The Anti-Aging Effects of DHEA

CARRIE DECKER, ND 

This review of literature, pertaining to the effects of DHEA on aging, stems from a clinical case I saw early on in my practice when I was seeing patients in a variety of smaller towns in Wisconsin. Not surprisingly, many of them were what you might expect of Wisconsinites: hardy, dependable folk, never to miss a day of work on the farm despite every imaginable weather system moving through. The case I am speaking of involved an elderly gentleman, nearly 80 years of age, who was still doing everything it took to run his dairy farm. He didn’t have a specific problem that he came in for; rather, he was looking for support with his energy levels. (If the reader doesn’t have familiarity with the amount of effort this gentleman’s day-to-day occupation demands, it should suffice to say that it would leave me feeling exhausted as well!) 

This gentleman came in with a box of numerous self-selected supplements, likely purchased in response to many infomercials and print media targeting an aging population. After reviewing the supplement facts for each and every product, I found that this elderly rotund gentleman was taking 300 mg of DHEA each day. Although at the time I wasn’t quite sure if any long-term safety data were available for that high of a dose, especially in the elderly, it definitely wasn’t a dose I was ready to recommend. I advised that he limit his DHEA intake to 50 mg daily and have further labs done to rule out common causes of fatigue, like anemia, hypothyroidism, or other pathology. He never came back for a return visit, so I have nothing more to say about his case specifically. 

I’m probably not alone as a practitioner, outside of those who specialize in anti-aging therapies or hormone replacement, in lacking knowledge of the wide array of clinical research on DHEA with regard to aging, as well as its safety at higher doses, such as this one. Herein, I will review the research in this realm, as well as studies related to DHEA and sexual health, which is also a common challenge with aging. 

DHEA: The Basics 

DHEA and its sulfated form, DHEA-S, are the most abundant steroid hormones in the human body.¹ They are primarily produced in the adrenal cortex, with smaller amounts of DHEA being synthesized in the ovaries and testes. Research suggests that DHEA and DHEA-S are also produced in the brain.² DHEA is a precursor to estradiol, estrone, testosterone, and 5α-dihydrotestosterone (5α-DHT).³ DHEA has roughly 1/20^th of the androgen potency of testosterone.⁴  

Much like estrogen and testosterone, levels of DHEA and DHEA-S decrease with age and are approximately 25% of their peak values by age 70.^2,5 Thus, we see substantial research regarding DHEA and its supplementation surrounding common concerns with aging: libido, bone health, body composition, metabolism, and skin integrity and appearance.  

One of the first questions on practitioners’ minds is what impact DHEA supplementation has, not only on levels of DHEA and DHEA-S, but also their downstream hormone metabolites, estradiol and testosterone. Concerns about prostate hyperplasia and hormone-sensitive cancers exist with therapies known to augment these hormones, and are well justified. 

Effect of DHEA Supplementation on Hormones  

In a small short-term study designed to look at the effects of DHEA supplementation on hormone levels, 24 healthy elderly adults, ages 60 to 79, were given 25-50 mg of DHEA for 8 days. Blood levels of DHEA, DHEA-S, and several downstream hormone metabolites were assessed on days 1 and 8.³ Supplementation of 25 mg of DHEA was adequate to restore DHEA-S levels to that of young adults, while at 50 mg the level remained in the normal range for young men but exceeded the upper normal level for healthy women.  

On the day it was taken, supplementation of DHEA significantly increased levels of DHEA, DHEA-S, and estrone in both men and women. A significant increase in estradiol level was seen in women but not in men on day 8 only.³ In men, DHEA supplementation increased testosterone non-significantly, while in women, on day 8 a significant and dose-dependent increase in testosterone was seen. It is noteworthy that a similar increase in total testosterone was observed in the men and women; however, it was only significant in the women, as baseline levels were less than 1/10^th that of the men.³ 

In this short trial, no accumulation of steroids (DHEA, DHEA-S, testosterone, estradiol, and estrone) was observed, with the area under the curve (AUC) at day 8 for these hormones not being statistically different than on day 1. Comparing hormone profiles from day 1 to day 8, in women, a trend towards increased estradiol and estrone levels (suggesting hormone accumulation) was observed, but was not significant. The authors of the study concluded, “No worrying transformation to androgen and estrogen was recorded; indeed, the limited increased estradiol in aged women could be predicted to be beneficial.”³ 

