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Testosterone is a hormone secreted by the ovaries, adrenal glands and testes. Testosterone is the primary male sex hormone, responsible for male sexual development and critical in maintaining erectile function, libido, normal energy levels, and mood, and building muscles and burning fat. It is responsible for supporting immune function, bone density, and skin tone. It also controls a whole range of other physiological functions throughout the body in both males and females.

Testosterone levels decline with age. The decline begins when a man is in his mid to late 30s, and by the age of 80, is only 20% of what it was in youth. While the total testosterone does not drop drastically the free testosterone, which is the biologically active form, does decline dramatically with age. Free testosterone makes up about 2- 3% of the total amount secreted. Increased estrogen levels and insulin resistance in men can also cause a drop in the free testosterone levels. It has been found that diabetic men with elevated hemoglobin A1C levels have lower levels of testosterone and this association is independent of obesity and body fat distribution.

The number of men in the U.S., between the ages of 45 and 70 years, is expected to increase from 46 million in 1990 to 81 million by 2020. Currently more than 5 million men in the United States suffer from the effects of hypogonadism or low testosterone levels.

Testosterone in Women

Most of the research on testosterone replacement has focused on men. Nevertheless, healthy women naturally have small amounts of testosterone. It is produced primarily in the ovaries. Testosterone levels tend to peak when a woman is ovulating, increasing libido for reproduction. It also appears to enhance the function of estrogen and progesterone. Women who replace progesterone without testosterone often require slightly greater doses of progesterone. Testosterone may also improve various symptoms of menopause including ‘hot flashes,” weight gain, fatigue, lethargy and may decrease the risk of breast cancer.

Most women begin to experience symptoms of testosterone deficiency after menopause, when their testosterone levels generally decline by about 50%. However, a variety of conditions can cause a decline long before menopause. Some of these conditions include childbirth, endometriosis, birth control pills, ovarectomy, depression, and abuse of alcohol and narcotics. Additionally, some medications may interfere with the bioavailability of testosterone, such as Provera, Prozac and Zoloft or other antidepressants, and some antipsychotic medications.

Typical symptoms experienced by women with low testosterone levels include

  • Decreased libido
  • Orgasms may be absent or significantly decreased
  • Sexual fantasy may be significantly decreased or absent
  • Vaginal dryness
  • Lack of energy and stamina
  • Flabbiness and muscular weakness
  • Diminished overall vitality
  • Loss of hair
  • Loss of coordination and balance
  • Decreased armpit, pubic and body hair
  • Memory loss
  • Arthritis
  • Bladder symptoms
  • Depression
Common Factors that Can Reduce Total Testosterone Production
    • COPD/hypoxia
    • Asthma
    • Corticosteroid use
    • Presence of cancer
    • Cancer chemotherapy
    • Obesity
    • Malnutrition
    • Critical illness
Some drugs and substances compete for testosterone cellular receptors or change metabolism indirectly, resulting in the same effect as a low testosterone level
    • Antifungal drugs (as above)
    • Pesticides
    • Spironolactone
    • Some cancer chemotherapy drugs
    • Thiazide diuretics
    • DHEA
Estradiol’s Relationship to Testosterone

The enzyme system called aromatase, found mainly in fat cells, converts a portion of testosterone to estrogen. Rising estrogen levels reduce the available free testosterone. The testosterone-to-estrogen ratio in men generally increases with age.

Many lifestyle behaviors are directly related to estrogen elevations. The most common causes of midlife estrogen increases in males include:

  • Age-related increases in aromatase activity
  • Alteration in liver function
  •  Zinc deficiency
  • Obesity
  • Overuse of alcohol, which decreases key estrogen metabolizing enzymes in the liver, such as the P450 enzyme system
  • Drug-induced estrogen imbalance
  • Ingestion of estrogen-enhancing food or environmental substances
  • Excess testosterone by injection
  • High cortisol levels
Factors that increase aromatization of testosterone to estrogen include
      • Age
      • Genetics
      • Obesity
      • High cortisol levels.
      • Triggers for cortisol include:
      • Low carbohydrate intake
      • Skipping meals
      • Dieting
      • Chronic stress
      • Chronic lack of sleep
      • Alcohol
      • Glucocorticoid steroids
      • Overdoing exercise
      • High-fat diet
      • Alcohol
      • Grapefruit
      • Low soy intake
      • Zinc deficiency (e.g., from diuretics, diet, age, illness)
      • Vitamin C deficiency
      • Impaired liver function, or drugs which impair liver function
      • A healthy liver eliminates surplus estrogen and SHBG
      • NSAIDs
      • Statins
      • Some heart and blood pressure medications
      • Some anti-depressants
      • Diuretics
      • Excess testosterone injection (less-so with transdermal and even less with pellet delivery system)
      • Hypothyroidism – low T3
      • Hyperinsulinism
      • Proinflammatory cytokines – COX-2, IL-6, TNF alpha
      • Increased growth hormone levels
      • Low melatonin levels

Andropause Screening
Your doctor will make the diagnosis of andropause based upon your symptoms, physical findings and blood tests.

Symptoms of testosterone deficiency may arise even when a laboratory test indicates a “normal” level. The reason is that many lab tests do not address the amount of “free” testosterone available to deliver the desired benefits. “Free” testosterone refers to the amount of circulating testosterone most biologically available. In addition, the presence of other hormones can influence the levels of free testosterone.

