As both an adrenal and a sex hormone, Dehydroepiandrosterone (DHEA) emerges as a vital player in the world of hormone balance. As with all hormones, healthy DHEA levels are all about balance.
As an adrenal hormone, DHEA plays a role in anabolic processes such as energy production; cell repair; bone, brain and muscle health; and immune function. Its ability to convert into androgenic and estrogenic hormones demonstrates additional functions in reproduction, libido and sexual response, mood regulation, sleep, and more.
It is important to understand the nuanced interplay between DHEA levels and health outcomes, to elucidate the symptoms of imbalanced DHEA levels and appropriate testing for DHEA levels. Then, one can unlock avenues for optimization through natural interventions and targeted supplementation.
Dehydroepiandrosterone (DHEA) is a steroid hormone primarily produced by the adrenal glands, though it is also synthesized in smaller quantities by the ovaries, testes, and brain. Considered the most abundant steroid hormone in the human body, DHEA serves as a precursor to both androgens and estrogens, including testosterone and estradiol.
Dehydroepiandrosterone (DHEA) is primarily produced from cholesterol, a precursor molecule synthesized by the body. Cholesterol undergoes a series of enzymatic reactions in the adrenal glands, where it is converted into pregnenolone. Pregnenolone is then further metabolized to form DHEA through a sequence of enzymatic steps.
This process primarily occurs in the zona reticularis, the innermost layer of the adrenal cortex, although smaller amounts of DHEA are synthesized in other tissues such as the ovaries, testes, and brain.
DHEA-S levels peak around the mid-twenties and gradually decline to approximately 20% by age 70. Unfortunately, there are no feedback mechanisms to restore DHEA levels once they begin to decrease.
As DHEA and its downstream metabolites decline the brain loses the protective effects of sex steroids, becoming more susceptible to the neurotoxic effects of cortisol and other damaging factors. This decline in DHEA-S levels leads to a constant cortisol level, resulting in an elevated cortisol/DHEA-S ratio. [5.]
The imbalance between high cortisol and low DHEA-S levels can create adverse conditions for the hippocampus, potentially contributing to neurodegenerative diseases. Brain imaging studies have shown a close association between decreased DHEA-S levels and reduced hippocampal function in Alzheimer's disease. [15.]
DHEA-S is the sulfated form of DHEA. The overwhelming majority of circulating DHEA in the blood is the sulfated form, DHEA-S. Its actions are very similar to DHEA, although some of its mechanisms, or how it performs those actions, are different. [PEREZ] Additionally, because it binds more strongly to its carrier protein albumin, DHEA-S has a longer half-life and it does not exhibit the same diurnal variations that cortisol and DHEA do. [KAMIN, STARKA]
Because of its longer half-life, DHEA-S serves as a reliable marker of adrenocortical activity and chronic stress levels, offering insight into long-term stress accumulation. In contrast, DHEA levels may provide a glimpse into the body's immediate response to acute stressors. By assessing DHEA-S levels, we gain valuable insight into the systemic biological reservoir of DHEA within the body.
DHEA has many health and wellness benefits. Some of its main functions include:
Precursor to sex hormones: DHEA serves as a precursor to both androgens (such as testosterone) and estrogens (such as estradiol), playing a vital role in reproductive health and sexual development and contributing to the pool of available anti-aging hormones.
Hormonal balance: DHEA helps maintain hormonal equilibrium by modulating the activities of other hormones, including cortisol, androstenedione, and progesterone.
Metabolism: DHEA influences metabolism by promoting fat breakdown, enhancing insulin sensitivity, and supporting glucose utilization, thereby affecting energy production and storage. [9., 14. ]
Immune function: DHEA has immunomodulatory effects, regulating the activity of immune cells and cytokines to support immune responses and protect against infections. [3.]
Brain function: DHEA plays a role in cognitive health and mental well-being, with potential effects on memory, mood regulation, and neuroprotection. [26.]
Bone density: DHEA contributes to bone health by stimulating osteoblast activity and collagen synthesis, thereby maintaining bone density and strength. [12.]
Anti-aging effects: DHEA has been associated with anti-aging properties, including its potential to enhance skin health, improve muscle mass and strength, and support overall vitality and longevity. [22.]
DHEA-S, the sulfated form of DHEA, is the most abundant steroid hormone in the body, and a precursor to both androgens and estrogens including testosterone and estradiol, so it can be considered a “prohormone pool” from which the body can make more androgens and estrogens in times of depletion.
