Testosterone Replacement: The Male Andropause

Testosterone Replacement:
The Male Andropause

Why aren’t men taking the same sort of hormone replacement that women are? Why isn't testosterone the treatment of choice for the aging male? Many physicians practicing today are beginning to conclude that an eventual surge of male hormone replacement is the only logical approach to the health needs of the older male.

Of course, there are many psychological, historical, and societal reasons why it hasn't happened yet, including, I'm quite sure, a macho reluctance on the part of many men to concede the possibility of their sex hormone production being in any way inadequate.

There's a crystal clear biological reason, too: A man's level of testosterone doesn't suddenly fall off the edge of the table, the way a menopausal woman's estrogen and progesterone levels do. There's no screaming emergency in the hormone department, no hot flashes, no alarming decline in bone, no sudden genital atrophy. Men can pretend nothing is happening to them.

All the same, it is.

By the time they reach their seventies, most men have 30 to 50 percent less testosterone than they had when young. This clearly has an effect on their sex drive, which we'll explore in a moment. But, if you're a man, be aware that it weakens you in many other ways as well. Together with the decline in growth hormone, testosterone's drop shares responsibility for the loss of muscle mass and the subsequent erosion of strength. There's evidence as well that the testosterone dip contributes to loss of bone. Of even more significance for your basic survival, there have been striking studies done in the past five years that have shown that lower testosterone levels correlate with increased risk for heart disease—exactly the opposite of what doctors used to imagine the male hormone's cardiovascular effects were. It was almost a cliche, you know: Poor men, their sex hormones kill them. In fact, nothing could be further from the truth.

Finally, there is a correlation between loss of testosterone and a generalized loss. of functionality. Eugene Shippen, M.D., one of the most experienced doctors I know in this field, reports that every man in his eighties or nineties who he treats and who's still physically and mentally vigorous has high normal testosterone levels for his age. He's never seen an exception!

Perhaps it makes sense to start testosterone supplementation as one gets older. I wonder.

ISN'T THIS A BIG, BAD STEROID?

Before we go any further, it's best to admit that testosterone has a terrible reputation. It is, after all, the principal anabolic steroid in the human body. The exact name is androgenic-anabolic steroid, and we get that term from the two Greek words andro and gennan, meaning "male-producing," and from another Greek word, anabold, meaning "to build up." And some men (and a few women) certainly do get built up. We all have images of overdeveloped and overambitious athletes taking illegal steroids on the q .t. to gain an edge, their biceps bulging like melons about ready to pop through the tightly stretched, fat-free flesh of their arms. The consequences for their health are serious. Unnatural levels of steroid hormones can cause sterility, coronary artery disease, serious liver damage, and brain tumors. The latter was what Lyle Alzado, the All Pro defensive lineman for the Los Angeles Raiders and an admitted steroid abuser, died of.

So steroids are dangerous? Absolutely, but slow down and consider what we mean here. Steroids taken at levels the human body was never meant to handle are exceedingly dangerous. Young men and women have no business taking artificial steroids. They are already enjoying their natural maximum levels of testosterone. Assuming your glands were functioning normally when you were in your twenties, you can be quite certain that the level of testosterone you had then was the highest nature intended you to have: your natural max. As a result, the average twenty-year-old male who wants to get athletic is usually going to find himself building a fairly formidable set of muscles simply with the aid of natural exertion. Young women can create smaller but highly efficient musculature if they want to, too.

At this point, let me reiterate something that was thoroughly discussed elsewhere on this website. Testosterone is not exclusively a male hormone. Women secrete testosterone at about one-tenth the level of their male counterparts. And their testosterone is exceedingly important to them just as it is to the male half of the human race. In fact, many doctors are now beginning to add small amounts of testosterone to the estrogen and progesterone replacement plan that they prescribe for their postmenopausal female patients. The results are excellent. So go back to the subject of Estrogen details, if you're a woman. The rest of this webpage is going to concentrate on the men. For them, testosterone may be both life-saving and life-enhancing.

Let's return to what this is about—that is, hormone replacement therapy, not self-induced hormone overdoses. There is no evidence at all to suggest that testosterone supplementation to replace the amounts lost as the result of aging can cause damage to the male body. All the evidence shows the exact contrary. So, in reading below, put out of your mind those frightening images of beefed-up, overly aggressive football players damaging their health and breaking the law to further their careers. Hundreds of thousands of men are, indeed, doing that—including teenage boys. One study reports that 7 percent of male high school seniors have taken anabolic steroids. This is potentially tragic, but it has nothing to do with the subject of this here. Like human growth hormone, testosterone is a natural hormone that promotes cell growth, protein synthesis, and healing. Because it's a very special hormone—a sex hormone—it also in some measure promotes sexual vigor. These are desirable objectives, and they can be best obtained by maintaining the normal and not by supplementing into the range of the abnormal.

