Analog SFF, December 2005

by Dell Magazine Authors

  Well, if we accept that supposition, it's difficult to understand how any women, save genetic abnormalities, ever become angry or violent, given the small average quantity of testosterone in women compared to men. Nevertheless, it happens, and more frequently than many people would care to admit. The argument is often made that prenatal exposure to hormones is more critical to personality than one's own postnatal levels, and that is probably true, but there is no good scientific evidence to show that in primates, higher levels of testosterone cause higher levels of violence. The “'roid rage” displayed by athletes injecting large quantities of black market anabolic steroids is often seen in those with high estradiol levels, as evidenced by the athlete's shrunken testes and fatty tissue deposition in the breasts. It seems probable that an unsuitable combination of hormones makes it harder to think, thus making violence more likely.

  In any case, researchers eventually realized that rebound estradiol was ruining all their gains. There had to be a better way to supplement testosterone. A few researchers went back to bio-identical testosterone and figured out methods to deliver it slowly, without the sharp peaks in blood level caused by injections. This was more complicated than making a “tiny time pill,” since nothing could change the dangers of popping bio-identical testosterone like a vitamin tablet, but it turned out to be a much more successful approach. Not only did the test subjects show greatly improved testosterone/estrogen ratios with few side effects, the delivery systems (skin patches, sublingual tablets, gels, and pellets) could be patented!

  While a delivery system is nowhere near as profitable as an original drug, in the case of testosterone, the safety profile made it the only choice.

  The Andropause

  Estimates have it that 20% of men above 60 years of age are deficient in testosterone. Since this is embarrassing to admit to, and hormonal screenings are not widely done, it is likely that the problem is under-reported. This low-testosterone state is referred to by many names: andropause, hypogonadism, “the gray years,” and “male menopause.” The latter term makes about as much sense as “jumbo shrimp,” but most people use it in preference to the more logical andropause. (The existence of this syndrome is still disputed by those who believe it isn't real if it isn't as sudden and dramatic as the female version.)

  Andropause is characterized by fatigue, low or zero libido, weight gain, osteoporosis, insomnia, cognitive impairment, and depression. Often these men don't care that they're not interested in sex anymore—that's another symptom—but they're miserable at not being able to recognize themselves in the sharp-voiced, grumpy, forgetful person they've become. A number of medications—Prednisone, Tagamet, Prozac, Aldactone, Dilantin—can cause this syndrome at a relatively young age, but no matter when andropause occurs, the sufferer shouldn't resign himself to enduring this ghostlike existence. And he no longer has to.

  The goal is, as anthropologist Ashley Montague said, to “die young, as late as possible.” And what could be better than to live a happier, healthier life that costs less than an unhealthy and unhappy one?

  Testosterone Replacement

  According to the October 2004 issue of Pharmacy Times, between 1998 and 2003, sales of testosterone products increased from $18 million to $400 million. Business is definitely booming.

  Because of the abuse of anabolic steroids, testosterone is now classified as a controlled substance. You can't buy it without a prescription. Also, since a normal hormone level for one man may be quite abnormal for another, you can't just walk into a doctor's office and walk out with a box of testosterone patches. Taking blood levels provides only a partial answer, because most men don't have their own youthful blood levels to compare them to. Supplementing to a level right for any individual can be tricky, and side effects can occur, ranging from a possible decrease in HDL, the good cholesterol, to an increase in PSA, an important early warning sign of abnormal prostate growth.

  It's unclear, however, whether testosterone and other androgens cause prostate growth or inhibit it. There's evidence on both sides. Generally, American physicians tend to regard testosterone as dangerous to the prostate, while their European counterparts incline to the opposing view. It's also unclear whether testosterone will exacerbate existing cancer, but most doctors would consider that a serious contraindication.

  Finally, there are some men for whom testosterone replacement does not work, probably because hypertensive and/or oxidative damage to small blood vessels has gone on past the point of no return. For those in whom it can work, the question of which form of testosterone replacement to use is critical to success or failure.

  There are six principle methods: lozenges, patches, gels and creams, pellets, injections, and dietary.

