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Andropause - The Male Andropause

The Male Andropause

1996 Michael Schachter, M.D., F.A.C.A.M.

Between the ages of 40 and 55, men can experience a phenomenon which is similar to the female menopause that is referred to as male andropause.

When a woman reaches her late forties or early fifties, she undergoes bodily changes associated with reduction of female sex hormones and the ending of her periods. These changes are often associated with symptoms such as hot flashes, mood swings and/or depression, vaginal dryness, atrophic changes in the vagina and skin, reduced sexual desire, and an accelerated bone loss leading to osteoporosis. These changes in a woman are called the female menopause. The symptoms and signs associated with this condition can generally be corrected with the judicious use of natural hormonal replacement therapy. Unfortunately, most gynecologists today do not use natural female hormones for replacement, but rather synthetic hormones or hormones that do not entirely match the female hormones that are being replaced.

The concept of a male andropause has been more controversial than that of the female menopause, with many arguing that it doesn't exist. part of the reason for the controversy is that, in contrast to women, men do not have a clear-cut external signpost, namely the cessation of menstruation. Nevertheless, even though women do have this clear-cut demarcation, the changes that take place in their bodies associated with the stopping of menstruation, occur gradually over months or even years. This period, during which a woman may experience irregular menstrual periods, hot flashes, mood swings and other bodily changes, is often called the peri-menopausal period.

A man often begins to experience changes in his body somewhere between ages 40 and 55. These bodily changes may be accompanied by changes in attitudes and moods. During this time a man frequently begins to question his values, accomplishments and the direction of his life. The entire gestalt of these changes has led to the notion of the mid-life crisis. In this series, I'll not focus on all aspects of these changes, but rather on the physical bodily changes that has been termed the male menopause or andropause. We'll look at what occurs and what can be done to slow down these inevitable changes of aging.

The physical changes that occur with andropause may be divided into: (1) urinary and sexual changes and (2) more generalized changes. The urinary-sexual changes, which may occur in any combination and in varying degrees, include: (1) reduced sexual desire or libido, (2) reduced sexual potency or difficulty developing or maintaining erections, (3) ejaculatory problems, (4) reduced fertility, and (5) urinary problems, such as increased urinary frequency-especially at night, a weak urinary stream, hesitancy during urination, difficulty starting urination, and urinary incontinence. All of these changes, as I shall show, may be due, at least in part, to a gradual failure of the testes' production of testosterone, the male sex hormone. This would be analogous to the changes seen in a woman, who at the time of menopause, has a reduction in the female sex hormones, estrogen and progesterone.

Metabolic Effects of Testosterone

The importance of testosterone to sexual and urinary functioning seems intuitively evident. What is not so apparent is the role of testosterone in more generalized functions. Testosterone is an anabolic hormone, which means it helps to build protein tissue, including muscles, bones and connective tissue. This gives it a role in preventing and treating osteoporosis in both men and women. Testosterone is helpful in building muscle mass, as every weight lifter knows. Unfortunately, many weight lifters and athletes misuse the synthetic analogues of testosterone, called anabolic steroids, by taking excessive doses, which can result in serious adverse consequences. A deficiency of testosterone may bring about a weakness in muscles and bones. This tissue deficiency of testosterone is characteristic of the andropause.

Testosterone has additional profound metabolic effects. It plays a role in preventing and treating diabetes mellitus. This disease is characterized by high blood sugar because the cells are not able to take in sugar and metabolize it properly. Sugar enters the cells of the body as a result of the action of insulin combining with insulin receptors on the cells. A problem with these insulin receptors may result in a reduction of sugar entering the cells and consequently an increase in blood sugar characteristic of diabetes. Testosterone helps the insulin receptors to work more efficiently, thus reducing the tendency toward diabetes, which increases with age.

