Hepatitis, inflammation of the liver, showing disarray of the hepatocytes or liver cells.
The hepatobiliary system comprises the liver and gall bladder. The liver functions as the body’s key detoxification system for toxins, pharmaceuticals, and hormone breakdown products. Without the liver functioning at optimal capacity, the body would literally poison itself. Peak liver function ensures that the body is able to neutralize harmful compounds and regulate sugar and lipid metabolism. The gall bladder serves as a storage vessel for bile, which is used in the digestion of food.
Abnormal levels of protein, albumin, globulin, albumin/globulin ratio, bilirubin, alkaline phosphatase, lactic dehydrogenase (LDH), AST (SGOT), ALT (SGPT), iron, cholesterol, and lipoproteins indicate potential liver/biliary problems. These may include liver damage induced by alcohol or drug abuse, liver cancer, or obstruction of the bile duct, among others. Together, ALT and AST allow for differential diagnosis of disorders associated with the hepatobiliary system and pancreas. High levels of alkaline phosphatase may also indicate abnormally high levels of vitamin D or diseases of the liver or bones.
The kidneys, a component of the urinary system, help regulate blood pressure and are responsible for regulating the pH, mineral concentration, and water composition of blood. The kidneys filter and remove waste (especially urea) from the blood and eliminate it along with water as urine. Checking your kidney function can help you avoid irreversible kidney damage from medications and illnesses.
Kidney function can be assessed by evaluating blood levels of blood urea nitrogen (BUN), uric acid, creatinine, BUN/creatinine ratio, sodium, potassium, and chloride ions. BUN measures urea nitrogen, a breakdown product of protein metabolism, in the blood. Most diseases affecting the renal system affect urea excretion by the kidneys and will elevate BUN levels. Creatinine, a breakdown product of muscle creatine phosphate, is excreted by the kidneys, and its level may be used to assess the rate of kidney filtration. Abnormally high creatinine levels may indicate impaired renal function, renal failure, or dehydration, and decreased levels may indicate liver disease. The BUN/creatinine ratio may help determine factors causing decreased kidney function, such as dehydration. Sodium, potassium, and chloride ion levels help evaluate hydration status and electrolyte balance. High levels of potassium may indicate renal failure or dehydration, while low levels can occur with diarrhea, vomiting, or excessive sweating.
Testosterone (free and total)
The hormone testosterone plays different roles in men and women, including the regulation of fertility, libido, and muscle mass. It exists as free testosterone, which is active and unbound, as well as in a form bound to either albumin or sex hormone binding globulin (SHBG). Included in both the Male and Female Panels, testosterone is produced in the testes in men, in the ovaries in women, and in the adrenal glands of both men and women.
Approximately 50% of testosterone is bound to SHBG and the remainder to albumin. 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.6
Total testosterone is useful for assessing gonadal, adrenal, and pituitary function in men. In women, total testosterone can help in the evaluation of Stein-Leventhal (polycystic ovarian) syndrome, testosterone-producing tumors of the ovary, tumors of the adrenal cortices, and congenital adrenal hyperplasia.
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 diease. In women, high levels of free testosterone may indicate hirsuitism, which causes excessive hair growth on the face and chest, and is often indicative of polycystic ovaries. Increased testosterone in women also suggests low estrogen levels.
Importance of Testosterone in Men
In men, testosterone production is stimulated by luteinizing hormone, which is produced by the pituitary gland. Luteinizing hormone stimulates the Leydig cells in the testes to produce testosterone. Testosterone levels normally decline with age, dropping to approximately 65% of young adult levels by age 75.7 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, erectile dysfunction, loss of muscle tone, increased abdominal fat, low bone density, depression, Alzheimer’s, and heart disease.
The studies described below underscore the value of maintaining youthful free testosterone levels:
• Depression. The relationship between depression and testosterone was assessed in 856 men between the ages of 50 and 89. The study results showed depression was significantly correlated with lower levels of bioavailable (free) testosterone levels, leading the researchers to suggest, “testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone.”8
• Type II diabetes. A recent study in the Journal of Clinical Endocrinology and Metabolism found a link between type II diabetes and decreased testosterone levels in men. According to S. Dhindsa and colleagues, 33% of study subjects with type II diabetes had low testosterone levels. This deficiency, referred to as hypogonadism, was the result of pituitary gland malfunction. This study was the first to link hypogonadism with type II diabetes.9
• Atherosclerosis and heart disease. The relationship between coronary artery disease and testosterone levels was investigated in men aged 40-60 with and without atherosclerosis. Investigators in Poland found a significant association between diminished testosterone and decreases in insulin sensitivity and HDL. The study authors concluded that low levels of total testosterone often appear with features of metabolic syndrome, and may be involved in the pathogenesis of atherosclerosis.10
• Alzheimer’s disease. A study from the University of Texas found that elderly hypogonadal males with newly diagnosed Alzheimer’s re-sponded favorably to testosterone replacement therapy. Following treatment with intramuscular testosterone (200 mg every two weeks for one year), patients showed improvements in the Initial Alzheimer’s Disease Assessment Scale cognitive subscale as well as the Mini Mental Status Examination. The placebo-treated group “deteriorated gradually.” The investigators concluded that testosterone “could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer’s disease.”11
Importance of Testosterone in Women
Although women produce only small quantities of testosterone, mounting evidence indicates that this important hormone helps women maintain 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 experienced a slight increase in resting metabolic rate.12
Progesterone (Female Panel only)
Progesterone, a steroid hormone produced in men and women, is synthesized in a biochemical pathway leading from cholesterol to pregnenolone to progesterone, which in turn is a precursor to other steroid hormones, including cortisol, estrogen, and testosterone. In women, progesterone is produced in the corpus luteum of the ovary, in smaller amounts by the adrenal glands, and in copious amounts by the placenta during pregnancy.
