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SIDE EFFECTS OF TESTOSTERONE SUPPLEMENTS

High-dose testosterone does not linger unchanged in a man’s bloodstream and must be processed (metabolized) by the body. Some testosterone wends its way through a man’s bloodstream unaltered, but a portion is transformed to other active products like the powerful male hormone dihydrotestosterone or the female hormone estradiol or is alternatively transformed into inert hormone by-products.
Testosterone, when it is unaltered, acts directly on male hormone — androgen — receptors, not just to help build muscle but also to activate androgen receptors in the skin. The skin responds by cranking out more and more of an oily skin secretion called sebum. Acne blossoms when skin sebum levels are high. On the other hand, that portion of testosterone that is metabolized to dihydrotestosterone (DHT) has an entirely different effect. DHT build-up in scalp hair follicles contributes to male-pattern baldness. Men who overstock their body with testosterone supplements often have abundant chest hair (due to testosterone) but sparse scalp hair (caused by high DHT levels). Minimizing the transformation of testosterone to DHT with a medication like finasteride (Propecia) lowers blood DHT levels and helps reverse the process of balding in men.

The fraction of testosterone transformed to estradiol sets the stage for another problem. When a man’s blood estradiol is high enough, the glut in this female hormone can cause him to have embarrassing breast enlargement. The technical term for breast enlargement occurring in the male is “gynecomastia.”

TESTOSTERONE INCREASES MUSCLE AND DECREASES FAT

Although men and women who compete in sports routinely depend on testosterone to increase muscle bulk, tone, and function, doctors have had a hard time accepting what for athletes is a matter of faith. This is because those who do use supplemental male hormones also train vigorously. It has been impossible to sort out how much improvement in a man or woman’s athletic performance is due to obsessive and diligent training and how much to testosterone.

Doctors’ experience with hypogonadal men — that is, men with lower than normal testosterone levels — has been instructive. When testosteronedeficient men are given just enough hormone to regularize their blood testosterone levels, they have an unequivocal 11-percent increase in lean body (muscle) mass. Further, individual muscle groups such as upper arm and thigh muscle mass expanded by 21 percent and 11 percent, respectively, with proper hormone treatment. This impressive augmentation of muscle bulk can occur after just ten weeks of testosterone therapy.
But these were not normal men, for below-normal testosterone levels had left them with below-normal muscle mass. The testosterone treatment merely brought them back to their predetermined baseline, and no further. For men who already have normal male hormone levels, the advantages of further testosterone supplementation are less clear.

Designing a study to answer a question as apparently straightforward as “Does testosterone use increase a man’s strength?” has proven to be a remarkably challenging task.

Much of our current thinking about anabolic steroids changed on July 4, 1996. On that date, Dr. Shalender Bhasin and his colleagues in California and Oregon reconciled the differences between skeptical physicians and steroid-conscious athletes.

In a carefully controlled study, Dr. Bhasin demonstrated for the first time that massive doses of androgens, in this case 600 mg of testosterone weekly (roughly fifteen times the normal man’s testosterone output of 42 mg per week), did increase weight, muscle mass, and strength.

The greatest gains in muscle mass and strength were observed in trained athletes who received testosterone and also participated in a supervised exercise program. Athletes in the testosterone plus exercise group who weighed 167 pounds at baseline weighed 180 pounds after ten weeks of high-dose testosterone. Their bench-press strength — 213 pounds before-was 261 pounds at week ten.

Trained athletes who exercised regularly but received placebo injections had no significant weight gain (188 at start, and 190 pounds at ten weeks). Their bench-press strength was 240 pounds before and 261 pounds after ten weeks of supervised training.

Thus, compared to placebo-treated men, testosterone-treated athletes gained thirteen more pounds (most of it muscle) and could lift more weight than they could at the outset. The eleven-pound weight gain and the ability to bench press twenty-seven more pounds than the placebo-treated men was significant, proving that massive doses of testosterone did increase weight, muscle mass, and muscle strength.

But what about the average man or the proverbial “couch potato” who does not have the time, energy, or inclination to commit himself to a lengthy and intensive program of physical conditioning? Will he also experience an increase in body weight and improved muscle strength after receiving enormous amounts of testosterone? The answer is “yes,” but to a significantly lesser degree.

