Dehydroepiandrosterone (DHEA), a hormone produced by the adrenal glands, is a precursor to the sex hormones estrogen and testosterone. Blood levels of DHEA peak in one’s twenties and then decline dramatically with age, decreasing to 20-30% of peak youthful levels between the ages of 70 and 80. DHEA is frequently referred to as an “anti-aging” hormone.
Recently, researchers in Turkey found that DHEA levels were significantly lower in men with symptoms associated with aging, including erectile dysfunction.9 Healthy levels of DHEA may support immune function, bone density, mood, libido, and healthy body composition.
Elevated levels of DHEA may indicate congenital adrenal hyperplasia, a group of disorders that result from the impaired ability of the adrenal glands to produce glucocorticoids.
Supplementation with DHEA increases immunological function, improves bone mineral density, increases sexual libido in women, reduces abdominal fat, protects the brain following nerve injury, and helps prevent diabetes, cancer, and heart disease.
Emerging research suggests that DHEA may have antidepressant effects. In a report in the January 2006 issue of the American Journal of Psychiatry, investigators found that in HIV-infected men and women, supplementation with DHEA was superior to placebo in treating non-major depression (with a response rate of 62% vs. 33%, retrospectively).
In another study from the National Institute of Mental Health, investigators found that DHEA significantly improved midlife-onset major and minor depression in men and women aged 45 to 65 years old.
Furthermore, a recently published study from Israel demonstrated that DHEA administration decreased self-administration of cocaine in rats, suggesting a potential for DHEA in reducing cravings and supporting recovery from addiction.15
In a recent study published in the Journal of Investigative Dermatology, scientists demonstrated that DHEA levels were significantly lower in elderly persons predisposed to chronic wound conditions, such as venous ulcers, and that administration of DHEA accelerated wound healing in aging mice.This led the research team to suggest that DHEA supplementation may be a safe, effective strategy to improve wound healing in the elderly.
Natural therapies may help to optimize DHEA levels.You may wish to discuss with your doctor the use of pregnenolone or DHEA. Those with estrogen-related cancers such as breast or prostate cancer should not use DHEA.
Prostate-specific antigen (PSA) (Men Only)
Prostate-specific antigen (PSA) is a protein manufactured by the prostate gland in men. Elevated levels may suggest an enlarged prostate, prostate inflammation, or prostate cancer. PSA levels may also be used to monitor the efficacy of therapeutic regimens for prostate conditions.
Elevated levels of PSA may not necessarily signal prostate cancer, and prostate cancer may not always be accompanied by expression of PSA. Levels can be elevated in the presence of a urinary tract infection or an inflamed prostate. A PSA level over 2.5 ng/mL, or a PSA doubling time (the time required for PSA value to double) of less than 12 years, may be a cause for concern.
The American Cancer Society recommends annual PSA testing for men beginning at age 50. Men who are at high risk should begin PSA testing at age 40-45. PSA levels increase with age, even in the absence of prostate abnormalities.
More than 15% of men with PSA values between 2.6 and 4.0 ng/mL who are 40 years or older have prostate cancer, according to a prostate cancer screening study published in 2005 in the Journal of Urology.
According to a study published in the Journal of the American Medical Association, 25% of patients with normal digital rectal exams and total PSA levels of 4.0-10.0 ng/mL have prostate cancer.19 In a later study published in the New England Journal of Medicine, investigators recommended that “lowering the threshold for biopsy from 4.1 to 2.6 ng per milliliter in men younger than 60 years would double the cancer-detection rate from 18 percent to 36 percent.”20 It should be noted that levels below the currently recognized cutoff of 4.1 ng/mL may not distinguish between prostate cancer and benign prostate disease.