In a longer follow-up study designed as a randomized, double-blind, placebo-controlled trial (RDBPCT), a population of 280 men and women, ranging in age from 60 to 79 years, were given 50 mg of DHEA or placebo daily for a year.⁵ With supplementation, DHEA-S levels were restored to “normal youthful levels” in both sexes. In men, there was no significant increase in testosterone. In women, however, testosterone levels in 14 subjects were significantly higher by month 6, exceeding the normal range for menstruating women. There was a trend of increasing estradiol levels in men at month 12, whereas in women this increase was significant, with levels falling within normal ranges of the early follicular phase of menstruating women. No adverse effects associated with DHEA supplementation were noted, and there was no significant change in the prostate specific antigen (PSA) levels in the men.⁵  

Long-Term DHEA Use in Individuals 65+  

In this aforementioned 1-year study of DHEA supplementation at 50 mg/day, numerous clinical parameters were also assessed.⁵ Changes were most noteworthy in the women, particularly those over 70 years of age. DHEA supplementation positively affected bone health, decreasing bone turnover in women over age 70, and significantly improved most parameters related to libido in this age group of the women as well. In all individuals taking DHEA, there was a significant increase in skin hydration and sebum levels, and facial yellowness decreased. There also was a significant increase in epidermal thickness on the dorsal hand in the individuals whose baseline DHEA-S levels were in the lowest quartile.⁵  

The overall findings of this study were well summarized in the authors’ conclusion: “A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging.”⁵ 

Additional human studies in aging individuals (typically 65 years or older) have shown that long-term DHEA supplementation at 50 mg/day for 6 months to 2 years may decrease insulin resistance, triglycerides, and the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α⁶; enhance the effects of weight training on muscle mass⁷; decrease arterial stiffness⁸; improve bone mineral density (BMD) ⁹; and decrease visceral and subcutaneous fat.¹⁰ At a dose of 25 mg/day for 6 months, DHEA supplementation also improved cognitive scores in women with mild-to-moderate cognitive impairment.¹¹  

In these studies,^5-11 no serious adverse events attributed to DHEA supplementation were reported; however, over the long time-period, there were some serious adverse events in the older population included in the studies. Mild adverse events included increased acne and facial hair growth in a small number of the women. There were no changes in PSA levels and liver function tests, and no increases in mammogram or Pap smear abnormalities in the studies in which these parameters were assessed. 

Interestingly, a study of middle-aged practitioners of Tai Chi found that these individuals had significantly higher levels of DHEA-S and lower levels of cortisol, shedding light on a potential mechanism by which this practice enhances longevity.¹²  

Other Specific Applications 

DHEA & Libido 

In addition to the findings in women age 70 and older, DHEA may improve libido in younger individuals, primarily females. In postmenopausal women, age 50 to 60, DHEA at a low dose of only 10 mg/day for 12 months was shown to significantly improve sexual function and frequency compared to the control intervention (400 IU of vitamin D).¹³ In a population of men and women with hypoactive sexual desire disorder, at a dose of 100 mg/day for 6 weeks, treatment with DHEA significantly improved sexual arousal and satisfaction in women. In the men, however, no improvements were seen.¹⁴  

It is not uncommon for women to have sexual side effects from oral contraceptive (OC) use, with a small but still substantial percentage experiencing a decline in libido.¹⁵ In women taking OCs, the addition of 50 mg/day of DHEA significantly improved numerous markers of sexual function, which had declined with initiation of the OC medication.¹⁶ The women who had higher free testosterone levels during DHEA administration were found to experience greater effects of DHEA on sexual arousal and desire. 

In women, DHEA conversion to testosterone by the adrenals is the primary source of testosterone; hence, with adrenal insufficiency, women often experience a decline in libido. In men, however, sexual function and testosterone levels are largely preserved.¹⁷ Multiple studies have shown that 50 mg of DHEA is a suitable dose for women with adrenal insufficiency, in addition to other indicated treatments.^18-20 This dose also supports improvements in hormone levels, metabolic parameters, well-being, anxiety and depression, and frequency of sexual thoughts and interest. Furthermore, DHEA has been shown to improve alertness, stamina, and sexual interest or activity in women with hypopituitarism when added to other indicated hormone replacement therapies.²¹  

Supplementation with DHEA has been shown to enhance sexual arousal in postmenopausal women acutely as well. In a RDPBCT with crossover, oral administration of 300 mg of DHEA significantly increased both the mental and physical arousal response to viewing an erotic video 60 minutes later.²² However, a similarly designed study did not show a significant effect in premenopausal women.²³  

