"Midlife crisis" -- this is often the transitional period for men when they experience what is termed as the “second childhood”. This period usually starts from age 40 to 45. It is also called andropause or male menopause because its symptoms coincide with the decrease in a class of male hormones called androgen. All men are affected, although some to a larger degree than others. A thorough knowledge of the underlying hormonal and physiological changes will better prepare all males to deal with this phase of life.

The male reproductive regulatory system consists of four components:

1. the central nervous system (CNS) including the hypothalamus.
    
2. the pituitary gland.
    
3. the testes; and
    
4. the end organs where testicular steroids act.

The master control starts in the hypothalamus where gonadotropin-releasing hormone (GnRH) is synthesized and is released in a pulsatile fashion into a vascular network that connects the hypothalamus to the pituitary gland. GnRH production and release is controlled by numerous neurotransmitters, including norepinephrine, dopamine, and endorphins. GnRH regulates the release of two pituitary hormones - the gonadotropins - luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a pulsitile fashion. LH regulates the production and secretion of testosterone by the Leydig cells of the testes, and FSH stimulates spermatogenesis.

Testosterone is the hormone responsible for making the male body "masculine." Testosterone influences the growth and development of the male sex organs, muscles, beard and body hair, and plays a key role in maintaining human health, strength and energy.

Testosterone circulates in the blood in several forms. It can be bound to both albumin and sex hormone-binding globulin (SHBG) where it is referred to as "bound testosterone." This is the least active form. It can also circulate in a free (unbound) form, which is considered the most active. Abut 97 of the testosterone is bound, leaving only about 3 percent biologically active to do the job.  Laboratory measurements should include both free testosterone and total testosterone. Serum levels of testosterone start rising about 15 minutes after oral administration and stay elevated for around 3 hours. Blood testosterone levels usually peak in around 1 to 1.5 hours and swiftly return to normal baseline levels.

Testosterone can exert its effects directly on the testosterone receptors in cells. It can also be converted to two active metabolites - dihydro-testosterone (DHT) through the enzyme 5 alpha reductase.

Testosterone is also converted into estrogen by an enzyme call aromatase. Aromatase in a very important enzyme. It is increased by the aging process, illness, obesity, alcohol, excessive dietary estrogen, and numerous drugs that reduce the P450 linked detoxification system in the liver. Reduction of liver clearance of estrogen into inactive metabolites lead to increased estrogen level in the body. These include non stoeriodal anti-inflammatory drugs ( ibuprofen, diclofenac), aspirin, acetaminophen; certain antibiotics such as sulfas, tetracyclines, penicillins; cholesterol lowering drugs (Statins) such as lovastatin; heart medications such as propanolol, quinidine, methydopa, and coumadin;

Zinc deficiency is common in the modern day processed food diet. Prostate has the highest zinc concentration of any organ in the body, and it is interesting to note that zinc deficiency leads to an increase in aromatase and therefore an increase in estrogen in the male.

An increase in estrogen also occupies the testosterone receptors in the brain and acts as a negative feedback mechanism to shut off the production of gonadotrophin releasing hormone (GnRH), leading to the decrease secretion of FSH and LH and reduced testosterone production from the Ledig cells in the testis. Excessive estrogen is therefore an antagonist of testosterone. Increased in estrogen has also been linked to increase clotting of arteries in man. With the aging process, most male also gain weight. Over 60 percent of adults in the United States are considered obese. Obesity leads to the increase of estrogen production in the fat cell. The increase in estrogen in male is therefore one of the defining characteristics of midlife in the male. During the aging process, the testosterone to estrogen ratio goes from 50 to 1 during the sub-clinical phase of aging (age 25-35) to 20 to 1 during the transitional and clinical phase of aging (age 35-45, and age over 45 respectively). At old age, the ratio is more like 7 to 1. A Japanese Study have shown that men whose prostates were most enlarged had a higher level of estrogen and not testosterone.

