Uncover the significance of adrenal dehydroepiandrosterone (DHEA)

DHEA becomes a source of estrogens and androgens after menopause via steroidogenesis10

After menopause, all estrogens and androgens are made locally from DHEA in peripheral tissues10

Premenopause

KEY: ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; DHT = dihydrotestosterone; E2 = estradiol; LH = luteinizing hormone; GnRH = gonadotropin-releasing hormone

Reproduced from Labrie. 2010.10

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Before menopause, in addition to estrogens secreted by the ovary, DHEA is secreted by the adrenal glands and converted into androgens and/or estrogens10

Postmenopause

KEY: ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; DHT = dihydrotestosterone; E2 = estradiol; GnRH = gonadotropin-releasing hormone

After menopause, since the ovaries stop producing estrogens, the adrenals are the primary source of DHEA for the local formation of estrogens and androgens in the vagina.10

.

Effect of DHEA on vaginal wall tissues

Estrogens and androgens, made locally from adrenal DHEA, are active in all three layers of the vagina9

Preclinical data demonstrated their activities in a mammalian model9,19

  • Induced mucification of the epithelium (first layer) or superficial layer of the vaginal mucosa10
  • Increased density of collagen fibers in the second layer (lamina propria): major component of the vaginal wall9,10
  • Stimulated muscular third layer10
  • Increased estrogen receptor alpha in lamina propria and muscularis19
  • Increased vaginal weight9
  • Enhanced nerve sensitivity via androgenic action of DHEA9

Marked decline in DHEA during aging10,20

Decreasing DHEA decreases local androgen and estrogen production in tissues with cell-specific STEROIDOGENIC enzymes10

Reproduced from Labrie. 2010.10

  • Maximal values of DHEA are present at the age of 3010
  • At menopause, DHEA has decreased by an average of 60% along with androgens and estrogens10

Reduced DHEA levels are often insufficient to maintain the vaginal wall epithelium—and can contribute to dyspareunia.18

Learn how postmenopausal dyspareunia affects sexual health

References

1. Nappi RE, Kingsberg S, Maamari R, Simon J. The CLOSER (CLarifying Vaginal Atrophy’s Impact On Sex and Relationships) survey: implications of vaginal discomfort in postmenopausal women and in male partners. J Sex Med. 2013;10(9):2232-2241. 2. Berger L, El-Alfy M, Martel C, Labrie F. Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and sex steroid receptors in the rat vagina. J Steroid Biochem Mol Biol. 2005;96(2):201-215. 3. Goldstein I, Dicks B, Kim NN, Hartzell R. Multidisciplinary overview of vaginal atrophy and associated genitourinary symptoms in postmenopausal women. Sex Med. 2013;1(2):44-53. 4. Goldstein I. Female sexual function and dysfunction. In: Raz S, Rodriguez L, eds. Female Urology. 3rd ed. Philaelphia, PA: Saundes Elsevier;2008:505-524. 5. Goldstein I. Recognizing and treating urogenital atrophy in postmenopausal women. J Womens Health (Larchmt). 2010;19(3):425-432. 6. Jannini EA, d’Amanti G, Lenzi A. Histology and immunohistochemical studies of female genital tissue. In: Goldstein I, Meston CM, Davis S, Traish A, eds. Women’s Sexual Function and Dysfunction: Study, Diagnosis, and Treatment. Boca Raton, FL: CRC Press;2005:125-133. 7. Mac Bride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc. 2010;85(1):87-94. 8. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013;20(9):888-902. 9. Labrie F, Martel C, Pelletier G. Is vulvovaginal atrophy due to a lack of both estrogens and androgens? Menopause. 2017;24(4):452-461. 10. Labrie F. DHEA after menopause: sole source of sex steroids and potential sex steroid deficiency treatment. Menopause Manag. 2010;19:14-24. 11. Castelo-Branco C, Cancelo MJ, Villero J, Nohales F, Juliá MD. Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas. 2005;52(Suppl 1):S46-S52. 12. Wysocki S, Kingsberg S, Krychman M. Management of vaginal atrophy: implications from the REVIVE Survey. Clin Med Insights Reprod Health. 2014;8:23-30. 13. Semmelink HJ, de Wilde PC, van Houwelingen JC, Vooijs GP. Histomorphometric study of the lower urogenital tract in pre- and post-menopausal women. Cytometry. 1990;11(6):700-707. 14. Sturdee DW, Panay N; International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010;13(6):509-522. 15. American College of Obstetricians and Gynecologists Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin No. 119: Female sexual dysfunction. Obstet Gynecol. 2011;117(4):996-1007. Reaffirmed 2015. 16. Labrie F, Bélanger A, Pelletier G, Martel C, Archer DF, Utian WH. Science of intracrinology in postmenopausal women. Menopause. 2017 Jan 16. doi: 10.1097/GME.0000000000000808. 17. Archer DF, Labrie F, Bouchard C, et al; VVA Prasterone Group. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause. 2015;22(9):950-963. 18. Labrie F, Archer DF, Koltun W, et al; VVA Prasterone Research Group. 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. 19. Berger L, El-Alfy M, Labrie F. Effects of intravaginal dehydroepiandrosterone on vaginal histomorphology, sex steroid receptor expression and cell proliferation in the rat. J Steroid Biochem Mol Biol. 2008;109(1-2):67-80. 20. Labrie F, Luu-The V, Labrie C, Simard J. DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology. Front Neuroendocrinol. 2001;22(3):185-212. 21. Portman DJ, Gass ML; Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Maturitas. 2014;79(3):349-354. 22. Galinsky AM, Waite LJ. Sexual activity and psychological health as mediators of the relationship between physical health and marital quality. J Gerontol B Psychol Sci Soc Sci. 2014;69(3):482-492.