Effect of DHEA on Skin Aging in Postmenopausal Women

Summary

The purpose of the study is to determine the response of skin parameters related to skin aging to the local action of DHEA in postmenopausal women.

Timeline

Start

2004-11-01

Primary completion

2005-11-24

Completion

2008-11-13

Publications

• Background Baulieu EE, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Faucounau V, Girard L, Hervy MP, Latour F, Leaud MC, Mokrane A, Pitti-Ferrandi H, Trivalle C, de Lacharriere O, Nouveau S, Rakoto-Arison B, Souberbielle JC, Raison J, Le Bouc Y, Raynaud A, Girerd X, Forette F. 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. doi: 10.1073/pnas.97.8.4279.
• Background Bardon S, Vignon F, Chalbos D, Rochefort H. RU486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via the progesterone receptor. J Clin Endocrinol Metab. 1985 Apr;60(4):692-7. doi: 10.1210/jcem-60-4-692.
• Background Belanger A, Candas B, Dupont A, Cusan L, Diamond P, Gomez JL, Labrie F. Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. J Clin Endocrinol Metab. 1994 Oct;79(4):1086-90. doi: 10.1210/jcem.79.4.7962278.
• Background Benz DJ, Haussler MR, Thomas MA, Speelman B, Komm BS. High-affinity androgen binding and androgenic regulation of alpha 1(I)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells. Endocrinology. 1991 Jun;128(6):2723-30. doi: 10.1210/endo-128-6-2723.
• Background Burger HG, Hailes J, Menelaus M, Nelson J, Hudson B, Balazs N. The management of persistent menopausal symptoms with oestradiol-testosterone implants: clinical, lipid and hormonal results. Maturitas. 1984 Dec;6(4):351-8. doi: 10.1016/0378-5122(84)90008-2.
• Background Casson PR, Andersen RN, Herrod HG, Stentz FB, Straughn AB, Abraham GE, Buster JE. Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women. Am J Obstet Gynecol. 1993 Dec;169(6):1536-9. doi: 10.1016/0002-9378(93)90431-h.
• Background Chesnut CH 3rd, Ivey JL, Gruber HE, Matthews M, Nelp WB, Sisom K, Baylink DJ. Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action. Metabolism. 1983 Jun;32(6):571-80. doi: 10.1016/0026-0495(83)90027-6.
• Background Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, Hennekens C, Rosner B, Speizer FE. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995 Jun 15;332(24):1589-93. doi: 10.1056/NEJM199506153322401.
• Background Coleman DL, Leiter EH, Schwizer RW. Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. Diabetes. 1982 Sep;31(9):830-3. doi: 10.2337/diab.31.9.830.
• Background Davis SR, McCloud P, Strauss BJ, Burger H. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Maturitas. 1995 Apr;21(3):227-36. doi: 10.1016/0378-5122(94)00898-h.
• Background DeFazio J, Meldrum DR, Winer JH, Judd HL. Direct action of androgen on hot flushes in the human male. Maturitas. 1984 Jul;6(1):3-8. doi: 10.1016/0378-5122(84)90060-4.
• Background Diamond P, Cusan L, Gomez JL, Belanger A, Labrie F. Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. J Endocrinol. 1996 Sep;150 Suppl:S43-50.
• Background El-Alfy M, Luu-The V, Huang XF, Berger L, Labrie F, Pelletier G. Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry. Endocrinology. 1999 Mar;140(3):1481-91. doi: 10.1210/endo.140.3.6585.
• Background El-Alfy M, Pelletier G, Hermo LS, Labrie F. Unique features of the basal cells of human prostate epithelium. Microsc Res Tech. 2000 Dec 1;51(5):436-46. doi: 10.1002/1097-0029(20001201)51:53.0.CO;2-T.
• Background Gordon GB, Shantz LM, Talalay P. Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone. Adv Enzyme Regul. 1987;26:355-82. doi: 10.1016/0065-2571(87)90023-9.
• Background Grodin JM, Siiteri PK, MacDonald PC. Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab. 1973 Feb;36(2):207-14. doi: 10.1210/jcem-36-2-207. No abstract available.
• Background Henderson E, Yang JY, Schwartz A. Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication. AIDS Res Hum Retroviruses. 1992 May;8(5):625-31. doi: 10.1089/aid.1992.8.625.
• Background HENNEMAN PH, WALLACH S. A review of the prolonged use of estrogens and androgens in postmenopausal and senile osteoporosis. AMA Arch Intern Med. 1957 Nov;100(5):715-23. doi: 10.1001/archinte.1957.00260110031005. No abstract available.
• Background Johnston CC Jr, Epstein S. Clinical, biochemical, radiographic, epidemiologic, and economic features of osteoporosis. Orthop Clin North Am. 1981 Jul;12(3):559-69.
