New Research Substantiates the Anti-Aging Properties of DHEADecember 2010
By Kirk Stokel
Combat Metabolic Disorders
We’ve known for over a decade that DHEA protects against obesity and its consequences in aging and diabetic animals.47,48 In 2009, scientists confirmed that low DHEA levels in men were linked to diabetes and coronary heart disease.49 DHEA powerfully modulates gene expression to shift the metabolic balance in favor of energy utilization and away from storage as fat.50
DHEA also activates gene expression of cellular machinery that affects a cell’s consumption of fats and sugars to remove them from circulation.51,52 These molecules help correct harmful lipid abnormalities and unhealthy body fat distribution—a possible mechanism by which DHEA decreases total body fat.53,54
In 2007, researchers demonstrated in aged rats fed a high-fat diet that DHEA increased body protein, while decreasing total caloric intake, body weight, body fat, and total size and number of fat cells.55 In a related experiment, researchers discovered that DHEA could change the composition of adipose tissue, boosting levels of beneficial omega-3 fatty acids while reducing harmful omega-6 fatty acids.56
A human study showed how powerfully these DHEA effects can modify body composition.4 When 52 elderly men and women took 50 mg per day of DHEA or placebo for 6 months, it reduced stubborn abdominal and subcutaneous body fat. Insulin levels dropped significantly in supplemented patients as well, indicating enhanced insulin sensitivity. The researchers concluded appropriately that “DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.”
DHEA is highly protective against diabetes and its complications. In diabetic rats, DHEA prevented increases in oxidant stress and oxidative damage related to the disease. It also significantly improved blood vessel relaxation, improving blood flow.57 DHEA induces genes in muscle tissue that increase uptake and utilization of blood glucose as energy, significantly lowering blood sugar in diabetic animals.58 In humans with type 2 diabetes, DHEA counteracts oxidative imbalance and the formation of deadly advanced glycation end products (AGEs), and downregulates the inflammatory TNF-alpha system—effects that may prevent the onset and slow the progression of deadly diabetes.59
Cardiovascular Disease Defense
The past several years have witnessed extraordinary advances in our understanding of DHEA’s cardioprotective power—and its relationship to cardiovascular disease.
A 2009 study of 153 diabetic men with stable coronary heart disease (CHD) found that 77% were DHEA-S deficient, significantly more than in healthy peers.60 Over the next 19 months of follow-up, 43 of those men died of CHD; the data showed that low DHEA-S and low testostosterone levels were two of the four most significant predictors of death.
Another 2009 study of 247 men with a mean age of 76 years revealed that those with low DHEA-S had a 96% increased risk of diabetes and a 48% increased risk of coronary heart disease.49
A 2009 study from the University of Pennsylvania discovered a surprisingly close relationship between mortality and the trajectory of DHEA-S decline in older adults.61 Specifically, a rapid or erratic decline in DHEA-S predicted earlier death, and both together increased the death rate by nearly threefold! Regular blood testing for healthy DHEA-S levels are the only way to detect these lethal changes in DHEA levels early. It is of paramount importance that you have your DHEA-S levels checked at least once a year.
A Mayo Clinic study found that DHEA supplementation (50 mg per day) in women with low DHEA levels and low adrenal function improved plasma DHEA content, significantly lowered total cholesterol, and tended to reduce triglyceride and low-density lipoprotein (LDL) levels.62 But supplemented patients also had reductions in their beneficial high-density lipoprotein (HDL) levels. This study suggests that long-term studies are needed to determine the impact of DHEA supplementation on cardiovascular risk in women with low adrenal function.
Additional support for DHEA’s benefits in patients suffering from vascular disease came in two remarkable 2009 studies.63,64 The first examined vascular remodeling, a dangerous process that occurs when vessels are injured by atherosclerosis.63 Vascular remodeling can impede blood flow and ultimately worsen cardiovascular disease.65
DHEA significantly inhibited vascular remodeling in a rabbit model of carotid artery injury and limited deadly buildup of smooth muscle in vessel walls.63 Another study of rabbits fed a high-fat diet showed that DHEA supplements restored oxidative balance, lowered lipid levels and inflammatory damage, and prevented heart muscle tissue death and dysfunction, delaying the onset of cardiac damage.64
Enhanced Well-Being and Libido Even in Challenged Populations
Studies as early as 2000 demonstrated how DHEA improved well-being and could help to manage menopause without deleterious effects.28,66 In 2006 it was revealed that 50 mg per day of DHEA could improve psychological well-being even in challenging populations such as those with decreased pituitary function.67
DHEA exerted a remarkably positive effect on health-related quality of life in women taking long-term steroids for lupus (chronic steroid therapy can produce powerful depression and reduction in quality of life measures).68 Of particular importance, the DHEA-supplemented groups also reported improvement in sexuality.