Testosterone, together with its metabolites, is collectively known as androgens. As a group of steroid hormones, they stimulate the development of masculine characteristics and are responsible for male puberty characterized by deepening voice, broadening shoulders, and moustache growth. The hallmark of andropause is declining testosterone levels.

Testosterone levels begin to decline with age after maturation. This is accompanied by the concurrent appearance of a myriad of related physiological changes commonly associated with aging. These changes include diminished libido, reduced frequency of sex (the "senior slump"), erectile dysfunction, infertility, changes in body composition, reductions in body and facial hair, and osteoporosis. Andropause is in effect the reverse of puberty.

In addition, mood inventory scores indicate that during andropause, men report levels of anger, confusion, depression, and fatigue that are significantly higher than those reported by men with normal testosterone levels. The average human male begins to feel some symptoms of andropause after 40 to 45 years old, which is followed by rapid deterioration after the age of 50.

Many of the symptoms accompanying the andropause and the aging processes in men are similar to those of hypogonadism. We can attribute at least some of these symptoms to a decrease in testosterone levels, including:

1. Sexual Functions. Coital frequency declines rapidly with age from a mean maximal coital frequency of about 4 times per week at age 25, to once a week at age 50, 3 times a month at age 70, and 1.7 times a month between the ages of 75 and 79 years. Impotence also increases dramatically with age. It is rare before the age of 30. It is observed in 8 percent of people over 50 years old, 20 percent of those over 65 years old, close to 40 percent for those who are 70 years old.
    
2. Body Composition. The amount of lean body mass in the sedentary person decreases by approximately 10 percent for every decade after the age of 30. You could have lost 30-40 percent of your lean body mass by age 60. Aging is accompanied by a decrease in lean body mass (LBM) and a concurrent significant increase in fat mass. Although aging itself is an important determinant of body composition, plasma total testosterone levels are not correlated to fat mass, regardless of age. The decrease of muscle mass is highly correlated to free testosterone levels, which persists after correction for age. Testosterone supplementation increases muscle mass.

Aging males, like hypogonadal men, accumulate preferentially visceral fat. This accumulation is a major cause of insulin resistance and the atherogenic lipid profile. This suggests that obesity in elderly men is a more important health hazard than in young men. Contrary to popular belief, clinical trials have shown that a low androgen status increases the risk of coronary artery disease (CAD) or atherosclerosis. It was previously believed that testosterone and other androgens had the opposite effect since men have higher rates of heart disease generally than women. Researchers now find that low androgen levels were associated with an increased incidence of CAD. Men with CAD had a 22 percent lower 'free androgen index'.

While decreased free and total testosterone levels can lead to increased fat mass, it could also be suggested that the decrease in testosterone levels in the aging male is the consequence of an increase in fat mass. In other words, there is a likely bi-directional relationship, the exact mechanism of which is still not fully known. Obesity is a multi-factorial disease that also includes genetic, social and psychological factors.

Low testosterone is also associated with a myriad of other metabolic and hormonal imbalances, including:

• Increase in blood cholesterol, an independent risk factor for heart disease.
• Increase in blood triglyceride, an independent risk factor for heart disease.
• Increase insulin level - leading to sugar imbalance.
• Increase in estrogen - associated with higher stroke and heart attacks in male.
• Increase in Lp (a), an independent risk factor for cardiac disease
  Increase fibrinogen, the basis of blood clots.
• Decrease growth hormone, leading to decline in energy and muscle mass.
   

Two factors may contribute to accelerated hypogonadism in aging men. The first is a slightly decreased production of testosterone and the second is an increase in the circulating fraction of testosterone bound to SHBG.

Semen analysis in elderly men revealed an alteration in sperm counts in varying degrees from normal to increased or a decreased sperm motility and increase in abnormal sperm forms. This finding in older men suggests some degree of primary testicular failure.