Erectile Dysfunction 

Multiple population studies have shown an inverse relationship between DHEA levels and the incidence of erectile dysfunction (ED).^24,25 In addition to being a testosterone precursor, DHEA’s demonstrated anti-inflammatory and vasodilatory effects suggest its potential benefit in the treatment of ED.²⁶  

There is not a preponderance of evidence that suggests DHEA may be useful in ED, although 2 studies have demonstrated a positive impact. In one small prospective study without placebo, supplementation with 50 mg of DHEA for 6 months was shown to improve ED in the men who were naïve to both hormone replacement and treatment for ED.²⁷ Men with hypertension and those with ED having no known organic etiology both saw significant improvements in multiple International Index of Erectile Function (IIEF) sub-scores after treatment, while those with diabetes mellitus and neurological disorders did not see any change.  

In a RDBPCT of men with ED without subclassification of etiology, treatment with 50 mg/day of DHEA for 6 months was associated with significantly higher scores on all IIEF domains compared to placebo²⁸; however, the study had a fairly high dropout rate, especially in the placebo group, due to an insufficient response to treatment. 

Other Groups 

DHEA has also been shown to improve various markers of bone health in women with anorexia nervosa^29-31 and in women taking glucocorticoids for extended periods of time, ranging from 6 months to more than 3 years.^32-34 In these studies, the dose of DHEA ranged from 25 to 200 mg, with the period of treatment being up to 1 year. In the study administering the highest dose (200 mg) for the longest period of time (1 year), no adverse effects were reported; however, there was a significant increase in testosterone, but not estradiol, levels.³³  

Intravaginal Use 

Multiple studies have shown that intravaginal preparations of DHEA improve dyspareunia, vaginal tissue atrophy, and related genitourinary symptoms in postmenopausal women.^35-37 Long-term treatment with intravaginal preparations, at doses of up to 13 mg/day, has been shown to be very effective for these local tissue-related complaints, with little to no change in serum sex steroid levels.³⁸  

Potential Contraindications & Adverse Effects  

With DHEA, mild adverse effects are typically not seen acutely, but can be seen with prolonged use. Testing of DHEA levels to ensure they are not high or in the high-normal range prior to therapy initiation may help prevent untoward effects. Adverse effects are mild and may include complaints of oily skin, hair growth, acne, and body odor^39,40 – signs we typically associate with increased testosterone levels. However, hair loss can also be seen, as DHEA converts to more potent androgens in the hair follicle, which can interfere with hair growth.⁴¹ Studies suggest that the other epidermal effects also may be related to steroidal production in the skin,⁴² which oral DHEA supplementation additionally enhances, and to which some individuals may be more sensitive.  

As mentioned, in men, long-term studies have shown DHEA did not have adverse effects on prostate markers.^5,28 In elderly women – although a small, yet significant, increase in estradiol level has been seen with daily supplementation of 50 mg of DHEA – in the studies that also examined mammography and Pap smear results, no increase in abnormalities were observed.  

Clinically, DHEA is often used at a low dose initially, and if there are no significant adverse effects, the dose is gradually increased to levels shown to be effective. To the knowledge of this author, studies have not shown DHEA supplementation to be safe in individuals with a history of breast or hormone-sensitive cancers, and therefore should be avoided in this population.  

Closing Comments 

Given the inevitable decline in DHEA and its downstream hormones that we all experience with aging, it is no surprise to see substantial research with DHEA supplementation focused on age-related changes. Much like the benefits we see with the replacement of estrogen and testosterone, similar effects may be seen with DHEA. While estrogen and testosterone are prescription only, because DHEA is considered a dietary supplement in the United States, it is available for use by practitioners without prescribing rights as well as by consumers. Thus, it is important to understand both its clinical indications as well as its potential for mis-use – such that the next elderly gentleman you see in your practice with a chief complaint of fatigue is correctly advised of more appropriate alternate interventions. 

References: 

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2. Maninger N, Wolkowitz OM, Reus VI, et al. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009;30(1):65-91. 

3. Legrain S, Massien C, Lahlou N, et al. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab. 2000;85(9):3208-3217. 

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7. Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab. 2006;291(5):E1003-E1008. 

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12. Lai HM, Liu MSY, Lin TJ, et al. Higher DHEAS Levels Associated with Long-Term Practicing of Tai Chi. Chin J Physiol. 2017;60(2):124-130. 

