Clinical Uses for DHEA Supplementation in Male Patients

Optimizing hormonal health and preventing age-related decline

By Briana Cain, ND

Discover the clinical applications of DHEA supplementation in male patients, focusing on its benefits for cardiovascular health, bone density, cognitive function, and hormonal optimization. Learn how to integrate DHEA into personalized treatment protocols for enhanced patient outcomes.

The Role of DHEA in Male Health

Dihydroepiandrosterone (DHEA) and its sulfate compound. DHEA-S are the predominant steroid hormones the adrenal gland produces, specifically in the Zona Reticularis, the reticular zone of the adrenal cortex¹. The hypothalamus produces the corticotropin-releasing hormone, which travels to the anterior pituitary and signals the release of adrenocorticotropic hormone (ACTH). The adrenals produce DHEA in response to ACTH. 

DHEA is a reservoir from which more potent sex hormones can be formed, including testosterone, dihydrotestosterone, progesterone, estrone, and estradiol4. DHEA-S is considered a large plasma supply of DHEA because the two hormones can readily be interconverted by extra-adrenal sulfotransferase and sulfatase enzymes. The serum concentration for DHEA is relatively low. In contrast, DHEA-S levels are higher and have a longer metabolic clearance rate making DHEA-S a more valuable serum for clinical use. Depending on several factors, including serum concentrations of sex hormones, cortisol, genetics, gender, and adrenal health, DHEA can have clinical applications in treating various disease conditions. 

In men, DHEA supplementation proves valuable for increasing testosterone levels, decreasing adipose, increasing bone density, and improving endothelial function. Although there is some debate about how DHEA accomplishes positive outcomes in these areas, from a clinical perspective, DHEA supplementation can still be beneficial, considering DHEA levels decline with age. DHEA levels can decline earlier in life as a result of poor lifestyle choices such as alcohol abuse and smoking, poor sleep, chronic high stress, chronic pain, untreated thyroid dysfunction, and hypogonadism. 

DHEA and Cardiovascular Health

Supporting Testosterone and Endothelial Function

Coronary artery disease remains the leading cause of mortality in the United States, with a more frequent incidence in men than women. Age-related declines in testosterone and DHEA contribute to endothelial dysfunction and increased coronary artery disease (CAD). It is established that testosterone replacement at physiologic dosing for men who present with a deficiency helps to improve cardiovascular health and reduce the incidence of coronary artery disease. 

However, DHEA supplementation, in combination with testosterone replacement therapy, increases free testosterone levels, making testosterone more bioavailable. In addition, DHEA improves endothelial function by reducing plasminogen activator type 1 (PAI-1)5. Endothelial dysfunction increases PAI-1 concentration, decreasing fibrinolysis and exacerbating coronary artery disease. 

Increased free testosterone level under the influence of DHEA supplementation improves lean body mass. It reduces adipose tissue, improves insulin response, decreases inflammation, and reduces cardiovascular risk factors. DHEA and testosterone have independent influences on improved CAD risk, but they provide a more holistic approach to improved cardiovascular function in men6. While DHEA and testosterone are potentially cardio-protective hormones, lifestyle factors remain the most significant predictor of CAD risk. They must be addressed in treatment protocols for cardiovascular disease and prevention.

Enhancing Bone Density with DHEA

Osteopenia and osteoporosis are most often conditions identified in female patients due to a dramatic drop in estrogen during menopause, however, men are estimated to lose bone mineral density (BMD) at a rate of 1% per year with advancing age³. One in eight men over 50 will experience a loss of BMD sufficient to cause hip and vertebral fractures associated with increased morbidity and mortality. Age-related hormonal decline is the primary contributing factor to osteoporosis in male patients. 

