Male Menopause (Andropause)
Beginning at about 30 years of age, the level of testosterone in men will decrease about 10% every decade. If testosterone levels fall below a level necessary to sustain hormone-dependent tissues, affected men may suffer from anemia, decreased energy, motivation, and self-confidence, diminished muscle mass, thinning of the skin, abdominal obesity, reduced sexual desire, difficulty with erections, orgasmic dysfunction, and depressed mood. In addition, men with abnormally low testosterone levels are at an increased risk for osteoporosis, cardiovascular disease, dementia, and diabetes. Nonetheless, andropause, also known as male androgen deficiency and male hypogonadism, is one of the most underdiagnosed and undertreated medical conditions.
Andropause is very common, although there is no agreement on the actual prevalence of hormone deficiency in aging men, and estimates vary widely. For example, a study published in the Journal of Clinical Endocrinology and Metabolism in 2001 placed the incidence of andropause in the range of 1 of 5 men older than 60 years of age, 1 of 3 men older than age 70, and half of men older than age 80. In contrast, a study published in the International Journal of Clinical Practice suggested that andropause occurred earlier and was more frequent, affecting more than 1 of 3 men older than age 45.
An andropause that occurs earlier than anticipated (i.e., before the 45 years of age) is usually related to genetic factors, illness, surgery, medical therapy, or trauma.
Causes of Early Andropause
Low HDL Levels
In my own patient population, an underappreciated but common cause of early andropause is an inherited disorder of lipid metabolism. Men who are affected have an abnormally low level of a component of cholesterol known as high-density lipoprotein (HDL). HDL is sometimes referred to as the “good cholesterol,” since cardiovascular disease is less likely to develop in men and women who have high levels of HDL. In affected men, the low HDL level is often accompanied by an elevation of another component of cholesterol known as triglycerides. Men in this category seem to be at greatest risk for an early andropause. This is an important finding, and studies have shown that men with higher levels of testosterone are more likely to have higher HDL levels than men with lower levels of testosterone. Accordingly, all men with low HDL levels should be tested for the presence of an abnormally low testosterone level. In addition, hormone-deficient men (and women) with low HDL levels are also at an increased risk for cardiovascular disease and diabetes. Women with abnormally low HDL and elevated triglyceride levels are also at an increased risk for hormonal disorders, including infertility and menstrual irregularities.
Elevated Prolactin Levels
Some men have an early andropause secondary to an elevated blood level of a pituitary hormone called prolactin. Excess production of prolactin can be due to a prolactinoma (a benign tumor of the pituitary), certain medications, hypothyroidism, or emotional stress. The pituitary is a located at the base of the brain and is sometimes referred to as the master gland because of its role in regulating growth and metabolism. Some prescription medications that are known to elevate the concentration of prolactin in the bloodstream include drugs used for psychiatric disorders such as Stelazine and Haldol, and Reglan, a medication used to treat gastroesophageal reflux. Increased prolactin levels are frequently seen in people with hypothyroidism, and men with elevated prolactin levels should be tested for this problem. Vigorous nipple stimulation may also cause an increase in prolactin. Some authorities think that magnetic resonance imaging of the head should be performed in all men with low testosterone levels that are not directly attributable to any known cause, even if the prolactin level is normal. Their rationale is that prolactin secretion from an existing tumor can be pulsatile or intermittent and may be missed by blood tests.
Cancer treatment, including chemotherapy, radiation, and surgical removal of one or both testicles, is a potential cause of early andropause.
Profound weight loss, compulsive exercising, direct injury to the testicles, and debilitating illness including kidney failure, adrenal insufficiency, and acute psychiatric depression are also potential causes of early andropause. An infection of the testicles such as that caused by the mumps virus can also be responsible for this condition. Although it not generally recognized, hemochromatosis, a disorder of abnormal iron storage, may compromise testicular function.
The Diagnosis of Andropause
Why is Andropause Under-Diagnosed?