In a recently published study in the journal Urology, prostate cancer was detected in 22% of patients with PSA levels between 2.0 and 4.0 ng/mL, and most of those cancers biopsied were significant, leading researchers to conclude that an “important number of cancers could be detected in the PSA range of 2.0 to 4.0 ng/mL.”21 In another study, investigators in Spain detected significant cancers in some patients with a PSA range between 1.0 and 2.99 ng/mL.Although the risk of developing cancer for those in the low PSA range is small, the authors said, it is still relevant.22
A healthy Mediterranean-type diet may offer protection against prostate cancer and other diseases associated with aging. Natural therapies may also help support prostate health.You and your physician may wish to discuss the use of saw palmetto, beta-sitosterol, pygeum, and nettle root extracts.
Thyroid Stimulating Hormone (TSH)
Secreted by the pituitary gland, thyroid stimulating hormone (TSH) controls thyroid hormone secretion in the thyroid. When blood levels fall below normal, this indicates hyperthyroidism (increased thyroid activity, also called thyrotoxicosis), and when values are above normal, this suggests hypothyroidism (low thyroid activity). Overt hyper- or hypothyroidism is generally easy to diagnose, but subclinical disease can be more elusive.
Because the symptoms of thyroid imbalance may be nonspecific or absent and may progress slowly, and since many doctors do not routinely screen for thyroid function, people with mild hyper- or hypothyroidism can go undiagnosed for some time. Undiagnosed mild disease can progress to clinical disease states. This is a dangerous scenario, since people with hypothyroidism and elevated serum cholesterol and LDL have an increased risk of atherosclerosis.
Mild hypothyroidism (low thyroid gland function) may be associated with reversible hypercholesterolemia (high blood cholesterol) and cognitive dysfunction, as well as such nonspecific symptoms as fatigue, depression, cold intolerance, dry skin, constipation, and weight gain. Mild hyperthyroidism is often associated with atrial fibrillation (a disturbance of heart rhythm), reduced bone mineral density, and nonspecific symptoms such as fatigue, weight loss, heat intolerance, nervousness, insomnia, muscle weakness, shortness of breath, and heart palpitations.
One study found that TSH levels greater than 2.0 mU/L increase the 20-year risk of developing hypothyroidism, while another study found that TSH levels greater than 4.0 mU/L increase the risk of heart attack in elderly women.43 Recently, published data showed that subclinical hypothyroidism was associated with an increased risk of congestive heart failure among older adults with TSH levels of 7.0 mU/L or greater.
In healthy postmenopausal women,TSH levels at the low end of the normal range (0.5-1.1 mU/L) are associated with low bone mineral density and a 2.2-fold greater risk of osteoporosis, according to a study published in 2006 in the journal Clinical Endocrinology.
Measuring TSH is the best test for assessing thyroid function. Currently, the American Thyroid Association recommends screening for TSH levels beginning at age 35, and every five years thereafter. If results are abnormal, assessing TSH in conjunction with levels of triiodothyronine (T3) and thyroxine (T4) blood levels may help assist definitive diagnosis.
Natural therapies may help to support thyroid health and optimize TSH levels.You may wish to discuss with your doctor the use of L-tyrosine, iodine, and selenium.
Thyroid stimulating hormone (TSH) is secreted by the pituitary gland and serves to control thyroid hormone secretion in the thy- roid.Thyroxine (T4) and triiodothyronine (T3, free) are hormones that are released from the thyroid. Iodine that is taken up by the thy- roid is incorporated in T3 and T4 (so called because they have three and four iodine atoms, respectively), which serves to increase the body’s basal metabolic rate, regulate growth and development, increase cardiac output, increase the metabolism of cholesterol, increase the number of LDL receptor sites in the liver, and inhibit TSH secretion.
Normally, a decrease in T3 and T4 stimulates TSH release from the pituitary that, in turn, stimulates T3 and T4 production and secretion, and growth of the thyroid gland. When T3 and T4 levels are increased, TSH production is shut down via negative feedback channels.
