Archive for Hormones

Medications, Chemicals, and Sexual Potency

// October 29th, 2010 // No Comments » // Hormones, Sex

You depend on your own internal body chemistry to remain sexually interested, active, and fertile. Anything that interferes with the transmission of your body’s own internal messages can disrupt your sexual life. External chemicals in the form of prescription medications, alcohol, nicotine, or recreational drugs, alone or collectively, can intrude to disable a man’s sex life. This chapter provides a guide to the types of commonly consumed prescription and nonprescription substances that can interfere with a man’s libido, erections, ejaculation, and fertility.

Medication-induced impotence is a major problem. In a survey of 1,180 men, medications were recognized as the single most common cause of impotence. The ingredients in many medications cause impotence by disrupting crucial sexual chemistry. In some cases, the medication deadens sex drive or libido. Other chemicals impede a man’s ability to have erections; and a few interfere with ejaculation. In most instances, once the relationship between the medication and the sexual dysfunction is recognized and the offending substance is discontinued, sexual function returns to normal.Medications that can interfere with normal male sexual function are routinely prescribed to treat high blood pressure, heart problems, elevated blood-cholesterol levels, stomach ulcers, anxiety, and depression. These are among the most common medical problems.Physicians are often aware that the medications they prescribe can impair sexual function. They continue to write prescriptions for these medications for three important reasons:

1. The medication may be more effective than any other available drug.

2. The same medication that produces a sexual side effect in one patient may be benign in the majority of others. (Indeed, only a fraction of men taking the same medication will suffer some impairment in sexual function.)

3. Failure to treat may actually place the man at high risk for the subsequent development of impotence. This is especially true in hypertensive men.

WHAT CAN BE DONE WITH DHT?

// October 29th, 2010 // No Comments » // Hormones

Our group has been involved in projects using DHT in gel form to treat two groups of men — those with a condition called AIDS wasting syndrome (AWS) and elderly men with low serum testosterone levels.

We have used DHT gel to reverse some of the ravages of AWS. Men with AWS suffer a progressive weight loss and become disabled and fatigued and are unable to do any meaningful work. In our short-term studies of men with AWS, we found the following.

Prior to treatment, all men with AWS had established a pattern of progressive and intractable weight loss. During only eight weeks of daily DHT treatment, these desperately ill men reclaimed their appetite, put on weight, and increased their strength. Treatment with DHT gel allowed them to reverse course: to eat more heartily and have a significant increase in their total body weight and capacity for physical work. Unlike other AWS treatments, where fluid retention or increased fat accounted for most of the weight gain, the DHT-gel-treated men’s weight gain was entirely due to buildup of increased muscle — lean body — mass.

We have been encouraged by our results in men with AWS and along with others are now evaluating DHT gel in elderly men with low testosterone levels.

You will undoubtedly hear more about DHT in the near future.

WHY DOES TESTOSTERONE BUT NOT DIHYDROTESTOSTERONE TREATMENT INCREASE A MAN’S PSA LEVELS?

// October 29th, 2010 // No Comments » // Hormones

A man’s prostate gland siphons testosterone from his bloodstream. Then an enzyme within the prostate gland converts the trapped testosterone to DHT. It is this DHT made by and retained within the prostate that is one of the factors responsible for prostate gland growth. As far as we know, the prostate gland does not pluck DHT from a man’s bloodstream. Further, when blood DHT levels rise, testosterone levels decline, making less testosterone available for the prostate gland to ensnare. With less testosterone to trap, DHT levels within the prostate gland decline; and prostate growth can be held in check. How do we know this?

Older men given testosterone usually have a slight but significant increase in their prostate specific antigen (PSA) levels. But when similarly aged men are given large doses of DHT, their PSA levels do not change. There are probably two reasons for this. When men receive testosterone supplements, their blood testosterone levels increase, making more testosterone available for the prostate to trap and convert to DHT. But when men receive large doses of DHT, their testosterone levels actually decline. There is not as much bloodstream testosterone for the prostate gland to trap, so less is available for conversion to DHT within the prostate gland.

There is a second and more subtle sequence of events that explains why testosterone, but not DHT, stimulates the prostate to generate more PSA. A female hormone, estradiol, is one of the natural by-products of testosterone metabolism. It turns out that estradiol is yet another stimulus to prostate gland growth. Dihydrotestosterone cannot be further metabolized to estradiol or any other prostate-stimulating estrogen. Thus, giving a man more testosterone will raise blood testosterone, estradiol, and dihydrotestosterone levels. The increases in blood testosterone and blood estradiol provide the prostate with two potent hormonal stimuli to prostate growth. Testosterone does this by being trapped by the prostate gland, and after being transformed to DHT, it can increase the growth of the prostate gland. Estradiol then is free to exert a direct stimulatory impact on other prostate cells.

DHT, on the other hand, does not enter the prostate gland and cannot be transformed into another male hormone or estradiol and therefore deprives the prostate of both testosterone and estradiol, nullifying the growth-promoting impact of these two hormones. As a consequence, neither PSA levels nor prostate size increase during DHT treatment.

The ability of DHT to maintain a male hormone presence while simultaneously lowering estradiol levels is what makes DHT an ideal hormone to treat young boys who develop breast enlargement (gynecomastia). DHT has not yet been approved for this use in this country, but in France, where DHT is approved, teenage boys with gynecomastia have benefited from DHT treatment. Published reports indicate that boys’ breast size returns to normal with DHT treatment.

IS DHT AN IMPORTANT HORMONAL REGULATOR OF MALE SEXUALITY?

// October 29th, 2010 // No Comments » // Hormones

Several lines of reasoning indicate that DHT may be a more important modulator of male sexuality than previously believed. When 100 healthy young male army recruits had baseline hormone measurements and then were asked to record their sexual activity, those with the highest baseline serum DHT level proved to be the most sexually active.

But isn’t DHT the hormone that stimulates prostate growth? Wouldn’t raising a man’s DHT level cause his prostate to enlarge, making it more likely that he would develop BPH? Apparently not.

PROPECIA FOR MEN WITH MALE-PATTERN BALDNESS

// October 29th, 2010 // No Comments » // Hormones

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?

// October 29th, 2010 // No Comments » // Hormones

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?

TESTOSTERONE FOR POSTMENOPAUSAL WOMEN

// October 29th, 2010 // 1 Comment » // Hormones

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?

// October 29th, 2010 // No Comments » // Hormones

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?

// October 29th, 2010 // No Comments » // Hormones

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.

AAS USE AND THE “ARRAY”

// October 29th, 2010 // No Comments » // Hormones, Steroids

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