An overview of dehydroepiandrosterone (EM-760) as a treatment option for genitourinary syndrome of menopause

References

• Portman DJ, Goldstein SR, Kagan R. The treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review. Climacteric. 2019;21(1):65–72.
   Google Scholar
• Simon JA, Goldstein I, Kim NN, et al. The role of androgens in the treatment of genitourinary syndrome of menopause (GSM): International Society for the Study of Women’s Sexual Health (ISSWSH) expert consensus panel review. Menopause. 2018;25(7). DOI:10.1097/GME.0000000000001138.
   Web of Science ®Google Scholar
• Gandhi J, Chen A, Dagur G, et al. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016;215:704–711.
   PubMed Web of Science ®Google Scholar
• Traish AM, Vignozzi L, Simon JA, et al. Role of androgens in the genitourinary structure and function: implications in the genitourinary syndrome of menopause (GSM). Sex Med Rev. 2018;6:558–571.
   PubMed Web of Science ®Google Scholar
• Simon JA, Kokot-Kierepa M, Goldstein J, et al. Vaginal health in the United States: results from the vaginal health: insights, views & attitudes survey. Menopause. 2013;20:1043–1048.
   PubMed Web of Science ®Google Scholar
• DiBonaventura M, Luo X, Moffatt M, et al. The association between vulvovaginal atrophy symptoms and quality of life among postmenopausal women in the United States and western Europe. J Womens Health (Larchmt). 2015;24:713–722.
   PubMed Web of Science ®Google Scholar
• 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. Menopause. 2014;21:1063–1068.
   PubMed Web of Science ®Google Scholar
• World 2020 Website, 2017. [cited 2017 Aug 24]. Available from https://www.populationpyramid.net/world/2020
   Google Scholar
• Kingsberg SA, Krychman M, Graham S, et al. The women’s EMPOWER survey: identifying women’s perceptions on vulvar and vaginal atrophy and its treatment. J Sex Med. 2017;14:413–424.
   PubMed Web of Science ®Google Scholar
• Barlow DH, Cardozo LD, Francis RM, et al. Urogenital aging and its effect on sexual health in older British women. J Obstet Gynaecol. 1997;104:87–91.
   Google Scholar
• Barlow D, Samsioe G, van Geelen JM. A study of European women’s experience of the problems of urogenital ageing and its management. Maturitas. 1997;27:239–247.
   PubMed Web of Science ®Google Scholar
• Kyvernitakis I, Kostev K, Hars O, et al. Discontinuation rates of menopausal hormone therapy among postmenopausal women in the post-WHI study era. Climacteric. 2015;18:737–742.
   PubMed Web of Science ®Google Scholar
• Kyvernitakis I, Kostev K, Hars O, et al. Persistency with estrogen replacement therapy among hysterectomized women after the Women’s Health Initiative study. Climacteric. 2015;18:826–834.
   PubMed Web of Science ®Google Scholar
• Portman D, Shulman L, Yeaw J, et al. One-year treatment persistence with local estrogen therapy in postmenopausal women diagnosed as having vaginal atrophy. Menopause. 2015;22:1197–1203.
   PubMed Web of Science ®Google Scholar
• Rahn D, Ward RM, Sanses TV, et al. Society of gynecologic surgeons systematic review group. Vaginal estrogen use in postmenopausal women with pelvic floor disorders: systematic review and practice guidelines. Int Urogynecol J. 2015;26:3–13.
   PubMed Web of Science ®Google Scholar
• Anonymous. To combat the annoying symptoms of the menopause. N Y Med J. 1910;91:756.
   Google Scholar
• Bachmann G, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002;77(4):660–665.
   PubMed Web of Science ®Google Scholar
• Borell M. Organotherapy and the emergence of reproductive endocrinology. J Hist Biol. 1985;18:1–30.
   PubMed Web of Science ®Google Scholar
• Labrie F, Martel C, Belanger A, et al. Androgens in women are essentially made from DHEA in each peripheral tissue. J Steroid Biochem Mol Biol. 2017;168:9–18.
   PubMed Web of Science ®Google Scholar
• Bienenfeld A, Azarchi S, Lo Sicco K, et al. Androgens in Women: androgen mediated skin disease and patient evaluation (Part I). J Am Acad Dermatol. 2018. DOI:10.1016/j.jaad.2018.08.062.
   Web of Science ®Google Scholar
• Beato M, Sanchez-Pacheco A. Interaction of steroid hormone receptors with transcription initiation complex. Endocr Rev. 1996;17(6):587–609.
   PubMed Web of Science ®Google Scholar
• Nallasamy S, Yoshida K, Atkins M, et al. Steroid hormones are key modulators of tissue mechanical function via regulation of collagen and elastic fibers. Endocrinology. 2017;158(4):950–962.
   PubMed Web of Science ®Google Scholar
• Labrie F, Belanger A, Luu-The V, et al. DHEA and the intracrine formation of androgens and estrogen’s in peripheral target tissues: its role during aging. Steroids. 1998;63(5–6):322–328.
   PubMed Web of Science ®Google Scholar
• Webb SJ, Geoghegal TE, Prough RA, et al. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab Rev. 2006;38(12):89–116.
   PubMedGoogle Scholar
• Labrie F, Bélanger A, Cusan L, et al. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab. 1997;82:2396–2402.