When TSH, T3, or T4 levels fall above or below normal, this is referred to as hypothyroidism (low thyroid activity) or hyperthyroidism (increased thyroid activity, also called thyrotoxicosis). Overt hyper- or hypothyroidism is generally easy to diagnose, but subclinical disease is a bit more elusive.
In the National Health and Nutrition Examination Survey (NHANES III), hypothyroidism was found in 4.6% (4.3% mild and 0.3% clinical disease) of a cross-sectional population in the US and hyperthyroidism in 1.3% (0.5% clinical and 0.7% mild) of the same study group. Because mild (or “subclinical”) symptoms may be non- specific (or absent) and progress slowly, and thyroid functions are not routinely screened, people with mild hyper- or hypothyroidism may go undiagnosed. Undiagnosed mild disease may progress to clinical disease states. People with hypothyroidism and elevated serum cholesterol and LDL have an increased risk of atherosclerosis.
Mild hypothyroidism (low thyroid gland function) may be associated with reversible hyper-cholesterolemia (high blood cholesterol) and cognitive dysfunction, as well as such nonspecific symptoms as fatigue, depression, cold intolerance, dry skin, constipation, and weight gain. Mild hyperthyroidism is often associated with atrial fibrillation and reduced bone mineral density and nonspecific symptoms such as fatigue, weight loss, heat intolerance, nervousness, insomnia, muscle weakness, dyspnea, and palpitations, among others. Measurement of TSH is the best test for assessing thyroid function. Currently, the American Thyroid Association recommends TSH testing beginning at age 35, and every five years thereafter.73 Comparing the ratios between TSH, T3, and T4 blood levels, though, may elucidate definitive diagnosis.This is extremely important, given that the majority of people with mild hypo- or hyperthyroidism are asymptomatic, and levels of thyroid hormones may be depressed or elevated only slightly.
IU/mL, investigations have shown that blood levels equal and greater than 2.0 mcIU/mL may actually indicate adverse health effects:
- TSH >2.0 mcIU/mL increased the 20-year risk of thyroid- induced autoimmune attack.74
- TSH >4.0 mcIU/mL increased the risk of heart attack.
On the positive side, when TSH levels are 2.0-4.0 mcIU/mL, cholesterol levels decline in response to T4 therapy.
The table above summarizes characteristic thyroid panel results from persons with overt or mild hypo- or hyperthyroidism.
Free T3 is valuable in confirming the diagnosis of hyperthyroidism when an elevated free or total T4 level is found. Abnormal concen- trations may be seen in T3 toxicosis in the presence of normal T4 levels.
Testosterone (Free and Total)
Testosterone is produced in the testes in men, in the ovaries in women, and in the adrenal glands of both men and women. Men and women alike can be dramatically affected by the decline in testosterone levels that occurs with aging.
In the serum of both men and women, less than 2% of testosterone typically is found in the free (uncomplexed) state. Unlike bound testosterone, the free form of the hormone can circulate in the brain and affect nerve cells.Testosterone plays different roles in men and women, including the regulation of fertility, libido, and mus- cle mass. In men, free testosterone levels may be used to evaluate whether sufficient bioactive testosterone is available to protect against abdominal obesity, mental depression, osteoporosis, and heart disease. In women, low levels of testosterone have been associated with decreased libido and well-being, while high levels of free testosterone may indicate hirsutism (a condition of excessive hair growth on the face and chest) or polycystic ovarian syndrome. Increased testosterone in women may also indicate low estrogen levels.
Men: In men, testosterone levels normally decline with age, dropping to approximately 65% of young adult levels by age 75.47 This drop in testosterone is partially responsible for the significant physiological changes seen in aging men. In fact, low levels of testosterone are associated with numerous adverse health conditions, including diminished libido, metabolic syndrome, erectile dysfunction, loss of muscle tone, increased abdominal fat, low bone density, depression, Alzheimer’s disease, type II diabetes, and atherosclerosis.
