Hormone Salivary Testing: Key To Improving Hormone Balance
By Ward Dean, MD, and Jim English
Hormone Replacement Therapy (HRT) is a mainstay of traditional medicine. HRT has been augmented over the last decade by the introduction of a number of non-prescription, supplemental hormones, including natural estrogen, progesterone, thyroid, DHEA, melatonin and pregnenolone, as well as natural estrogens and testosterone from compounding pharmacies. The availability of these supplemental hormones has benefited countless health-conscious consumers. However, proper timing and dosage is essential if one is to obtain maximum benefit from their powerful effects.
Salivary Hormone Levels
Salivary hormone measurements have been used for many years as a research tool, but have only recently gained popularity in clinical use. Although hormones are present in saliva in fractional amounts compared to their levels in blood, using sophisticated radio-immunoassay (RIA) and enzyme techniques, highly accurate levels of hormones can be determined in saliva. Although the absolute values of the hormones in saliva are, of course, different from those in blood, the salivary levels are accurate, reproducible and clinically relevant. Additionally, salivary hormone testing offers a number of advantages over blood testing. First, salivary hormone testing is non-invasive and painless. Second, the testing can be done at any time, anyplace, at the convenience of the patient. This allows for testing in a stress-free environment, and at the proper times to determine peak hormone levels, since hormones rise and fall predictably at certain times of the day. For example, melatonin levels peak between 1 AM and 3 AM; DHEA, cortisol and the sex steroids (estrogen, progesterone and testosterone) are highest in the morning. In addition, because salivary testing is less expensive than blood testing, multiple and sequential tests of several hormones can be performed, providing even greater amounts of information regarding the complex interaction of hormones. Third, salivary hormone levels may be even more accurate than serum levels as an indicator of hormone activity. The reason is that all of the hormone in the saliva is the active, free hormone. On the other hand, a large percentage of the hormones in blood are bound to plasma proteins, rendering them inactive. Saliva samples avoid these problems by giving an index of the free hormone levels.
Hormones and Aging
According to the central thesis of The Neuroendocrine Theory of Aging (Vladimir Dilman, MD, PhD, D.M.Sc., and Ward Dean, MD), aging is caused by an age-related loss of hypothalamic and peripheral sensitivity to hormones and other signaling substances. This loss of hypothalamic sensitivity results in a progressive shifting of homeostasis in the body and alteration of metabolic levels of hormones, neurotransmitters, and cell signalers. These metabolic shifts are believed to cause aging and the diseases of aging. Salivary Hormone Testing: Primary Hormones and Their Effects While salivary hormone testing does not diagnose specific pathologies, it is helpful for evaluating fundamental regulatory systems of the body. Among the hormones that can be conveniently measured in saliva include:
Cortisol is a catabolic hormone that is essential to life. Release of high amounts of cortisol for short periods enables the body to deal with stress by elevating blood glucose, decreasing protein synthesis, and promoting fatty acid mobilization, thereby making these substances available for energy and for synthesis of other compounds needed by different tissues of the body. Cortisol also helps to control allergies and inflammation by stabilizing lysozomes.
Elevated Cortisol Levels
Prolonged periods of exposure to elevated levels of cortisol (such as occurs during chronic stress) cause a number of adverse effects in the body. These include hypertension, reduced glucose tolerance (development of diabetes), loss of even more hypothalamic glucocorticoid (cortisol) receptors (creating a vicious cycle), and increased neuronal cell death in the brain. After age 40, the appearance of many people undergoes a characteristic change with age. Their faces become moon-like, and fat accumulates around their waists. There is usually a relative loss of fat and muscle on the arms and legs. When these changes are severe, they cause the person to resemble someone with Cushings disease. Cushings disease results from excessive release of cortisol by the adrenal glands (Fig. 1).
In many ways, the metabolic and physiologic changes caused by aging are similar to the bodys response to chronic stress. Thus, Vladimir Dilman coined the term hyperadaptosis to describe the effects of aging as a form of chronic stress, characterized by prolonged exposure to excess cortisol levels, and caused by the loss of hypothalamic sensitivity to the inhibitory effects of cortisol.
