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7-keto Dehydroepiandrosterone Dhea

 

DHEA Introduction

Dehydroepiandrosterone (DHEA) is a hormone which serves as a precursor for other steroid hormones in the body. DHEA is made primarily in the cortex of the adrenal glands. A small amount, especially in women, is also formed in the gonads. [1] Pregnenalone and cholesterol are the precursor molecules in the formation of DHEA. Conversion of pregnenalone to DHEA is catalyzed by the p450c17 enzyme system. Estradiol, estrone, testosterone, and androstenedione are made also from DHEA.

DHEA has received popularity as an anti-aging hormone. Sustained levels of DHEA have been linked to longevity, and it has been postulated that DHEA supplementation can provide protection against the effects of aging. After age 30, production of DHEA from the adrenal gland progressively declines. However, some physicians believe that DHEA is unlikely to significantly increase the length of a person’s life. [2]

This reasoning spawns from conflicting research, such as a study in rats that showed some rats live longer when supplemented with DHEA, while others do not. In addition, measured DHEA levels are normal in patients with the abnormal aging condition, Progeria. This finding is quite significant because these patients would show decreased levels if DHEA were indeed a factor in aging. However, despite the results of these particular studies, many physicians still believe that research has validated the claim that DHEA may improve the quality of a one’s life.

Although DHEA primarily serves as a precursor for other steroid hormones, it appears to have other functions in the body. For example, preliminary research has shown that DHEA may influence immune function and also impact muscle metabolism. [3] Research has also shown that declining levels of DHEA have been linked to numerous diseases of lifestyle, and chronic disorders such as; diabetes, obesity, heart disease, arthritis, cancer, stress, allergies, hypercholesterolemia (high cholesterol), fibromyalgia, and autoimmunity. Another interesting function that is continually being study studied is DHEA’s impact upon memory enhancement and cognitive functioning. [4]

Perhaps the most interesting research is regarding the anti-glucocorticoid effects of DHEA. [5] It has been theorized that by acting against glucocorticoids, including cortisol, DHEA exerts the majority of its physiological, biological, and biochemical effects. Like DHEA, glucocorticoids are also produced in the cortex of the adrenal gland and function to raise glucose levels in the plasma. It is primarily cortisol that acts to maintain blood glucose levels within normal ranges.

DHEA Food Sources

DHEA is a hormone found in the human body therefore food sources do not exist. DHEA must be taken in supplement form. Some supplements may contain wild yam extract which has bee suggested to convert to DHEA in the body. However, the validity of this statement is uncertain. [3] Pregnenalone is also sold in supplement form, and as mentioned previously, it is a direct precursor of DHEA. Some people theorize that pregnenalone may be safer than DHEA, but there is no evidence to support this suggestion. [3] Furthermore, pregnenalone will eventually be converted to DHEA.

DHEA Uses

As discussed, DHEA is often used as an anti-aging hormone and receives the most attention as a treatment for this purpose. Research has shown DHEA to be effective for the treatment of systemic lupus erythematosus (SLE). Studies have shown that female patients given high doses of DHEA (200mg/d) for three months experienced improvement in the SLE Disease Activity Index, which is used to rate the severity of symptoms of this condition. [6, 7] Patients taking DHEA could also decrease their dose of corticosteroids, while those taking placebo actually had to increase their dose of prescribed medication.

The treatment of osteoporosis with DHEA has received some interest in clinical research. DHEA has been observed to be lower in women with osteoporosis versus controls. [8] A number of studies have been conducted in postmenopausal women. Research has examined the effects of DHEA on various tissues, including the bone mineral density in this demographic. [9, 11] Significant increases in bone mineral density were measured in patients using either a DHEA cream or an oral supplement.

DHEA may be used for Alzheimer's disease, as it has been shown to enhance memory and cognitive function. [12-14] It appears that slightly higher doses than are physiological required are needed to obtain noticeable effects from DHEA in this context.

Other conditions for which DHEA may be useful include; rheumatoid arthritis, asthma, menopausal syndrome, certain acute lethal viral infections, and erectile dysfunction. [15-19] Patients with bipolar disorder and hypo-manic depression should only take DHEA under the supervision of their physician, due to possible aggravations of the disorders.

DHEA Dosages

The dosage of DHEA from supplementation varies and is, largely, dependant upon what disorder or dysfunction is being treated. Because of potential side effects and toxicities (see below), DHEA supplementation should only be taken under physician supervision. As well, physicians will have access to reliable, safe sources of the supplement.

For patients with measured low levels of serum DHEA, a physiological dose should be prescribed. This equates to approximately 5-10 milligrams per day in women, and 10-20 milligrams per day in men. Doses may be slightly modified based on individual blood levels. It is suggested that the only time women under forty take DHEA is when they have measurably low DHEA levels in their blood, or if they are being treated for a particular disorder (e.g. autoimmune disease, rheumatoid arthritis). [2] Actually, as women approach menopause, DHEA levels increase. Therefore, it is even more important to perform lab tests because excessive DHEA will cause virilism (facial hair growth and acne).