Additional research supports an excitatory effect for DHEA on sexuality—especially in women. In one study, sixteen sexually functional postmenopausal women were randomly given either placebo or a single DHEA supplement of 300 mg, 60 minutes before presentation of an erotic video.69 Women in the supplement group showed significantly greater mental and physical sexual arousal during the video than did the control women. The supplemented women also reported a greater increase in positive affect (generally feeling good) compared to placebo recipients.
A 2009 animal study may shed light on some of the physical causes behind these benefits: DHEA applied to the smooth muscle of rabbit clitoris resulted in significant relaxation,70 allowing the increased blood flow and engorgement that results in enhanced sensitivity during sexual arousal.
Favorable Gene Expression for Youthful, Glowing Skin
A growing body of scientific evidence suggests that DHEA has especially favorable effects on skin health and appearance. In a 2000 laboratory study, DHEA was shown to increase production of collagen—the protein that gives youthful skin its suppleness—while decreasing production of the collagenase enzymes that destroy it.71
It wasn’t until 2008, however, that Canadian scientists discovered more than 50 DHEA-responsive genes in the skin of women using a topical DHEA crème.72 DHEA “switched on” multiple collagen-producing genes and reduced expression of genes associated with production and cornification (hardening) of the tough keratinocytes that form calluses and rough skin. The researchers concluded, “DHEA could exert an anti-aging effect in the skin through stimulation of collagen biosynthesis, improved structural organization of the dermis while modulating keratinocyte metabolism.”
Other unexpected benefits of topical DHEA on aging skin are emerging. DHEA treatment increases production of sebum, or skin oil.73 Sebum not only contributes to smooth, supple skin; it also contains myriad antimicrobial components that prevent infection and irritation. Topical DHEA also improves skin “brightness” and counteracts the “papery” appearance of aging skin, combating the epidermal thinning that is a visible hallmark of aging.73 The study authors note that these are “beneficial effects on skin characteristics that are rarely provided by topical treatments.”
In the past few years alone, significant scientific substantiation of DHEA’s anti-aging effects has emerged. Its neuroprotective effects are now recognized as being vital in protecting memory and reducing depressive symptoms in older adults. DHEA enhances bone health by improving mineralization to reduce fracture risk. DHEA modulates immunity in a coordinated fashion, boosting resistance to infection while quelling dangerous inflammation. DHEA supports cardiovascular health and activates genes that prevent cardiovascular risk factors, including diabetes and obesity. DHEA is intimately involved in improving quality of life and bolstering sexual arousal, while dramatically improving the appearance of healthy, youthful skin. As little as 50 mg of DHEA per day may favorably alter gene expression to inhibit multiple factors implicated in metabolic syndrome; boost bone strength; enhance cognitive function and memory; and ward off osteoarthritis. DHEA topical crèmes allow ready application of DHEA to the site of action.
Note: Individuals who have been diagnosed with a hormone-dependent cancer should not supplement with DHEA until their cancer is cured.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
1. Dharia S, Parker CR Jr. Adrenal androgens and aging. Semin Reprod Med. 2004 Nov;22(4):361-8
2. Jo H, Park JS, Kim EM, et al. The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2003 Aug;11(8):585-94.
3. Jankowski CM, Gozansky WS, Schwartz RS, et al. Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial. J Clin Endocrinol Metab. 2006 Aug;91(8):2986-93.
4. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004 Nov 10;292(18):2243-8.
5. Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2006 Nov;188(4):541-51.
6. Ritsner MS, Gibel A, Ratner Y, Tsinovoy G, Strous RD. Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychopharmacol. 2006 Oct;26(5):495-9.
7. Schmidt PJ, Daly RC, Bloch M, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005 Feb;62(2):154-62.
8. Fukai S, Akishita M, Yamada S, et al. Association of plasma sex hormone levels with functional decline in elderly men and women. Geriatr Gerontol Int. 2009 Sep;9(3):282-9.