The main endocrine glands include the pituitary gland, pancreas, ovaries, testes, thyroid gland, and adrenal glands. These hormone-producing glands secrete their products directly into the bloodstream. Although andropause is the most common disorder of the endocrine system, many if not most physicians do not place this condition high on their list of diagnostic possibilities. Consequently, health professionals attribute known andropause-associated symptoms such as fatigue, changes in body composition, and sexual dysfunction to other causes. Hormone-deficient men are often told that their problems are due to depression, relationship issues, medication intolerance, or “just getting older.”
In addition, the decrease in testosterone levels that characterizes andropause occurs more gradually and is generally less complete than the decrease in sex-hormone levels that accompanies the menopausal process in women. Thus, the symptoms experienced by men are more subtle and typically less severe than those that accompany menopause. And, in contrast to menopause, there is no defining event such as cessation of menstruation or loss of fertility to announce that andropause, whether age-related or early, has transpired.
How is Andropause Diagnosed?
I never make the diagnoses of andropause using blood tests alone. It is important to carefully consider the patient’s history and symptoms as well as to perform a detailed physical examination for changes that may be attributable to hormone deficiency.
What are the Symptoms of Andropause?
The signs and symptoms that suggest andropause are fatigue, infertility, erectile dysfunction, small testes, diminished muscularity and strength, an increase in breast tissue and diminished pubic, axillary, and facial hair. The more severe and prolonged the hormone deprivation, the greater the potential for distressing symptoms and negative consequences. If the deficiency has been longstanding, there may be a loss of bone mineral density leading to an increased potential for fractures. Other potential manifestations include an increase in body fat, mild anemia, poor motivation, depressed mood, irritability, sleep disturbances, and difficulty with concentration and memory.
Do Hormone-Deficient Men Suffer from Hot Flashes and Sweats?
Yes, some men do, but this occurs with far less frequency than would be expected in menopausal women.
What Level of Testosterone is Normal in Men?
Most laboratories report the normal value for total testosterone somewhere in the range of about 240 to 950 nanograms per deciliter (ng/dl) and the normal range for free testosterone about 9 to 30 ng/ml. Total testosterone is a measure of the portion of testosterone that is bound to the proteins in the blood plus the portion that is unbound to blood protein. Free testosterone, the unbound portion, is thought to exert the most hormonal activity or influence on hormone-sensitive tissues. Accordingly, some authorities suggest that assays of free testosterone are the most accurate measure of hormonal activity.
Why Not Just Rely on the Blood Test to Make the Diagnosis?
The blood levels associated with signs and symptoms of with low testosterone will vary from patient to patient. Further, there is no uniform testing method used to assess testosterone levels or agreement by clinicians defining the testosterone level beneath which a patient is considered to be hormone-deficient. Accordingly, the Institute of Medicine, a Washington, D.C.-based organization that serves as a health advisor to the nation, recommends that the symptoms of andropause and not just the testosterone level should be considered in the diagnosis. Nonetheless, many, if not most health professionals persist in using laboratory values as the sole criteria for the diagnosis of andropause. And, unfortunately, if a physician rigidly adheres to this rationale, he or she is underdiagnosing and ultimately undertreating men who are suffering from the symptoms and signs of andropause.
The following story illustrates the problems that hormone-deficient men may encounter in attempting to resolve their problems with hormone deficiency:
Mike is a 65-year-old man who came to my office with symptoms of fatigue, a loss of libido, difficulty with erections, and a diminished urge to ejaculate. “I’m so tired that when I get home from work…I sit down in my chair and I don’t want to get up. I don’t even think about sex anymore, and even if I use Viagra and actually get an erection it doesn’t last long or feel as good as it should. Half the time I don’t even ejaculate, and what’s worse, I don’t even care.” Mike had seen another physician and was told that his testosterone level was “normal” and that his problems did not have a hormonal basis. Mike asked his physician if he could try hormone therapy to see if it made him feel any better. His physician declined, telling him that he was not a candidate for testosterone replacement. I looked at the records Mike had brought with him. His total testosterone level was about 400 ng/dl, a value considered in the lower range of “normal” by most laboratories. Regardless, Mike’s symptoms were suggestive of being andropause-related. I told him that if he was interested, we would start him on a program of testosterone replacement and that there was a very good chance it would resolve some of his problems. Three weeks after starting testosterone, Mike had considerably more energy and a mild increase in his libido. At 8 weeks after beginning treatment, Mike shared that his desire for sex was not like it was when he was 18, but it was “pretty good.” Although he was still using Viagra, he was not having any problems maintaining his erections and sex was more pleasurable. Mike was having intercourse about twice a week, and he had an increase in his desire and ability to ejaculate.