Low Cortisol Levels
Although chronically elevated levels of cortisol are generally harmful, and relative hypercortisolemia occurs with age, there are times when additional cortisol is beneficial and necessary. For example, (1) when allergies strike, (2) when the adrenals are exhausted due to chronic stress, or (3) when an additional stressor is experienced which exceeds the bodys ability to adapt, it is sometimes necessary to temporarily augment the bodys own cortisol production. A safe, natural way to supplement the bodys endogenous cortisol production, and to give the adrenals a rest is to use an extract from licorice known as glycerhizin (CortiTrophin™). In doses of 25 to 100 mg per day, glycerhizin mimics many of the actions of cortisol to benefit a wide range of conditions, including colds and flu, asthma, allergies, chronic fatigue, hypoglycemia, and other acute stressful conditions. Glycyrrhizin should not be used for more than several weeks at a time to prevent the adverse effects of excess cortisol.
DHEA, the most abundant steroid in the body (except for cholesterol), is produced by the adrenal glands. Production of DHEA drops precipitously with advanced age. A critical marker of ones overall hormonal health is the ratio of serum cortisol to DHEA. Under normal conditions, cortisol is held in balance (or homeostasis) with DHEA. DHEA production begins to decline after about age 25, dropping by about 80-85% of peak production levels by age 75 (Fig. 2).
Cortisol levels, on the other hand, rise and remain elevated during the afternoon and evening in response to stress. The effect of this alteration in adrenal rhythm, or imbalance of cortisol and DHEA, can have serious adverse effects on health. Supplemental DHEA has been postulated to have beneficial effects on heart disease, immune function and well-being. Dosages of DHEA found to be effective usually range from 12.5 to 50 mg per day.
Progesterone is a steroid hormone similar in structure to the other steroid hormones estrogen, cortisol, DHEA and pregnenolone. Progesterone is a precursor to most steroid hormones and performs a myriad of important functions, including balancing against the toxic and harmful effects of excessive estrogen. Progesterone is produced in the ovaries of menstruating women and by the placenta during pregnancy. About 20-25 mg of progesterone are produced per day during a womans monthly cycle, and up to 300-400 mg are produced daily during pregnancy. Many women claim they feel better during the third trimester of their pregnancy than at any other time of their lives. This is due, in part, to the high levels of progesterone that produce increased energy and a state of well-being. Conversely, after delivery, progesterone production drops suddenly and many women develop postpartum depression due to extremely low levels of progesterone. (1) Some of the most common symptoms of an imbalance in progesterone levels include weight gain, fatigue, loss of libido, depression, headaches, joint pain and mood swings.
Estrogen regulates the menstrual cycle, promotes cell division, and causes secondary female characteristics during puberty. In non-pregnant, pre-menopausal women, only 100-200 micrograms of estrogen are secreted daily. But during pregnancy, much more is secreted. An important difference between estrogen and progesterone is that high amounts of estrogen are toxic to the body and create a number of harmful side effects. On the other hand, progesterone is free of side effects, even in high amounts. (2) Many women suffer from a syndrome known as Estrogen Dominance. According to John Lee, MD, who pioneered research in this area, estrogen unopposed by progesterone results in a number of adverse effects. These include hypertension, salt and water retention, abnormal blood clotting, excessive body fat, hypothyroidism, painful breasts, fibrocystic breast disease, increased risk of endometrial cancer (cancer of the uterus) and breast cancer. (3) Estrogen dominance occurs when progesterone production falls to approximately 1% of its pre-menopausal level. At this time, the production of estrogen falls to about 50% of its premenopausal levels. This dramatically alters the estrogen-to-progesterone ratio, causing estrogen to become toxic without progesterone to oppose it. As a result, the risks for breast and uterine cancer, fibrocystic breast disease, ovarian cysts, uterine fibroids, cervical erosions and/or dysplasia, and osteoporosis increase. (4) The problems of estrogen dominance are not confined to post-menopausal women only. Today, it is extremely common for women to experience recurring menopausal-type complaints that begin 10 to 15 years before the time of their menopause (when menstruation ceases). Women as young as thirty years of age often complain of menopausal-type problems. This is known as pre-menopause syndrome. (5)