However, after controlling for age, the correlation between serum testosterone levels and sexual activity was not significant. This suggests that reduced testosterone levels are not likely to be responsible for sexual dysfunction and hypogonadism in and of itself is an uncommon cause of impotence in elderly male.

Based on these findings, the supplementation of testosterone in older men to improve erectile function may be of little benefit. Nevertheless, studies have also shown that aging men with high sexual activity levels have greater plasma testosterone concentrations than men with less sexual activity. Although decreases in serum testosterone may have a correlation with the diminished sexual activity in older men, this effect is probably minor compared with the contributions of psychological, social and other health factors such as cardiovascular diseases. Indeed, the question of whether or not to use testosterone as a replacement strategy in andropause use is not clear-cut.

The vast majority of men do not experience a loss of testosterone production compared to the total loss of estrogen as occurs in women. As a result, they do not generally experience hot flashes. Hot flashes in men mostly occur when there is a complete loss of testosterone such as during gonadal failures, pituitary problems or treatments for advanced prostate cancer.

Numerous researches have been conducted to explore the mechanism that triggers the decreased testosterone production with age. Theories that have been proposed include:

1. Loss of Hypothalamic Sensitivity. Dr. V. Dilman proposed that the major factor in aging is the dysfunction of the male reproductive homeostat (hypothalamic - pituitary - testes axis), which leads to the progressive loss of hypothalamic sensitivity to the inhibitory effects of testosterone. This loss of hypothalamic sensitivity to the negative feedback loop of testosterone has been confirmed by a number of indirect studies.
    
2. Testicular Defect. Some researchers postulated that during aging, there is a concurrent decreased Leydig cell's response to LH. It is likely that this loss of Leydig cell activity is due to a desensitization of sex hormone receptors due to prolonged hyperstimulation by chronically elevated levels of LH (primarily) and FSH (both of which are the result of the loss of hypothalamic sensitivity).
    
3. SHBG Level Increase. Levels of total plasma testosterone are known to have a progressive age-related decrease after the age of 50. One explanation is that both SHBG levels increase with age and albumin level decrease with age. This results in a decline in bioavailable testosterone. It has been noted that the decline in bioavailable testosterone is greater than the decline in total circulating testosterone. The circulating testosterone, which is bound to SHBG, is biologically less active than the free form.
    
4. Circadian Rhythm Dysfunction. Many people past the age of 40 have increased difficulty sleeping. A variety of factors such as stress, diet and a disturbance of the sleep wake cycle can influence sleep quality. All these factors pose as adverse effects on other biological rhythms, resulting in a dramatic shift of the circadian rhythm of testosterone production. Testosterone levels in young men are highest in the evening and early morning. However, this rhythm is greatly attenuated in older men. Therefore, maintaining a good nights sleep as well as a regular sleep-wake cycle is a sensible approach to reducing stress and normalizing our biological clock.

Other Hormone Deficiencies

Other important hormones that have reduced production levels from age 30 onwards include Human Growth Hormone, Melatonin, DHEA, and Pregnenolone

Growth hormone level in the body reaches its peak in the late teens. Then it starts its long decline at the rate of 14 percent reduction for each decade thereafter. By age 60, you could have lost as much as 60 percent of the amount of growth hormone in your body.

The growth hormone has been touted as the “elixir of growth” ever since Dr. Rudman published his landmark study in the New England Journal of Medicine. Dr. Rudman gave a group of healthy aging adults a high dose, low frequency program of synthetic growth hormone injections for six months. The results showed a significant increase in lean body mass and a reduction of body fat. Dr. Rudman concluded that the growth hormone injections changed the body composition consistent with 10 to 15 years of aging. Since then, many studies and clinical trials have been conducted on growth hormone.

The deficiency of the human growth hormone causes many changes of somatopause with similar symptoms as testosterone deficiency. The replacement of testosterone without replacing growth hormone generally does not produce maximum effective results as both hormones work in synergistically with each other to produce the best results.