Supplementation for the treatment of diseases such as osteoporosis or autoimmune disease is in the range of 50 - 100 milligrams daily. This level of DHEA therapy may cause acne in some women during the first few weeks that therapy is initiated.

DHEA Toxicities and Deficiencies

DHEA Deficiency

DHEA and DHEA-S (sulfate) can be tested by measuring blood serum levels. If low levels are observed, a patient can be treated with a physiological dose of DHEA. Generally, DHEA declines with age and clinicians have observed that supplementation at a physiological dose can promote an increase in the perception of mental and physical well-being in these adults. [1] Men may suffer from fatigue and/or low libido as a result of a DHEA deficiency.

DHEA Toxicities

DHEA supplementation in high doses can cause problems, such as impairment of the body’s ability to biosynthesize its own DHEA. [20] High dose DHEA can also be toxic to the liver and result in hepatic damage from oxidative destruction. Animal studies have also demonstrated the development of hepatocellular carcinomas. [21] To minimize this type of damage, DHEA supplements should be taken with antioxidants, especially vitamins C and E, and selenium. Excessive amounts of DHEA have also been linked to breast and prostate cancers. [3]

Common side effects include oily skin, acne, excessive hair growth (in women), and heart palpitations. Excessive amounts of DHEA has also been linked to aggravations of bipolar disorder and hypo-manic depression.

Patients with Grave’s disease who have thyrotoxicosis should take DHEA with caution, as it has been shown to increase the action of thyroid hormone. Caution should also be exercised if taking Synthroid (L-thyroxine), or other supplemental thyroid hormones.

References

1. Powell, D. Endocrinology and Naturopathic Therapies. Bastyr University, Kenmore, WA 2002;82.

2. Murray M and Pizzorno J. Encyclopedia of Natural Medicine, 2nd Ed. Prima Publishing, Rocklin, CA 1998;172-173.

3. AANP. Nature’s Pharmacy- Your Guide to Healing Foods, Herbs, Supplements and Homeopathic Remedies. Publications International Ltd., Lincolnwood, IL 2001;267-268.

4. Yen SS, Morales AJ and Khoram O. Replacement of DHEA in Aging Men and Women: Potentail Remedial Effects. Ann NY Acad Sci 1995;774:128-142.

5. Kalimi R and Regelson W. Anit-glucocorticoid effects of dehydroepiandrosterone (DHEA). Mol Cell Biochem 1994;131:99-104.

6. Van Vollenhoven RF et al. An open study of DHEA in systemic lupus erythematosus. Arthritis Rheum 1994;37(9):1305-1310.

7. Van Vollenhoven RF et al. DHEA in systemic lupus erythematosus: Results of a double-blind, placebo-controlled randomized clinical trial. Arthritis Rheum 1995;38:1826-1831.

8. Szathmari M et al. DHEA sulphate and bone mineral density. Osteoporosis Int 1994;4:84-88.

9. Labrie F et al. Effect of 12 month DHEA replacement therapy on bone, vagina and endometrium in postmenopausal women. J Clin Endcrinol Metab 1997;82:3498-3505.

10. Diamond P et al. Metabolic effects of 12-month percutaneous DHEA replacement therapy in postmenopausal women. J Endocrinol 1996;150:S43-S50.

11. Baker B. DHEA increases bone mineral density in women. Fam Pract News 2000(Nov 1):24.

12. Kalimi M and Regelson W. The biological role of DHEA. De Gruyter, New York, NY 1990

13. Yen SS et al. Replacement of DHEA in aging men and women: potential remedial effects. Ann NY Acad Sci 1995;774:128-142.

14. Morales AJ et al. Effects of replacement dose of DHEA in men and women of advancing age. J Clin Endocrinol Metab 1994;78(6):1360-1367.

15. Hall GM and Spector TD. Depressed levels of DHEA sulfate in postmenopausal women with rheumatoid arthritis but no relation with axial bone density. Annals Rheum Dis 1993;52:211-214.

16. Giltay EJ et al. Effects of DHEA administration on disease activity in patients with rheumatoid arthritis. Br J Rheumatol 1998;37:705-706.

17. Weinstein RE et al. Decreased adrenal sex steroid levels in the absence of glucocorticoid suppression in postmenopausal asthmatic women. J Allergy Clin Immunol 1996;97:1-8.

18. Loria RM et al. Protection against acute lethal viral infections with native steroid DHEA. J Med Virol 1988;26:301-314.

19. Reiter WJ et al. DHEA in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology 1999;53:590-595.

20. Balch PA. Prescription for Nutritional Healing: The A-Z Guide to Supplements, 2nd Ed. Penguin Putnam, Inc. New York, NY 2002;160-161.

21. Rao MS. Hepatocarcinogenicity of DHEA in the rat. Cancer Res 1992;52:2977-2979.