For example, placebo-treated untrained men had no increase in body weight and could bench press the same amount of weight before and at week ten of the study. With testosterone, their weight increased from 181 to 189 pounds. Their bench-press prowess, 213 pounds at baseline, was up to 231 pounds after ten weeks of high-dose testosterone therapy, once again demonstrating the profound impact of very large doses of testosterone on both muscle mass and muscle strength. (See Table 13.2. )

To achieve these striking results, doctors had to give deep intramuscular injections of extraordinary doses of testosterone. Blood testosterone levels increased to values a man would never be able to achieve on his own. Those who volunteered to take part in this study had entirely normal serum testosterone values between 430 and 550 ng/dl. (The normal serum testosterone range is 300-1,000 ng/dl.) The amount of testosterone administered left men so awash in testosterone that one week after the last testosterone injection, serum testosterone levels were 3,244 ng/dl, or 300 percent higher than the highest serum testosterone level a man could hope to achieve naturally.

Because serum testosterone levels reached such extraordinary heights, far greater than would be possible under normal physiologic conditions, the dose of testosterone administered is said to be “supraphysiologic,” that is, more than the body is programmed to make or cope with. During ten weeks of supraphysiologic testosterone treatment, men noted some increased acne, but not much else in the way of adverse effects. Tests designed to test their level of aggression before and during the onslaught of testosterone did not uncover any heightened tendency toward aggressive or antisocial behavior. But this was only a short-term study. The adverse effects of large doses of testosterone are more readily apparent with long-term high-dose testosterone use.

WHAT DOES TESTOSTERONE DO TO MAINTAIN A MAN’S HEALTH?

Testosterone made in the testicles is released into a man’s bloodstream to transform cells scattered throughout the body. As an androgen (a male hormone), testosterone can only work on androgen receptors. Cells without androgen receptors would not be expected to, and do not, respond to testosterone. However, androgen receptors are widespread. So this male hormone can accelerate, slow down, or wreak havoc with a remarkably diverse array of individual and uniquely male physical responses.

As one would expect, testosterone is vital for normal male sexual behavior. Testosterone has other functions — some advantageous, others less savory, and still others downright harmful. Listed below are some of the ways testosterone makes its presence known in different parts of the body. Testosterone interacts with androgen receptors on muscle to increase muscle mass and seeks out bone marrow androgen receptors to stimulate bone marrow to make more red blood cells. Other consequences of testosterone-androgen receptor interplay force the kidney to hold on to more sodium, stimulate the skin to develop acne, help build strong bones, increase body hair while simultaneously accelerating the loss of scalp hair, and thicken a man’s vocal cords, giving him a deep voice.

Testosterone’s power in bringing about all of these remarkable physical changes is well documented, but when most men think of testosterone, they tend to focus primarily on the muscle-building and sexuality-enhancing properties of this male hormone. Other, more subtle issues like the important role of testosterone in maintaining a woman’s sex drive and the invigorating

THE CLOUD OVER TESTOSTERONE

All is not wine and roses; testosterone also has a dark side because it is a steroid. The word “steroid” refers to the peculiar chicken-wire structure of this hormone. Other vital hormones made in the adrenal glands and the ovaries also have a steroid configuration. These steroid hormones course innocently through our bloodstreams every moment of every day. Neither the ovary’s estrogens nor the adrenal gland’s cortisone shares testosterone’s nefarious legacy.
• When you read in the paper that an athlete has been disqualified from competition because he or she “tested positive for steroids,” testosterone or one of its close androgenic (male hormone) relatives is the steroid they are referring to.
• Rival industries, one devoted to promoting, the other to detecting, illegal male hormone use among athletes are now firmly in place.
• Androgen enthusiasts have amassed enough information to publish their own Anabolic Steroid Hormone Users Bible with surprisingly accurate descriptions of individual anabolic steroids and tips on how to cope with common problems linked with steroid use. This information is considered so valuable that it is printed in blue ink on thin paper so that it cannot be photocopied.
• The anabolic steroid watchdogs, on the other hand, have been busy devising methods to detect inappropriate and illegal use of male hormone supplements in athletes and bodybuilders. It is now possible to distinguish between a competitive athlete’s own naturally occurring male hormones and illegal male hormone supplements just by examining athletes’ urine samples to look for the telltale disruptions in the testosterone-epitestosterone ratios.
• To bedevil those intent on rooting out inappropriate anabolic steroid use, an equally ardent counterindustry has conjured up means to avoid detection by spiking the urine with a few drops of alcohol to foil test results.
• When lawyers seek to find extenuating circumstances to explain what motivated their client to commit some violent act, they frequently invoke “steroid rage” defense. They use this strategy to plead that the “accused should be excused” because at the time of the crime while in the grip of these mighty male hormones, he was powerless to control his aggression.
• In Europe, Israel, and California, men convicted of repeated sexual offenses for molesting children are offered the opportunity to avoid, or have a more lenient, prison sentence if they agree to a chemical castration to nullify the impact of testosterone as one means of discouraging further deviant sexual behavior.
• Does this mean that testosterone turns men into sexual deviants? No, but men who are inclined to a pattern of aberrant sexual behavior need testosterone to fuel their misdirected sexual urges. Take away their testosterone, and they stop preying on children.