9. Valenti G, Ferrucci L, Lauretani F, et al. Dehydroepiandosterone and cognitive function in the elderly: The InCHIANTI Study. J Endocrinol Invest. 2009 Oct;32(9):766-72.
10. Davis SR, Shah SM, McKenzie DP, Kulkarni J, Davison SL, Bell RJ. Dehydroepiandrosterone sulfate levels are associated with more favorable cognitive function in women. J Clin Endocrinol Metab. 2008 Mar;93(3):801-8.
11. Ritsner MS, Strous RD. Neurocognitive deficits in schizophrenia are associated with alterations in blood levels of neurosteroids: A multiple regression analysis of findings from a double-blind, randomized, placebo-controlled, crossover trial with DHEA. J Psychiatr Res. 2010 Jan;44(2):75-80.
12. Bazin MA, El Kihel L, Boulouard M, Bouët V, Rault S. The effects of DHEA, 3beta-hydroxy-5alpha-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse. Steroids. 2009 Nov;74(12):931-7.
13. Chen C, Lang S, Zuo P, Yang N, Wang X. Treatment with dehydroepiandrosterone increases peripheral benzodiazepine receptors of mitochondria from cerebral cortex in D-galactose-induced aged rats. Basic Clin Pharmacol Toxicol. 2008 Dec;103(6):493-501.
14. Taha A, Mishra M, Baquer NZ, Sharma D. Na+ K(+)-ATPase activity in response to exogenous dehydroepiandrosterone administration in aging rat brain. Indian J Exp Biol. 2008 Dec;46(12):852-4.
15. de la Torre JC. Pathophysiology of neuronal energy crisis in Alzheimer’s disease. Neurodegener Dis. 2008;5(3-4):126-32.
16. Camus V. Evaluation of the depressive symptomatology in the elderly. Psychol Neuropsychiatr Vieil. 2004 Sep;2 Suppl 1:S13-17.
17. Djernes JK. Prevalence and predictors of depression in populations of elderly: a review. Acta Psychiatr Scand. 2006 May;113(5):372-87.
18. Akinola M, Mendes WB. The dark side of creativity: biological vulnerability and negative emotions lead to greater artistic creativity. Pers Soc Psychol Bull. 2008 Dec;34(12):1677-86.
19. Wang HT, Chen SM, Lee SD, et al. The role of DHEA-S in the mood adjustment against negative competition outcome in golfers. J Sports Sci. 2009 Feb 1;27(3):291-7.
20. Strous RD, Maayan R, Lapidus R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry. 2003 Feb;60(2):133-41.
21. Herbert J. Neurosteroids, brain damage, and mental illness. Exp Gerontol. 1998 Nov-Dec;33(7-8):713-27.
22. Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry. 1999 Jun 15;45(12):1533-41.
23. Strous RD, Maayan R, Kotler M, Weizman A. Hormonal profile effects following dehydroepiandrosterone (DHEA) administration to schizophrenic patients. Clin Neuropharmacol. 2005 Nov-Dec;28(6):265-9.
24. Rabkin JG, McElhiney MC, Rabkin R, McGrath PJ, Ferrando SJ. Placebo-controlled trial of dehydroepiandrosterone (DHEA) for treatment of nonmajor depression in patients with HIV/AIDS. Am J Psychiatry. 2006 Jan;163(1):59-66.
25. Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009 Jan;30(1):65-91.
26. Mo Q, Lu S, Garippa C, Brownstein MJ, Simon NG. Genome-wide analysis of DHEA- and DHT-induced gene expression in mouse hypothalamus and hippocampus. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):135-43.
27. Pinnock SB, Lazic SE, Wong HT, Wong IH, Herbert J. Synergistic effects of dehydroepiandrosterone and fluoxetine on proliferation of progenitor cells in the dentate gyrus of the adult male rat. Neuroscience. 2009 Feb 18;158(4):1644-51.
28. Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4279-84.
29. Jankowski CM, Gozansky WS, Kittelson JM, Van Pelt RE, Schwartz RS, Kohrt WM. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin Endocrinol Metab. 2008 Dec;93(12):4767-73.
30. von Muhlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int. 2008 May;19(5):699-707.
31. Weiss EP, Shah K, Fontana L, Lambert CP, Holloszy JO, Villareal DT. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr. 2009 May;89(5):1459-67.
