DHEA and 7 keto-DHEA
Dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S are endogenous hormones secreted by the adrenal cortex and testes (in males). In young adults the adrenal cortex secretes approximately 4 mg of DHEA and 25 mg of DHEA-S per day. Some 64-74% of the DHEA-S produced each day is converted to DHEA while 13% of the DHEA produced is metabolized into DHEA-S. As they are interconvertible the terms DHEA and DHEA-S are often used interchangeably even though DHEA-S is considered more biologically active than DHEA.
The concentration of DHEA-S in circulation is the highest among all steroids and is only surpassed by cholesterol. DHEA has been referred to as the “mother hormone” because it is a precursor for many other hormones such as testosterone, oestradiol, oestriol and oestrone. DHEA and DHEA-S serve as the precursors to approximately 50% of androgens in adult men, 75% of active oestrogens in premenopausal women and almost 100% of active oestrogens after menopause. DHEA may also be able to increase levels of progesterone. Although not directly converted to progesterone, it may, through a feedback mechanism, indirectly increase the production of progesterone. Both DHEA and progesterone are produced from pregnenolone. If enough DHEA is present the pregnenolone will primarily be converted to progesterone rather than DHEA.
As mentioned above young healthy adult male produces approximately 30mg of DHEA a day while women produce about 20mg a day. DHEA levels have however been shown to progressively decline with age at a relatively constant rate of 10% per decade. By the age of 70 to 80 the DHEA levels are only 20% (men) and 30% (women) of those observed between the ages of 20 to 30. This age related decline in DHEA levels has led to the notion that the relative DHEA deficiency of older age may be a causative factor in diseases of aging. Many studies have demonstrated a strong association between the decline in DHEA levels and increase in cardiovascular morbidity in men, breast cancer in women and a decline of immunocompetence during aging.
Scientists assumed that DHEA was simply a reservoir upon which the body could use to produce more of the other hormones. However, scientists recently have shown that cells contain specific DHEA receptors which suggests that DHEA has functions of its own. By replenishing dwindling levels of DHEA several benefits may result; improved sex drive, enhanced immune function, renewed energy and stamina, better sleep, brighter mood and keener memory. Although these results are impressive the real benefit of DHEA is in its potential at preventing and treating cardiovascular disease, high cholesterol, diabetes, obesity, cancer, Alzheimer’s disease, memory disturbances, menopause, osteoporosis, immune system disorders, chronic fatigue and recently has been highly publicised as an anti-aging drug due to its rejuvenating effects. Some of these beneficial effects are examined further below:
(1) Fatigue – One of the most common reasons DHEA is prescribed is to overcome fatigue and adrenal exhaustion. When the adrenal glands production of DHEA and/or cortisol are constantly low for most of the day it will leave you with the following symptoms: low energy levels, inability to tolerate exercise, depression, dark circles under the eyes, lack of mental alertness, headaches, oedema, salt and/or sugar cravings, feeling tired all the time, mentally and emotionally overstressed, light headedness, heartburn, low blood pressure, recurrent infections and trouble sleeping. Continuous DHEA deficiencies will eventually cause a hormonal cascade effect which will adversly effect thyroid and sex hormone levels resulting in very poor health. By supplementing DHEA the burden is removed from your adrenal glands allowing energy levels and stamina to be revived with in a few weeks.
If cortisol levels are also found to be low it may be increased by either using the precursor pregnenolone or by using low dose cortisol itself. DHEA/Pregnenolone or DHEA/cortisol combinations are commonly prescribed to overcome adrenal exhaustion (see information on Treating adrenal exhaustion).
(2) Immune Function – Animal studies show that DHEA protects against viral, bacterial and parasitic infections. It has been suggested that the increased cortisol/DHEA ratio that occurs with aging increases the suppression of cellular immunity. DHEA has been shown to significantly increase immune mediators in aging men and women such as monocytes, B cells, T-cell receptors and natural killer cells. By taking DHEA for immune-crippling diseases like chronic fatigue syndrome and AIDS the immune system is strengthened boosting energy, relieving depression and sharpening thinking.
(3) Osteoporosis – It has been proposes that DHEA is able to stimulate bone formation and calcium absorption as well as inhibit bone resorption.
(4) Aging – Preliminary results suggest DHEA is able to retard the aging process. It is able to improve muscle wasting, weakness, tremulousness and other signs of aging after several weeks of therapy.
(5) Heart Disease – DHEA has been shown to reduce high cholesterol levels, thwart blood clot formation and encourage blood vessels to relax which all help prevent heart disease.
(6) Improves Low Libido – DHEA is able to rejuvenate sex drive in older men and women.
(7) Other – DHEA has shown to improve various types of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowl disease. It is currently being investigated for the treatment of various cancers such as breast cancer, colon cancer and liver cancer. It also has been shown to improve memory, brightens mood and gives a sense of well being.
Unfortunately very few Australian doctors are aware of DHEA because it is not listed in their medical reference books. This is because being a natural hormone it cannot be patented so there are no financial incentives for pharmaceutical companies to do the very expensive research and development to register it as a commercial product in Australia. It is available in Australia with a valid doctors prescription. However in many countries overseas its use is considered so safe it is registered as a supplement and available over the counter in health food stores and pharmacies. As almost all Australian medical reference books used by our doctors only list registered products providing information supplied by the pharmaceutical companies DHEA is omitted from these texts. The dosage protocols used here is therefore determined by pioneering medical doctors in America and Europe. It has been successfully used by hundreds of thousands of people throughout America and Europe, and more recently in Australia, with a very impressive track record.