Mike’s story is unfortunately commonplace. He was experiencing symptoms suggestive of hormone deficiency, but he had laboratory evidence of testosterone levels that were low but still in the “normal” range. Consequently, he was told his problems were unrelated to a hormone problem and he was denied a trial of therapy.
The Treatment of Andropause
Andropause is treated by replacing testosterone—the hormone that’s missing. An ideal program of hormone replacement in men would follow the same principles as one for hormone replacement in menopausal women. The difference, of course, is that only testosterone is replaced and that men require a considerably higher dose than would be appropriate for women. Accordingly, the form of testosterone used should be indistinguishable from that produced by the testes and should be delivered into the bloodstream intact and in sufficient quantity to exert its intended effect. I will only mention testosterone- containing transdermal patches, gels, injections, and implantable pellets as appropriate treatment options. Other treatments are available, but they are used with lesser frequency.
Naturally-occurring testosterone is not effective when given as an oral tablet, since it is deactivated during its passage through the gastrointestinal tract. Accordingly, it is necessary to chemically alter the structure of testosterone if it is to be used for oral administration. The most well-known oral preparation is methyltestosterone. These formulations have the potential to cause liver toxicity, and since more ideal options are available, I don’t prescribe them.
Injections of testosterone are an effective and useful therapy, but they must be given at 2- to 4-week intervals. The testosterone level is relatively high in the first few days after the injection and tapers off over the next 2 to 4 weeks, at which time another injection is required.
Androderm is a patch containing testosterone that is applied to the skin once every 24 hours. Testosterone is available in a topical gel form under the brand names AndroGel, Testim, and Fortesta. There is also a topical solution available marketed under the name Axiron. The topical formulations are applied once or twice daily to dry clean skin. Each product has its own specific instructions as to the area of the body where it is to be applied. Testosterone-containing pellets are available and can be surgically implanted into the subcutaneous tissue of the buttock. From there, testosterone is released gradually into the bloodstream. The day-to-day levels are relatively stable, but as would be expected, they decrease over time. After a period of 3 to 6 months, when the testosterone concentration decreases below an acceptable level, the procedure can be repeated.
How Effective is Testosterone Replacement?
If the problems treated are secondary to testosterone deficiency and the replacement regimen is appropriate, the treatment is very successful. Within a few weeks, there is an improvement in energy, motivation, mental processing, and sense of well-being. A return of libido, sexual response, and erectile function typically may take a bit longer, but should be well established by 8 to 12 weeks and should continue to improve over the next few months. Assuming a reasonable diet, a modicum of exercise, and the absence of a significant coexisting disease process, there is an increase in muscle mass, strength, and stamina. Andropause-related bone loss will stop, but unfortunately, if there has been a significant decrease in bone mineral content, a return to the bone density that existed before the patient’s hormone deficiency will not be possible.
Does Testosterone Replacement Always Help Men with Erectile Problems?
Often it does, especially when it is combined with Viagra and similar products such as Cialis and Levitra. This class of medications is known as phosphodiesterase type 5 (PDE5) inhibitors, and when these drugs are used in combination with testosterone, in many cases they are capable of restoring erectile function even when either testosterone or a PDE5 inhibitor used alone has been unsuccessful. In addition, the combination appears to improve orgasmic function. However, if the erectile dysfunction is related to medication, alcoholism, a psychiatric or neurologic disorder, diabetes, a vascular problem, or a debilitating disease, there may be limited or no improvement.