32. Buford TW, Willoughby DS. Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab. 2008 Jun;33(3):429-33.
33. Kim SK, Shin MS, Jung BK, et al. Effect of dehydroepiandrosterone on lipopolysaccharide-induced interleukin-6 production in DH82 cultured canine macrophage cells. J Reprod Immunol. 2006 Jun;70(1-2):71-81.
34. Nawata H, Yanase T, Goto K, Okabe T, Ashida K. Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Ageing Dev. 2002 Apr 30;123(8):1101-6.
35. Frantz MC, Prix NJ, Wichmann MW, et al. Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors. Crit Care Med. 2005 Aug;33(8):1779-86.
36. Marcu AC, Paccione KE, Barbee RW, et al. Androstenetriol immunomodulation improves survival in a severe trauma hemorrhage shock model. J Trauma. 2007 Sep;63(3):662-9.
37. Oberbeck R, Deckert H, Bangen J, Kobbe P, Schmitz D. Dehydroepiandrosterone: a modulator of cellular immunity and heat shock protein 70 production during polymicrobial sepsis. Intensive Care Med. 2007 Dec;33(12):2207-13.
38. Burdick NC, Dominguez JA, Welsh TH, Jr., Laurenz JC. Oral administration of dehydroepiandrosterone-sulfate (DHEAS) increases in vitro lymphocyte function and improves in vivo response of pigs to immunization against keyhole limpet hemocyanin (KLH) and ovalbumin. Int Immunopharmacol. 2009 Jul 29.
39. Mills SJ, Ashworth JJ, Gilliver SC, Hardman MJ, Ashcroft GS. The sex steroid precursor DHEA accelerates cutaneous wound healing via the estrogen receptors. J Invest Dermatol. 2005 Nov;125(5):1053-62.
40. Romanutti C, Bruttomesso AC, Castilla V, Bisceglia JA, Galagovsky LR, Wachsman MB. In vitro antiviral activity of dehydroepiandrosterone and its synthetic derivatives against vesicular stomatitis virus. Vet J. 2009 Nov;182(2):327-35.
41. Acosta EG, Bruttomesso AC, Bisceglia JA, Wachsman MB, Galagovsky LR, Castilla V. Dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit Junin virus replication in vitro. Virus Res. 2008 Aug;135(2):203-12.
42. Santos CD, Toldo MP, Santello FH, Filipin Mdel V, Brazão V, do Prado Júnior JC. Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi. Vet Parasitol. 2008 May 31;153(3-4):238-43.
43. Brazão V, Santello FH, Caetano LC, Del Vecchio Filipin M, Paula Alonso Toldo M, do Prado JC, Jr. Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats infected with Trypanosoma cruzi. Immunobiology. 2009 Jul 4.
44. Caetano LC, Santello FH, Del Vecchio Filipin M, et al. Trypanosoma cruzi: dehydroepiandrosterone (DHEA) and immune response during the chronic phase of the experimental Chagas’ disease. Vet Parasitol. 2009 Jul 7;163(1-2):27-32.
45. Harding G, Mak YT, Evans B, Cheung J, MacDonald D, Hampson G. The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: potential steroid-sparing role for DHEA. Cytokine. 2006 Oct;36(1-2):57-68.
46. Choi IS, Cui Y, Koh YA, Lee HC, Cho YB, Won YH. Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Korean J Intern Med. 2008 Dec;23(4):176-81.
47. Hansen PA, Han DH, Nolte LA, Chen M, Holloszy JO. DHEA protects against visceral obesity and muscle insulin resistance in rats fed a high-fat diet. Am J Physiol. 1997 Nov;273(5 Pt 2):R1704-1708.
48. Richards RJ, Porter JR, Svec F. Long-term oral administration of dehydroepiandrosterone has different effects on energy intake of young lean and obese male Zucker rats when compared to controls of similar metabolic body size. Diabetes Obes Metab. 1999 Jul;1(4):233-9.
49. Ponholzer A, Madersbacher S, Rauchenwald M, Jungwirth S, Fischer P, Tragl KH. Vascular risk factors and their association to serum androgen levels in a population-based cohort of 75-year-old men over 5 years: results of the VITA study. World J Urol. 2009 Jun 28.
50. Tagliaferro AR, Davis JR, Truchon S, Van Hamont N. Effects of dehydroepiandrosterone acetate on metabolism, body weight and composition of male and female rats. J Nutr. 1986 Oct;116(10):1977-83.