With advancing age, progesterone levels decline. Following menopause, progesterone levels decrease dramatically to nearly undetectable levels; along with estrogen, low progesterone may be responsible for bone loss leading to osteoporosis. Low progesterone levels may also be associated with irregular menstrual cycles, heavy bleeding, endometriosis and uterine fibroids, tender breasts, and mood swings. High levels of progesterone relative to estrogen can cause increased insulin levels, decreased insulin sensitivity, weight gain, reduced libido, and depression.
Dehydroepiandrosterone, or DHEA, is a hormone produced by the adrenal glands. Serum levels of its sulfated form, DHEA-S, measure adrenal cortical function. Elevated levels, which peak during one’s twenties, may indicate congenital adrenal hyperplasia, a group of disorders that result from the impaired ability of the adrenal glands to produce corticosteroids. Between the ages of 70 and 80, DHEA-S levels decline to 20-30% of peak value. Clinical trials are evaluating DHEA’s role in memory and Alzheimer’s.
According to researchers, DHEA-S may be implicated in longevity. Men with high levels of DHEA may be less likely to die of cardiovascular disease by affecting levels of the inflammatory cyto-kines interleukin-6 and TNF-alpha, which are part of the inflammatory cascade that is associated with heart disease, Alzheimer’s, and even certain cancers.13
In non-pregnant women, estradiol is the most commonly measured type of estrogen. Its levels vary throughout the menstrual cycle, and drop to low but constant levels after menopause. Increased levels of estradiol in woman indicate an increased risk of breast or endometrial cancer.14,15 Low levels may increase the risk for bone fractures.
A recent study from the Netherlands found a clear association between estradiol levels and vertebral fractures in elderly women. Women with the lowest levels of estradiol had more than a twofold greater risk of incident vertebral fractures, independent of bone mineral density. Women with low estradiol combined with high sex hormone binding globulin concentrations had a 7.8 times higher risk of incident vertebral fracture. Researchers found no clear association between testosterone and vertebral fracture risk in women.16
Men produce estradiol in much smaller amounts than do women. For men, estradiol is an indicator of hypothalamic and pituitary function. Increased levels of estradiol, along with decreased levels of testosterone, may accompany diminished sex drive and difficulty with urination. In men, estradiol and testosterone levels should be tested together.
In men, estrogen deficiency is implicated in the pathogenesis of osteoporosis. A study from Denmark examined a group of men diagnosed with osteoporosis. It found that none of the cases was attributable to hypogonadism (low testosterone), while 38% of men had undetectable levels of estradiol. Investigators concluded, “estrogen deficiency is much more prevalent than androgen deficiency in primary male osteoporosis,” and future “screening tests for osteoporosis in men should therefore include assessment of serum estradiol.”17
Homocysteine is an amino acid formed during the metabolism of methionine. Elevated homocysteine levels are an independent risk factor for coronary artery disease and stroke. Data also indicate that homocysteine levels may be increased in patients with depression. Deficiency of folic acid, a B vitamin that plays important roles in mood and homocysteine breakdown, may be the link between depression and elevated homocysteine.18
Researchers in the Netherlands investigated whether homocysteine levels were a risk factor for cognitive decline in normal individuals between the ages of 30 and 80. Follow-up after six years revealed that while “a relation between vitamin B12 or folic acid and cognition was almost absent, elevated homocysteine concentrations were associated with prolonged lower cognitive performance in this normal aging population.”19
Incremental increases in homocysteine levels correlate with increased risk for coronary artery disease. Data from the Physicians’ Health Study, which included 14,916 healthy male physicians with no prior history of heart disease, showed that highly elevated homocysteine levels were associated with a more than threefold increase in the risk of heart attack over a five-year period.20
Homocysteine is also becoming recognized as an independent risk factor for bone fractures. According to two studies published in the New England Journal of Medicine in 2004, high homocysteine levels are associated with osteoporotic hip fracture. Dutch researchers studied the association between homocysteine
levels and the incidence of osteoporotic fracture in 2,406 subjects aged 55 and older. They found that an “increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.” The authors noted that while folic acid supplements can effectively reduce homocysteine levels, additional studies are needed to assess whether such therapy will reduce the risk of fracture.21
These results were corroborated in another study that assessed the association between homocysteine levels and risk of hip fracture in men and women enrolled in the Framingham Heart Study. RR McLean and colleagues said their findings “suggest that the homocysteine
concentration, which is easily modifiable by means of dietary intervention, is an important risk factor for hip fracture in older persons,” but that further “population-based research is needed to examine the role of homocysteine in osteoporosis and osteoporotic fracture and to determine whether nationwide folic acid fortification of food will help to reduce rates of hip fracture in the United States.”22