DHEA exerts a modulating influence on various hormonal pathways. In addition to its function as an androgen and estrogen prohormone, it helps regulate the synthesis and metabolism of other hormones including pregnenolone, often considered “the mother hormone” because it is the first steroid hormone produced from cholesterol. [16.]
By acting as a buffer against the effects of stress and aging, the effects of DHEA can counterbalance the activity of cortisol, the body's primary stress hormone. This intricate interplay between DHEA and other hormones underscores its significance in maintaining optimal health and well-being.
DHEA is taken up by local tissues and metabolized into other steroid hormones including estrogen and testosterone. DHEA has its own functional properties, and also exerts its effects through its metabolite steroid hormones. [22.]
DHEA is commonly tested in blood, although saliva and urine tests are also widely available. Each has its benefits and drawbacks:
Blood testing for DHEA involves collecting a blood sample from a vein in the arm, typically in the morning when DHEA levels are highest. The sample is then sent to a laboratory for analysis. Blood testing offers a direct measurement of circulating DHEA levels, providing a comprehensive assessment of hormonal status.
It is important to understand that serum tests assess levels of DHEA-S, or the sulfated form of DHEA, in the blood.
The secretion rate of DHEA-S into the bloodstream is only slightly higher than that of DHEA. However, due to its longer half-life of approximately one day, DHEA-S levels are approximately a thousand-fold higher.
DHEA-S predominantly binds to albumin, with only a small fraction being unbound to proteins and none bound to sex hormone-binding globulin (SHBG).
Because of its high concentration and minimal variability, DHEA-S serves as an excellent indicator of adrenal cortex androgen production. Alongside testosterone, DHEA-S assays are preferred for initial screening tests to assess elevated androgen levels in hirsutism, with approximately 84% of affected women exhibiting elevated androgen levels.
Benefits: Blood testing is considered the gold standard for assessing DHEA levels, offering accurate and reliable results with a relatively simple sample process. It allows for precise quantification and enables healthcare providers to monitor changes in hormone levels over time.
Drawbacks: Blood testing via venipuncture can be invasive and uncomfortable for some individuals. Additionally, DHEA levels in the blood fluctuate throughout the day, making timing of the blood draw critical for accurate interpretation.
Additionally, DHEA levels reported in blood testing do not always differentiate between free and bound hormones, which may be misleading for clinicians when patients present with symptoms of DHEA deficiency with normal blood test results.
In contrast to serum samples, saliva testing may assess DHEA and/or DHEA-S levels, although DHEA-S levels are preferred due to their stability and higher concentration in saliva. [5.] Saliva testing involves collecting a saliva sample using a swab or collection device. [23.]
Saliva testing is often preferred for assessing bioavailable (free) hormone levels, as it reflects the active fraction of hormones available at local tissue levels.
Benefits: Saliva testing is non-invasive and easy to perform, making it convenient for patients. It provides a snapshot of bioavailable DHEA levels, which may offer insights into hormone activity at the tissue level.
Because of the stability of steroid hormones in saliva samples, the timing of sample retrieval may matter less than with blood testing. [10.]
Drawbacks: Saliva testing may be less accurate than blood testing for quantifying total DHEA levels. Factors such as oral contamination and variability in saliva flow rates can affect test results. Standardization of saliva testing protocols is essential to ensure consistency and reliability.
Urine testing involves collecting a urine sample, typically over a 24-hour period, to assess DHEA-S levels. Urine testing captures free, or unbound, hormones, which are bioavailable. Because urine testing highlights the metabolites of steroid hormones, it can demonstrate a more comprehensive picture of hormone production and breakdown.
Benefits: Urine testing offers a non-invasive and convenient method for assessing overall DHEA production and clearance. It provides information on DHEA metabolism and can be useful for evaluating long-term hormone balance. It also offers insight into the dynamic balance between steroid hormones.
Drawbacks: Urine testing may be less sensitive than blood testing for detecting subtle changes in DHEA levels. It requires proper collection and handling of urine samples to ensure accuracy, and results may be influenced by factors such as hydration status and kidney function.
The interpretation of DHEA test results depends on various factors, including the testing method used, reference ranges provided by the lab, and individual patient characteristics. In general, higher DHEA levels may indicate increased adrenal gland activity or supplementation, while lower levels may suggest adrenal insufficiency or aging-related decline.