Testosterone is the steroid hormone that is responsible for the normal growth and development of the male sex organs, muscles, beard and body hair. Testosterone also plays a key role in maintaining human health, strength and energy. While primarily considered a male hormone, testosterone also promotes muscle growth, maintains mood, and boosts sex drive in women. With advancing age, testosterone levels begin to decline (Fig. 3). Simultaneously, a number of related physiological changes occur. These include decreased muscle mass, increased body fat, reduced physical energy and endurance, gradually decreasing libido accompanied by reduced frequency of sex, loss of bone density, and increased cholesterol and circulatory system changes. The average human male begins to feel some of the signs of aging after age 40, with rapid deterioration after 50 years of age. (6)
In men, researchers found that higher levels of testosterone are associated with lower blood pressure, reduced risk of heart attacks, improved immune function, and reduced body fat. The researchers measured testosterone levels (using saliva samples) in more than 4,300 men between the ages of 32 and 44 years. They found that those men who had the highest levels of testosterone had a 45% lower risk of high blood pressure, a 72% lower risk of having a heart attack, and an 8% lower risk of having three or more colds a year. (7)
Androstenedione is produced in the body from either 17-alpha-hydroxyprogesterone or DHEA (dehydroepiandrosterone). Androstenedione possesses both androgenic (masculinizing) and anabolic (tissue-building) properties. The anabolic effects of androstenedione were ignored by the scientific community until 1962, when two researchers conducted an experiment in which normal women were given either 100 mg of DHEA or 100 mg of androstenedione. The study found that both hormones led to elevated testosterone levels, but androstenedione increased testosterone levels twice as much as DHEA. (8) To date, the main concern regarding the use of androstenedione is a tendency for some men to convert androstenedione to either estradiol or estrone. Consequently, it may be prudent to avoid this potential problem by taking substances that control the metabolism of estrogen in the body. These include aromatase inhibitors which block the conversion of testosterone to estrogen (such as the drug Arimidex), and estrogen metabolizers such as DIM (diindolylmethane) and Indole-3-Carbinol (I3C). I3C and DIM (such as VRPs new BioDIM™) are phytonutrients derived from the cruciferous vegetables of the Brassica genus, (cabbage, broccoli, cauliflower and brussels sprouts). These phytonutrients have been shown to initiate a series of reactions in the body that culminates in the elimination of estrogen (Vitamin Research News, Oct. 1999). In the women given DHEA, testosterone levels (normally less than 199 ng/dl), rose to 280 ng/dl within 60 minutes. The second group, taking androstenedione, had testosterone levels elevated as high as 660 ng/dl an hour later, a three-fold increase above normal levels! Significantly, this testosterone increase was transient, and lasted only a couple of hours — and remained at peak levels for only a few minutes — just as occurs naturally in our bodies. (8) Confirmation of the effectiveness of androstenedione is contained in a German patent which claims that 50 mg of oral androstenedione can raise plasma testosterone levels in men from 140% to 183% of normal. Thus, androstenedione may provide a truly physiologic (natural) way to restore flagging testosterone levels in aging men and women to those of young, healthy adults.
Among the approaches Dilman proposed to delay (and even reverse) the aging process and ameliorate the diseases of aging are: (1) Restore hypothalamic sensitivity; and (2) Restore hormone levels to more youthful values by implementing hormone replacement therapy (Dilman and Dean, 1992).
Although much remains to be learned, salivary hormone testing is an invaluable tool for personal anti-aging/life extension programs, offering a better understanding of ones individual hormone status, and allowing for greater individual control when employing therapeutic approaches to enhance quality of life and prevent age-related degenerative diseases.