Management of Low Testosterone Levels
One way to help maintain (if not actually increase) testosterone levels is by reducing excess body fat. Weight training is another way to raise testosterone levels in both males and females. Additional lifestyle changes include avoiding excess alcohol and high-fat diets, increasing intake of soy products, taking caution with drugs that impair liver function, and managing stress. Avoid over-the-counter agents promising to improve testosterone levels, such as androstenedione. Testosterone replacement therapy, when prescribed by your physician, can dramatically augment the benefits of these lifestyle changes.

In general, natural testosterone replenishment for andropausal men has the potential to prolong the quality-of-life by decreasing many diseases of aging. Testosterone protects against cardiovascular disease; it can raise HDL cholesterol, and lower LDL cholesterol levels. It can decrease blood pressure, excess body fat, and symptoms of arthritis. Testosterone is a memory enhancer for many men. It stimulates the cardiovascular system, the neurologic system, muscles, bones and the vascular system. It prevents tendon and joint degeneration and osteoporosis.

Testosterone Replacement Therapy
Studies over the past decade show that replacing testosterone can help restore men’s health. Men receiving testosterone replacement are more likely to experience:

Increased bone density, bone formation and bone minerals.
Increased energy
Improvement in sexual function and desire
Decreased body fat
Increased muscle strength, and diameter of muscle fibers
Improved blood glucose levels
Decreased blood pressure
Lower cholesterol and triglycerides
Increased HDL cholesterol (transdermal testosterone)
Increased apolipoprotein A and decreased lipoprotein A
Decreased heart disease
Improvement in autoimmune disorders
Improved wound healing
Improved urinary function
Researchers report that women who receive testosterone replacement therapy after menopause experience an increase in sexual drive and response, frequency of sexual intercourse, number of sexual fantasies, and level of sexual arousal. Testosterone generally helps control a woman’s libido, and is known to improve clitoral and nipple sensitivity as well as the quality of orgasm.

Testosterone contributes to overall muscle tone. Prior to menopause, many women experience the embarrassment of a leaky bladder. This problem may be related to diminishing testosterone levels, because the pelvic muscles are particularly dependent on testosterone. Many women find that testosterone replacement, combined with Kegel exercises, strengthens and tones those muscles.

Recent research suggests that testosterone may increase the bone’s ability to retain calcium. Women who experience very rapid bone loss are typically deficient in both estrogen and testosterone. It appears that both testosterone and estrogen independently improve bone density.

Regimens of Administration and Usual Starting Dose
Testosterone can be replaced with oral medication, by injection, with implantable pellets, , patches, and creams. Each may have advantages and disadvantages. Your doctor will help you determine the best form of administering testosterone replacement.

Monitoring Testosterone Replacement
Your physician will monitor blood levels every few months until dosages are adjusted to achieve optimal levels and outcomes.

Side Effects Associated with Testosterone Replacement
Side effects may include:

• The most common immediate side effects (occurring in approximately no more than 6% of users) include:

• Acne, not limited to the face; could be on the back sides

• Oily skin

• Application site reaction

• Headache

• Hypertension (high blood pressure)

• Abnormal liver function tests

• Non-cancerous prostate disorder

• Greasy hair

• Strong body odor

• Aggressiveness; bossiness

• Scalp hair loss

• Growth of facial hair

• An increase in hemoglobin and hematocrit (Hgb and Hct)

• more common when replacement is by injection

• may be treated by donating blood or therapeutic phlebotomy

• Male pattern baldness and gynecomastia (breast enlargement) can occur when too much of the testosterone is aromatized to estrogen.

• Diminished sperm production and a 25-30% reduction in the size of the testicles may develop. Excess doses of testosterone may suppress FSH enough to inhibit sperm production.

• In insulin-dependent diabetics, testosterone replacement may reduce insulin requirements.

• The concurrent use of testosterone with corticosteroids may enhance edema formation.

• Testosterone replacement may also increase clearance of the drug propranolol.

• Geriatric patients may be at a slightly increased risk for the development of prostate enlargement when replacing testosterone.

• Edema may be a complication with testosterone replacement in patients with pre-existing cardiac, renal, or hepatic disease, secondary to sodium retention.

• Insomnia or sleep disturbances. Replacement therapy may potentiate sleep apnea in some chronic disease patients, although studies have shown it can actually ameliorate symptoms of sleep apnea.

• Could turn occult prostate or breast cancer lesions into active ones

Many physicians still hesitate to prescribe testosterone replacement for women because of the potential virilizing side effects. While excessive doses of testosterone can lead to “masculine” characteristics, a typical woman’s dose would be so small that these effects are rare. Additionally, many of the reported side effects from testosterone are those associated with synthetic testosterone-like drugs, not natural bio-identical testosterone. While side effects are uncommon, if they occur, back off on the dose of the testosterone and notify your physician.

Concurrent Nutritional Supplementation
The following nutritional supplementation is frequently recommended whenever testosterone replacement therapy is used

DIM or Indole-3-Carbinol
Chrysin, if estradiol levels climb in males
Beta Sitosterol
Your doctor will determine if one of more nutritional supplements may be advisable for you.

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