   PubMed Web of Science ®Google Scholar
• Orentreich N, Brind JL, Rizer RL, et al. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984;59:551–555.
   PubMed Web of Science ®Google Scholar
• Labrie F, Bélanger A, Bélanger P, et al. Androgen glucuronides instead of testosterone, as the new markers of androgenic activity in women. J Steroid Biochem Mol Biol. 2006;99:182–188.
   PubMed Web of Science ®Google Scholar
• Simuniae V. Local estrogen treatment in patients with urogenital complaints. Int J Gynaecol Obstet. 2003;82:187–197.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP) Assessment Report Intrarosa. 2017. [cited 2019 Dec 17]. Retrieved from https://www.ema.europa.eu/en/documents/assessment-report/intrarosa-epar-public-assessment-report_en.pdf
   Google Scholar
• Intrarosa, DHEA intravaginal (prasterone, intravaginal) dosing, indications, interactions, adverse effects, and more. Published March 12, 2018. [ cited May 25, 2019]. https://reference.medscape.com/drug/intrarosa-dhea-intravaginal-prasterone-intravaginal-1000137#5
   Google Scholar
• Archer DF, Labrie F, Bouchard C, et al. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause. 2015;22(9):950–963.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Labrie F, Archer DF, Bouchard C, et al. Prasterone has parallel beneficial effects on the main symptoms of vulvovaginal atrophy: 52-week open-label study. Maturitas. 2015;81(1):46–56.
   PubMed Web of Science ®Google Scholar
• Archer DF, Labrie F, Montesino M, et al. Comparison of intravaginal 6.5Mg (0.50%) prasterone, 0.3Mg conjugated oestrogens and 10 mcg estradiol on symptoms of vulvovaginal atrophy. J Steroid Biochem Mol Biol. 2017;174:1–8.
   PubMed Web of Science ®Google Scholar
• Sauer U, Talaulikar V, Davies MC. Efficacy of intravaginal dehydroepiandrosterone (DHEA) for symptomatic women in the peri- or postmenopausal phase. Maturitas. 2018;116:79–82.
   PubMed Web of Science ®Google Scholar
• Labrie F, Archer DF, Bouchard C, et al. Intravaginal dehydroepiandrosterone (prasterone), a highly effective treatment of dyspareunia. Climacteric. 2011;14:282–288.
   PubMed Web of Science ®Google Scholar
• Labrie F, Archer DF, Martel C, et al. Combined data of intravaginal prasterone against vulvovaginal atrophy of menopause. Menopause. 2017;24(11):1246–1256.
   PubMed Web of Science ®Google Scholar
• Bouchard C, Labrie F, Derogatis L, et al. Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study. Horm Mol Biol Clin Investig. 2016;25(3):181–190.
   PubMed Web of Science ®Google Scholar
• Labrie F, Archer DF, Bouchard C, et al. Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women. J Sex Med. 2014;11:1766–1785.
   PubMed Web of Science ®Google Scholar
• Portman DJ, Labrie F, Archer DF, et al. Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Menopause. 2015;22:1289–1295.
   PubMed Web of Science ®Google Scholar
• Chin SN, Trinkaus M, Simmons C, et al. Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer. Clin Breast Cancer. 2009;9(2):108–117. Epub 05/ 13/2009.
   PubMed Web of Science ®Google Scholar
• Baumgart J, Nilsson K, Evers AS, et al. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause. 2013;20(2):162–168.
   PubMed Web of Science ®Google Scholar
• Alliance for Clinical Trials in Oncology, National Cancer Institute, Mayo Clinic. Prasterone (Dehydroepiandrosterone) in treating postmenopausal cancer survivors with vaginal symptoms. ClinicalTrials.Gov. https://clinicaltrials.gov/ct2/show/results/NCT01376349
   Google Scholar
• EndoCeutics, Inc., AMAG Pharmaceuticals, Inc. Effect of intravaginal prasterone on symptoms of VVA in women under treatment with an aromatase inhibitor for breast cancer. https://clinicaltrials.gov/ct2/show/NCT03740945
   Google Scholar
• Naumova I, Castelo-Branco C. Current treatment options for postmenopausal vaginal atrophy. Int J Women’s Health. 2018;10:387–395.
   PubMed Web of Science ®Google Scholar
• Constantine G, Graham S, Portman DJ. Female sexual function improved with ospemifene in post-menopausal women with vulvar and vaginal atrophy: results of a randomized, placebo-controlled trial. Climacteric. 2015;18:226–232. [Osphena]
   PubMed Web of Science ®Google Scholar
• Goldstein AT, Pukall C, Brown C, et al. Vulvodynia: assessment and Treatment. J Sex Med. 2016;13(4):572–590.
   PubMed Web of Science ®Google Scholar
• Simon J, Altomare C, Sort S, et al. Overall safety of ospemifene in postmenopausal women from placebo-controlled phase 2 and 3 trials. J Women’s Health. 2018;24(1):14–23.
   Google Scholar
• Fought BM, Soulban G, Year J, et al. Ospemifene versus local estrogen: adherence and costs in postmenopausal dyspareunia. J Comp Off Res. 2019;8:1111–1123. Epub 2019 Aug 21.
   Google Scholar
• Barton DL, Shuster LT, Dockter T, et al. Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance). Support Care Cancer. 2018;26(4):1335–1343.
   PubMed Web of Science ®Google Scholar