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PROPECIA FOR MEN WITH MALE-PATTERN BALDNESS

Symptoms of balding are not subtle. Men will note some early hair loss simply by looking in the mirror. Almost all men experience, and accept, some thinning of the hair as they age, but when there is an accelerated hair loss at an early age, men do become concerned. The 1-mg finasteride pill sold under the name of Propecia is prescribed for younger men who are troubled by the distinctive and selective pattern of hair loss, commonly referred to as male-pattern baldness.

The striking observation that scalp hair loss (balding) never occurs in men with low serum DHT levels was the stimulus for this research. Doctors were to determine whether lowering a man’s DHT level would reverse or slow down the rate at which he became bald. Only limited studies have been done on this topic, but those that are available indicate that the 1-mg dose of finasteride (Propecia) does lower serum DHT levels by about 65 percent and slows down the rate of hair loss in men with male-pattern baldness. Hair growth resumes with continued use of Propecia and starts to fill in areas that had started to bald. But proving this turned out to be an unusually onerous task.

Balding studies are more difficult to do than studies on urinary flow and prostate size. To give you an example of how demanding this research is, consider the following. In evaluating the effect of finasteride on prostate symptoms, all investigators had to do was ask their patients to fill out a questionnaire on their patterns of urination and arrange for ultrasound studies to determine prostate size before and after treatment.

To do hair-loss studies, doctors had to identify and mark out a single twoinch circular area on the top of a man’s scalp as the target area. Then at each visit, they had to count one by one each and every hair in that target area before, during, and after treatment. The results of two combined studies involving more than 1,500 men yielded the following. Men who had 876 hairs in the target area before had on average 983 hairs after treatment, for a net gain of 107 hairs after one year. This does not seem like much but may be enough for those who are distressed by their hair loss. Men with male-pattern baldness age 18-41 years who take Propecia seem to be pleased with the results.

Side effects were similar to what was observed when the 5-mg finasteride (Proscar) dose was used to treat BPH. Sexual side effects, including impotence, loss of sex drive (libido), and ejaculatory problems, occur in about 4 percent of men who take finasteride at this lower 1-mg dose. This once again raises questions about the importance of DHT as a sexually significant male hormone.

WHAT IS DIHYDROTESTOSTERONE?

Dihydrotestosterone is created when a man’s body decides what to do with all the testosterone he has. By an efficient means of disposal called metabolism, a man’s body is equipped to convert testosterone to other sexually active hormones or innocuous inactive hormones. The testosterone that is manufactured in a man’s testicles is released into his bloodstream and may do a number of things. It can:
1. Act directly on androgen receptors in the brain, muscle, and bone to maintain libido (sex drive), muscle mass, and bone strength;
2. Become a totally different hormone, either a more powerful male hormone called dihydrotestosterone or a female hormone called estradiol (E2);
3. Be transformed into inactive or inert steroid products that have no known function and simply wash out of a man’s system.

Whether testosterone will be converted to a female hormone or a more powerful hormone is not a matter of chance. Different enzymes determine the fate of testosterone. The aromatase enzyme, abundant in fat cells, changes testosterone into the female hormone estradiol (E2). A totally different enzyme called 5-alpha reductase is plentiful only in selected parts of the body, including a man’s prostate and in those hair follicles that grow hair on his head.

Once testosterone (T) enters a man’s prostate gland or his scalp hair follicles, the 5-alpha reductase enzyme goes to work to convert T to DHT, but the rate of transformation of T to DHT may be more aggressive in some men than in others.
Men born without the 5-alpha reductase enzyme cannot convert T to DHT. They seem odd at birth but do grow up to be normal-looking, healthy, well-muscled adult men who have normal T but low DHT levels in their bloodstreams. Men with low DHT levels have a tiny prostate gland as well as a luxuriant head of hair.

They never develop prostate enlargement or go bald!

What would happen if we found a way to lower DHT levels in a normal man? Would his prostate gland shrink? Would he be able to grow more hair on his head? Those were the questions asked by scientists at Merck who went on a diligent search to discover a medication that could allow man to maintain abundant blood testosterone levels while selectively decreasing his DHT. They found finasteride.