What Happens to Men?

Why do so many men feel despair and decline in their fifties and early sixties? A masculine tradition of "keeping it all in" has throttled open discussion of this phenomenon. At best there are rather vague and patronizing references to a "midlife crisis," but nobody seems to know just what that is or why it should be happening. The male andropause is a hidden pause; it's nothing like the perfectly evident transition that a woman in her early fifties is experiencing. Neither hot flashes like blow torches, nor the complete cessation of entire biological systems.

Yet many men—and doctors know this—are experiencing a deep grinding desperation in this period of their life. I've seen men come close to suicide, only to recover when something was done about their hormones. Sexual malaise is an obvious element. Most men begin to experience at least some reduction in desire, in frequency of erections, in overall sexual function in their forties. Whether all this change is due to testosterone decline is not entirely clear, but there is little doubt that much of it is. Testosterone has a very direct influence on sexuality. Younger men who have uncharacteristically low hormonal levels generally have low sex drives, but they will display increased sexual interest and activity if given testosterone replacement. The reverse effect occurs when drugs designed to suppress testosterone are given to men suffering from prostate cancer. Impotence usually results. There are reports that indicate that there is a testosterone threshold—which varies considerably from person to person—below which sexual function is impaired.

Of course, though testosterone declines steadily with age, many if not most men remain sexually potent right into old age. It is not impotence so much as a declining interest and enthusiasm that usually occurs. How burdensome that will be depends on the personality of the individual male.

It would seem that the loss of enthusiasm for life that afflicts many men in middle age is a combination of a number of factors. The physical factors—declining sexual vigor and diminished strength, energy, and muscle mass—are closely related to the slipping level of testosterone. Some mental and psychological symptoms may also be the result of this slippage. The mental energy and excitability of youth can fall off very sharply as testosterone declines. That high testosterone levels are partly responsible for that energy is certainly indicated by the fact that many men recover their creativity and drive after testosterone replacement therapy. You probably remember my mentioning in the that estrogen is the steroid hormone of most significance to brain function and that in men testosterone is chemically reformulated into estrogen in the brain. Without proper levels of testosterone that is clearly hard to do.

Testosterone is a hormone of marvelous versatility. Like the other anti-aging hormones we've discussed, its effects are widespread in the body and far from limited to what one might expect from a "sex" hormone. Dr. Richard S. Wilkinson has related the following case.

One of his patients, a wealthy research physicist, started experiencing physical problems in his late forties—allergies and a back problem came first. A general sense of being "run-down" followed in the succeeding years. At fifty-five, a severe heart irregularity was added to the list. The physicist turned to the world-famous Scripps Clinic in southern California, but an extensive workup (at a cost I shudder to contemplate) found nothing to explain his growing debilitation. Pressed by their patient, who was neither personally nor scientifically inclined to accept easy answers, they could only suggest that perhaps he was "aging a little faster than normal."

I need hardly say that that workup did not include checking his blood testosterone levels. The physicist decided to seek his own answers. He wondered why his energy was so low and why so many parts of his body seemed incapable of working well more or less simultaneously. Being professionally knowledgeable about feedback mechanisms, his interest turned toward the endocrine hormones, clearly one of the body's main feedback control systems.

Eventually he found a physician who was willing to work with him in investigating his hormones. They quickly scored two bulls eyes. The wealthy physicist proved to have both low thyroid function and a low testosterone level—either one of these would have been sufficient to account for his fatigue. The story, of course, has a happy ending. Thyroid therapy and testosterone replacement returned the patient to virtually the man he had been ten years before. I've seen stories like this end sadly. I suspect the right approach not only rejuvenated the physicist but per- haps saved him from an early death.

Testosterone has to be taken seriously. It's not just an essential part of your sex life or a dubious muscle aid for foolhardy athletes. Let's look at the history of this hormonal treatment.

SOME VERY ODD ATTEMPTS

The idea of restoring the male sex hormones as a means of rejuvenation is not a new one. Indeed, its history is long, colorful, and somewhat bizarre.1

The forefather of testosterone replacement therapy was undoubtedly Charles Edouard Brown-Sequard, a prominent French professor of physiology, who announced on June 1, 1889, that he had discovered a rejuvenating therapy. The seventy-two-year-old scientist believed that he had reversed his own decline by injecting himself with a liquid extract derived from the testicles of dogs and guinea pigs. These injections, he told his audience at the Societe de Biologie in Paris, had radically increased his physical strength and intellectual energy, as well as lengthening the arc of his urine.