DHEA (Dehydroepiandrosterone)

DHEA, an adrenal hormone, is the most abundant steroid hormone in the body. DHEA levels plummet dramatically with age, more than any other hormones, after peaking at around age 20. At the age of 40, production levels are only half the amount compared to age 20. By age 80, production levels are only five percent of the peak levels.

William Regelson, M.D. (1995), reviewed the effect on male sexual function as documented in the groundbreaking Massachusetts Male Aging Study. This study investigated primarily the sexual function and activity in men aged 40 to 70. Of the 17 hormones measured in each man, only DHEA showed a direct and consistent correlation with impotence. As DHEA levels declined, the incidence of impotence increased. Other reported effects of increased DHEA included a reduction in blood insulin and glucose, increased lean body mass and reduction in fat, increased bone density and lowered cholesterol and blood pressure. DHEA rejuvenates virtually every organ system so it "actually makes you look, feel, and think better."

Pregnenolone

Pregnenolone is produced in the adrenal gland. Its production declines with age. Pregnenolone blocks and reverses many age-accelerating effects of excess cortisol.

Pregnenolone is also a potent neuronutrient that improves memory, concentration and moods. It enhances brain function by facilitating the transmission of nerve impulses so that brain cells can communicate more easily. Pregnenolone can help to fight depression too. In one study, people who were not depressed had twice the amount of pregnenolone circulating in their bloodstreams.

Pregnenolone has the unique ability to balance all other hormones. It stimulates the production of other hormones only when they are needed.

Melatonin

Melatonin is produced in the pineal, which is located deep within the brain. Production levels of melatonin is reduced during the day and increased in the night. The amount of melatonin produced during the night is ten times the amount produced during the day.

Melatonin is also a potent antioxidant that protects the pineal gland against free radical damage and helps defend our immune system. Researchers now believe that the pineal gland also drives the aging process.

As you get older, the pineal gland produces less melatonin. The decline in production is slow and gradual after the age of 20. The loss is accelerated after the age of 40. Melatonin is usually not recommended for people under 40 years of age solely for its anti-aging benefits. This is because their production levels of melatonin have not yet declined significantly. Melatonin is commonly recommended for jet lag and as a sleeping aid, but we know that it can do much more.

Numerous scientific studies are currently underway to study the relationship of melatonin and longevity. In one interesting experiment, aging mice that received pineal gland from younger mice was discovered to have their life span increased by a third. Conversely, young mice given pineal gland from old mice had their life span reduced by one-third.

1. Testosterone Replacement Therapy (TRT)

Both men and women produce testosterone. The amount produced by women is much smaller and production comes from the adrenal glands. A decline in the testosterone level is associated with decrease in sex drive and libido in both sexes. Testosterone replacement therapy (TRT) re-energizes the entire body, increases lean muscle mass, and reverses the fat accumulation and muscular atrophy characteristic of aging.

TRT also considerably improves the quality of life in men after middle age. The replacement of testosterone may also prolong lifespan by reducing the severity of age-associated diseases such as osteoporosis and cardiovascular disease, which are among the leading causes of disability and death.

For men, replacement and restoration of testosterone level in men to the level of a 30 to 40 year old male has shown significant anti-aging effects. The normal blood level of testosterone ranges from 15-100 mg/dL in women and from 300-1,200 mg/dL in men.

Pre TRT workup should include a complete history and physical examination, together with a battery of blood test including male hormonal profile and cancer screening test such as PSA to rule out any relative or absolute contraindications to testosterone replacement therapy.

Various forms of synthetic testosterone have traditionally been used. These include oral, sublingual, intra-muscular injection, intramuscular pallets, and trans-dermal patches and creams. While these synthetic hormones have been widely used with beneficial effects, there are drawbacks to their use.

Oral synthetic preparations result in short-term elevation and undesirably high inter-individual and intra-individual variability of concentrations of testosterone. There are also commonly associated elevations of liver function test and abnormalities at liver scans. Despite this, oral preparations still constitute about a third of prescriptions filled in the United States. Some common forms are pure testosterone, methyltestosterone, sublingual methyltestosterone, and fluoxymesterone.

