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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.

How to Test Testosterone Level?

While it is convenient to think of testosterone as “the male hormone,” there is still more to the story. When testosterone leaves the testicles, it is immediately seized upon and yoked to a blood protein called sex hormone binding globulin (SHBG). The SHBG + Testosterone complex is what the standard testosterone test measures. But when testosterone is linked this way to SHBG, it is ineffective as a male hormone. Only when testosterone is “free” can it work properly. Most often, doctors measure total testosterone levels, not the “free” testosterone. This works out well for younger men.

However, for men past the age of fifty, the “free” testosterone measurement provides a more accurate reflection of their male hormone output, as does another test referred to as “bioavailable testosterone” (BT).

How to Enhance a Man’s Testosterone Output?

Three techniques, one old and two new, have been developed to allow men to increase the testosterone output of their testicles.

Human Chorionic Gonadotropin is an LH surrogate. The testicles of men with secondary hypogonadism are inherently normal but lack the appropriate stimulus to make testosterone. If that stimulus can be provided, the testicles should be able to function once again.

Produced by women during pregnancy, human chorionic gonadotropin (hCG) acts directly on a man’s testicular Leydig cells to stimulate testosterone production. Synthetic hCG is available and when injected into the muscle of the shoulder or buttocks enters the bloodstream and acts just like LH to provoke a brisk increase in serum testosterone levels. Unfortunately, the effect of a single hCG injection is short-lived; twice-weekly injections are needed. This is more troublesome than a testosterone injection once a month. Today, hCG treatment is reserved for infertile men with low sperm counts.

HCG acts directly on the testicle, bypassing the hypothalamus and pituitary. The two new treatment methods increase testosterone production by activating a man’s hypothalamus or pituitary.

GnRH Pump Therapy. Dr. William Crowley of Massachusetts General Hospital has developed a small battery-powered pump that is loaded with the hypothalamic hormone GnRH. The patient wears the device on his hip. A thin tube extending from the pump ends in a needle that is placed under the skin of impotent men with GnRH deficiency (idiopathic hypogonadotropic hypogonadism). The pump is programmed to release pulses of GnRH to stimulate pulsatile release of both pituitary LH and FSH. Exposed to LH pulses, the testicle starts manufacturing testosterone, and potency is restored. Pulsatile FSH release is also activated so that sperm production increases gradually. This enables a group of men previously thought to be hopelessly impotent and infertile to have a normal sex life and become fathers.

Clomiphene. Clomiphene, a medication commonly used to treat infertile women, can also stimulate testosterone production in some men with secondary hypogonadism. Clomiphene is effective in men because it increases pulsatile pituitary LH stimulation of the testicle. Early pilot studies have been encouraging. One clomiphene tablet every other day can maintain normal testosterone levels. This avoids the peaks and valleys of blood testosterone values resulting from testosterone injections. We know this about clomiphene because several investigators, my own group included, have performed clinical investigations to determine how this medication activates and enhances testosterone secretion in men. Clomiphene therapy for men is still considered an experimental or investigational treatment. Clomiphene is currently an FDA-approved medication only for the treatment of infertility in women.

Newer Testosterone Delivery Systems

In addition to the testosterone patches, other products are just now being developed for testosterone-deficient men. One company is developing a sublingual (under the tongue) testosterone pill that allows testosterone to be absorbed through the mouth, bypassing the stomach and thereby avoiding the liver toxicity associated with currently available testosterone tablets. Another pharmaceutical firm is investigating testosterone and dihydrotestosterone gels that are rubbed directly on the skin and absorbed into the bloodstream. These gels will be sold as “single-dose sachets.” The sachets will look like the ketchup packets currently available at local fast-food chains. Men will tear the top off the sachet and rub the gel on the surface of their skin. Absorption is rapid, and blood testosterone levels increase within a few minutes to an hour after the gel is applied. In early studies, rashes have not been a problem. A new drug application for the testosterone gel is currently pending before the FDA.

Others are working on the development of very long-acting testosterone implants to provide a stable source of testosterone for several months. The impetus for the development of this wide array of testosterone products may relate to the perceived needs of the increasing numbers of healthy older men in whom advancing years and retreating testosterone production coincide.