51. Poczatková H, Bogdanová K, Uherková L, et al. Dehydroepiandrosterone effects on the mRNA levels of peroxisome proliferator-activated receptors and their coactivators in human hepatoma HepG2 cells. Gen Physiol Biophys. 2007 Dec;26(4):268-74.
52. Karbowska J, Kochan Z. Effect of DHEA on endocrine functions of adipose tissue, the involvement of PPAR gamma. Biochem Pharmacol. 2005 Jul 15;70(2):249-57.
53. Smith KJ, Skelton HG. Peroxisomal proliferator-activated ligand therapy for HIV lipodystrophy. Clin Exp Dermatol. 2001 Mar;26(2):155-61.
54. Kochan Z, Karbowska J. Dehydroepiandrosterone up-regulates resistin gene expression in white adipose tissue. Mol Cell Endocrinol. 2004 Apr 15;218(1-2):57-64.
55. de Heredia FP, Cerezo D, Zamora S, Garaulet M. Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats. Br J Nutr. 2007 Mar;97(3):464-70.
56. de Heredia FP, Larque E, Zamora S, Garaulet M. Dehydroepiandrosterone modifies rat fatty acid composition of serum and different adipose tissue depots and lowers serum insulin levels. J Endocrinol. 2009 Apr;201(1):67-74.
57. Yorek MA, Coppey LJ, Gellett JS, et al. Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function. Am J Physiol Endocrinol Metab. 2002 Nov;283(5):E1067-1075.
58. Sato K, Iemitsu M, Aizawa K, Ajisaka R. DHEA improves impaired activation of Akt and PKC zeta/lambda-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats. Acta Physiol (Oxf). 2009 Nov;197(3):217-25.
59. Brignardello E, Runzo C, Aragno M, et al. Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients. Diabetes Care. 2007 Nov;30(11):2922-7.
60. Ponikowska B, Jankowska EA, Maj J, et al. Gonadal and adrenal androgen deficiencies as independent predictors of increased cardiovascular mortality in men with type II diabetes mellitus and stable coronary artery disease. Int J Cardiol. 2009 Apr 21.
61. Cappola AR, O’Meara ES, Guo W, Bartz TM, Fried LP, Newman AB. Trajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study. J Gerontol A Biol Sci Med Sci. 2009 Dec;64(12):1268-74.
62. Srinivasan M, Irving BA, Dhatariya K, et al. Effect of dehydroepiandrosterone replacement on lipoprotein profile in hypoadrenal women. J Clin Endocrinol Metab. 2009 Mar;94(3):761-4.
63. Ii M, Hoshiga M, Negoro N, et al. Adrenal androgen dehydroepiandrosterone sulfate inhibits vascular remodeling following arterial injury. Atherosclerosis. 2009 Sep;206(1):77-85.
64. Aragno M, Meineri G, Vercellinatto I, et al. Cardiac impairment in rabbits fed a high-fat diet is counteracted by dehydroepiandrosterone supplementation. Life Sci. 2009 Jul 3;85(1-2):77-84.
65. Mitchell GF. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol. 2008 Nov;105(5):1652-60.
66. Stomati M, Monteleone P, Casarosa E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol. 2000 Oct;14(5):342-63.
67. Brooke AM, Kalingag LA, Miraki-Moud F, et al. Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement. J Clin Endocrinol Metab. 2006 Oct;91(10):3773-9.
68. Nordmark G, Bengtsson C, Larsson A, Karlsson FA, Sturfelt G, Rönnblom L. Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity. 2005 Nov;38(7):531-40.
69. Hackbert L, Heiman JR. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women. J Womens Health Gend Based Med. 2002 Mar;11(2):155-62.
70. Lee SY, Myung SC, Lee MY, et al. The effects of dehydroepiandrosterone (DHEA)/DHEA-sulfate (DHEAS) on the contraction responses of the clitoral cavernous smooth muscle from female rabbits. J Sex Med. 2009 Oct;6(10):2653-60.
71. Lee KS, Oh KY, Kim BC. Effects of dehydroepiandrosterone on collagen and collagenase gene expression by skin fibroblasts in culture. J Dermatol Sci. 2000 Jun;23(2):103-10.
72. Calvo E, Luu-The V, Morissette J, et al. Pangenomic changes induced by DHEA in the skin of postmenopausal women. J Steroid Biochem Mol Biol. 2008 Dec;112(4-5):186-93.