Today virtually everyone agrees that the improvements Brown-Sequard observed were due to the power of suggestion. Nonetheless, the aging physiologist had revived, in a more sophisticated form, ideas that have a long history in human culture and popular medicine. The ancient Egyptians had attributed medicinal value to the testicles, and the Roman naturalist, Pliny the Elder, reported that the oil-soaked penis of a donkey and the honey-coated penis of a hyena were used as sexual fetishes. Medical authorities in ancient India had recommended the ingestion of testis tissue as a cure for impotence. A German compendium of remedies published in 1754 mentions the use of horse testicles and the sexual parts of marine animals as aphrodisiacs .

Putting to one side the obvious element of wishful thinking in these "therapies," there is perhaps in all of them a vague insight into the possibility that the functions of the testicles might be restored by finding some replacement for the substances they produce.

Another approach was an actual testicle transplant, and this extraordinary notion actually met with some success. In 1912, two physicians in Philadelphia transplanted a testicle into a patient. Apparently the surgery was successful, but reports of its long-term effects have not survived. A year later in Chicago, Dr. Victor Lespinasse removed a testicle from a donor, fashioned it into three transverse slices, and inserted them into a sexually dysfunctional patient who had lost both his own testicles. The man felt so invigorated sexually that within a matter of days, he stormed out of the hospital in search of satisfaction. Lespinasse reported that two years later the man's sexual function was still intact.

Further efforts were made by Dr. Leo L. Stanley, resident physician at San Quentin prison in California. Starting in 1918, he began transplanting testicles from recently executed prisoners into inmates, some of whom reported the recovery of sexual potency. Stymied by the "scarcity of human material," Stanley went on to transplant the testes of rams, goats, deer, and boars into men with some reported success. This dubious approach was soon followed by the Russian-French surgeon, Serge Voronoff, who made a fortune in the 1920s with his controversial "monkey gland" transplants. This line of treatment soon acquired an unfortunate aura of quackery that still hangs over the whole subject of male hormone replacement.

The abuse of steroids for muscle building and the fear that testosterone, if given to women, would result in virilizing side effects such as deeper voices and hirsutism, were not helpful either.

Nonetheless, for a moment in the 1930s and 1940s, it seemed that testosterone therapy might take off. The necessary scientific foundation for real testosterone replacement was laid in 1935 when Dutch doctors isolated testosterone and created a synthetic form of it for the first time. Doctors began using it in men with hypogonadism—that's medicalese for levels of testosterone so low as to prevent normal sexual development. Soon older men whose testosterone decline had caused impotence were also being treated. Such uses are still regarded as medically sound.

What didn't happen for men, however, was what has occurred with postmenopausal women since the 1950s—a full-scale program of hormone replacement essentially designed to counteract aging. Only in the 1990s has it become apparent that this is both a logical-and perhaps inevitable-next step.

TESTOSTERONE PROTECTS HEALTH

In the last seven or eight years, scientific interest in the male hormone has come alive. Studies have been conducted on men in their middle years or older who have low or normal testosterone levels for their age range. Almost invariably, the results have been positive. Men have gained muscle and consequent strength, there have been indications of a slowdown in bone resorption (the process of bone loss), there has been increase in sexual desire and functionality, and studies have shown better spatial cognition and word memory.

Does all this have an impact on longevity? Does testosterone deserve to be regarded as one of the pro- longevity hormones? I don't have any doubt that eventually it will be seen as one of the more powerful of them, especially in males.

Let's be very practical for a moment. We all know that heart disease eventually ends the life of the majority of American males. How does testosterone relate to this?

Its original imagined relationship was by way of a bit of popular mythology. Doctors, I've found, are as prone to simplistic thinking as anyone else. Therefore, they didn't object when in a classic of faulty logic, the following syllogism was constructed: "Males have most of the heart attacks and males have most of the testosterone, therefore testosterone causes heart attacks. Only, it ain't so. A long string of studies has demonstrated the opposite. Consider a few of the most recent.

Dr. Gerald Philips's team at the Columbia University College of Physicians and Surgeons followed fifty-five men with chest pain or other signs of atherosclerotic heart disease and set about measuring their levels of testosterone. Then they took angiograms (pictures of their coronary arteries) and found that there was a clear correlation. The men with low levels of testosterone were far more likely to have significantly clogged arteries than the men with high levels. Moreover, the men with low testosterone levels had higher levels of such cardiovascular risk factors as fibrinogen and insulin and lower levels of heart-protective HDH (good) cholesterol.