Finasteride cross-checks the 5-alpha reductase enzyme and stymies a man’s ability to convert testosterone to dihydrotestosterone. Finasteride pills are now approved for two uses, one to prevent or reverse prostate enlargement in older men and the other to increase scalp hair growth in men who are starting to experience male-pattern baldness. Finasteride pills are packaged in different doses. The 5-mg formulation of finasteride is called Proscar. This medication is often prescribed for middle-aged and older men who are known to have enlarged prostate glands, a condition called benign prostatic hyperplasia (BPH). The 1-mg finasteride dose sold as Propecia is used to treat men who have thinning hair, a condition known as male-pattern baldness.

How well does either finasteride pill work to decrease prostate size or reverse male-pattern baldness?

AIDS AND TESTOSTERONE

A below-normal serum testosterone level (hypogonadism) is the most common hormone abnormality found in men with acquired immunodeficiency syndrome (AIDS). In some cases, this is the result of viruses or other microorganisms invading and disabling the testicle’s testosterone-producing capability. More often, the hypogonadism results from subnormal pituitary signals to the testicle, a condition referred to as secondary hypogonadism. Dr. Adrian Dobs of Johns Hopkins University Medical School was one of the first to note that men with AIDS experience many of the symptoms of hypogonadism. In one of her earlier studies in men with AIDS, she noted that 28 of 42 (67 percent) complained of decreased libido, and 14 Of 42 (33 percent) said they were impotent. In addition to the common symptoms immediately attributed to their hypogonadism, men infected with the AIDS virus often experience unexplained decline in weight and loss of muscle mass. This condition is referred to as the AIDS wasting syndrome (AWS) and, in addition to all the other problems AIDS patients have to cope with, AWS is a major cause of morbidity and premature death. We know that in men with spontaneous hypogonadism, loss of weight and muscle mass is common and that for these hypogonadal men, testosterone treatment helps restore weight and strength. Could testosterone treatment work as well in men with AWS?

Preliminary data from Drs. Judith and Richard Rabkin of the College of Physicians and Surgeons, Columbia University, suggest that providing supplemental testosterone or a testosterone analogue, like mesterolone, to men with AIDS who have low serum testosterone levels is beneficial, producing clear improvements in sexual interest, arousal, and overall sense of wellbeing. Some have even speculated that supplemental testosterone may also have a positive mood-elevating impact similar to that seen with traditional antidepressant therapy.

Men with AIDS were treated with a conventional dose of 100 mg of testosterone per week for eight weeks. They had a significant gain in weight and noted enhanced sexual interest and more energy, suggesting that this form of androgen supplementation is effective in alleviating many of the problems that men with AIDS find so troubling.

As more men with AIDS were subjected to detailed hormonal studies, it became apparent that not all, even those who were suffering from AWS, had below-normal testosterone levels. In June 1996, Dr. Richard Horton of the University of Southern California Medical School found that some men with AWS have normal testosterone levels but are unable to efficiently convert testosterone to a second male hormone, dihydrotestosterone (DHT). He speculated that it was the subnormal DHT levels that were most likely responsible for their inability to gain weight in AWS.

TESTOSTERONE FOR POSTMENOPAUSAL WOMEN

Recognizing that testosterone is the major male hormone and estrogens the hormones of femininity does not mean that gender alone determines exclusive rights to either hormone. Men have small amounts of an estrogen, specifically estradiol, in their bloodstream, and in parallel fashion, women’s adrenal glands and ovaries routinely produce small amounts of testosterone. The exact role of the sex hormones of the opposite sex in people has been something of a mystery, but there is increasing evidence that a man’s estrogens play a role in stimulating prostate gland growth and that testosterone’s presence in a women may be a key factor in maintaining her libido.

Our knowledge of the factors that stimulate or suppress male sexual function, though imperfect, is nonetheless substantially more advanced than our understanding of the hormonal determinants of female sexuality. In adolescent boys, timing of androgen (testosterone) secretion and sexual interest coincide, whereas in young women, androgen secretion and orgasmic capacity are not closely linked. Male hormone production is evident in young girls as early as age ten, when the first wisps of pubic hair appear in response to the increased secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S), but orgasms are not evident until later. Further, a woman’s androgen levels, both adrenal DHEA and ovarian testosterone, remain fairly constant after the late teens or early twenties, whereas her capacity for orgasms increases steadily.