What is it about testosterone that inspires so much passion? How much of what they say is true? We are just starting to get answers to these questions.

THE MALE HORMONE (ANDROGEN) MYSTIQUE

Testosterone!

Before Viagra, everybody was talking about testosterone.

Newsweek’s cover story on testosterone, coupled with a feature on another male hormone called DHEA, antedated that same weekly magazine’s different, but equally enthusiastic, cover story on Viagra. Both testosterone and DHEA were also featured in prominent stories in the Wall Street Journal, and on the CBS Evening News. Male hormones were then and still are one hot topic.

Testosterone, we are told, will give men of all ages massive muscles, invigorate aging men, spice up the sexual desire of menopausal women. Further, this special male hormone is said to work wonders to improve flagging muscle strength and is being touted as a panacea to resolve many of the problems currently plaguing both young and older men and women today. Could all this hype really be true, and if so, why aren’t more men taking testosterone supplements?

The Testosterone Renaissance

Testosterone has spawned its own myths and legends. This chapter deals with the role of testosterone in maintaining a man’s health and vitality. The muscle-building properties of testosterone have attracted considerable attention and have created a culture of testosterone abuse. This quintessential male hormone is needed to maintain every man’s sexuality and fertility and is more important than previously believed in sustaining a woman’s sexuality.Here, you will find discussions on the following:

Two grown men, a seventeen-year-old boy, and a woman want testosterone.

Glenn at 28 already looks like he has had more than his share of testosterone. Fully dressed, there is every reason to believe him when he tells me he is a competitive bodybuilder. His gray “big and tall” men’s suit jacket can barely contain arms that are the size of an average man’s thighs. During the day, he works at his job selling electronics, but at night he pursues his passion. In every spare moment, he is at the gym working to further define his

muscle groups to impress the judges when he oils up and steps on the stage to “display.” He has not yet won any major competition but is hopeful that someday he will. It is his belief that with just the right dose of testosterone his chances will improve.

Glenn may be correct, but in order to achieve his goals, he will need massive doses of testosterone as well as other muscle-building (anabolic) male hormone (androgenic) steroids (AAS). (See the section “How Do Athletes and Bodybuilders Use AAS?” later in this chapter.) Their use may cause side effects (breast enlargement, acne, edema, and balding), requiring yet an additional array of medications. Glenn must also be willing to skirt the law, for testosterone supplement use is approved only for hypogonadal men and in wasting states such as occur with cancer or AIDS.

Abner, age fifty-seven, is no bodybuilder but would like a better body. He, too, works out at a place across town from Glenn’s gym. Even though he is there five nights a week and occasionally on Saturday, Abner still does not have the brawn he desires. He envies Burton, who has the immediately adjacent locker and has become more heavily muscled. Abner is at a loss to explain why. Like Burton, he takes Mega-Man vitamins, in addition to vitamin E, creatine, saw palmetto, selenium, and zinc. Abner was sure he was doing everything in his power to protect his health. But he wasn’t taking testosterone. Burton was. So Abner was wondering if testosterone would do as much for him as he reckoned it had done for Burton. Then one night, his wife mentioned that Abner’s erection was not as strong as it had once been. First thing the following morning, Abner called for an appointment, started reading everything he could, and came to the office armed with fully highlighted and underlined books on testosterone.