Clinically, DHEA testing is often used to assess adrenal function, diagnose adrenal disorders such as adrenal insufficiency or adrenal hyperplasia, and monitor hormone replacement therapy.
However, it's essential to interpret DHEA test results in the context of the patient's clinical presentation, medical history, and other hormone levels. Additional testing and clinical evaluation may be necessary to confirm diagnosis and guide treatment decisions.
Signs and symptoms of high DHEA levels may include:
High DHEA can occur due to pathology, or disease, as well as from functional causes. Some causes of high DHEA include:
Adrenal tumors: Adrenal tumors, such as adrenal adenomas or adrenal carcinomas, can lead to excess production of DHEA and other androgens.
Polycystic ovary syndrome (PCOS): PCOS is a common hormonal disorder characterized by enlarged ovaries with multiple small cysts. It often results in elevated levels of androgens, including DHEA.
Congenital adrenal hyperplasia (CAH): CAH is a group of genetic disorders that affect the adrenal glands' ability to produce cortisol and aldosterone. It can lead to overproduction of androgens, including DHEA.
Adrenal hyperplasia: Adrenal hyperplasia refers to the excessive growth of adrenal tissue, which can result in increased production of adrenal hormones, including DHEA.
Medications: Certain medications, such as corticosteroids or androgenic steroids, can lead to elevated DHEA levels as a side effect. Over-supplementation of DHEA can also cause elevated levels.
Rare disorders: Rare conditions, such as Cushing's syndrome or androgen-secreting tumors outside the adrenal glands (e.g., ovarian or testicular tumors), can also cause high DHEA levels.
Stress: acute stress can cause an elevation in DHEA levels; studies have shown that chronic stress may cause an increase or a deficiency in DHEA over time. [6., 13.]
PCOS is a common cause of elevated DHEA levels in women, although CAH or an adrenal tumor are less-common causes.
Polycystic ovary syndrome (PCOS) is a hormonal disorder characterized by imbalanced hormone levels, including elevated androgens (such as testosterone) in women of reproductive age. It often leads to irregular menstrual cycles, ovarian cysts, and symptoms like acne, hirsutism (excess hair growth), and infertility.
Due to the complex interactions between hormones and metabolism, PCOS is often accompanied by metabolic issues including insulin resistance, which predisposes individuals to a higher risk of type 2 diabetes and metabolic syndrome.
Many women with PCOS who have high androgens including elevated DHEA levels benefit from foundational treatments including diet and lifestyle modifications, and targeted supplement or medication therapy, to restore hormone balance.
Diet:
Lifestyle:
Supplements:
Medications:
It is important to consult a healthcare provider prior to initiating supplement or medication therapy for high or low DHEA levels.
DHEA plays a pivotal role in various physiological functions, but its levels naturally decline with age. Manifestations of DHEA deficiency can encompass a range of symptoms reflecting its influence on hormone balance and overall well-being.
Symptoms Associated with DHEA Deficiency:
Note: While DHEA levels naturally decline along the lifespan, individuals experiencing symptoms of deficiency should consult healthcare professionals for proper evaluation and management.
Strategies for addressing low DHEA levels in women should involve a multifaceted approach aimed at optimizing overall hormone balance and supporting adrenal function. Diet, lifestyle, and supplementation are all potential factors that can promote healthy DHEA levels in women.
Diet:
Lifestyle:
Supplements:
Consult with a healthcare professional before starting any supplementation regimen to ensure safety and efficacy, especially if there are underlying health conditions or medication interactions.
DHEA, a precursor hormone produced by the adrenal glands, has been implicated in weight management and metabolism in women.
While research on the direct relationship between DHEA levels and weight loss is limited, some studies suggest that DHEA supplementation may promote reductions in abdominal body fat and improvements in body composition by enhancing metabolic rate and insulin sensitivity. [20., 21.] Specifically, resistance training may offer the most benefit. [4.]
However, individual responses to DHEA supplementation vary, and its efficacy as a standalone weight loss aid remains inconclusive. It's important for women considering DHEA supplementation for weight management to consult with a healthcare professional to determine its appropriateness and ensure safe and effective use.
DHEA is available as an over the counter supplement, although it is important to note that DHEA is banned for use by the National Collegiate Athletic Association, the International Olympic Committee, and the World Anti-Doping Agency (WADA) because of its androgenic effects.