Another role of testosterone is to help regulate the immune system. patients with autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis appear to benefit from testosterone. It has been used to improve appetite, increase weight in malnourished patients, improve wound healing and increase resistance to infection. By building protein, it builds body mass while at the same time reducing obesity. It also seems to lower serum lipids, such as cholesterol and triglycerides and has been used in Europe to treat patients with gangrene of the feet, coronary artery heart disease, high blood pressure, and other cardiovascular diseases. A man's general motivation, aggression and drive also seem to be related to tissue levels of testosterone.

So, the reduced production of testosterone by the testes with aging may indeed contribute to many of the physical, emotional and mental changes that are seen during this andropausal period. The question then becomes whether or not men may benefit by the administration of natural testosterone in physiologic doses to replace deficient testosterone of andropause. This is directly analogous to the use of natural female hormones, estrogen and progesterone during menopause in women. Furthermore, just as younger women may benefit from the administration of natural female sex hormones if they are deficient for various reasons, so may younger men benefit from the administration of natural testosterone if they are deficient.

What is testosterone and how does it relate to other hormones Testosterone, like all of the other sex hormones, is chemically a steroid hormone. A steroid is an organic (carbon containing) compound consisting of a four-ring structure. In addition to the sex hormones, estrogen and progesterone, other steroid compounds important to the body are vitamin D, cholesterol, and hormones from the adrenal cortex, including cortisone, hydrocortisone, aldosterone, and DHEA. Cholesterol, that most maligned compound, is the mother of all of these compounds.

Testosterone works directly on many tissues of the body. But, dihydrotestosterone or DHT, a hormone derived from testosterone, is much more potent than testosterone, and acts on the prostate gland and other sexual organs. DHT is produced within the prostate gland and some other organs from testosterone by the enzyme 5-alpha reductase. Without DHT a male would not develop his external sexual organs or his prostate. DHT is necessary for the normal growth and development of the prostate. Its presence is also necessary for the pathologic enlargement of the prostate, known as benign prostatic hyperplasia (or BpH) in older men. Because the presence of DHT is necessary for the development of BpH, a recent therapeutic approach to treating this condition is to reduce the formation of DHT by blocking the enzyme 5-alpha reductase. This can be done by the new, highly promoted drug finasteride (or proscar), which has been approved by the FDA for this purpose. The herb serenoa repens (or saw palmetto) also has this effect, as one of its actions. What is not discussed in the literature of these 5-alpha reductase inhibitors is that testosterone may be converted to one of two compounds. The first is DHT as we've been discussing. The second is estradiol, the female sex hormone. So, a blockage of DHT formation, may lead to an increased level of estradiol via the enzyme aromatase. Increased levels of estrogen may play a role in the development both of prostate cancer and BpH.

The position of most urologists has been to view the therapeutic use of testosterone, especially for men with enlarged prostates, with great skepticism, since its presence is needed for the development of a benign prostatic hyperplasia or BpH. Other reasons for urologists reluctance to use testosterone include: (1) early testosterone enthusiasts promoted the belief that testosterone held the key to the fountain of youth, a view ridiculed by conventional medicine, (2) the fact that since the 1940's, it has been known that the growth and spread of prostate cancer was largely dependent upon the presence of testosterone, and (3) the abuse of testosterone analogues or anabolic steroids by athletes, resulted in the FDA classifying testosterone and derivatives as dangerous drugs.

Although the predominant view about benign prostatic hyperplasia or BpH is that it is due to a buildup of DHT, this hypothesis is far from proven. Two conditions must be present for BpH to occur. They are: (1) a man must be at least in his forties or fifties, as it never occurs in younger men, and (2) DHT needs to be present for BpH to occur. But, as men grow older, their blood levels of testosterone and DHT tend to decrease rather than increase. A more characteristic finding in BpH is that estrogens and the estrogen to testosterone ratio tends to increase with age in men. It is this increased ratio of estrogen to testosterone that may be more responsible for the development of BpH and prostate cancer than DHT and testosterone.