  Lozenges absorbed through the gums are an easy and reliable way of increasing testosterone. About 9% of patients experience gum irritation initially, but at least some of that goes away, and the lozenge is not affected by eating, tooth brushing, or drinking alcohol. It should be taken two or three times a day, as levels begin to fall five or six hours after the lozenge is gone. This may be irksome to remember, but that mimics testosterone's normal diurnal rise and fall in young men, which is all to the good. Since testosterone lozenges are not yet mass-marketed, they are made by a compounding pharmacy according to a doctor's specifications.

  Patches do not need to be made by a compounding pharmacy; you can buy them anywhere that sells prescriptions. The cash price is about $200 a month, and the chief side effect is a red circle on the skin from the patch adhesive, which sometimes turns into a rash. Providing a slow, steady release of testosterone, patches work well for men who need a medium-sized boost in hormonal levels, up into the 500 ng/dl range. Those with higher levels in youth may still not feel normal in this range, and would probably do better with lozenges or pellets.

  Gels and creams are convenient and easy to use, provided you accurately measure your daily amount. They're used once or twice a day, and women find this delivery method particularly useful for their own supplementation needs. Gels and creams cause less skin irritation than patches—creams are the best of the three—but there is a possibility some could rub off on your partner. Gels are available in regular pharmacies; creams must be mixed in compounding pharmacies. Cost is about $200 per month.

  Pellets are surgically implanted in the buttocks every four to six months. This is a minor procedure done with a painkiller, and delivers a slow, steady infusion in the 600 to 900 ng/dl range. The main side effect is extrusion of the pellets, which occurs in about 8% of patients. When calculated by the year, the cost is slightly less than for patches or lozenges. The FDA approves only one manufacturer in the U.S., Bartor Pharmacal in Rye, New York.

  Injections are the cheapest way to go and cause the most unwanted side effects, including the worst rebound in estradiol. Most of the studies showing negative effects from testosterone used injections. Not recommended.

  Fortunately, in a large proportion of men with declining levels of free testosterone and increasing levels of estradiol, hormone ratios can be dramatically improved by simple, inexpensive lifestyle and dietary changes. Simple changes are sometimes the most difficult to stick with, but in this case, they're certainly worth the effort.

  If you're overweight, lose weight. Please, not an extremely low-fat diet—that lowers testosterone, too. A sensible balanced diet combined with a minimum of two hours of exercise a week, aiming to cut 500 calories a day, will lose about a pound a week, 20 pounds in four months. Curbing alcohol consumption is another biggie. Even a few drinks inhibit the liver's ability to excrete estradiol, so you wind up with more estrogen circulating in your body—for women, the increase is a dramatic threefold after just one drink. (This doesn't mean eliminate alcohol, just cut back.) Taking 50mg of zinc twice a day does the opposite, decreasing estrogen by decreasing the aromatase conversion enzyme. Zinc also helps the testosterone system function better. It is quite common for people eating the standard American diet to be deficient in zinc.

/>   Eating more cruciferous vegetables, such as broccoli and cauliflower, will also help excrete estrogen. Vitamin C, one to three grams a day, and niacin are also good in this regard, but please don't take high doses of niacin (more than 250mg) if you're also taking a statin drug to lower cholesterol. Though some doctors do this deliberately, the combination increases your chance of developing rhabdomyolysis, a severe destruction of muscle tissue that can be fatal.

  My last suggestion is the supplement DHEA—the hormone dehydroepiandrosterone, made by the adrenal glands. Middle-aged men and women generally feel better when they take it. However, it can be converted to many other hormones besides testosterone, including estrogen. Women who take doses in excess of 50mg a day may produce too much testosterone, which can manifest as acne, facial hair, and deepening of the voice.

  What About Prostate Cancer?

  While some doctors believe that high testosterone levels cause prostate malignancy, there's little evidence for that, and much to contradict it.

  Two European doctors, British Dr. Malcolm Carruthers and French urologist Georges Debled, have treated thousands of men with testosterone over the last thirty years, and have not seen any increases in their patient population of either prostate cancer or benign prostatic hypertrophy.[10] This of course is not the same as doing a long-term longitudinal study, and until one is done, the sensible thing is to have a PSA test before supplementing with testosterone.

  The worst culprit appears to be the Western diet. In Okinawa and Hong Kong, yearly deaths from prostate cancer amount to four per 100,000—but after residents of these parts of the globe move to the U.S., their death rates rocket up to the same 28 per 100,000 as U.S. citizens who have lived here all their lives.[11] The primary protector in their diets appears to be tofu, which contains flavonoids. These compounds behave much like selective estrogen receptor modulators, the drugs used to prevent and treat breast cancer. Flavonoids are also found in flax, beans, tea, onions, and apples, but given the high levels in tofu, it might be a good idea to swap some of that estrogen-laden beef for an occasional tofu burger.