Risks and Side Effects of Testosterone Replacement
Testosterone-replacement therapy, when administered appropriately, is safe and is associated with few side effects. Among the purported risks of therapy, the most important concern for health professionals is the effect of treatment on the prostate and the red-cell concentration of the blood.
For many physicians, the primary concern regarding the use of testosterone replacement in older men is the fear that testosterone replacement therapy will either cause prostate cancer or stimulate the growth of an undiagnosed preexisting cancer of the prostate. However, there is compelling evidence that testosterone replacement in healthy and high-risk men does not increase the risk of prostate cancer. Regardless, pretreatment screening, especially in older men being considered for testosterone replacement, is prudent. The evaluation should include a digital rectal examination of the prostate and a blood test to measure the patient’s serum level of prostate-specific antigen (PSA). PSA is a protein produced by the cells of the prostate gland which is present in relatively small quantities in the serum of normal men and is often elevated in prostate cancer as well as some nonmalignant conditions. For example, the PSA level may be elevated if the prostate is enlarged or if the prostate is inflamed due to an infection. In addition, the PSA level may be elevated for a few days after ejaculation, bike riding, or a digital examination. Regardless, if either the digital rectal examination or the PSA level is abnormal, referral to a urologist to determine the cause for the elevation and to exclude the presence of prostate cancer would be in order before making a decision to begin therapy.
What if a Man is Suffering from Hormone Deficiency but has a History of Prostate Cancer?
Although it is not generally appreciated, a history of prostate cancer is not an absolute contraindication for testosterone-replacement therapy, and withholding therapy in hormone-deficient men who have been successfully treated for this form of cancer is not warranted. In the few men who have been treated with testosterone-replacement therapy after a surgical removal of the prostate, there has been no evidence of recurrence.
Benign Prostatic Hypertrophy (BPH)
BPH refers to the increase in the size of the prostate gland in middle-aged and elderly men. This condition is actually quite common, and about 50% of men have some evidence of an enlarged prostate by 50 years of age and about 75% by age 80. A prostate that becomes sufficiently large leads to symptoms such as urinary hesitancy, the need to urinate frequently, and—in extreme circumstances—urinary obstruction, or an inability to empty the bladder. Some physicians hesitate to prescribe testosterone to men with BPH because of a concern that the therapy will lead to a further increase in the size of the prostate and worsen symptoms. There have been some reports of a modest increase in the size of the prostate in some patients receiving testosterone therapy, but no increase in symptoms. In my own patient population, this has not been a problem.
Increased Concentration of Red Cells in the Blood
In some men, testosterone replacement, especially when administered by injection, has the potential to increase the production of red cells. This is a welcome effect in patients with andropause-associated anemia. The percentage of the blood that consists of red cells is called the hematocrit. If this percentage increases beyond expected normal limits, the blood becomes thicker, or more viscous. The concern is that blood that is more viscous is more likely to coagulate, and patients with thicker blood may have a higher incidence of cardiovascular complications. For this reason, it is important to obtain a pretreatment measurement of the patient’s hematocrit and intermittently monitor the patient’s blood for this possibility. If the patient’s pretreatment hematocrit is found to be elevated, an evaluation to elicit the cause would be reasonable before starting therapy. As a practical matter, men who have an elevated hematocrit before therapy are often discovered to have a genetic disorder of iron absorption. This condition is easily managed, and the patient can use testosterone replacement after the hematocrit is normalized.
What if the Hematocrit Becomes too High While using Testosterone?
If the hematocrit elevation can be attributed to treatment with testosterone, there are a number of effective options for restoring the concentration of red cells to a normal level. They include switching to another form of therapy, reducing the dose, or discontinuing therapy. Most of my patients in whom testosterone-related elevations in their red-cell volume develop are using injections as their form of therapy. Thus, simply switching an alternate method such as a testosterone transdermal gel often resolves the problem.
If Testosterone Injections are Likely to Cause an Elevation in Hematocrit, Why Not Just Use a Testosterone Gel to Begin With?
