Dehydroepiandrosterone (DHEA)

Overview

DHEA is the most abundant hormone synthesized and excreted by the adrenal glands. DHEA is the precursor for the synthesis of over 50 other hormones in the body. It is estimated that from 30 to 50 percent of testosterone in men and about 75 percent of estrogen in women is derived from DHEA. Impressive results from some DHEA studies prompted the media to tout DHEA as an “anti-aging” breakthrough. When given to elderly animals or humans, DHEA does tend to increase sex drive, improve energy, mood, and memory, enhance the immune system and increase muscle mass. Human production of DHEA normally peaks during our mid-20s and then begins a steady, progressive decline. Animal studies indicate that DHEA may be helpful for conditions such as obesity, cancer, Alzheimer’s disease, and general enhancement of the immune system. However, adequate human trials have not been conducted. Although DHEA is available without a prescription, it should be used with caution since it affects the levels of many other hormones in the body.

Dosage Info

Dosage Range

Commercially available doses range from 5-200mg. However, doctors have been known to request compounding pharmacists to prepare DHEA prescriptions for patients in doses ranging from 5-200mg per capsule. Men usually take higher doses than women.

Most Common Dosage

The most common dosage for DHEA is 25mg daily but ideally doses should be individualized to a patient’s individual needs.

Dosage Forms

Capsules, oral and sublingual tablets, liquid, and creams.

Adult RDI

None established

Adult ODA

None established

RDA

• : None established

Interactions and Depletions

Interactions

• Antidepressants
• Estrogen and estrogen-like medications
• Anticoagulant medications
• Central nervous system stimulants
• Diabetic / Hypoglycemic medications

Active Forms

Dehydroepiandrosterone and micronized dehydroepiandrosterone.

Absorption

Orally ingested DHEA is effectively absorbed from the stomach and intestines, while sublingual DHEA is quickly absorbed from the oral mucosa under the tongue, and creams and ointments are easily absorbed transdermally.

Toxicities & Precautions

General

To date, studies with DHEA report that it is safe when taken correctly.

Side Effects

The most common side effects from too much DHEA include acne, hirsutism, mood changes such as irritability and aggressiveness (1) , insomnia, fatigue and low energy. Other side effects that occasionally occur include headaches, nervousness, a deepening of the voice, and menstrual cycle irregularities. (2)

Functions in the Body

Hormone Production:

DHEA’s primary function in the body is to serve as the precursor the other hormones that are developed from it. (3)

Antioxidant:

In both animal (4) and human studies, (5) dehydroepiandrosterone has exhibited antioxidant activity. One study reported that DHEA prevents the oxidation of LDL-cholesterol, which suggests it may help prevent atherosclerosis. (6)

Cancer prevention:

In animal studies, DHEA has demonstrated antiproliferative and tumor preventive effects, which inhibits development of experimental tumors of the breast, lung, colon, liver, skin, and lymphatic tissue. (7) Several different mechanisms have been proposed to explain the underlying biochemical mechanisms for these effects. (8)

Anti-inflammatory:

DHEA can substantially lower the production of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)

Clinical Applications

Lupus

Most patients with lupus have low levels of DHEA. (9) , (10) DHEA may be an effective hormonal therapy for patients with systemic lupus erythematosus. Patients appear to gain incremental benefits over 3 to 12 months, resulting in a decrease in the number of lupus flare-ups and a reduction in the need to utilize steroid medications. (11) , (12)

Diabetes

Animal studies and preliminary human research suggests that DHEA may be therapeutically useful for people with diabetes. When given to postmenopausal women, DHEA enhanced insulin sensitivity and reduced triglyceride levels. (13) , (14)

Cervical Dysplasia

A pilot study of 12 women with low-grade cervical dysplasia found that DHEA administered intravenously was well tolerated and was efficacious in 10 of the 12 women. (15)

Aids

It has been reported that DHEA reduces the replication of the HIV-1 virus. (16) Also, DHEA levels are lower in individuals with HIV and AIDS than in normal controls, and DHEA levels continue to decline as the disease progresses. (17) DHEA’s immune-enhancing effects may be related to its ability to increase the secretion of Interleukin-2 from activated T-cells. (18)

Since DHEA levels decline as the disease state progresses, a randomized, double-blind placebo controlled trial involving 32 HIV infected individuals was carried out to determine if DHEA supplementation could improve the quality of life for these individuals. Compared to the placebo controls, those taking the DHEA-sulfate (DHEA-S) product experienced a significant increase in serum DHEA-S levels as well as a significant improvement in the Mental Health and Health Distress dimension of the Medical Outcomes Study HIV Health (MOS-HIV) Survey. (19)

Depression

Examination of a group of elderly individuals with major depression revealed that all had low levels of DHEA. Supplementation sufficient to bring their plasma DHEA levels to that of younger healthy adults improved their depression ratings and memory performance. (20) Evaluation of 82 children aged 8 to 16 years old with major depression revealed abnormally low morning levels DHEA and abnormally high evening levels of cortisol. (21)

Symptoms and Causes of Deficiency

Because of the large number of hormones that are derived from DHEA, declining levels of DHEA are associated with an increased risk to diseases of aging. These include an increased risk of developing Type 2 diabetes, (22) osteoporosis, depression, (23) obesity, decreased immune function, loss of strength and muscle mass, and memory problems.