  Pollution and Falling Sperm Counts

  As if changing your relationship with meat and vegetables weren't enough to deal with, we may also have serious problems with plastic wrap and pesticides.

  In 1992, a group of Copenhagen scientists correlated the results of 61 surveys of sperm count from around the world taken from 1940 to the 1990s, and published the results in the British Medical Journal. In the early surveys, 50% of the subjects had sperm concentrations of over 100 million per milliliter, but by the 1990s, that proportion had dropped to only 16%. The percentage of men with 20 million sperm per milliliter—now considered “low normal” in fertility clinics, though it was once three times that—climbed from 6% in the 1940s to 18% in the 1990s. Most of the surveys were done in the U.S. or western Europe, but low sperm counts were also found in India, Nigeria, and Peru.[12]

  Given the enormous variability among men—or even one man from one day to the next—it's difficult to pin down the cause. However, since testosterone exerts such a powerful effect on the quantity of human sperm, it's worth looking to see if there is anything in the environment hostile to testosterone that didn't exist in the 1940s.

  And there is. Phthalates, which have shown powerful anti-androgen effects in animal experiments, are everywhere in plastics, and prone to leach out during microwave cooking. The common exposures are below the levels that caused pathology in the animal experiments, but no one has done a study on phthalates and human sperm counts, so we don't know what the level of harm might be. Another problem chemical is dibromochloropropane, DBCP, which in small amounts proved extremely toxic to sperm in men exposed to it. Though banned, DBCP has shown a distressing tendency to hang on in the fat deposits of humans and animals. There are many other pesticides with estrogen-like effects, but again, we don't know the level of harm they may impose on testosterone or sperm. I'm not advocating the precautionary principle ("ban everything we imagine could be harmful"), nor claiming that any of this constitutes ironclad proof; I'm simply observing that there's something here that clearly merits scientific study.

  Coins In the Fountain of Youth

  Americans are rightfully concerned about Medicare's $100-billion cost balloon over last year's estimates, and if the past is any guide, that cost gap will explode again in 2011 when the Boomers start retiring. But suppose our pharmaceutical approach changes?

  What if, instead of treating each of the symptoms of andropause with its own drug, we treated them all with a single hormone? Or even more radically, what if a few of the drug companies did a big clinical trial comparing the standard treatments of Syndrome X with testosterone treatment? (It won't be easy, what with the difficulty of keeping testosterone trials blinded, but someone should be up to the challenge.)

  Add ‘em up. Viagra 100mg, $10 a tablet. Lipitor 20mg for cholesterol, $96 for 30 days. Fosamax 70mg for osteoporosis, $75 a month. Ambien 10mg for insomnia, $84 a month. I won't go into the drugs for Alzheimer's, which are really expensive. Suffice it to say that next to all this, $200 a month is a bargain, and the price will likely drop when increased demand increases competition and decreases manufacturing costs.

  Done correctly, male hormone replacement may not only reignite those smoldering home fires, it could save your brain, your heart, your bones, and quite possibly add years to your life. Not to mention Medicare's.

  We'll see what happens between now and 2011.

  About the Author:

  Fran Van Cleave is a pharmacist who writes freedom-oriented science fiction. She lives in Indiana with her philosopher husband.

  Bibliography:

  1. Tibblin, G. et al, “The pituitary-gonadal axis and health in elderly men: a study of men born in 1913,” Diabetes, 1996; 45(11); 1605-1609.

  2. Chou, T.M. et al., “Testosterone induces dilation of canine coronary conductance and resistance of arteries in vivo,” Circulation, 1996; 94(10): 2614-2619. See also Costarella, C.E., et al., “Testosterone causes direct relaxation of rat thoracic aorta,” Journal of Pharmacol Exp Ther, 1996; 277(1):34-39. See also Moller, J. and Einfeldt, H., Testosterone Treatment of Cardiovascular Diseases, Springer-Verlag, (Berlin), 1984.