The injectable synthetic testosterone is esterfied. They are safe, effective, and the least expensive androgen preparations available. They require an injection into a large muscle. It is slowly absorbed and last longer. It takes effect over several days or weeks. Injections eliminate the natural daily diurnal rhythm of testosterone production-high at night and early morning and low during the day. Testosterone enanthate and cypionate are forms commonly used. They have comparable pharmacokinetics. Both result in supra-physiologic concentration of testosterone for 1 to 4 days after injection. A satisfactory regimen is to administer 200 mg of one of these esters once every two weeks intramuscularly, but a more physiologic replacement therapy would be 100 mg of one of these on a weekly basis.

Trans-dermal synthetic TRT systems are perhaps the most commonly used. It comes in the form of scrotal and non-scrotal forms. Clinical studies have shown that both are effective forms of androgen replacement. The advantage of the scrotal form is that it produces high levels of circulating DHT due to the high 5-alpha-reductase enzyme activity of scrotal skin. It also requires shaving of the scrotum. Inadequate scrotal size and adherence problems are limitations. Skin irritation does occur in those with sensitive skins. Non-scrotal skin patch’s advantage is that the serum testosterone concentration profile mimics the normal circadian variation observed in healthy young men. Skin irritation is more common, with over 50 percent experience some form of site reaction sometime during the treatment. Pretreatment with corticosteroid creams (not the ointment forms) has been shown to reduce the severity and incidence of skin irritation without significantly affecting testosterone absorption from the patch.

Androgen replacement can have undesirable side effects, including frequent or persistent erections, nausea, vomiting, jaundice, ankle swelling, or virilization of female sexual partner. Breast enlargement can also develop as testosterone can be converted to estrogen via the enzyme aromatase. More serious complications include water retention, liver toxicity, cardiovascular disease, sleep apnea, and prostate enlargement. These risks are relatively uncommon when the dosage is closely monitored to that found physiologically in the body.

Androgens are contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate. They also should not be considered in those with known hypersensitivity to the preparation or in patients with compromised cardiac, renal, or hepatic functions.

While there is no direct evidence that link testosterone replacement to accelerated prostate enlargement, there is a correlation between testosterone treated hypogonaldal men and normal men with prostrate volume and age.

Prostate cancer is an androgen-responsive cancer, although there is no evidence to directly indicate that testosterone therapy causes prostate cancer. If prostate cancer cells already exist in the body, the disease may be stimulated to spread. Therefore, pre-treatment screening for any prostate dysfunction is mandatory. A digital rectal examination (DRE) and laboratory test for prostate specific antigen (PSA) should be checked before initiation of therapy and every 3 to 6 months thereafter. An abnormal DRE, an increase in PSA of more than 2 ng/dl, or a total PSA of greater than 4.0 ng/dl requires further urological evaluation. Other tests include hemotocrit, bone density, and plasma lipids on an annual basis.

Results of testosterone replacement may not be evident for several weeks. Impotence may not be corrected after several months of therapy despite improvement in other andropause symptoms. For these patients, evaluation for causes of erectile dysfunction other than hypogonadism due to andropause is indicated.

Close monitoring of serum testosterone levels should be carried out for patients on testosterone. Other signs, such as acne, increase breast size, and tenderness should be checked to ensure no excessive circulating androgens. After one week or more of trans-dermal TRT, serum testosterone levels can be measured about 12 hours after patch application and dosage adjusted accordingly. For oral methyltestosterone therapy, no assays are available to monitor therapy. For patients on the injectable form, nadir testosterone levels should be obtained 3 to 4 months prior to the next injection.

Recently, natural forms of testosterone have become available which possess all the benefits of synthetic hormones and little adverse side effects. They are available from specialized compounding pharmacy under the prescription of a physician.