Examples of Clinical Cases and Therapeutic Solutions Derived from Salivary Hormone Testing
1. Progesterone Deficiency/Estrogen Dominance
42-year-old female experienced increased breast tenderness, headaches and fluid retention prior to menses over a two-year period. Her fibrocystic breasts and uterine fibroids continued to worsen. The salivary progesterone level in the second half of her cycle (luteal phase) was found to be low relative to estrogen, which was high-normal. Supplementation with progesterone skin cream during the luteal phase resulted in an improvement in symptoms.
2. Progesterone/Estrogen Insufficiency
This 63-year-old woman had never taken hormones since her menopause at age 51. She complained of vaginal dryness with painful intercourse, urethral irritation with urination and a bone density scan revealed osteoporosis in her hip and spine. Both her salivary estrogen and progesterone levels were low. Supplementation with natural progesterone skin cream improved her symptoms to some extent, but complete resolution of her complaints was obtained with the addition of an oral biestrogen (estradiol + estriol). Her bone density will be followed with yearly measurements, and is expected to improve. Appropriate nutritional interventions and a weight-bearing exercise program have also been made.
3. Age-Related DHEA Decline
Stressed-out, 53-year-old businessman complained of poor recovery from workouts, loss of muscle tone, and flagging energy. His saliva DHEA-S level was low. Oral DHEA supplementation resulted in weight loss, increased energy, an improvement in muscle tone, and an overall improved sense of well-being.
4. Multiple Hormone Insufficiency
47-year-old female complained of excessive fatigue, hot flushes and marked chemical sensitivity. Saliva testing revealed low levels of cortisol (AM and PM), DHEA and estradiol, pointing strongly toward adrenal exhaustion.
5. Cortisol/DHEA Imbalance
A 45-year-old vegetarian woman complained of hypoglycemia and fatigue. Salivary cortisol was low whereas DHEA was high. Her sex hormones were relatively normal. Empirical supplementation with DHEA would not have been successful for this patient. Her problem was thought to be related to low protein intake.
6. Testosterone Deficiency
Male: A 73-year-old male complained of excessive fatigue, loss of interest in sex, and general mental lethargy. Salivary testosterone levels were found to be low, and use of testosterone resulted in a marked improvement.
Female: A 43-year-old female complained of low sex drive and weight gain, despite supplementation with oral triple estrogen and progesterone skin cream following hysterectomy/oophorectomy to treat endometriosis. Salivary testing found her testosterone levels below normal, and supplementation resulted in an improved sex drive and a modest weight loss.
7. Inappropriate Hormone Replacement
A 53-year-old woman who stopped menstruating at age 52, and was convinced to take oral estrogen and medroxyprogesterone acetate (MPA, a synthetic form of progesterone) for relief of hot flashes. She complained of weight gain, fluid retention, migraines, and the persistence of hot flashes. Her ratio of salivary progesterone-to-estrogen was very low, indicating a lack of progesterone and a relative excess of estrogen. Use of progesterone skin cream in place of the MPA allowed her to halve her estrogen dosage. Her hot flashes stopped, and her other symptoms disappeared. She was ecstatic to report that she felt normal again.
Saliva estrogen and progesterone levels on day 21 of the menstrual cycle of a 33-year-old woman having difficulty conceiving for more than one year revealed normal estradiol but subnormal progesterone output, suggesting a possible reason for her infertility.
9. Polycystic Ovaries
A 29-year-old woman presented with excessive facial/body hair growth, acne, and weight gain about the waist. Suffering these problems since puberty, she had been on several low-fat/high-carb diets, resulting in rebounds and even more weight gain. Menstrual periods were irregular. Saliva testing during the second half of the menstrual cycle (luteal phase) indicated high-normal estradiol, low progesterone, and high androgens, both DHEAS and testosterone. Further examination by her doctor revealed cystic ovaries. Dietary modification (removal of refined carbohydrates, pastas, chips, pastries, sodas etc.) and use of natural progesterone restored normal menstrual cycles and resolved the cystic ovaries.
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