13. Genazzani AR, Stomati M, Valentino V, et al. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric. 2011;14(6):661-668. 

14. Bloch M, Meiboom H, Zaig I, et al. The use of dehydroepiandrosterone in the treatment of hypoactive sexual desire disorder: a report of gender differences. Eur Neuropsychopharmacol. 2013;23(8):910-918. 

15. Burrows LJ, Basha M, Goldstein AT. The effects of hormonal contraceptives on female sexuality: a review. J Sex Med. 2012;9(9):2213-2223. 

16. van Lunsen RHW, Zimmerman Y, Coelingh Bennink HJT, et al. Maintaining physiologic testosterone levels during combined oral contraceptives by adding dehydroepiandrosterone: II. Effects on sexual function. A phase II randomized, double-blind, placebo-controlled study. Contraception. 2018;98(1):56-62. 

17. Lang K, Burger-Stritt S, Hahner S. Is DHEA replacement beneficial in chronic adrenal failure? Best Pract Res Clin Endocrinol Metab. 2015;29(1):25-32. 

18. Arlt W, Justl HG, Callies F, et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab. 1998;83(6):1928-1934. 

19. Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999;341(14):1013-1020. 

20. Dhatariya K, Bigelow ML, Nair KS. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes. 2005;54(3):765-769. 

21. Johannsson G, Burman P, Wirén L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab. 2002;87(5):2046-2052. 

22. Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med. 2002;11(2):155-162. 

23. Meston CM, Heiman JR. Acute dehydroepiandrosterone effects on sexual arousal in premenopausal women. J Sex Marital Ther. 2002;28(1):53-60. 

24. Reiter WJ, Pycha A, Schatzl G, et al. Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction. Urology. 2000;55(5):755-758. 

25. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151(1):54-61. 

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27. Seftel A. Dehydroepiandrosterone in the treatment of erectile dysfunction in patients with different organic etiologies. J Urol. 2002;168(2):867-868. 

28. Reiter WJ, Pycha A, Schatzl G, et al. Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study. Urology. 1999;53(3):590-594. 

29. DiVasta AD, Feldman HA, Beck TJ, et al. Does hormone replacement normalize bone geometry in adolescents with anorexia nervosa? J Bone Miner Res. 2014;29(1):151-157. 

30. Gordon CM, Grace E, Emans SJ, et al. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metab. 2002;87(11):4935-4941. 

31. Gordon CM, Grace E, Emans SJ, et al. Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa. J Bone Miner Res. 1999;14(1):136-145. 

32. Papierska L, Rabijewski M, Kasperlik-Załuska A, et al. Effect of DHEA supplementation on serum IGF-1, osteocalcin, and bone mineral density in postmenopausal, glucocorticoid-treated women. Adv Med Sci. 2012;57(1):51-57. 

33. Mease PJ, Ginzler EM, Gluck OS, et al. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2005;32(4):616-621. 

34. Sánchez-Guerrero J, Fragoso-Loyo HE, Neuwelt CM, et al. Effects of prasterone on bone mineral density in women with active systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2008;35(8):1567-1575. 

35. Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2018;25(11):1339-1353. 

36. Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016;23(3):243-256. 

37. Labrie F, Derogatis L, Archer DF, et al. Effect of Intravaginal Prasterone on Sexual Dysfunction in Postmenopausal Women with Vulvovaginal Atrophy. J Sex Med. 2015;12(12):2401-2412. 

38. Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause. 2009;16(5):897-906. 

39. Løvås K, Gebre-Medhin G, Trovik TS, et al. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab. 2003;88(3):1112-1118. 

40. Finckh A, Berner IC, Aubry-Rozier B, So AK. A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia. J Rheumatol. 2005;32(7):1336-1340. 

41. Kasick JM, Bergfeld WF, Steck WD, Gupta MK. Adrenal androgenic female-pattern alopecia: sex hormones and the balding woman. Cleve Clin Q. 1983;50(2):111-122. 

42. Slominski A, Zbytek B, Nikolakis G, et al. Steroidogenesis in the skin: implications for local immune functions. J Steroid Biochem Mol Biol. 2013;137:107-123. 

Carrie Decker, ND graduated with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, OR. Prior to becoming a naturopathic physician, Dr Decker was an engineer and obtained graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign, respectively. She continues to enjoy academic research and writing and uses these skills to support integrative medicine education as a writer and contributor to various resources. Dr Decker supports Allergy Research Group as a member of their education and product development teams.