• Background Johnston CC Jr, Hui SL, Witt RM, Appledorn R, Baker RS, Longcope C. Early menopausal changes in bone mass and sex steroids. J Clin Endocrinol Metab. 1985 Nov;61(5):905-11. doi: 10.1210/jcem-61-5-905.
• Background Kapur SP, Reddi AH. Influence of testosterone and dihydrotestosterone on bone-matrix induced endochondral bone formation. Calcif Tissue Int. 1989 Feb;44(2):108-13. doi: 10.1007/BF02556469.
• Background Labrie C, Belanger A, Labrie F. Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate. Endocrinology. 1988 Sep;123(3):1412-7. doi: 10.1210/endo-123-3-1412.
• Background Labrie F. Intracrinology. Mol Cell Endocrinol. 1991 Jul;78(3):C113-8. doi: 10.1016/0303-7207(91)90116-a.
• Background Labrie F, Belanger A, Cusan L, Candas B. Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology. J Clin Endocrinol Metab. 1997 Aug;82(8):2403-9. doi: 10.1210/jcem.82.8.4161.
• Background Labrie F, Belanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab. 1997 Aug;82(8):2396-402. doi: 10.1210/jcem.82.8.4160.
• Background Labrie F, Belanger A, Simard J, Van Luu-The, Labrie C. DHEA and peripheral androgen and estrogen formation: intracinology. Ann N Y Acad Sci. 1995 Dec 29;774:16-28. doi: 10.1111/j.1749-6632.1995.tb17369.x. No abstract available.
• Background Labrie F, Diamond P, Cusan L, Gomez JL, Belanger A, Candas B. Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab. 1997 Oct;82(10):3498-505. doi: 10.1210/jcem.82.10.4306.
• Background Labrie F, Luu-The V, Labrie C, Belanger A, Simard J, Lin SX, Pelletier G. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev. 2003 Apr;24(2):152-82. doi: 10.1210/er.2001-0031.
• Background Labrie F, Luu-The V, Lin SX, Labrie C, Simard J, Breton R, Belanger A. The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology. Steroids. 1997 Jan;62(1):148-58. doi: 10.1016/s0039-128x(96)00174-2.
• Background Labrie F, Luu-The V, Lin SX, Simard J, Labrie C. Role of 17 beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues. Trends Endocrinol Metab. 2000 Dec;11(10):421-7. doi: 10.1016/s1043-2760(00)00342-8.
• Background Labrie F, Simard J, Luu-The V, Bélanger A, Pelletier G, Morel Y, Mebarki F, Sanchez R, Durocher F, Turgeon C, Labrie Y, Rhéaume E, Labrie C, Lachance Y. The 3b-hydroxysteroid dehydrogenase/isomerase gene family: lessons from type II 3b-HSD congenital deficiency. In: Signal Transduction in Testicular Cells. Ernst Schering Research Foundation Workshop. Hansson V, Levy FO, Taskén K (eds), Berlin, Heidelberg, New York, Springer-Verlag, Vol. Suppl. 2: pp. 185-218, 1996.
• Background Leiblum S, Bachmann G, Kemmann E, Colburn D, Swartzman L. Vaginal atrophy in the postmenopausal woman. The importance of sexual activity and hormones. JAMA. 1983 Apr 22-29;249(16):2195-8.
• Background Li S, Yan X, Belanger A, Labrie F. Prevention by dehydroepiandrosterone of the development of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene (DMBA) in the rat. Breast Cancer Res Treat. 1994 Feb;29(2):203-17. doi: 10.1007/BF00665681.
• Background MacEwen EG, Kurzman ID. Obesity in the dog: role of the adrenal steroid dehydroepiandrosterone (DHEA). J Nutr. 1991 Nov;121(11 Suppl):S51-5. doi: 10.1093/jn/121.suppl_11.S51.
• Background Mazess RB. On aging bone loss. Clin Orthop Relat Res. 1982 May;(165):239-52.
• Background MIGEON CJ, KELLER AR, LAWRENCE B, SHEPARD TH 2nd. Dehydroepiandrosterone and androsterone levels in human plasma: effect of age and sex; day-to-day and diurnal variations. J Clin Endocrinol Metab. 1957 Sep;17(9):1051-62. doi: 10.1210/jcem-17-9-1051. No abstract available.
• Background Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. 1994 Jun;78(6):1360-7. doi: 10.1210/jcem.78.6.7515387.
• Background Need AG, Horowitz M, Bridges A, Morris HA, Nordin BE. Effects of nandrolone decanoate and antiresorptive therapy on vertebral density in osteoporotic postmenopausal women. Arch Intern Med. 1989 Jan;149(1):57-60.
• Background Nestler JE, Barlascini CO, Clore JN, Blackard WG. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab. 1988 Jan;66(1):57-61. doi: 10.1210/jcem-66-1-57.
• Background Notelovitz M, Watts N, Timmons C, Addison A, Wiita B, Downey L. Effects of estrogen plus low dose androgen vs estrogen alone on menopausal symptoms in oophorectomized/hysterectomized. North Am. Menopause Soc., Montreal 1991, 101.