Studies indicate that supplemental DHEA in elderly men increases BMD. The process by which this occurs is somewhat unclear but may be related to DHEA’s ability to increase testosterone levels. Testosterone plays an important role in the maintenance of BMD by stimulating the proliferation of preosteoblasts and differentiation of osteoblasts¹⁰. Men undergoing androgen deprivation therapy as a result of prostate cancer treatment often develop osteopenia or osteoporosis. Aromatase activity resulting in the conversion of testosterone to estrogen is also important. Estrogen suppresses osteoclast formation and reduces bone resorption activity⁷. Considering DHEA is a precursor to estrogen, the increase in BMD by DHEA supplementation may also be related to increased estrogen levels. As testosterone and DHEA decline with age, so does estrogen. Estrogen is required for various biochemical processes in men, and physiologic levels are vital.

DHEA and Stress Response

DHEA plays a crucial role in regulating the body’s stress response. Produced in the adrenal glands alongside cortisol, DHEA works inversely with cortisol, meaning that elevated cortisol levels suppress DHEA production. DHEA can help to regulate cortisol and influence stress response. 

DHEA enhances immune function and helps balance the stress response. Chronic stress– due to factors like strain, chronic pain, or lack of sleep often leads to elevated cortisol, decreased DHEA levels, and decreased testosterone (free & total), which can impair immune function, reduce muscle mass, and increase the risk of diabetes and hypertension.

If the patient is in the fourth, fifth, or sixth decade of life, hormonal decline due to aging is also a contributing component. Chronic elevated cortisol can result in bone loss, a decrease in muscle mass, recurrent infections, type 2 diabetes, and hypertension². Not only does cortisol have a direct negative effect on these conditions, but its suppression of DHEA further exacerbates them. 

Male patients under persistent stress may present with optimal total testosterone levels but have low levels of free circulating testosterone. This is a result of suppressed DHEA-S and the ability of cortisol to increase the liver’s production of sex hormone-binding globulin. These patients are ideal candidates for DHEA supplementation, potentially other hormone therapies for balancing or replacement, and lifestyle counseling.

Cognitive decline is a primary concern for many male patients as they age. Cortisol levels do not appear to decline with age; therefore, impairments in cognition and mood may result from cortisol unopposed by declining DHEA. DHEA binds various sites in the brain and can act as a gamma-aminobutyric acid type A (GABA-A) receptor agonist and improves N-methyl-D-aspartate-induced (NMDA) neuronal excitability⁸. 

Any compound exemplifying these characteristics has been found to impart a memory-enhancing effect. DHEA protects neurons from the toxic effects of glucocorticoids. Elevated levels of glucocorticoids in the brain may result in anxiety, depression, and other mood disturbances. This appears to be another case for DHEA supplementation in our elderly male patients. However, studies indicate that DHEA supplementation in the seventh decade has no positive impact on memory or mood. 

There is an indication that supplemental DHEA initiated earlier in life and used for an extended duration has a more promising capability of preventing age-related cognitive decline in men³. Therefore, DHEA-S levels should be evaluated in male patients beginning in the third decade of life when DHEA-S peaks but then declines substantially thereafter. The ideal time for DHEA supplementation to be initiated to prevent cognitive decline is most likely in the fourth or fifth decade of life, depending on clinical need.

Numerous studies have been conducted on supplemental DHEA using dosing strategies ranging from 10mg to 100mg daily DHEA. The problem with higher doses of supplemental DHEA is the potential for increased generation of estrone, estradiol, and dihydrotestosterone (DHT). 

While slight increases in estradiol can be beneficial, more extreme elevations can cause mood disturbance, gynecomastia, and prostate irritation. Elevated estrone also has risks tied to the formation of deep vein thrombosis. 

DHT is a potent androgen with a strong binding affinity to androgen receptors and is often implicated in prostate pathologies. Many studies indicate that even at higher doses, supplemental DHEA does not influence elevations in estrone, estradiol, and DHT significantly enough to pose problems.