  3. Lichtenstein, M.J. et al, “Sex hormones, insulin, lipids, and prevalent ischemic heart disease,” American Journal of Epidemiology, 1987, 126(4): 647-657.

  4. Wu, S. and Weng, X., “Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients,” Chinese Medical Journal, 1993; 106:415.

  5. Phillips GB, Pinkernell BH, Jing TY. “The association of hypotestosteronemia with coronary artery disease in men.” Arterioscler Thromb. 1994; 14:701-6.

  6. Caron P, Bennet A, Camare R, Louvet JP, Boneu B, Sie P. “Plasminogen activator inhibitor in plasma is related to testosterone in men.” Metabolism. 1989; 38:1010-5.

  7. Kate Wong, “Testosterone Prevents Key Alzheimer's Abnormality,” Scientific American 2002 (Online news). www.sciam.com/article.cfm?articleID=0003B6C5-D3F5-1CCE-B4A8809EC588EEDF

  8. Rudman D. et al, “Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men,” Journal of Clinical Endocrinology, 1994; 40: 653-661.

  9. Whittington R, Faulds D. “Hormone replacement therapy. A pharmacoeconomic appraisal of its role in the prevention of postmenopausal osteoporosis and ischaemic heart disease.” Pharmacoeconomics 1994;5(6):514-548.

  10. Carruthers, Malcolm. Maximising Manhood: Beating the Male Menopause. Chapter 6, 131-157. London: HarperCollins Publishers, 1996.

  11. World Health Organization 1996; Japan Ministry of Health and Welfare 1996; Rose, D.P., A.P. Boyer, and E.L. Wynder 1986. International comparisons for cancer of the breast, ovary, prostate, and colon, and per capita food consumption. Cancer 58: 2363-71.

  12. E. Carlson et al., “Evidence for decreasing sperm quality of semen during past 50 yea
rs,” British Medical Journal, vol 305, 1992, pp. 609-13.

  Copyright (c) 2005 Fran Ban Cleave

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  The Alternate View

  by John G. Cramer

  THE BALL LIGHTNING PUZZLE

  When I was a nuclear physics graduate student some decades ago, I spent some time teaching myself about plasma physics by reading textbooks. While doing this, I also tried to apply the ideas I was learning to a very mysterious physical phenomenon, ball lightning. Eventually I became frustrated and put the problem aside. Except for using ball lightning as a techno-prop in my first novel, Twistor, I had more or less forgotten about this puzzling phenomenon until recently, when I had the pleasure of a visit from Professor Peter Handel of the University of Missouri in St. Louis, one of the theorists who have developed a possible explanation of the phenomenon. I will devote this column to ball lightning.

  Few people have actually seen ball lightning, because its production seems to be a very rare event. Nevertheless, the phenomenon has been widely reported since the Middle Ages. Over 10,000 reports of observations of ball lightning have been collected in a database in Russia, primarily from reports from Russia, Japan, and Europe. While this suggests that ball lightning may occur frequently, all attempts by scientists at systematic detection and observation have failed. Handel suggests (see below) that this failure may be because such scientific “lightning observatories” have been placed in mountainous regions (because there is more lightning there), while ball lightning is observed mainly in flat landscapes.

  A typical observation goes something like this. There is a normal lightning strike, and afterwards a glowing ball is observed. The ball may range from tennis ball to beach ball size. It may hover in the air or move horizontally, often erratically, or bounce or roll on the ground, or climb a tree or utility pole, or race along a power line. Its color is usually a brilliant white, but bright red, blue, and green glows have also been reported. Some observers have reported seeing tangled filamentary structures within the ball. It sometimes makes a buzzing, hissing, or frying noise and may have an acrid odor like ozone or sulfur dioxide, or nitric oxide. It usually lasts a few seconds, and its disappearance may be silent, or may be punctuated by a loud bang or explosion, perhaps with glowing streamers. The ball lightning may float into a building or car or airplane, but curiously seems to do little damage when this happens, despite its sometimes explosive and high-energy behavior in open areas. There have been many reports of a lightning ball passing through a glass windowpane, occasionally damaging the glass, but usually not. There have also been reports of ball lightning quenching in a tub of water and bringing the water to a boil. There was one incident where a lightning ball quenched in a rain barrel, and the water temperature was measured shortly afterwards. The amount of energy contained in a lightning ball is variable and not well quantified, but it is estimated to range from about 102 to 108 joules.