Problems with Testosterone Patch Therapy

To be effective in transferring testosterone from the patch into a man’s bloodstream, patches must remain in close proximity to the skin. The adhesive in the patch usually takes care of this, but the bond between the adhesive and skin breaks down when men sweat. None of the patches are effective when wet. Men who like to go to the gym to exercise learn this very quickly and will often remove their patch and store it on a shelf in their lockers just before starting their workout. Then they can work up a sweat during exercise or plunge into a pool or hot tub without compromising the effectiveness of their patch. When they have concluded their workout they can shower and towel off, and once dry, can safely reaffix the testosterone patch to maintain its effectiveness.

It is not just those men who exercise at the gym who must follow these guidelines. Men who sweat copiously while gardening or doing heavy labor or perspire during periods of increased stress must be aware that sweating will limit the effectiveness of their testosterone-impregnated patches and take similar precautions.

Skin Reactions with Testosterone Patches

The key element needed for the patches to work is a substance called a chemical “enhancer.” It is the enhancer that makes it possible for testosterone to get out of the patch, go through the skin, and enter the bloodstream. Differences in enhancer properties define both effectiveness and toxicity, with Testo-derm’s enhancer working only when applied to thin scrotal skin, whereas the enhancer in the Androderm and Testoderm TTS patches is significantly stronger, permitting diffusion of testosterone across all skin surfaces, but not without extracting a toll. Skin irritation, rashes, itching, and occasionally blisters and hives are among the reactions commonly associated with the use of the Androderm and Testoderm TTS patches. (Curiously, skin irritation is less common with the scrotal Testoderm patch.) Some men have no skin irritation at all with either the Androderm or Testoderm TTS body patch, whereas others do. Men who have fairer skin seem to be more likely to develop these skin reactions and rashes. Those who are susceptible to skin reactions can minimize or totally prevent the occurrence of the rash by pretreating the skin with a pea-sized dollop of a cortisone-like cream called triamcinolone. (I usually offer a prescription for triamcinolone cream whenever I write a prescription for either Androderm or Testoderm TTS patches.)

TREATMENTS TO INCREASE A MAN’S TESTOSTERONE LEVELS

Testosterone Pills and Injections

Hormone therapy returns sexual function to the vast majority of men with specific disturbances in their body chemistry. The basic principle of any hormone therapy is to re-create a state of hormonal equilibrium. For men with thyroid or adrenal hormone disorders, this can be accomplished with hormone pills. Unfortunately, such is not the case for impotent men with testosterone deficiency.

Testosterone pills are available, but they are less effective than testosterone given by injection. Testosterone pills are not well absorbed from the stomach, and blood testosterone does not always reach useful therapeutic levels. The pills also have a serious side effect — liver damage.

Giving testosterone injections once a week, every two weeks, or even once a month, although effective, causes wide fluctuations in serum testosterone levels, with highest values occurring shortly after injection. Then, with normal metabolism, levels fall until the next injection. This results in a variable sexual response. Adjusting the dose or frequency of testosterone injections smoothes out testosterone levels and maintains a steady state of sexual function.

Testosterone Skin Patches

Prescribing testosterone has, until recently, been fairly prosaic, for doctors had only to choose between the daily administration of a testosterone pill or periodic testosterone injections to maintain normal testosterone levels in the bloodstream of testosterone-deficient men. Testosterone pills had been under a cloud because they were burdened by a legacy of liver toxicity. No comparable problem plagued testosterone injections, but even though they were safe, their effectiveness depended on their being given as deep intramuscular injections every two to three weeks. Although both testosterone pills and injections worked, they were considered to be far from ideal, and scientists started looking for new, less toxic and more convenient ways to provide a man with the testosterone he needed. That is what spurred the development of the testosterone skin patch.

Doctors have been rubbing medications on the skin surface for years with good results, for they knew that blood circulating under the skin and nourishing it would absorb and transport medicine from the skin into the bloodstream. Cigarette smokers eager to stop can go into any drug store and pick up a set of nicotine-impregnated skin patches programmed to deliver progressively decreasing amounts of that drug to help them kick the nicotine habit.

Today postmenopausal women have, at their disposal, a variety of estrogen-containing pills and at least two different types of estrogen skin patches to overcome their diminished estrogen production, but until recently, the production of a testosterone patch seemed to stymie scientists. However, the technical problems that plagued early efforts of testosterone-patch development have been overcome. Today, there are three testosterone skin patches available. They are marketed under the names Testoderm, Androderm, and Testoderm TTS.

All three patches provide a steady supply of testosterone, helping to stabilize serum testosterone levels in testosterone-deficient men, and they avoid the dramatic swings in serum testosterone levels that occur with testosterone injections. However, to maintain their effectiveness, patches must be changed daily and applied properly.