Dr. George Debled's Testosterone Treatment

This is the argument presented by European urologist, George Debled, M.D. Since the mid 1970's, he has run a clinic for men, which specializes in sexual dysfunction and prostate problems. During this time, he has treated approximately 2,000 patients. On all of these patients, he orders a battery of blood tests, which he calls a male hormonal profile. What he's found is that young men with impotency or libido problems often have hormone profiles similar to older men with similar problems and BpH. Testosterone and especially free testosterone levels are reduced and other hormones, such as estrogen and prolactin are increased.

Dr. Debled points out that testosterone is necessary to nourish all of the tissues of the male urinary and reproductive systems, including the prostate. It nurtures the development of muscles and is necessary for proper muscular functioning. When the muscles of the bladder and the prostate do not receive sufficient testosterone, they tend to function poorly, atrophy and fibrose. This may then help to explain some of the symptoms of BpH. Rather than trying to inhibit the formation of DHT, Debled administers testosterone to all of these patients. Having successfully treated over 2,000 patients with impotency and prostate problems over the past 15 years, Dr. Debled believes that he can forestall BpH surgical procedures for at least 10 years by giving men testosterone. He has also noticed that his patients have a much lower incidence of prostate cancer than would be expected, suggesting that testosterone rather than causing cancer may actually be a preventive. Next week I'll conclude this series on the male andropause.

Men receiving Dr. Debled's testosterone treatment reported improvement in urinary and sexual functioning, as well as a broad range of generalized improvements, including positive effects on muscle strength, the cardiovascular system, the immune system and drive and motivation. Incidence of prostate cancer was reduced, rather than increased.

In the United States, testosterone is available from any pharmacy as an intramuscular injection. Two of the common forms are the shorter acting testosterone propionate and longer acting testosterone cypionate. The former is given two or three times a week and the latter every one to three weeks. The only oral or sublingual testosterone preparation available commercially in the U.S. is methyl testosterone. However, because of the extra methyl group, this is not a natural testosterone. Methyl testosterone has been removed from the market in Europe because of its potential liver toxicity and possible carcinogenic potential. A transdermal patch of natural testosterone applied to the scrotum was recently approved by the FDA.

A variety of natural testosterone preparations are available from compounding pharmacies. These include oral capsules, sublingual lozenges, topical creams and topical gels. The dosage must be highly individualized because of different levels of absorption and because considerable amounts of testosterone taken orally may be lost through liver detoxification mechanisms. The male testes produce about 15 mg of testosterone daily. This fact should be utilized in determining appropriate dosage, since we are simply trying to supplement a shortage of testosterone production.

Dr. Debled's therapy focuses almost completely on testosterone replacement to treat andropause. My view is that this treatment should be incorporated into a comprehensive treatment approach which emphasizes lifestyle, including an optimal diet, nutritional supplements, exercise, stress management, detoxification procedures and energy balancing. part of this program would involve attention to cleaning up the environment. In addition to replacing testosterone if it is deficient, the rest of the endocrine system should also be balanced. This may involve the administration of thyroid hormone, DHEA or physiologic doses of cortisol. Some recent studies on aging indicate that the administration of optimal doses of human growth hormone may also be extremely useful when it is deficient. Male andropause is largely a preventable and treatable condition.

Andropause or Viropause

Keywords: testosterone, DHEA, human growth hormone, androgen, viropause, andropause, male menopause, male climactera, impotence, depression, testicle, testis, midlife crisis

This article discusses andropause or viropause -- a syndrome associated with lack of or absence of testosterone. Even in healthy men, by the age of 55, the amount of testosterone secreted into the bloodstream is significantly lower than it was just ten years before. In fact, by age 80, most male hormone levels have decreased to pre-puberty levels. There are two general forms found in adult men who had normal hormone levels through puberty and young adulthood and who experience normal sexual development. One form, analogous to female menopause, as associated with the rapid drop of testosterone levels. Typical symptoms of this include:

