintain the level of free or active T. As we age, our bodies take longer to “clear” the estrogen in our bodies and higher than healthy levels of estrogen are common, especially in men who are obese or who are regular social drinkers. Long term safety has been demonstrated in DIM.
NETTLE ROOT: In Germany, nettle root has been used to treat BPH for years. It is believed to act like saw palmetto in its inhibition of 5-alpha reductase enzyme. 9 Nettle root is also considered helpful because it may displace testosterone from SHBG (sex hormone binding globulin).10 Therefore it may be useful for men who have a physiologic level of total testosterone but a low level of FREE testosterone. Suggested oral dose-240mg/day, and may be combined with saw palmetto in some formulations.
LYCOPENE: This carotenoid gives tomatoes that luscious red color. Studies have consistently shown evidence of the benefit of tomatoes was strongest for cancers of the prostate, lung, and stomach. Dr. Omer Kucuk, MD, professor of medicine and oncology at the Barbara Ann Karmanos Cancer Institute in Detroit, MI, adds clinical support to the epidemiological evidence of health benefits of tomatoes. Dr. Kucuk and colleagues followed 35 men with localized prostate cancer who were scheduled to undergo surgical removal of the prostate. For 3 weeks prior to surgery the study participants were randomly assigned to receive twice daily either 250mg of standardized tomato extract (equal to 15mg Lycopene) or no intervention. Following removal of the prostates, the glands were analyzed to determine whether there were any differences between the 2 study groups. The treated group had smaller tumors, and these were more likely to be confined to the prostate. Levels of serum PSA were found to decline in the Lycopene group but increased in the non-treated group. Also, the tumors showed signs of regression and decreased malignancy. Further research is warranted to establish a link between dietary supplements of natural whole tomato extract and prostate cancer prevention and treatment.13
NOTE: The H. Lee Moffitt Cancer Center in Tampa, Florida is using 15mg Lycopene capsules in their new study #0105 “ A Randomized Pilot Clinical Trial of the Action of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy”. The study is funded by the NCI (National Cancer Institute).
1. Om AS,Chung KW.Dietary zinc deficiency alters 5 alpha reduction and aromatization of testosterone and androgen and estrogen in rat liver. J Nutr 1996; 126:842-848.
2. Shippen,E., Fryer W. The Testosterone Syndrome. New York: M. Evans and Company, Inc; 1998:185-186.
3. Campbell DR, Kurzer MS. Flavinoid inhibition of aromatase enzyme activity in human preadipocytes. J Steroid Biochem Mol Bio 1993; 46:381-388.
4. Walle UK, Galijatovic A, Walle T. Transport of the flavinoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2.Biochem Pharmacol 1999; 58:431-438.
5. Wolfman C, Viola H, Pladini A, et al. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav 1994; 47:1-4.
6. Eckhart P. Invitation for a clinical trial for prostate cancer treatment. Prostate Cancer Hormone Therapy. 1997. Available at: http:// dreckhart.hypermart.net. Accessed January 14,2000.
7. Ling YZ, Li JS, Kato K, et al. Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy,20-oxime and aziridine prenene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase. Bioorg Med Chem 1998; 6:1683-1693.
8. Marks LS, Partin AW, Epstein JI,et al. Effects of saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol 2000; 163:1451-1456.
9. McCaleb RS. The Encyclopedia of Popular Herbs: Your Complete Guide to the Leading Medicinal Plants. Roseville,CA; Prima Pub: 2000.
10. [No author listed] Nettle root inhibits binding of DHT. SmartBodyz Nutrition. 1996. Available at http://www.smartbodyz.com/nettle-3.htm. Accessed Oct. 3,2000.
11. Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst 1997; 89:718-723.
12. Michnovicz JJ, Bradlow HL.Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 1991; 16:59-66.
13. Kucuk, O. “Phase II Randomized Clinical Trial of Lycopene Supplementation before Radical Prostatectomy,” Cancer Epidemiology Biomarkers and Prevention, August 2001.
14. Dr. David Zava, PhD. Research ZRT Labs.
Note: Article used with permission Bruce Biundo, BS Pharm, RPh- Professional Compounding Centers of America, Inc. Houston, Texas-November 2001.