• Background Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984 Sep;59(3):551-5. doi: 10.1210/jcem-59-3-551.
• Background Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet. 1985 Aug 17;2(8451):373-7. doi: 10.1016/s0140-6736(85)92506-1.
• Background Rasmussen KR, Arrowood MJ, Healey MC. Effectiveness of dehydroepiandrosterone in reduction of cryptosporidial activity in immunosuppressed rats. Antimicrob Agents Chemother. 1992 Jan;36(1):220-2. doi: 10.1128/AAC.36.1.220.
• Background Riggs BL, Wahner HW, Dunn WL, Mazess RB, Offord KP, Melton LJ 3rd. Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981 Feb;67(2):328-35. doi: 10.1172/JCI110039.
• Background Savvas M, Studd JW, Fogelman I, Dooley M, Montgomery J, Murby B. Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women. BMJ. 1988 Jul 30;297(6644):331-3. doi: 10.1136/bmj.297.6644.331.
• Background Schriock ED, Buffington CK, Hubert GD, Kurtz BR, Kitabchi AE, Buster JE, Givens JR. Divergent correlations of circulating dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding. J Clin Endocrinol Metab. 1988 Jun;66(6):1329-31. doi: 10.1210/jcem-66-6-1329.
• Background Schwartz AG, Pashko L, Whitcomb JM. Inhibition of tumor development by dehydroepiandrosterone and related steroids. Toxicol Pathol. 1986;14(3):357-62. doi: 10.1177/019262338601400312.
• Background Sherwin BB. Affective changes with estrogen and androgen replacement therapy in surgically menopausal women. J Affect Disord. 1988 Mar-Apr;14(2):177-87. doi: 10.1016/0165-0327(88)90061-4.
• Background Sherwin BB, Gelfand MM. Effects of parenteral administration of estrogen and androgen on plasma hormone levels and hot flushes in the surgical menopause. Am J Obstet Gynecol. 1984 Mar 1;148(5):552-7. doi: 10.1016/0002-9378(84)90746-4.
• Background Sherwin BB, Gelfand MM. Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause. Am J Obstet Gynecol. 1985 Jan 15;151(2):153-60. doi: 10.1016/0002-9378(85)90001-8.
• Background Sherwin BB, Gelfand MM. The role of androgen in the maintenance of sexual functioning in oophorectomized women. Psychosom Med. 1987 Jul-Aug;49(4):397-409. doi: 10.1097/00006842-198707000-00009.
• Background Sourla A, Richard V, Labrie F, Labrie C. Exclusive androgenic effect of dehydroepiandrosterone in sebaceous glands of rat skin. J Endocrinol. 2000 Aug;166(2):455-62. doi: 10.1677/joe.0.1660455.
• Background Steinberg KK, Freni-Titulaer LW, DePuey EG, Miller DT, Sgoutas DS, Coralli CH, Phillips DL, Rogers TN, Clark RV. Sex steroids and bone density in premenopausal and perimenopausal women. J Clin Endocrinol Metab. 1989 Sep;69(3):533-9. doi: 10.1210/jcem-69-3-533.
• Background Studd J W, Collins W P, Chakravarti S, Newton J R, Oram D, Parsons A. Estradiol and testosterone implants in treatment of psochosexual problems in postmenopausal women. Br. J. Obstet. Gynecol. 84: 314-315, 1987.
• Background Suzuki T, Suzuki N, Daynes RA, Engleman EG. Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin Immunol Immunopathol. 1991 Nov;61(2 Pt 1):202-11. doi: 10.1016/s0090-1229(05)80024-8.
• Background Tchernof A, Despres JP, Belanger A, Dupont A, Prud'homme D, Moorjani S, Lupien PJ, Labrie F. Reduced testosterone and adrenal C19 steroid levels in obese men. Metabolism. 1995 Apr;44(4):513-9. doi: 10.1016/0026-0495(95)90060-8.
• Background Vermeulen A, Deslypere JP, Schelfhout W, Verdonck L, Rubens R. Adrenocortical function in old age: response to acute adrenocorticotropin stimulation. J Clin Endocrinol Metab. 1982 Jan;54(1):187-91. doi: 10.1210/jcem-54-1-187.
• Background Vermeulen A, Verdonck L. Radioimmunoassay of 17beta-hydroxy-5alpha-androstan-3-one, 4-androstene-3,17-dione, dehydroepiandrosterone, 17-hydroxyprogesterone and progesterone and its application to the human male plasma. J Steroid Biochem. 1976 Jan;7(1):1-10. doi: 10.1016/0022-4731(76)90156-4. No abstract available.
• Background Zumoff B, Strain GW, Miller LK, Rosner W. Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab. 1995 Apr;80(4):1429-30. doi: 10.1210/jcem.80.4.7714119.
• Results Labrie F, Cusan L, Gomez JL, Martel C, Berube R, Belanger P, Chaussade V, Deloche C, Leclaire J. Changes in serum DHEA and eleven of its metabolites during 12-month percutaneous administration of DHEA. J Steroid Biochem Mol Biol. 2008 May;110(1-2):1-9. doi: 10.1016/j.jsbmb.2008.02.003. Epub 2008 Feb 14.

Drugs

Indications