  • Fatigue, loss of a sense of well being -- 82%
  • Joint aches and stiffness of hands -- 60%
  • Hot flashes, sleep disturbances -- 50%
  • Depression -- 70%
  • Irritability and anger -- 60%
  • Reduced libido -- 80%Reduced potency -- 80%
  • premature aging
  • Changes in hair growth and skin quality

Sounds familar..... for women at midlife..... because it is the same condition because the relationship between the ovaries, estrogen, the brain, and the pituitary are exactly the same as the relationship between the testis, testosterone, the brain, and the pituitary. Acute andropause in men is relatively uncommon, compared to acute menopause in women, because testicular function declines gradually in most men. There are a number of common causes, however, for acute testicular failure in adult men and these include:

  • viral infections such as mumps (which fortunately has been eradiacated by immunization)
  • surgical removal of or surgical injury to the testis and male reproductive tract ( testicular cancer, hernia repairs, vasectomies)
  • diseases when the immune system attacks and destroys the testis such as variations of systemic lupus erythematosis
  • subtle genetic abnormalities which permit normal adult development but lead to premature testicular failure (such as chromosomal mosaicism)
  • generalized vascular diseases such as diabetes and perhaps even problems caused by heavy smoking
  • chemotherapy
  • pituitary tumors (very rare)

The second form of this syndrome is more insidious since it occurs gradually. It is often confused with male midlife psychological adjustment disorders because it exactly mimics depression in midlife men. Male hormones decline gradually. Testosterone (from the testis), human growth hormone (from the pituitary), and DHEA and androstenedione (from the adrenal gland) all begin to drop. For many men, this does not occur until their 60s or 70s but there are older where it occurs much earlier. In addition, there is proteins in the blood which bind testosterone in a biologically inactive form. These are called sex human binding proteins or globulins. Their levels can rise in response to many conditions including medical disorders and exposure to other hormones including phytoestrogens (estrogens derived from plant sources such as soy) and other environmental estrogen -like compounds (pesticides, hormones used in agribusiness to produce fatter animals, etc.) As an example, there is some data suggesting that men on low fat or vegetarian diets have lower testosterone levels. The overall effect of rising sex hormone binding proteins is that there is less bio-available testosterone.

Diagnosis

First, men need to disassociate their ego from their testicles. Men needs to realize and accept that this disorder exists, that it is a simple endocrine problem which is no different than thyroid disease or diabetes, and that it can be treated. Spouses and employers also need to be aware that this is real so they can identify these men at risk early before their work, home, and families are disrupted. perhaps, more important, physicians, psychologists, and other health providers need to be taught about this condition. The current paradigm in medicine is that there is no biological basis for behavioral changes in midlife men so it is ignored. But the diagnosis is quite simple--namely measuring either free testosterone blood levels or, as recommended by Dr. Malcolm Carruthers, computing the free androgen index <FAI> (total testosterone x 100 /sex hormone binding globulin). There is some controversy as to what level of testosterone in men is normal with low end values ranging from 250-400ng/dl.

NORMAL ANDROGEN LEVELSmeanrange
Free testosterone -- men700 ng/dl300-1100
Free testosterone -- women40 ng/dl15-70
Free Androgen Index70-100%

At a free androgen index less than 50% , symptoms of andropause appears. Of course, good medical care dictates that a comprehensive medical and psychological assessment along with a thorough laboratory assessment are necessary.

Testosterone Replacement Therapy

There is good evidence that testosterone levels drop as a man ages. There is a huge debate whether the testosterone level in older men should be adjusted up the mean testosterone levels in younger men.

What are the risks

prostate cancer-- At autopsies, most men by age 50 have nests of atypical cells in their prostate which look like prostate cancer cells. There is a great deal of concern among urologists-- particularly in the US when medical malpractice suits are a major concern-- that increasing testosterone levels might activate prostate cancer. On the other hand, there is a good screening test called prostate Specific Antigen (pSA) which all men over age 50 should have performed annually and which is relatively effective in detecting early prostate cancer. There is no evidence in the medical literature that testosterone replacement therapy increases the risk of prostate cancer.