Thyroid Hormone Disorders

The thyroid hormone thyroxine stabilizes the body’s metabolism and allows us to proceed on an even keel from day to day. Both excessive and inadequate thyroxine production (hyperthyroidism and hypothyroidism) can interfere with normal male sexual function.

The diagnosis of thyroid hormone disorders is usually not difficult in young men. Nervousness, palpitations, weight loss, tremor, and anxiety are manifestations of excessive thyroid hormone secretion. Fatigue, lethargy, slowness of thought, constipation, dry skin, cold intolerance, and a deepening voice are indications of hypothyroidism.

In the older man, symptoms are more subtle. An irregular heartbeat or unexplained weight loss may be a clue to an overactive thyroid. Memory loss can reflect inadequate thyroid production. In the middle-aged or older male, impotence may be the only obvious evidence of either condition.

Daniel, a fifty-two-year-old scientist, became impotent shortly after his divorce. His impotence was thought to be related to depression, and he had been seeing a psychiatrist for about one year. He had made some progress coping with his postdivorce depression, but his impotence persisted. Now he had a new problem — his left breast seemed to be growing.

Physical examination revealed a rapid pulse and a slightly enlarged thyroid. Daniel’s’ left breast was indeed large and glandular. His hands trembled. The thyroid enlargement, increased breast size, rapid pulse, and tremor suggested the possibility of an overactive thyroid. Blood tests provided confirmation. With treatment, thyroid hormone levels normalized, breast tissue receded, and potency was restored.

Disorders of thyroid function are generally not considered in the evaluation of impotence despite the fact that loss of libido (in about 70 percent of cases), impotence (in about 55 percent of cases), and breast enlargement (incidence unknown) are prominent in hyperthyroid men. It remains unclear exactly how hyperthyroidism predisposes men to these sexual problems. The hyperthyroid state does create several associated hormonal abnormalities. Testosterone production is adequate, but the body converts an inordinate amount of the testosterone into an estrogen hormone (estradiol). Correction of the hyperthyroidism diminishes the stimulus for excessive estrogen production and coincides with a return of libido and potency.

Men with underactive thyroids tend to have low serum testosterone levels. Correction of the hypothyroidism usually allows serum testosterone levels to return to normal, and sexual function resumes. Unfortunately, some hypothyroid patients experience failure of both thyroid and testicular hormone secretion. For those men, treatment with thyroid hormone and testosterone together is necessary to restore metabolic, and then sexual, health.

Men with hypothyroidism have one other hormone abnormality that contributes to their sexual dysfunction. Their serum prolactin levels are often elevated. For them, bromocriptine treatment is unnecessary; thyroid hormone alone will normalize prolactin levels. Once prolactin levels normalize, sexual function resumes.

Tumors of the Hypothalamus

Although the hormones responsible for triggering testicular hormone secretions are based in the pituitary, hormones released by an area of the brain called the hypothalamus govern the fate of these pituitary hormones. Tumors of the hypothalamus severely limit the pulsatile release of hormones.

Hormone pulses must occur with sufficient frequency and reach sufficient amplitude to be effective. If the pulses occur infrequently, or with too little vigor, testosterone levels fall and men become impotent.

Time takes a toll on the intensity of the hypothalamic-pituitary signal to the testicle. With aging, the hypothalamus slows down and pulses with less strength. This may be one of the explanations for the fall in testosterone levels in men as they age.

What Is Prolactin and Why Does It Disrupt Male Sexual Function?

We frankly do not know why men have prolactin-producing capability at all. Prolactin serves an important function in women, but only at a specific moment in their reproductive lives. At the end of a woman’s pregnancy, her pituitary produces and releases generous amounts of prolactin into the bloodstream to stimulate breast-milk production. Nursing mothers usually have no menstrual periods because prolactin levels, when elevated, extinguish the pulses of pituitary hormones required to activate the normal menstrual cycle. When a woman stops nursing, prolactin levels decrease, pulsatile pituitary hormone secretion resumes, and menstrual function returns.

How does this relate to impotence in men? The same hormonal events that cause hyperprolactinernic women to stop menstruating while they are nursing also causes hyperprolactinemic men to become impotent.