From my perspective, a testosterone gel is an ideal replacement regimen. However, these preparations are expensive, and if the patient does not have prescription coverage, the expense may be prohibitive. This is particularly an issue for hormone-deficient men who are retired, older than 65 years of age, and purchase their medications on an out-of-pocket basis. Many of my patients find that a good alternative is to obtain testosterone-gel formulations from selected compounding pharmacies, where they are available at a fraction of the cost.
Years ago, I discussed the issue of hematocrit elevations in some testosterone users with the late Dr. R. Don Gambrell, a pioneer in the treatment of sex-hormone disorders of both and women. He told me that he advised his male patients with testosterone-associated elevations of their hematocrit to donate blood to the Red Cross on a regular basis. He said that this lowered their concentration of red cells to an acceptable level and allowed them to continue their treatment. Apparently, his local Red Cross was quite fond of him. I have suggested this approach to some patients, and it has been effective in keeping their hematocrit at reasonable levels. Nonetheless, if these options do not reduce the hematocrit, or if the cause of the elevated hematocrit is in question, referral to a hematologist, a specialist in blood disorders, is indicated.
Are Their Other Side Effects or Risks?
Other purported side effects of nonoral testosterone replacement include sleep apnea, edema, breast enlargement, lowering of the sperm count, skin irritation, acne, oily skin, and liver toxicity.
The association between testosterone therapy and sleep apnea is mentioned in the literature; however, there is no convincing evidence of a causal relationship and I doubt one exists.
Edema, or swelling of the lower legs, has been mentioned in the literature as a potential side effect, but I have seen this only rarely in my patients.
Increase in Breast Tissue
An increase in breast tissue, an unusual side effect associated with testosterone replacement, is troubling to men who are affected. In the past, options for addressing this issue included discontinuing therapy, reducing the dose, radiation therapy, or surgery. Unfortunately, these options were either invasive or denied the patient the benefit of optimum therapy. However, these drastic measures are no longer necessary, since breast-tissue stimulation in susceptible persons can be prevented with the use of an oral medication called an aromatase inhibitor.
Decreased Sperm Count
Monthly injections of testosterone have been shown to reversibly lower the sperm count, but they cannot be relied on to prevent pregnancy. Once therapy has been discontinued, the sperm count will usually return to pretreatment levels.
Skin irritation can be troublesome for users of the testosterone patch Androderm, and the manufacturer recommends that the patch be placed on a different area of skin daily to help prevent this problem. Nonetheless, the skin reaction can be severe and persistent enough in about 5% of patients to require that they discontinue the patch. Skin irritation is less of a problem with the testosterone-gel preparations, and I have not seen it.
Acne and Oily Skin
Acne and oily skin are generally limited to persons who have had this problem in the past. In persons who are receiving testosterone, these conditions are a result of restoring the skin to its pre-hormone-deficient state.
Toxic effects in the liver are limited to users of oral testosterone preparations, and I have not seen them with the use of nonoral products.
Andropause, also known as male hypogonadism, male-androgen deficiency, and male-hormone deficiency, is the most common disorder of the hormone-producing glands, the endocrine system. Although andropause is often associated with the aging process, it occurs with frequency in young men. Nonetheless, for the reasons discussed this condition is underdiagnosed and undertreated. Despite the effectiveness and safety of testosterone-replacement therapy, affected men who are unaware that they are hormone deficient suffer needlessly from the symptoms and the short-term and long-term health consequences of hormone deficiency.
A thorough discussion of andropause is beyond the scope of this website and as such this is a limited, simplistic, and incomplete treatment of a topic that is clearly complex. Nonetheless, it should be apparent to the reader that although the symptoms and timing of andropause and menopause may differ, the defining element in both conditions is a state of hormone deficiency. Although the precise nature and function of the specific organ systems affected are sex-specific, the process that affects them is the same. Without treatment, no individual of either sex with a hormone deficiency will be capable of attaining an optimal life experience in terms of health, lifestyle, sexuality, or relationships.