Different types of DHEA supplements are available: DHEA, DHEA-S (the sulfated form of DHEA), and 7-keto DHEA.
DHEA-S is the sulfated form of DHEA. When it comes to which supplement to take, DHEA or DHEA-S, there is probably not much difference between the two because oral DHEA supplements are readily sulfated in the liver to DHEA-S via first-pass metabolism. Both forms will contribute to the overall prohormone pool in the body, and may contribute to raising levels of DHEA-S, estrogen, and testosterone in the blood.
7-keto DHEA is a metabolite of DHEA, and it is also available as an oral supplement. It’s been marketed as a weight loss supplement, although research is mixed regarding its ability to stimulate weight loss. [8.]
Unlike DHEA, 7-Keto DHEA does not convert into steroid hormones such as testosterone and estrogen. Along with its purported benefits on metabolism, It's also thought to enhance memory and boost the immune system. As we age, the levels of 7-Keto DHEA in our bodies decrease.
Dosage recommendations for DHEA vary widely, and depend on many factors including age, sex, and health status. Dosages tend to start at 5 mg orally and may go as high as 100-200 mg daily. Because DHEA is a hormone that can have many downstream effects, it is essential to work with a healthcare professional who can utilize appropriate testing and assessment to determine the best dose for an individual.
There is controversy regarding the best time of day to take DHEA supplements. Because DHEA is an adrenal hormone, and adrenal glands tend to make the most hormones in the morning, taking DHEA in the morning mimics the body’s natural hormonal rhythm and may be preferred. However, it should be noted that some research studies recommend nighttime dosing of DHEA. [25.]
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[1.] 004020: Dehydroepiandrosterone (DHEA) Sulfate | Labcorp. www.labcorp.com. https://www.labcorp.com/tests/004020/dehydroepiandrosterone-dhea-sulfate
[2.] Basu BR, Chowdhury O, Saha SK. Possible Link Between Stress-related Factors and Altered Body Composition in Women with Polycystic Ovarian Syndrome. J Hum Reprod Sci. 2018 Jan-Mar;11(1):10-18. doi: 10.4103/jhrs.JHRS_78_17. PMID: 29681710; PMCID: PMC5892097.
[3.] Buford TW, Willoughby DS. Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Applied Physiology, Nutrition, and Metabolism. 2008;33(3):429-433. doi:https://doi.org/10.1139/h08-013
[4.] Copeland JL, Consitt LA, Tremblay MS. Hormonal Responses to Endurance and Resistance Exercise in Females Aged 19-69 Years. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2002;57(4):B158-B165. doi:https://doi.org/10.1093/gerona/57.4.b158
[5.] Dehydroepiandrosterone Sulfate Clinical Information. https://www.zrtlab.com/images/documents/dhea-s_saliva_test_specifications.pdf
[6.] Dutheil F, de Saint Vincent S, Pereira B, Schmidt J, Moustafa F, Charkhabi M, Bouillon-Minois JB, Clinchamps M. DHEA as a Biomarker of Stress: A Systematic Review and Meta-Analysis. Front Psychiatry. 2021 Jul 6;12:688367. doi: 10.3389/fpsyt.2021.688367. PMID: 34295276; PMCID: PMC8290065.
[7.] Heaney JL, Carroll D, Phillips AC. DHEA, DHEA-S and cortisol responses to acute exercise in older adults in relation to exercise training status and sex. Age (Dordr). 2013 Apr;35(2):395-405. doi: 10.1007/s11357-011-9345-y. Epub 2011 Nov 22. PMID: 22105939; PMCID: PMC3592957.
[8.] Jeyaprakash N, Maeder S, Janka H, Stute P. A systematic review of the impact of 7-keto-DHEA on body weight. Arch Gynecol Obstet. 2023 Sep;308(3):777-785. doi: 10.1007/s00404-022-06884-8. Epub 2022 Dec 25. PMID: 36566478; PMCID: PMC10348924.
[9.] Karbowska J, Kochan Z. Effects of DHEA on metabolic and endocrine functions of adipose tissue. Horm Mol Biol Clin Investig. 2013 Aug;14(2):65-74. doi: 10.1515/hmbci-2013-0009. PMID: 25436721.
[10.] Kells J, Dollbaum CM. Saliva tests, part 1: clinical use, elements of testing, and guidelines for posttreatment interpretation. Int J Pharm Compd. 2009 Jul-Aug;13(4):280-8. PMID: 23966517.