DHEA is absorbed very well when taken orally. Once absorbed it is mainly converted into DHEA-S during first pass metabolism by the liver with the majority (90%) of the oral dose entering general circulation as either DHEA or DHEA-S. Because DHEA taken orally is converted to a greater extend into the more biologically active DHEA-S metabolite compared to other methods of administration it is considered by some to be the preferred method of administering DHEA especially for adrenal fatigue cases. This is in contrast to much information on the internet which incorrectly claims DHEA taken orally is poorly absorbed or lost through through first pass metabolism and thus ineffective. After having tested 1000’s of people over the years on low dose DHEA slow release capsules the test results clearly indicate DHEA levels significantly increase to within the optimal range which is contra to many of these false claims.
The elimination half-life of DHEA is 15-38 minutes, whereas the half-life of DHEAS is 7-22 hours. As DHEA has a short half life it should be administered as a slow release capsule in order to minimize fluctuating levels.
DHEA may also be administered as a transdermal cream which is also easily absorbed and thus another recommended method to supplement DHEA. It is not metabolised into the more potent DHEA-S to the same degree as oral DHEA and thus may not be as effective for adrenal fatigue cases but certainly useful for anti-aging purposes. Ongoing monitoring of your levels must be done by either saliva or urine tests as standard serum blood tests will not accurately detect increasing levels due to it binding to red blood cell membranes after being absorbed by creams. The red blood cells are removed along with the DHEA attached to it before the serum is analyzed and thus the results are inaccurate. We have found a liposomal gel base provides better absorption when compared to a standard cream base.
DHEA has also been prescribed in subbuccal lozenges (troches) however due to its rapid absorption and short serum half-life this method creates wild fluctuations in DHEA levels and thus this method is not recommended.
Women – Doses for women is usually between 10-25mg daily.
Men – Doses are usually between 15 to 50mg daily.
Some claims on the internet suggest that 5mg should be the maximum dose and any dose above this is dangerous. Considering that an average healthy young adult naturally produces 20 -30mg of DHEA a day and if levels are found to be very low and thus they are only producing a few milligrams a day themselves an additional 5mg supplemented dose would not be sufficient to bring their total daily DHEA back up to the optimal 20-30mg a day. Furthermore having tested many patients on this dose we have found it is unable to get their levels anywhere near the optimal physiological range except in patients whom have only a slight DHEA deficiency which is what you would expect to see.
DHEA is taken in the morning to mimic the natural morning peak levels experienced during youthful years. It may be taken with or without food.
DHEA-S should be monitored while on replacement therapy and the dose adjusted so optimal physiological levels are obtained.
Note: Saliva Analysis is not recommended when using troches as they can adversely effect results for up to 36 hours after the last dose. Saliva or urine tests however are a must if using DHEA creams.
Drug Interactions – Drugs that may increase DHEA or DHEA-S levels include: alprazolam, amlodipine, benfluorex, diltiazam and metformin. Drugs that may reduce DHEA or DHEA-S levels include: aminoglutethemide, carbamazepine, dexamethasone, insulin and morphine.
Side Effects – Contrary to much information on the internet side effects are rare when DHEA is maintained at optimal physiological levels. A lot of negative information on DHEA can be found on the internet and is usually the result of a lack of experience, high doses, poor monitoring and poor dose management. If regular testing of DHEA and its potential metabolites is performed then any necessary dosage adjustments can be made before any symptoms develop. A major concern of using DHEA is the possibility that it may be converted into other hormones along the hormone cascade such as testosterone and the estrogens creating an unfavorable hormone imbalance. This conversion is only theoretical and rarely observed to occur to any significant degree in our practice. We have found that conversion is significant in only a minority of cases (5%) or more commonly when higher doses are used.
If physiological doses are used and adjusted to maintain test levels within the optimal physiological range there is usually no significant change in other hormone levels and no side effects. Therefore if DHEA is dosed according to test results there is little risk of creating a further hormone imbalance. In cases where conversion may occur significantly to create a hormone imbalance early testing will identify any problems hence the dose or the form of DHEA (7-keto) adjusted before any problems manifest physically.
As stated above higher doses of DHEA may increase testosterone levels and hence potentially can cause acne, irritability, and/or facial hair. In addition it may also cause fatigue, anger, insomnia, weight gain, sugar cravings, restless sleep, and mood changes. These side effects are reversed when the dose is reduced to a more physiological dose.
As a precaution men should also have regular prostate examinations while on DHEA as there is the potential for it to increase testosterone and 5-hydroxytestosterone levels which can potentially agrivate the prostate.
In certain cases where initial baseline hormone tests indicate low DHEA levels coupled with high testosterone and/or high estrogen levels it may be wise to supplement with 7-Keto DHEA instead of DHEA to prevent the possibility of elevating these any further. In addition some rare individuals taking DHEA may convert too much of it into the estrogens and/or testosterone would also benefit changing to 7-Keto DHEA.
Unlike DHEA itself the 7 keto form is unavailable for conversion into either testosterone or the estrogens in the steroid metabolic pathway thus eliminating the potential of increasing testosterone or estrogens. It must be understood that 7-Keto-DHEA IS NOT A BIOIDENTICAL HORMONE and we tend to reserve its use for these two situations only. We prefer to use DHEA itself where ever possible for a number of reasons:
- DHEA can be monitored by blood or saliva tests so doses can be individualised whereas 7-keto cannot be tested for and thus doses are only estimated.
- DHEA is cheaper
- From years of patient feedback it appears DHEA is more effective for treating adrenal fatigue symptoms when compared to its 7-keto metabolite. It has a greater effect in boosting your metabolism.
- DHEA has undergone more research.
- Most patients would benefit if some DHEA is converted into estrogens and/or testosterone as their levels are generally low and need to be improved.