Abner may qualify for testosterone treatment since he is at the age when a man’s testosterone output starts to wane. If he has a below-normal testosterone level, his doctor will have no qualms about providing him with a testosterone prescription. This may be all he needs to catch up with Burton at the gym. He has to be careful that the testosterone prescribed is safe and is not likely to cause any liver damage.

Steven, who says he is seventeen but looks closer to twelve, just wants to be normal so the other kids in his class will stop their teasing and using him for a punching bag. A tall, awkward youngster struggling to pitch his still soprano voice to a lower key, he feels like an alien adolescent, more milquetoast than manly. Would he benefit from a touch of testosterone?

Actually a little testosterone would be very helpful for Steven. There is fundamentally nothing wrong with this youngster other than a condition called delayed puberty. In time, his own body will provide the testosterone he needs, but that will not help him cope now. This is a controversial area, and some doctors are willing to sit back and let nature do the job. Others, sensing the youngster’s anguish, would be inclined to treat him with a little testosterone now and let him “catch up” to his classmates and then stop treatment when his body is ready to make its own testosterone. (See the section on “Trouble with Testosterone” later in this chapter.)

Then there is Linda, now age fifty-five, who says, “I have no sexual desire . . . absolutely none!” And she insists, “It wasn’t always like this.”

But when her fibroid-loaded uterus kept gushing blood, her doctors told her she had to have a hysterectomy. To be on the safe side and so she would never have to worry about ovarian cancer, they took out her ovaries along with her uterus in one operation when she was fifty-one. She has never been the same.

“There’s nothing wrong with my husband’s libido, and he’s starting to wonder why I’m never interested. My girlfriend who had the same problem no longer does because her gynecologist gave her something-she says it’s testosterone. Can that be right?”

Yes, it can be. We are just starting to learn how important testosterone is to a woman’s sex drive, mood, and desire. Testosterone provided in pills and patches has been used with considerable success recently in improving the sexual desire, mood, and well-being of women who, like Linda, are now postmenopausal and have lost the capacity to generate their own small but vital ration of testosterone.

Hormones, Impotence, and the Temporal Lobe

Our understanding of the hormonal interplay necessary for normal male sexual function continues to evolve. Medical professionals used to consider the pituitary the master gland, the agent that doled out specific instructions to regulate the function of the other endocrine glands — thyroid, adrenals, and testicles. Twenty years ago, it became clear that the pituitary could not discharge this important regulatory function on its own but was beholden to a higher hormonal power located in the hypothalamus. The pituitary was then more properly recognized as an intermediary existing to fulfill the hormone directives issued by the hypothalamus.

Just as we became comfortable with this concept, another area of the brain, the temporal lobe, entered the playing field. The role of the temporal lobe in hormone secretion appears to be more meddlesome than regulatory. This is especially true when viewing the effect of temporal lobe influences on male sexual function.

Scientists studying the temporal lobe in humans were fully aware of its critical role in the reproductive and sexual function of animals. Experimental destruction of a specific portion of the temporal lobe (the amygdala) caused testicular degeneration in male rats and cats. Implants of estrogen in rabbits’ amygdalae provoked hyperprolactinemia. But how do these animal experiments relate to humans?

As mentioned, some men suffer from a temporal lobe disorder called temporal lobe epilepsy (TLE). They have decreased libido and are often impotent. Some of these men have low serum testosterone levels; others have increased blood levels of prolactin.

TLE is different from other forms of epilepsy. Early symptoms are subtle and are characterized by a series of “spells.” Sudden attacks of abdominal pain, dizziness, fugue states, bed-wetting, and rage as well as auditory hallucinations may be clues to the presence of a temporal lobe disorder. The coexistence of a form of epilepsy and a hormone disorder initially created a dilemma for the physician. Which condition should be treated first?

Experience provided the answer. Patients with TLE and hypogonadism are, at first, unresponsive to testosterone injections, and those with TLE and hyperprolactinema do not benefit from bromocriptine. (This distinguishes them from other hypogonadal or hyperprolactinemic men.) Antiseizure medications such as phenytoin (Dilantin) or carbarnazepine (Tegretol) must be the first line of treatment. Then conventional hormone therapy is beneficial. (Frequently, the antiseizure medications not only control TLE symptoms but also allow serum hormone levels to return to normal.)