The best prognosticator of a woman’s sexual activity is her free testosterone level, but this hormone does not appear to influence female sexual behavior as much as cues from peer group women. Adolescent girls tend to be sexually active when their friends are.

Certain androgens such as androstenedione and free testosterone increase just prior to ovulation. This androgen burst coincides with increased sexual activity in all mammals except for the human female, who tends to have an increase in her sexual activity at the conclusion of her menstrual period when her androgens are at their lowest levels.

The pivotal role of testosterone in female libido has not been appreciated until recently and only in those women have had their ovaries surgically removed during a total abdominal hysterectomy. It was at this time that women noted a profound diminution in their sex drive. Initially, popular psychologists ascribed this diminution in libido to despondency over the loss of their uterus and inability to bear children. But women who had a simple hysterectomy with their ovaries left intact did not experience the same sexual fate as their sisters who had both their ovaries and uterus removed. There was something about their remaining ovarian tissue that allowed these women to maintain their libido. Now it appears that that something was testosterone.

Much of our current scientific knowledge about the role of testosterone in female sexuality comes from the extensive studies in Australia and Canada. Only recently has testosterone supplementation for postmenopausal women become popular in this country, and that has been largely due to the efforts of Dr. Susan Rako, a Boston psychiatrist who writes that she became interested in testosterone on her own in 1988 when “her hormones crashed” around the time of her menopause. Traditional HRT to correct her estrogen deficiency, it seems, was not sufficient to correct her “loss of sexual and vital energy.” With testosterone supplementation, she felt better and was energized and revitalized.

Eager to share her experience with others, she published a book entitled The Hormone of Desire: The Truth About Sexuality, Menopause, and Testosterone, extolling the benefits and downplaying the adverse effects of bolstering testosterone levels in postmenopausal women.

The very first reports of testosterone supplementation had indeed focused on postmenopausal women who, like Dr. Rako, complained of a loss of sexual desire while receiving conventional estrogen and progesterone hormone replacement therapy (HRT).

Studies in Australia and Canada relied on a visual analog scale, asking women “On a scale of 0-100 with 100 being entirely normal, how would you rate your sex drive?” before and during treatment. Women scored themselves low at 20 before and 85 after 6 weeks of estrogen plus testosterone, but were unchanged after estrogen alone.

In Canada, Dr. Barbara Sherwin evaluated not just libido but overall sense of well-being, energy, and appetite in postmenopausal women with no ovaries. She found that compared to placebo or estrogen alone, women who received a combination of estrogen and testosterone, this time by intramuscular injection and not by pellet implantation, had a significant improvement in their well-being, energy level, and appetite. This improvement carries a cost, for all of the testosterone-treated women grew hair on their faces and had a worsening of their cholesterol profile, making them theoretically more susceptible to atherosclerosis. Mindful of the need for safer testosterone delivery systems to activate libido without fostering facial hair growth, new testosterone cremes and lotions are being formulated.

Capitalizing on the recent enthusiasm for providing supplemental testosterone to enhance libido in postmenopausal women, some have started to cautiously explore the potential benefit of a combined estrogen and testosterone pill. Reasoning that unsightly facial hair and disordered lipid profiles are dose related, the manufacturers of Estratest, the most common estrogen and testosterone combination pill, have now come out with Estratest-LD, the LD signifying that the pill contains a lower dose of testosterone than the parent compound. However, the testosterone in both pills is methyltestosterone, one of the 17-alkylated testosterone products known to have significant side effects. We do not yet know the benefits of long-term androgen therapy in women, but we do know of some of the reported risks of this treatment. Most of the currently available testosterone in pills may carry a burden of liver toxicity. (See earlier comments on AAS.)

Doctors are still uneasy about issuing a blanket recommendation for testosterone pills for all postmenopausal women with diminished libido. As additional data emerge from placebo-controlled studies, we should be able to learn whether androgen supplementation is not only effective but also a safe treatment for postmenopausal women with low sexual desire and inhibited sexual arousal.

However, a limited trial of testosterone may be precisely what Linda needs. She may do just as well with either testosterone pills or patches to resurrect her lost libido. For example, to circumvent the liver toxicity of testosterone pills, testosterone patches have been used with some success.
The testosterone patches differ in some respects from those used by men both in dose and use. Men have to change their patches daily, but women seem to be able to go three to four days before changing patches. The use of testosterone patches in women is quite new. We will have a better sense of the value of testosterone patches in postmenopausal women when results of additional research studies are made available.