These are fairly convincing indications that testosterone is heart protective. Here are three other studies. In one, Swedish researchers gave testosterone for eight months to twenty-three middle-aged men. The men's blood sugar, diastolic blood pressure, and cholesterol all went down, and their insulin resistance improved. In another study, Dr. Joyce Tenover of the University of Washington gave testosterone to thirteen men whose natural levels were low and their muscle mass increased and both their total cholesterol and their LDL ("bad") cholesterol went down. These men randomly received injections of either testosterone or a placebo for three months. Dr. Tenover reports that twelve of the thirteen men knew without being told in which period they were receiving testosterone because they became aware of an increase in their sex drive, in their assertiveness in business dealings, and because of an improvement in energy level and general sense of well-being.

The final study is significant because of its relatively greater size. Epidemiologists at Vanderbilt University Medical Center examined the records of the Caerphilly Heart Disease Study, which followed 2,512 men in Wales between 1978 and 1982. Those who develope4 heart disease were found to have had significantly lower testosterone levels than their healthier brethren. Most heart protective indicators, including levels of good HDL cholesterol, were higher in the high-testosterone males.

TESTOSTERONE RESTORES VITALITY

And what if you're already old and somewhat tired? Can testosterone make a major difference? Although in my own practice, I usually combine testosterone replacement therapy with the other pro-longevity hormones; I've also talked to doctors whose specialty is testosterone. They report remarkable examples of relative rejuvenation from testosterone alone.

Dr. Eugene Shippen had an eighty-three-year-old patient named Jasper Saloway, who was recently widowed. At first, Jasper was severely depressed, but eventually he acquired a woman friend and began a romantic relationship. His depression went away, and his mood and functioning seemed excellent. But then, in the following year, he started going through a decline. He had headaches and dizzy spells, and his sex function declined. Dr. Shippen measured his testosterone level and found it was very low-around 150—very far from the desirable range of 500 to 800 ng/dL. He persuaded him to start taking testosterone, and around six weeks later Jasper came in for a review. His symptoms had gotten markedly better, and his energy level was much higher.

"But what about sex, Jasper?" Dr. Shippen asked.

"Oh, that—I got an erection you could have hung a paint bucket on."

We've already mentioned that testosterone can have positive effects on mental functioning. Another one of Dr. Shippen's patients was a dramatic example.

Charlie McCormick was a retired lawyer, eighty-five years old and happily married for more than fifty years. He gave every indication of someone who was becoming senile. He had been going downhill in energy and zest for a couple of years, but now when he came with his wife to see Dr. Shippen, the prognosis looked pretty grim. He sat slumped in his chair, not speaking, and didn't seem able to understand the questions that the doctor was asking him. Eventually Dr. Shippen had to get all the answers from Charlie's wife, and when Charlie left the room to have his blood drawn, she told him that he was like this almost all the time now. To Dr. Shippen this looked as if it were the early stages of Alzheimer's or else severe atherosclerosis affecting the oxygen supply to the brain. But under the circumstances and looking at the low testosterone on Charlie's blood test, he decided to gamble on its being hormonal shortages. With some difficulty, he convinced the McCormicks to try testosterone and come back to see him again in a few weeks.

When they did, Charlie looked more energetic, but, more importantly, he was able to understand all the questions that Dr. Shippen asked him. At another visit a few weeks later, the improvement was still more evident. Charlie was telling jokes and holding up his end of a reasonable conversation. Charlie's wife told the good doctor that he was a miracle worker. That was two years ago and since then Charlie—still on testosterone—has been feisty, functioning, and essentially back to normal.

It is simply a fact, which I have seen repeatedly in clinical practice, that a significant percentage of older people who seem to be failing have nothing seriously wrong with them except a correctable shortage of hormones—almost always the hormones we're writing about here.

WHO NEEDS TESTOSTERONE?

In a young man, testosterone levels will generally be between 800 and 1100 nanograms per deciliter (ng/dL). As men age, this goes down quite unpredictably. There are seventy-year-olds whose testosterone will be as high as 700, and others who will be at 200 or even lower. In my experience—and many doctors I've spoken to quote numbers not far different from this—a man with low blood levels of testosterone will experience a satisfying improvement in his energy and general well-being if he takes replacement doses that bring his levels into the 500 to 800 range. There does not seem to be any reason to aim for the high end of the youthful scale.