[11.] Kiani AK, Donato K, Dhuli K, Stuppia L, Bertelli M. Dietary supplements for polycystic ovary syndrome. J Prev Med Hyg. 2022 Oct 17;63(2 Suppl 3):E206-E213. doi: 10.15167/2421-4248/jpmh2022.63.2S3.2762. PMID: 36479481; PMCID: PMC9710389.
[12.] Kirby DJ, Buchalter DB, Anil U, Leucht P. DHEA in bone: the role in osteoporosis and fracture healing. Arch Osteoporos. 2020 Jun 5;15(1):84. doi: 10.1007/s11657-020-00755-y. PMID: 32504237.
[13.] Lennartsson AK, Theorell T, Rockwood AL, Kushnir MM, Jonsdottir IH. Perceived Stress at Work Is Associated with Lower Levels of DHEA-S. Esteban FJ, ed. PLoS ONE. 2013;8(8):e72460. doi:https://doi.org/10.1371/journal.pone.0072460
[14.] Li CJ, Lin LT, Tsui KH. Dehydroepiandrosterone Shifts Energy Metabolism to Increase Mitochondrial Biogenesis in Female Fertility with Advancing Age. Nutrients. 2021 Jul 17;13(7):2449. doi: 10.3390/nu13072449. PMID: 34371958; PMCID: PMC8308577.
[15.] Murialdo G, Nobili F, Rollero A, Gianelli MV, Copello F, Rodriguez G, Polleri A: Hippocampal perfusion and pituitary-adrenal axis in Alzheimer's disease. Neuropsychobiology 2000;42:51-57.
[16.] Neunzig J, Bernhardt R. Dehydroepiandrosterone sulfate (DHEAS) stimulates the first step in the biosynthesis of steroid hormones. PLoS One. 2014 Feb 21;9(2):e89727. doi: 10.1371/journal.pone.0089727. PMID: 24586990; PMCID: PMC3931814.
[17.] Patten RK, Boyle RA, Moholdt T, Kiel I, Hopkins WG, Harrison CL, Stepto NK. Exercise Interventions in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Front Physiol. 2020 Jul 7;11:606. doi: 10.3389/fphys.2020.00606. PMID: 32733258; PMCID: PMC7358428.
[18.] Thakker D, Raval A, Patel I, Walia R. N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstet Gynecol Int. 2015;2015:817849. doi: 10.1155/2015/817849. Epub 2015 Jan 8. PMID: 25653680; PMCID: PMC4306416.
[19.] Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016;2016:1849162. doi: 10.1155/2016/1849162. Epub 2016 Oct 23. PMID: 27843451; PMCID: PMC5097808.
[20.] Villareal DT, Holloszy JO. Effect of DHEA on Abdominal Fat and Insulin Action in Elderly Women and Men: A Randomized Controlled Trial. JAMA. 2004;292(18):2243–2248. doi:10.1001/jama.292.18.2243
[21.] Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. American Journal of Physiology-Endocrinology and Metabolism. 2006;291(5):E1003-E1008. doi:https://doi.org/10.1152/ajpendo.00100.2006
[22.] Webb SJ, Geoghegan TE, Prough RA, Michael Miller KK. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab Rev. 2006;38(1-2):89-116. doi: 10.1080/03602530600569877. PMID: 16684650; PMCID: PMC2423429.
[23.] Whetzel CA, Klein LC. Measuring DHEA-S in saliva: time of day differences and positive correlations between two different types of collection methods. BMC Res Notes. 2010 Jul 20;3:204. doi: 10.1186/1756-0500-3-204. PMID: 20646292; PMCID: PMC2916011.
[24.] Xenou M, Gourounti K. Dietary Patterns and Polycystic Ovary Syndrome: a Systematic Review. Maedica (Bucur). 2021 Sep;16(3):516-521. doi: 10.26574/maedica.2020.16.3.516. PMID: 34925611; PMCID: PMC8643565.
[25.] Yen SS. Dehydroepiandrosterone sulfate and longevity: new clues for an old friend. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8167-9. doi: 10.1073/pnas.161278698. PMID: 11459947; PMCID: PMC37415.
[26.] Zwain IH, Yen SSC. Dehydroepiandrosterone: Biosynthesis and Metabolism in the Brain. Endocrinology. 1999;140(2):880-887. doi:https://doi.org/10.1210/endo.140.2.6528