Heart disease--there is a major concern that increasing male androgen levels would also increase serum cholesterol and serum LDL-Cholesterol levels. Oral methyltestosterone in particular will raise blood cholesterol levels. This increases the risk for coronary artery disease. On the other hand, "good" cholesterol (HDL-Cholesterol increases with exercise. Men using testosterone supplementation should have their serum lipids carefully evaluated and rechecked periodically.

Liver Disease--the only orally available forms of testosterone for men in the USA contain methyltestosterone. Unfortunately, if used for sustained periods of time, it can damage the liver. The physicians Desk Reference cites several different forms of liver damage from high dose methyl- testosterone including liver cancer, cholestatic hepatitis, and other liver diseases.

Suppression of testicular function--As a general principle, whenever any hormone is administered, the gland which normal produces it ceases to function and recovery may be variable. patients with borderline low testosterone levels may commit themselves to lifelong therapy if they start with testosterone replacement.

What are the benefits

There is no doubt that the administration to testosterone to men with true testosterone deficency states will improve their health and sense of well being. The symptoms listed above will disappear. Unfortunately, impotence, or the inability to sustain and erection, does not respond well to testosterone therapy except perhaps only in men with severe hormone deficiencies. This comprises approximately 8-16% of men presenting to physicians with erectile disorders. There is no evidence that administering testosterone to men with borderline low testosterone levels will improve sexual functioning. For more information on erectile disorders, see our article on Impotence.

Forms of Testosterone for Men

  • pills
  • Methyltestosterone (Android,Virilon,Testred, Oreton) 10mg, 25mg (not recommended)
  • Testosterone undecanoate (Restandol, Andriol) 40mg, essentially a testosterone in oil preparation (not available in the USA)
  • Mesterolone (proviron) 25mg -- less potent (not available in the USA)
  • Transdermal preparations
  • Testosterone--transdermal (Testoderm, Testoderm TTS, Androderm)

Injections

The following forms of injectable testosterone is available in the USA.

  • Testosterone Cypionate 100 mg/ml
  • Testosterone propionate in Oil 100 mg/ml
  • Testosterone Enanthanate 200 mg/ml

The usual dose is 1cc injected weekly or bi-weekly. This route of administration eliminates the risk of liver damage which may be caused by methyltestosterone as well as eliminating the theoretical risk of changes in cholesterol caused by oral medications. The problem is fluctuating hormone levels and the discomfort of administration.

Subdermal pellets

Many years ago, the Food and Drug Administration approved the use of testosterone pellets for male hormone deficencies. They are manufactured in our office by a compounding pharmacist. We place 6-8 testosterone pellets under the skin. These pellets dissolve slowly over a period of approximately three to four months. This provides a normal and very stable serum testosterone level. I feel that the addition of androgens in this form causes less lowering of HDL cholesterol, as this does not pass through the liver.

The implant procedure consists of a small incision through which a trocar and cannula are inserted. The pellets are inserted through the cannula, and then the cannula is withdrawn. The incision is then closed with a Steri-Strip, and pressure is applied until bleeding stops, and the area is then covered with a dressing. We have not had any major problems in terms of side effects from this procedure. Some expertise is required in terms of placing the pellets so that underlying structures are not traumatized.

The average cost per visit (approximately every 3 months) is in the range of $250.00 to $300.00.

For a good reference, check out Malcolm Carruthers MD, Maximising Manhood, Harper Collins, London, 1997

Drs. Caroline Dott and Andrew Dott are professional lecturers and teachers with a special interest in the interactions between the biological and psychological bases of human behavior at midlife. Among their lecture topics are female and male menopause, the hormonal bases of human behavior, and issues related to depression and anxiety. They are available to travel and give seminars on the topics covered in this website both nationally and internationally.

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