Elevated serum prolactin levels create two problems that are inimical to sexual potency. With high serum prolactin levels, normal pulsatile GnRH and LH secretion does not proceed. This is why nursing mothers stop menstruating. Without pulsatile LH release, a man’s testicle is stranded without adequate stimulation and cannot produce its full ration of testosterone. Serum testosterone levels then fall. But giving more testosterone is not the remedy because elevated serum prolactin levels also prevent the body from responding normally to testosterone.

Two treatments — one surgical, the other medical — curtail excessive prolactin secretion by the pituitary.

Surgical removal of the prolactin-secreting pituitary tumor eliminates the source of excessive prolactin. Unfortunately, excision of only the pituitary tumor, while desirable, is not always feasible. Whittling away at the pituitary mass does make a significant dent in prolactin secretion but rarely decreases it to the normal range. In these cases, impotence persists.

Doctors have discovered that a chemical in the body called dopamine normally reins in pituitary prolactin secretion in men. Without dopamine, prolactin levels increase. A selective doparnine deficiency in the hypothalamus is therefore presumed to be responsible for hyperprolactinernia in men. By restoring dopamine levels to normal, pituitary prolactin production is suppressed.

Three medications, bromocriptine (Parlodel), pergolide (Permax), and cabergoline (Dostinex) have doparninelike properties, and any of them can

be an effective dopamine surrogate. When hyperprolactinemic men or women are treated with bromocriptine (Parlodel), pergolide (Permax) or cabergoline (Dostinex), serum prolactin levels promptly return to normal. Continued treatment is required to keep prolactin levels fully suppressed.

This treatment has been effective in two respects. Lowering serum prolactin levels to normal restores sensitivity to the sexual effects of testosterone. As serum prolactin levels fall, serum testosterone levels increase and potency returns. Bromocriptine (Parlodel) or cabergoline (Dostinex) treatment also decreases pituitary tumor size and shrinks prolactin-secreting tumor tissue.

In some impotent hyperprolactinernic men, bromocriptine (Parlodel) or cabergoline (Dostinex) treatment alone suffices. Men with recent onset of impotence and small pituitary tumors are more likely to respond. Other men, especially those with large pituitary tumors, are not able to revitalize their own testosterone-producing capability without the additional help of testosterone injections or patches. Once serum prolactin levels are normalized, these impotent men regain their responsiveness to the sexually stimulating effects of testosterone.

Vincent was forty-one, weak, fatigued, impotent, about to lose his business and maybe his wife. His doctor noted that Vincent had unusually low blood pressure and small testicles. X-rays disclosed an enlarged pituitary, and blood tests established that — as a consequence of inadequate stimulation from his pituitary — adrenal, thyroid, and testicular hormone production were subnormal. Treatment with adrenal and thyroid hormones so invigorated Vincent that he was able to return to work, and his business prospered. Testosterone injections normalized serum testosterone levels, but he remained impotent. Ordinarily, testosterone-deficient men experience a brisk increase in sexual desire and potency with testosterone therapy. Treatment failures occur in men who have, in addition to their testosterone deficiency, other problems such as neuropathy, vascular disease, depression, or hyperprolactinemia. In Vincent’s case, hyperprolactinemia was the culprit. His large pituitary gland, incapable of supporting function of his adrenal, thyroid, or testicle, was not totally inert, for it continued to produce prolactin in exorbitant amounts. Only when bromocriptine treatment normalized serum prolactin levels were testosterone injections effective in restoring Vincent’s sexual drive and potency.

Bromocriptine was the treatment of choice once it was established that Vincent’s sexual problems were linked with his high serum prolactin level. At that time, bromocriptine was the only medication available to normalize his serum prolactin level.

Subsequently another prolactin-lowering medication, pergolide (Permax), was made available. Both bromocriptine and pergolide will lower prolactin production, but to be effective, they must be taken every day. Cabergoline (Dostinex) also lowers prolactin production but differs from bromocriptine and pergolide because of its long duration of action. Taken once a week, or at most twice weekly, cabergoline is all that is needed to normalize serum prolactin and testosterone levels in the majority of hyperprolactinemic men and women.

Pituitary tumors are not the only causes of hyperprolactinemia. Many drugs used to treat high blood pressure, emotional problems, and gastric problems can compromise the action of doparnine and allow prolactin levels to increase. These problem drugs include reserpine (Serpasil), methyldopa (Aldomet), chlorpromazine (Thorazine), trifluoperazine (Stelazine), thioridazine (Mellaril), haloperidol (Haldol), prochlorperazine (Compazine), and metoclopramide (Reglan).