WHY IS OFF-LABEL AAS USE A PROBLEM?

To be useful as a pill, testosterone has to be physically altered. The chemical transformation needed to make testosterone pills effective also causes them to be dangerous. The most worrisome side effect of testosterone or any other AAS pill is liver damage. Use of testosterone pills can cause a man’s liver to become crammed full of blood-filled cysts, a condition known as peliosis hepatis. Blood can burst forth from these cysts, causing extensive abdominal bleeding. Fatal liver cancer has also occurred in AAS users. The warning accompanying all AAS pills follows:

Text of warning for all synthetic anabolic androgenic steroid medications as it appears in the 1999 Physician’s Desk Reference:

Peliosis hepatis, a condition in which liver and sometimes splenic tissue is replaced with blood-filled cysts, has been reported in patients receiving androgenic anabolic steroid therapy. These cysts are sometimes present with minimal hepatic dysfunction, but at other times they have been associated with liver failure. They are often not recognized until life-threatening liver failure or intra-abdominal hemorrhage develops. Withdrawal of the drug usually results in complete disappearance of lesions.

Liver cell tumors are also reported. Most often these tumors are benign and androgen-dependent, but fatal malignant tumors have been reported. Withdrawal of drug often results in regression or cessation of progression of the tumor. However, hepatic tumors associated with androgens or anabolic steroids are much more vascular than other tumors and may be silent until life-threatening intra-abdominal hemorrhage develops.

HOW COMMON IS AAS USE?

In today’s culture there is something of an epidemic of AAS use among adolescents and young men and women. One survey of high-school students documented that 5-10 percent of boys and 0.5-2.5 percent of girls admitted to AAS use. Results from another survey indicated that there were more than 1 million former or current AAS users in 1993. Over 50 percent of the lifetime users started at an average age of fifteen. Other surveys of several hundred thousand families have confirmed the appeal of AAS use for both adolescent boys and girls. Enhancement of body image or athletic skills is what draws adolescents and others to AAS drugs.

Over the past decade, there has been an extraordinary increase in the amount of androgens used by both men and women. The Food and Drug Administration, concerned with the burgeoning demand for male hormone supplements, has decided to lump testosterone with another class of powerful agents — narcotics — and insists that when doctors are prescribing testosterone they do so for the proper reasons. The FDA has sanctioned the use of testosterone and other testosterone-like medications for two reasons. One is the treatment of testosterone-deficient men. The other is to help reverse the ravages of other illnesses that cause muscle wasting and frailty.

Most physicians tend to be leery of prescribing testosterone or any other AAS drug for unapproved indications. Yet underground supplies of testosterone pills and other AAS pills are readily available from other sources. Those who do find a supply and are eager to indulge in “off-label” AAS use may be interested in why doctors are uneasy prescribing testosterone pills.

ANABOLISM-CATABOLISM AND ANABOLIC ANDROGENIC STEROIDS (AAS)

Anabolism, the building up of muscle, is the opposite of catabolism, the destruction of muscle. Men and women with diseases like cancer and AIDS become weak because of a breakdown of their muscles, a process known as catabolism. Testosterone and its clones reverse catabolism and speed anabolism and are referred to as anabolic (muscle-building) androgenic (male hormone) steroids (AAS).

Healthy men and women who use testosterone or other AAS pills in muscle-building programs are engaging in “off-label” AAS use.

Athletes know that large doses of testosterone or other AAS drugs are needed to help them achieve the bulk, strength, and size they need to be effective in competitive sports. Long-term consequences of male hormones on cholesterol and lipid profile or prostate gland size are of little concern to them when they are struggling to be a split second faster or lift five more pounds. Although most sports organizations have stipulations against the use of “performance-enhancing drugs,” few athletes heed these regulations and as role models have fostered an attitude encouraging rampant AAS use.