Dietary Sources

Plants do not produce DHEA. Significant amounts are only made by humans and other primates such as monkeys and apes. There are no good dietary sources of DHEA other than supplementation.

References

1. View Abstract: Dean CE. Prasterone (DHEA) and mania. Ann Pharmacother. Dec2000;34(12):1419-22.
2. View Abstract: Cizza G, et al. Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm Metab Res. Mar2001;33(3):138-43.
3. View Abstract: Spark RF. Dehydroepiandrosterone: a springboard hormone for female sexuality. Fertil Steril. Apr2002;77(Suppl 4):S19-25.
4. View Abstract: Shen S, Cooley DM, Glickman LT, et al. Reduction in DNA damage in brain and peripheral blood lymphocytes of elderly dogs after treatment with dehydroepiandrosterone (DHEA). Mutat Res. Sep2001;480-481(1-2):153-62.
5. View Abstract: Araghiniknam M, Chung S, Nelson-White T, et al. Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sci. 1996;59(11):PL147-57.
6. View Abstract: Khalil A, Fortin JP, LeHoux JG, Fulop T. Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation. J Lipid Res. Oct2000;41(10):1552-61.
7. View Abstract: Schwartz AG, Pashko LL. Cancer prevention with dehydroepiandrosterone and non-androgenic structural analogs. J Cell Biochem Suppl. 1995;22:210-7.
8. View Abstract: Williams JR. The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging. Lipids. Mar2000;35(3):325-31.
9. View Abstract: Suzuki T, et al. Low Serum Levels of DHEA May Cause Deficient IL-2 Production by Lymphocytes in Patients with SLE. Clin Exp Immunol. 1995;99(2):251-55.
10. View Abstract: Chang DM. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. Nov2002;46(11):2924-7.
11. View Abstract: Van Vollenhoven RF, et al. Studies of Dehydroepiandrosterone (DHEA) as a Therapeutic Agent in Systemic Lupus Erythematosus. Ann Med Interne. (Paris). 1996;147(4):290-96.
12. View Abstract: Chang DM. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. Nov2002;46(11):2924-7.
13. View Abstract: Casson P, et al. Replacement of DHEA Enhances T-lymphocyte Insulin Binding in Postmenopausal Women. Fertil Steril. 1995;63(5):1027-31.
14. Bates GW, et al. Dehydroepiandrosterone Attenuates Study-induced Declines in Insulin Sensitivity in Postmenopausal Women. Ann NY Acad Sci. Dec1995;774:291-93.
15. View Abstract: Suh-Burgmann E. Long-term administration of intravaginal dehydroepiandrosterone on regression of low-grade cervical dysplasia–a pilot study. Gynecol Obstet Invest. 2003;55(1):25-31.
16. View Abstract: Henderson E, Yang JY, Schwartz A. Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. AIDS Res Hum Retroviruses. May1992;8(5):625-31.
17. View Abstract: Mulder JW, Frissen PH, Krijnen P, et al. Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men. J Infect Dis. Mar1992;165(3):413-8.
18. View Abstract: Centurelli MA, Abate MA. The role of dehydroepiandrosterone in AIDS. Ann Pharmacother. May1997;31(5):639-42.
19. View Abstract: Piketty C, Jayle D, Leplege A, Castiel P, Ecosse E, Gonzalez-Canali G, et al. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clinical Endocrinology. 2001;55(3):325-330).
20. View Abstract: Wolkowitz OM, et al. Dehydroepiandrosterone (DHEA) Treatment of Depression. Biol Psychiatry. Feb1997;41(3):311-18.
21. View Abstract: Goodyer IM, et al. Adrenal Secretion during Major Depression in 8- to 16-year-olds, I. Altered Diurnal Rhythms in Salivary Cortisol and Dehydroepiandrosterone (DHEA) at Presentation. Psychol Med. Mar1996;26(2):245-56.
22. View Abstract: Aoki K. Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone. J Steroid Biochem Mol Biol. Jun2003;85(2-5):469-72.
23. View Abstract: Morrison MF, et al. DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years. Biol Psychiatry. Nov2001;50(9):705-11.