The natural alternatives to testosterone include the testosterone precursors, androstenedione and androstenediol, which are available in oral capsules or sublingual sprays.

While testosterone replacement is one of the most effective ways to relief andropause symptoms and may be indicated in the aging male with documented hypogonadism, this hormone should not be used in those with normal testosterone levels. Under the care of a knowledgeable physician, this therapy is very safe for the vast majority of andropause patients.

2. Growth Hormone (hGH)

The quick way to reverse the declining growth hormone (hGH) level is by hGH injections. A physician must monitor the injections. As with all hormones, growth hormone can be fatal if administered without proper precautions.

In particular, people with excessive lipids in their blood, diabetes, and abnormal liver function must have extensive medical workup prior to commencing treatment. The use of growth hormone also requires no pre-existing diabetes or cancer. The dose must be kept to a minimum or joint pains, heart failure or carpal tunnel syndrome may occur. Commonly used dosage is 1 IU per day by injection. This is a low dose, high frequency program that is quite different from the original study carried out by Dr. Rudman years back. Furthermore, for each five to six days of injections, there should be a one to two days of rest where the body is given oral supplementation such as secretagogue. The effectiveness of growth hormone therapy is measured through monitoring the IGF-1 level in the blood. This is the metabolite and marker of growth hormone. It is customary to try to achieve an IGF-1 level of 350 mg/dl as the end point in an anti-aging program.

While there is little doubt that growth hormone works, its use is not widespread due to its high cost and possible side effects if not monitored carefully.

Is there a natural way of replacing our growth hormone without drugs? Many physicians practicing anti-aging medicine believe so. These physicians believe in stimulating the pituitary gland to naturally increase the release of hGH. Substances that stimulate the pituitary gland in this manner are called secretagogues. Secretagogues are natural elements and side effects are rare. The results, though not as significant as injections, have been very encouraging. The replenishment of growth hormone from a deficient state can lead to an improved sex life; skin tone and can help to balance other hormones in the body including testosterone, DHEA, melatonin, pregnenolone, and progesterone.

Other ways to increase growth hormone release endogenously include intense strength training, cardiovascular exercises, calorie restrictions, and proper intake of nutritional supplementation, vitamins, antioxidants and amino acids such as glutamine, ornithine, arginine, and lysine that acts as a pro-hormones.

3. DHEA

Many people have reported more energy, ability to handle stress more easily, think more clearly and generally feel better, after receiving DHEA. Other benefits include enhanced immunity (stronger resistance to colds, flu etc) and lower cholesterol levels.

DHEA’s ability to rejuvenate the immune function is particularly worthy of consideration. It boosts antibody production; enhances the activity of monocytes and maximizes the anti-cancer function of immune cells known as T lymphocytes. When administered concurrently with a flu vaccine, DHEA has been shown to improve the effectiveness of the vaccine in laboratory animals and in aging humans.

One interesting note is that DHEA is not regulated by a negative feedback loop in the body. In other words, taking supplements of DHEA will not suppress the production of these hormones or cause the adrenal to rest and result in atrophy from the disuse. Theoretically, no “resting period” is required, although it is a good practice to have a resting cycle of a few weeks for every few months of therapy, as with all hormone replacement.

DHEA replacement therapy offers powerful health benefits and is virtually risk-free. The usual dose ranges from  25-50 mg.  It is interesting to note that DHEA does not work as well in men compare to women, and increasing DHEA dosage in men does may lead to a higher blood level but not necessary improve the symptoms of andropause. The ideal anti-aging strategy is to supplement both DHEA and its precursor, pregnenolone. Commercial DHEA products are made from diosgenin, an extract from the Mexican wild yam of the Dioscorea family. Biochemists can convert diosgenin to DHEA by engineering a series of chemical conversions, but such conversion only happens in the laboratory and not in the human body. The ingestion of Dioscorea plant extracts cannot possibly lead to the formation of DHEA in the body.