New research shows that low testosterone levels are a risk factor for ischemic heart disease in men. Recent research published in the journal Endocrinology Research showed a relationship between decreased testosterone levels and increased severity of thoracic aortic atherosclerosis in men.
Women: Following menopause, levels of testosterone in women decrease, along with a concomitant decline in libido, mood, and general well-being.Although women produce only small quantities of testosterone, evidence indicates that this important hormone helps women maintain sexual function, as well as muscle strength and mass. Investigators reporting in the Journal of Clinical Endocrinology and Metabolism found that when obese women were given low doses of a synthetic testosterone analogue, they lost more body fat and subcutaneous abdominal fat, and gained more muscle mass, than women given placebo.The testosterone-supplemented women also experienced a slight increase in resting metabolic rate.
Optimal testosterone levels may support healthy mood, libido, body composition, and cardiovascular wellness.You may wish to discuss with your doctor the use of supplements such as DHEA and pregnenolone. Speak to your physician to determine whether prescription testosterone may also be helpful for you.
Estradiol (and total estrogens)
Like testosterone, both men and women need estrogen for numerous physiological functions. Estradiol is the primary circulating form of estrogen in men and women, and is an indicator of hypothalamic and pituitary function. Men produce estradiol in much smaller amounts than do women; most estradiol is produced from testosterone and adrenal steroid hormones, and a fraction is produced directly by the testes. In women, estradiol is produced in the ovaries, adrenal glands, and peripheral tissues. Levels of estradiol vary throughout the menstrual cycle, and drop to low but constant levels after menopause.
In women, blood estradiol levels help to evaluate menopausal status and sexual maturity. Increased levels in women may indicate an increased risk for breast or endometrial cancer. Estradiol plays a role in supporting healthy bone density in men and women. Low levels are associated with an increased risk of osteoporosis and bone fracture in men and women as well. Elevated levels of estradiol in men may accompany gynecomastia (breast enlargement), diminished sex drive, and difficulty with urination.
Women: Diminished levels of estradiol correlate with low levels of bone mineral density, which is a strong risk factor for osteoporosis. Optimizing estradiol levels in early menopausal women has been associated with relief from hot flashes, irritability, and insomnia.56
According to a recently published report from the University of Michigan School of Public Health, lower estradiol levels in women are associated with higher levels of markers of cardiovascular disease risk.57
Men: In older men, low levels of estradiol have been linked with an increased risk of vertebral fractures; conversely, estradiol levels are found to be positively associated with bone mineral density, suggesting an association between low serum levels and the development of osteoporosis. A recent study from France found a correlation between low estradiol and skeletal frailty.
Significant positive correlations were found between estradiol levels and levels of total cholesterol, according to results from a recently published study of 111 men with stable coronary artery disease. Researchers suggested that estradiol has a possible role in “promoting the development of atherogenic lipid milieu in men with coronary artery disease.”
Optimal estradiol levels may support healthy bone density, cardio-vascular health, and well-being.You may wish to discuss with your doctor the use of supplements such as DHEA, pregnenolone, soy, black cohosh, and pomegranate. Speak to your physician to determine whether prescription therapies such as bioidentical estrogens may also be helpful for you.
Progesterone is a balancing hormone that works in a dynamic relationship with estrogen to regulate the menstrual cycle and the health of the reproductive organs.When women reach their 30’s and 40’s it is common to see a situation in which the balance of these two hormones is shifted too heavily toward estrogen. Estrogen dominance is often to blame for many symptoms including PMS, night sweats and depression. Balancing estrogen and progesterone can help balance these effects. Progesterone also provides important benefits for breast and bone health. Statistically women with higher progesterone levels have less breast cancer. Progesterone also has benefits in brain health by promoting energy production in brain cells and by protecting against nerve cell damage and brain aging.
Pregnenolone is made directly from cholesterol within the mito- chondria, and in turn is the substance from which the body manufactures DHEA and other steroid hormones, including testosterone, estrogens, cortisol, and aldosterone. It converts to DHEA and progesterone; in women, this conversion to progesterone is especially important, as it creates a balance with estrogen to reduce the risk of certain cancers.With the advent of degenerative disease, pregnenolone levels are generally suppressed.