If a man has been experiencing loss of sexual interest or occasional impotence, testosterone replacement can sometimes result in dramatic improvement. And some doctors have noted that a testosterone cream placed directly on the penis can help with erectile difficulties. But do remember that testosterone is not a cure-all. There are serious sexual problems that are not testosterone related. Impotence can result from advanced atherosclerosis that has severely weakened the blood supply to the penis (heavy smokers are particularly subject to this); from extreme obesity; and from diabetes, which sometimes damages the blood vessels and nerves in the penis.

The PSA Dilemma

Men are rightly fearful of prostate cancer, now the second highest killer cancer in males, and this sometimes makes them hesitant to embrace testosterone replacement. The prostate, a gland about the size of a walnut, makes the liquid portion of semen, tends to enlarge with age, and not infrequently becomes cancerous. It is usually a slow-growing cancer, and autopsies have shown that one out of three men who die over the age of eighty from other causes had prostate cancer without knowing it.

In the last decade, a test for a substance in the blood called prostate-specific antigen (PSA) has been refined sufficiently to give doctors a shot at diagnosing prostate cancer without a biopsy of the organ. It's usually considered—all other things being equal—that a middle-aged man with a PSA over 4 has some possibility of cancer; if the PSA is over 10, the indication becomes stronger, and a biopsy will be performed if it persists. Men with enlarged prostates or prostate infections (prostatitis) can have prostates in the 4-10 range and be quite free of cancer, so it's useful to estimate the size of the prostate and do a PSA-volume ratio in order to avoid unnecessary biopsies. A progressively rising PSA, in the absence of infections or other inflammation, is an indication for biopsy.

The relationship of all this to testosterone is quite simple. There is no evidence that testosterone will produce cancer cells in the prostate if there are none there, but it will stimulate cancer-cell growth that has already begun.

Thus, testosterone replacement therapy should always be accompanied in any man over forty with regular—preferably twice yearly—PSA tests and a yearly manual prostate exam. Because of this precaution, we can say that testosterone, far from being a cause of prostate cancer, will help to act as an early warning system. If any suspicion of prostate cancer does arise, a decision will almost certainly be made to stop testosterone therapy.

Administration

Testosterone can be administered through an unusual range of methods, and many doctors are vigorous advocates of different modes of administration. The one thing that can be said for certain is that oral administration of the natural form is poorly absorbed. Most oral testosterones go through the portal vein from the intestine to the liver and the liver inactivates a sizable percentage of the hormone. Some of this loss can be avoided by using the micronized form of testosterone suspended in oil. Some of that bypasses the liver and is absorbed by the lymphatic system, but, in my experience, such testosterone stays in the body for only an hour or two, and the effects rapidly fade. There are synthetic forms of testosterone—such as methyl-testosterone—which are well absorbed by mouth, with a long half-life, but I strongly advise against using them since there are reliable reports associating them with cancer of the liver.

Of the remaining methods of administration, I usually advise either injections or the use of creams and gels that are absorbed through the skin. The long-acting injectable testosterone comes in two forms, enanthate and cypionate. Both are in thick, viscous solutions to prolong their action. Once injected, the testosterone is slowly released into the body over a two- to three-week period, and during that time a more steady level of testosterone is maintained in the body—although it does slowly decline during that time. Between 100 and 200 mg are injected every two to three weeks. Blood levels are monitored. However, because of the thickness of the solution, a testosterone injection requires a relatively large needle, and some men are not enthusiastic.

Fortunately, creams and gels also work well, if applied daily on schedule. In fact, Dr. Eugene Shippen favors them over injections, because he believes the more variable levels they cause during the day are a better copy of what the body does on its own. Your body produces the lion's share of its testosterone during the nighttime hours—which is why young men so often wake with erections—and by applying a cream or a gel just before bedtime, a similar effect can be achieved. The cream is rubbed into the thin skin of the inside the thighs or the back, where absorption is best. If your pharmacy has the testosterone imbedded in a patch, you may opt for this mode, which is a little bit neater. Some men, however, will find that a patch can cause skin irritation. If you don't use a patch, the testosterone cream or gel should be well rubbed in.

There is yet another method of receiving testosterone. Drs. C. W. Lovell and Charlton Vincente have treated thousands of patients using pellets implanted under the skin in the upper buttocks once every six months. This method delivers a constant blood level of testosterone over a long period. Clearly, for maintaining a youthful testosterone profile, it's an excellent approach. There is, however, the inconvenience of a minor surgical procedure twice yearly. The cost of the procedure is not unreasonable.

All these methods are valid approaches to replacing testosterone, and I think men who are over fifty and whose blood levels of testosterone are below 400 should begin to consider such a replacement plan. The female menopause has become a standard subject for medical treatment. The less well defined male pause—the andropause—is certainly medically treatable, too. In my opinion, we men deserve no less.