4. Pregnenolone

Numerous studies have shown the effects of pregnenolone on the body and brain. It boosts energy, elevates mood and improves memory and mental performance. Pregnenolone also creates a sense of well being while improving the ability to tolerate stress. Furthermore, pregnenolone has a host of advantages which includes the ability to influence cerebral function, energy level, the female reproductive cycle, immune defenses, inflammation, mood, skin health, sleep patterns, stress tolerance, wound healing. Taking pregnenolone therefore normalizes and rejuvenates the entire adrenal cascade.

The normal starting dose is 15 mg, increasing up to 50 mg for men or women. There are minimal side effects. A laboratory, although good, is not necessary for doses below 200 milligrams per day. Pregnenolone should be derived from a pharmacologically pure product and not a yam-derived "precursor." A very safe dose is between 25 and 100 milligrams per day.

Although pregnenolone has not been studied as extensively as DHEA as it is a precursor of DHEA and since it appears to decline as rapidly as DHEA, pregnenolone should also be considered in a comprehensive hormonal replacement regimen.

Pregnenolone is best tested for its ability to alleviate depression, improve moods and enhance cognitive performance. It also has corticosteroid-like anti-inflammatory effects without the joint-destroying catabolic effects of corticosteroids (Regelson, 1995).

It is often recommended for anti-aging purposes that both pregnenolone and DHEA be taken together. Since some pregnenolone is converted into DHEA, the amount of DHEA intake can be lowered if both are taken together.

5. Melatonin

One of the causes of the disruptions of sleeping patterns during aging is the reduction in the nightly release of melatonin by the pineal gland. Many people have discovered that bedtime doses of melatonin restored their ability to obtain a sound and peaceful night’s sleep.

Melatonin levels are known to decline drastically with age. Since melatonin and FSH appear to be antagonistic in women, the same relationship may be true for men. It has been postulated that melatonin may even act to normalize (lower) gonadotropin levels. It is one of the few substances that have repeatedly been shown to extend the maximum lifespan of experimental animals. While low doses of melatonin (0.5 to 6 grams) act as a natural sleeping pill, high doses of melatonin (20 grams or more) have been used to fight cancer growth.

The exact dosage varies greatly between people. Trial and error is the best method. A higher dose does not mean more potency. Some people may feel better with a smaller dose. To normalize sleep and the biological clock, a good dosage to start is 1 mg and should be gradually increased if there are no side effects. A slight disorientation and dizziness may be experienced for the first few hours after waking up when melatonin treatment is first started. This sensation should go away after a few nights of melatonin use. If it persists, a reduced dose is recommended.

There are a few rules for the effective use of melatonin. Firstly, always take this hormone just before bedtime. If you take it earlier in the day, it may disrupt sleeping and waking cycles. Secondly, the dosage required to generate results varies from person to person. Some people may require 5 mg to work, while others only 1 mg. Start always at low dosage and work your way up slowly.

6. Androstenedione

Androstenedione, (pronounced "an-dro-stene-die-own,") is a natural steroid hormone produced by the adrenal cortex, ovary and testes. In the body Androstenedione is synthesized from dehydroepiandrosterone (DHEA) and then either converted into testosterone by 17ß-hydroxysteroid dehydrogenase, or into estrone by the aromatase enzyme complex. It is also found in meat and in the pollen of the Scotch Pine.  Tree It was first synthesized in the mid 1930s but was largely ignored by the scientific community until 1962. At that time, researchers conducted an experiment in which normal women were given either 100 mg of DHEA or 100 mg of androstenedione. The researchers found that while both hormones led to elevated testosterone levels, the increase from androstenedione was twice as much as DHEA. Testosterone is a hormone with a very short half-life in the body as the liver quickly metabolizes it. The increase of testosterone from this research mimics that of decay curve present normally in our body.