Clinical observation indicates otherwise. Lab testing on any male patient already supplementing DHEA should include estrone, estradiol, DHT, testosterone (free and total), and prostate-specific antigen (PSA) at the very least. LH and FSH should also be evaluated in a new patient who is not on testosterone replacement therapy to determine if the etiology of hypogonadism is primary or secondary. However, the use of DHEA as a supplement and its dosing are independent of LH and FSH levels. Once a patient is on testosterone replacement therapy, LH and FSH become suppressed and don’t provide much value.  In most cases, DHEA doses of 10-25mg daily for male patients are sufficient to optimize DHEA-S levels and minimize significant elevations in other hormone levels. 

DHEA supplements should be utilized in the micronized form to improve GI absorption. DHEA can also be compounded for topical use, but oral supplementation is adequate for most patients. The benefits of including DHEA in bioidentical hormone replacement therapy can positively impact improvements in health, symptom resolution, and longevity through chronic disease prevention. DHEA supplementation is best implemented under the supervision of a licensed healthcare professional despite its over-the-counter availability.

Case Study

A 58-year-old male with testicular hypofunction and hypothyroidism.

History

58-year-old, married, Caucasian male. Social drinker. Smokes 6-8 cigars a month. Resistance training 5 days a week. He consumes a strict carnivore diet, which he has done for 5 years. Has screening lab work performed every 6 months and a carotid artery ultrasound every 2 years. Carotid artery ultrasound has consistently yielded favorable results, lab values for inflammation are within normal limits, and his blood pressure is also normal. Cholesterol is slightly elevated due to a carnivore diet. Sleep and energy are good. Has been on thyroid replacement and testosterone replacement therapy for 22 years. Currently doing weekly intramuscular injections of testosterone cypionate. Tried various applications of testosterone, including sub-lingual and topical versions, in the past. He felt like he had plateaued in the gym and could not build lean muscle as effectively. I thought he had “passed his prime” when starting with our clinic.

Assessment

The patient is highly motivated to prevent chronic disease through diet, exercise, nutritional supplements, peptides, and bioidentical hormones. The patient drinks whiskey and smokes cigars socially, which brings him joy, and he is unwilling to discontinue. He generally feels good and enjoys a balance between his work and family life. Stress is low-moderate.  Alcohol consumption, cigar smoking, stress, and hypothyroidism most likely created an accumulated insult to his adrenal function, resulting in decreased DHEA levels. General environmental toxicity and the quality of animal products consumed while practicing a carnivore diet may also play a role. With no lab history before hypothyroidism diagnosis, it is impossible to determine at what point DHEA levels began to decline and whether or not it was a result of overcompensation by the adrenals as a result of hypothyroidism. It is theoretically possible that this may have been the root cause of decreased DHEA. Still, chronic stress and oxidation due to lifestyle are more likely, considering DHEA did not recover after thyroid hormones were balanced.  

The patient is receptive to advice to improve quality of life and prevent chronic illness. He considers himself well-educated about functional health. He agreed to an updated blood panel, including DHEA-S, which had never been tested with his previous provider. Lab values for testosterone and DHEA-S at baseline were as follows: Total testosterone = 998 ng/dL, Free testosterone = 7.8 pg/dL, DHEA-S = 76 ug/dL. All other lab values were within normal limits.

Plan

Continue to inject 120mg testosterone cypionate intramuscularly every 7 days and initiate 25mg micronized DHEA daily.

Follow-up

Subsequent labs were performed after 12 weeks of therapy. Lab values for testosterone and DHEA-S at 12 weeks were: Total testosterone = 1031 ng/dL, Free testosterone = 14.6 pg/dL, DHEA-S = 357 ng/dL. The patient reported feeling more balanced and having more stamina during exercise. He was surprised by the difference a DHEA supplement could make on his testosterone levels. Positive changes in free testosterone and DHEA-S levels were significant with DHEA supplementation in the patient’s protocol. By increasing DHEA and free testosterone levels, symptoms improved without the need for an increased dose of testosterone replacement therapy, which could lead to side effects and adverse long-term sequelae as a result of higher doses of testosterone.

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References

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