In men progesterone is important for prostate health and plays a role in preventing prostate cancer. It also helps to prevent bone loss in men as in women.
Somatomedin-C (insulin-like growth factor/IGF-I)
IGF-1 is the main effector of human growth hormone (HGH) activity and also affects glucose metabolism (insulin-like activity). Because it remains constant in the blood longer than HGH (which tends to fluctuate in response to various stimuli), it is a more accurate indicator of HGH deficiency, and is also more precise for monitoring HGH therapy than is testing HGH directly.
IGF-1 is critical in mediating the growth of muscle and other tissues, and normal levels steadily increase until 12-15 years of age, and then begin to decline. Up to one-third of skeletal muscle mass and strength is lost between the ages of 30 and 80. A study by Barton-Davis et al showed that IGF-1 overexpression in the muscle cells of mice can preserve the characteristics (morphological and functional) of the skeletal muscles of old mice such that they are equivalent to those of young adult muscles. Ruiz-Torres et al showed that when IGF-1 levels in older (over 70) males were similar to levels in younger males (up to 39 years), the older males do not show age- dependent decreases in serum testosterone and lean body mass, nor increases in fat body mass.
Low levels of IGF-1 have been implicated in the development of atherosclerosis.Van den Beld et al found that high free IGF-1 concentrations appeared to be correlated with reduced risk of atherosclerosis, suggesting that IGF-1 (along with endogenous testosterone and estrone) may play a protective role in the development of atherosclerosis in aging men.
A study by Carro et al suggests a role for IGF-1 as a neuroprotective hormone. Data show a correlation between lower levels of IGF-1 and higher levels of amyloid-B accumulation in the brains of Alzheimer’s patients. In studies of mutant mice, high amyloid-B levels are seen when serum IGF-1 levels are low. Conversely, the amyloid-B burden can be decreased by increasing levels of serum IGF-1. Investigators suggested that “circulating IGF-1 is a physiological regu- lator of brain amyloid levels with therapeutic potential.”
Elevated levels of IGF-1 may be indicative of acromegaly (gigantism) and diabetic retinopathy. Although it has been suspected that high levels of IGF-1 are associated with increased risk of prostate cancer, recent data suggest that IGF-1 may be serving as a tumor marker rather than an etiologic factor for the disease. The IGF-1 test (decreased levels) may also be used to evaluate pituitary insufficiency and hypothalamic lesions in children (diagnosis of dwarfism and response to therapy). Low levels have also been found in patients with amyotrophic lateral sclerosis.
Cortisol is an essential hormone that plays many vital roles, including helping the human body adapt to stress.Yet this naturally occurring hormone is one of the few whose levels in the body increase with age, with potentially damaging consequences that have been linked to depression, Alzheimer’s disease, and other maladies.
The good news is, new research on nutrients such as phosphatidylserine, DHEA, and ginkgo biloba offers valuable insights on how to control cortisol levels to promote optimal health.
Declining hormone levels are a hallmark of the aging process.The body’s production of DHEA, pregnenolone, and testosterone drops significantly as we age, and these changes in hormone levels can have dramatic effects on our health.
But not all hormones follow this pattern. One major exception is cortisol, a hormone released in response to stress.While cortisol plays vital roles in the body, excessive secretions of this hormone can have serious health implications, including loss of mental function, depression, and a reduction in lean tissue. Extreme overproduction of cortisol, as occurs in Cushing’s syndrome, results in increased body fat, decreased bone density, and severe muscle weakness.Thus it is critical to maintain cortisol levels within a healthy range. Fortunately, scientists have discovered that phosphatidylserine, DHEA, and ginkgo biloba can reduce cortisol levels, helping to keep this catabolic hormone from damaging your body.
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