Numerous studies have been undertaken through the years on the relationship between androstenedione intake and the raising of estrogen level. In an important study, Benjamin Z. Leder, MD, of Massachusetts General Hospital in Boston, conducted research involving 42 healthy men aged, 20 to 40-years-old. Of the 42 men, thirteen received no androstenedione, fifteen were given 100 mg a day for seven days, and 14 were given 300 mg a day for seven days. Hormone levels in the blood were tested before, during, and at the end of the study. On the average, men given 300 mg of androstenedione per day had an increase in blood testosterone levels of 34 percent. Researchers also noted a 128 percent increase in estradiol levels. In addition, the study showed an increase in estrone (another estrogen hormone) among those taking androstenedione. Study participants taking 100 mg per day showed some increases in estradiol but not testosterone levels. The authors reported that these increases were not statistically significant.

While androstenedione in high dose (300mg a day or more ) has been used primarily by athletes to enhance performance, such high dose is not warranted in an anti-aging setting. Low dose androstenedione has a place in the anti-aging protocol. For those whose testosterone levels may need a boost, low dose androstenedione (25-50 mg) may be considered at bedtime and again first thing in the morning. This will mimic the body's normal diurnal rhythms without stimulating the negative feedback mechanism. The amount of intake is best guided by symptoms instead of blood levels at this dosage, as it may not be evident on blood test.

It is important to have baseline testosterone, free testosterone, estrone, and estradiol level prior to commencing androstenedione. Those with low estrogen level will not have to worry about adding androstenedione to their anti-aging regiment.  Those with high estrogen level, or those who wish to err on the safe side, should consider zinc supplementation as well as phyto-nutrients. Zinc (50 mg a day) acts as a natural aromatase inhibitor to reduce estrogen level. Furthermore, intake of phytoestrogen through cruciferous vegetables (cabbage, broccoli, cauliflower and Brussels sprouts) that acts as estrogen blockers will further allay any fears. Some may wish to consider cruciferous extracts containing diindolymethane or isoflavone extracts as alternatives.

While androstenedione can be converted into estrone, the amount is minimal if the dosage is low (50 to 100 mg a day). Androstendiol can be used in combination with androstenedione for those who are concern of the excessive estrogen pathway, as androstenediol does not convert into estrogen directly.

Women may also benefit from occasional low-dose androstenedione use. It will probably be found to be of use in the maintenance of bone density and actual reversal of osteoporosis. Also, occasional use of androstenedione as a libido-enhancer has been reported, with onset of effects occurring within 30-60 minutes. Women using androstenedione for any use should be careful to adjust the dose downward-or discontinue use-should signs of secondary male characteristics be noted (i.e., voice deepening, hair or whiskers on upper lip, etc). 25 to 50 mg is all that is needed.

7. Progesterone

In addition to testosterone, men also make estrogen (primarily estradiol or E2) and progesterone in much smaller but significant amount. It is produced in the testes and in their adrenal glands. While the level of progesterone in male is significantly lower than in the female, some women's progesterone level fall below that of same-age men during menopause.

The male hormone, testosterone, is an antagonist to estradiol (E2). Like progesterone, testosterone can stimulate new bone formation, increase bone density, and a lack of it causes osteoporosis. It is made from progesterone. Men normally continue to produce relatively normal testosterone for their age well into there seventies. Contrary to common perception, testosterone does not cause prostate caner.  Since progesterone has an antagonistic effect on estrogen, and estrogen is an antagonist to testosterone,  application of progesterone cream will indirectly enhance the effect of testosterone.

Large doses of progesterone inhibit sexual behavior in male, but physiological doses appear to have enhanced sexual drive. Clearly testosterone alone is not the only driver of sexual function in male or in female.

All men over age 40 should consider natural progesterone replacement therapy, or even earlier if there is a history of prostate cancer or BPH (as we shall see later).  The amount needed is 10 mg a day, approximately half that used in women. No rest day is needed, and men should apply it on a daily basis.

One side benefit is that there is a reasonable chance that natural progesterone supplement decreases male balding due to the corresponding rise in testosterone. More research is needed in this area.