AAS USE AND THE “ARRAY”

Breast enlargement, acne, and edema are undesirable and disadvantageous to athletes and bodybuilders, so AAS users must resort to other medications — anti-estrogens to combat breast enlargement, anti-acne medications to cope with unwanted blemishes, and diuretics to purge the edema from their bodies. The supplemental medications needed to short-circuit the undesirable side effects of AAS are referred to as “the array.” Spawned by the latest advantages in pharmacology the “array” takes on each distressing symptom one at a time. To control acne, the antibiotic minocycline (Minocin) is used to blunt the impact of androgen excess on sebum production. Pills like the diuretic furosemide (Lasix), designed to rid the body of unwanted fluid, help control ankle swelling. To fend off breast enlargement, two different medications are called into play. The anti-estrogen tamoxifen helps diminish the male breast response to excessive estrogen in the bloodstream. Testolactone (Teslac) — a pill that disrupts a man’s ability to process male hormones like testosterone into female hormones like estradiol — has also found favor among bodybuilders. Dread of balding has created a demand for use of finasteride (Proscar or Propecia). These medications decrease conversion of testosterone to dihydrotestosterone (DHT) and are used to prevent hair loss from the scalp. The medications currently employed in the array are listed below.

The “Array” used to combat side effects of excessive male hormone use.
Symptom Treatment
Edema - Furosemide (Lasix)
Acne - Minocycline (Minocin)
Breast enlargement (Gynecomastia) - Tamoxifen, Testolactone (Teslac)
Balding -Finasteride as Proscar or Propecia

HOW DO ATHLETES AND BODYBUILDERS USE TESTOSTERONE AND OTHER ANABOLIC ANDROGENIC STEROIDS (AAS)?

The carefully crafted and meticulously executed Bhasin study cited above used a single consistent very high dose of testosterone. Its conclusions will most likely satisfy both scientists and athletes. But those who endorse and promote “off-label” AAS use view most scientific studies with disdain because these reports failed to replicate the complex sequencing of steroid administration preferred by those who rely on AAS to gain a competitive edge. Athletes tend not to take medication in the strictly controlled amounts required for credible research studies. Rather, they cycle AAS use to maximize benefit and decrease the risk of detection in urine assays. A practice known as “stacking,” the ritual sequencing of more than one steroid, is common. Athletes believe that by using more than one AAS they will be able to activate more and different types of androgen activity (androgen receptors). There is no scientific proof that this practice actually works, for there is only one androgen receptor and it is already filled to maximum capacity by the doses of AAS routinely used by athletes. Some also believe that optimum benefit cannot be achieved with any single AAS schedule. To avoid a “plateau,” they scramble the order of AAS administration, often beginning their cycle with low doses, then building with sequentially higher doses before tapering down just prior to competition, constructing in essence an AAS “pyramid.”

Androgens are known to be potent stimuli to prostate growth. Anxiety over the impact of unfettered, relentless androgen stimulation on prostate size has been a cause of considerable anxiety among physicians but has apparently not been one for athletes preoccupied with long-term consequences of “off-label” AAS use. Rather, it is the expectation of short-term gain, not long-term consequences, that is of paramount concern to the current crop of AAS aficionados. They tend to equate prostate problems with the remote destination of advanced age, which is not a primary concern of young competitive athletes.

AAS users believe they are clever enough to manipulate drug treatment to fend off the short-term adverse effects of AAS use and are cocky enough to believe they will have the same good fortune in sidestepping the more pernicious long-term consequences of continued androgen bombardment of their bodies. Still, several of the short-term problems — acne, fluid retention, balding, and breast enlargement — caused by high-dose AAS use do require attention. To cope with these bothersome problems, athletes have once again dipped into the pharmacy to concoct “the array.”

MALE BREAST ENLARGEMENT (GYNECOMASTIA)

Men may first notice embarrassing breast enlargement during their teenage years. The sudden surge in adolescent testosterone and its metabolic spinover seems to overwhelm the body at first. The temporary torrent of estradiol distorts the balance of power, altering the young teenager’s testosterone-estradiol T/E) ratio. For a brief period of time, the relative excess of female hormones in the young teenager’s bloodstream stimulates his breasts to start growing. Gradually, the T/E ratio tilts again in favor of testosterone. Then as estradiol levels dwindle, the stimulus to further breast growth first attenuates, then ceases. Occasionally, breast enlargement (gynecomastia) lingers into adulthood, causing significant chagrin. Grown men with large breasts may have to resort to surgery to reduce breast size. Innovative hormone treatments with dihydrotestosterone (DHT) may provide a nonsurgical alternative to restore normal breast size without resorting to surgery.