The diagnosis of TLE requires specialized testing. An unusual type of brain-wave test, the sleep-deprived electroencephalogram (EEG), detects subtle disturbances in temporal lobe electrical activity. A new diagnostic probe, single photon emission computerized tomography (SPECT scan), may also help. The SPECT scan registers different colors in relation to blood flow. Areas of greatest blood flow in the brain show up with the whitest colors. Since increased blood flow is one characteristic of seizureprone brain tissue, these areas light up on SPECT scan.

Hormone disorders are perhaps the most easily diagnosed causes of impotence, and hormone measurements should be an integral part of the early evaluation of the impotent man. Hormone abnormalities, once detected, can be treated with some dispatch and considerable success.

Who Does and Does Not Benefit from Hormone Therapy?

Hormone treatment is effective only in impotent men with bona fide hormone abnormalities. Indiscriminate use of testosterone, bromocriptine, or thyroid hormone is neither warranted nor effective; the practice of arbitrary administration of testosterone therapy to “boost” testosterone levels is similarly of no value. Testosterone increases libido and improves erectile function only in men with proven low testosterone production.

Adverse effects of hormone therapy are uncommon. Muscular discomfort from an injection can be minimized by rotating the site of injection. Skin irritation from testosterone patches can be minimized by pretreatment of the skin area with a pea-sized dollop of triamcinolone cream. Concern that long-term administration of testosterone by injection or patch might accelerate prostate growth or activate cancer in many testosterone-deficient men has not proven to be a significant problem to date.

Bromocriptine (Parlodel), pergolide (Permax), and cabergoline (Dostinex) can cause nausea and lightheadedness. Symptoms usually can be avoided by taking the drug with food or at bedtime and starting with low doses. For bromocriptine, the initial recommended dosage is half a tablet (1.25 mg), taken at bedtime with a snack, and then the dosage is gradually increased until serum prolactin levels are normal. With cabergoline (Dostinex), 0.5 mg once a week is the starting dose. If serum prolactin levels do not normalize, then twice-weekly cabergoline is recommended (Sunday and Thursday is what my patients prefer). Thyroid hormone administration is relatively free of side effects when dosages are monitored by appropriate blood tests.

If, in addition to hormone abnormalities other problems such as psychologic conflicts exist, the response to hormone therapy will be less than ideal. For this reason, a careful and comprehensive evaluation looking for all possible causes of impotence is recommended before embarking on a course of hormone therapy.

How Common Are Hormone Problems in Impotent Men?

Hormone abnormalities, once thought to be a rare cause of impotence, are now recognized with increasing frequency. In one study of 422 impotent men at a Veterans Administration hospital, disorders of hormone secretion were detected in 29 percent. Primary hypogonadism and secondary hypogonadism dominated (19 percent), while 4 percent had hyperprolactinemia and 6 percent had disorders of thyroid hormone production.

This coincided with our prior experience. In our 1980 study of 135 impotent men, evidence of hormone dysfunction was found in 34 percent, although we tended to see more hyperprolactinemic patients than our colleagues at the Veterans Administration hospital.

A 1989 survey evaluated hormone function in 600 impotent men in Florida. Thirty-two percent (192 of 600) were found to have disorders of hormone secretion including testosterone deficiency (26 percent), hypothyroidism (6 percent), and hyperprolactinernia (3 percent).

Finding Hormone Problems in Impotent Men

All the necessary hormone measurements needed to detect hormone abnormalities can be performed on a single blood sample. Hormone levels normally vary throughout the day but generally fall within a range that is bracketed by an upper and lower limit called the reference range. When a man’s blood hormone levels fall within the reference range, both physician and patient can safely assume that sexual dysfunction is due to some problem other than hormone malfunction.

Hormone values do have a tendency to bob up and down throughout the day. Bear in mind: Slight increases in serum prolactin levels above and modest decreases in testosterone below the accepted ranges may occur in perfectly normal potent men. Men whose impotence is truly caused by disorders of hormone production have sustained and persistently subnormal blood testosterone, elevated prolactin, or abnormal thyroid hormone levels.

Physicians should routinely measure serum testosterone, free testosterone, and prolactin values in impotent patients; thyroid hormone evaluation is usually reserved for those men who have symptoms or show physical signs compatible with disordered thyroid function.