Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review

References

• Labrie F, Belanger A, Pelletier G, et al. Science of intracrinology in postmenopausal women. Menopause 2017;24:702–12
   PubMedGoogle Scholar
• Labrie F, Martel C, Balser J. Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women: role of the ovary?. Menopause 2011;18:30–43
   PubMed Web of Science ®Google Scholar
• Davison SL, Bell R, Donath S, et al. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005;90:3847–53
   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 according to intracrinology. J Steroid Biochem Mol Biol 2017;168:9–18
   PubMed Web of Science ®Google Scholar
• Traish AM, Vignozzi L, Simon JA, et al. Role of androgens in female genitourinary tissue structure and function: implications in the genitourinary syndrome of menopause. Sex Med Rev 2018;6:558-71
   PubMed Web of Science ®Google Scholar
• Davis SR, Davison SL, Donath S, et al. Circulating androgen levels and self-reported sexual function in women. JAMA 2005;294:91–6
   PubMed Web of Science ®Google Scholar
• Guay AT, Jacobson J. Decreased free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) levels in women with decreased libido. J Sex Marital Ther 2002;28 Suppl 1: 129–42
   PubMed Web of Science ®Google Scholar
• Johnston S. Urogenital concerns. J Obstet Gynaecol Can 2006;28:S33–S42
   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;26:1335–43
   PubMed Web of Science ®Google Scholar
• Willhite LA, O'Connell MB. Urogenital atrophy: prevention and treatment. Pharmacotherapy 2001;21:464–80
   PubMed Web of Science ®Google Scholar
• Mac Bride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc 2010;85:87–94
   PubMed Web of Science ®Google Scholar
• Nappi RE, Palacios S. Impact of vulvovaginal atrophy on sexual health and quality of life at postmenopause. Climacteric 2014;17:3–9
   PubMed Web of Science ®Google Scholar
• Meisels A. The menopause: a cytohormonal study. Acta Cytol 1966;10:49–55
   PubMed Web of Science ®Google Scholar
• The North American Menopause Society. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013;20:888–902 quiz 903-4
   PubMed Web of Science ®Google Scholar
• Portman DJ, Gass ML. 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. Climacteric 2014;17:557–63
   PubMed Web of Science ®Google Scholar
• Freedman MA. Perceptions of dyspareunia in postmenopausal women with vulvar and vaginal atrophy: findings from the REVIVE survey. Womens Health (Lond Engl) 2014;10:445–54
   PubMedGoogle Scholar
• Chollet JA. Efficacy and safety of ultra-low-dose Vagifem (10 mcg). Patient Prefer Adherence 2011;5:571–4
   PubMed Web of Science ®Google Scholar
• Erekson EA, Li FY, Martin DK, et al. Vulvovaginal symptoms prevalence in postmenopausal women and relationship to other menopausal symptoms and pelvic floor disorders. Menopause 2016;23:363–75
   Web of Science ®Google Scholar
• Nappi RE, Kokot-Kierepa M. Vaginal Health: Insights, Views & Attitudes (VIVA) – results from an international survey. Climacteric 2012;15:36–44
   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;20:1043–8
   PubMed Web of Science ®Google Scholar
• Kingsberg SA, Wysocki S, Magnus L, et al. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women’s VIews of Treatment Options for Menopausal Vaginal ChangEs) survey. J Sex Med 2013;10:1790–9
   PubMed Web of Science ®Google Scholar
• Nappi RE, Mattsson LA, Lachowsky M, et al. The CLOSER survey: impact of postmenopausal vaginal discomfort on relationships between women and their partners in Northern and Southern Europe. Maturitas 2013;75:373–9
   PubMed Web of Science ®Google Scholar
• Wysocki S, Kingsberg S, Krychman M. Management of vaginal atrophy: implications from the REVIVE Survey. Clin Med Insights Reprod Health 2014;8:23–30
   PubMedGoogle Scholar
• Reiter S. Barriers to effective treatment of vaginal atrophy with local estrogen therapy. Int J Gen Med 2013;6:153–8
   PubMedGoogle Scholar
• Lara LA, Useche B, Ferriani RA, et al. The effects of hypoestrogenism on the vaginal wall: interference with the normal sexual response. J Sex Med 2009;6:30–9
   PubMed Web of Science ®Google Scholar
• Nappi RE, Kokot-Kierepa M. Women’s voices in the menopause: results from an international survey on vaginal atrophy. Maturitas 2010;67:233–8
   PubMed Web of Science ®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;14:413–24
   PubMed Web of Science ®Google Scholar
• Kingsberg SA, Krychman ML. Resistance and barriers to local estrogen therapy in women with atrophic vaginitis. J Sex Med 2013;10:1567–74
   PubMed Web of Science ®Google Scholar
• Edwards D, Panay N. Treating vulvovaginal atrophy/genitourinary syndrome of menopause: how important is vaginal lubricant and moisturizer composition?. Climacteric 2016;19:151–61
   PubMed Web of Science ®Google Scholar
• Eugster-Hausmann M, Waitzinger J, Lehnick D. Minimized estradiol absorption with ultra-low-dose 10 microg 17beta-estradiol vaginal tablets. Climacteric 2010;13:219–27
   PubMed Web of Science ®Google Scholar
• Pickar JH, Amadio JM, Bernick BA, et al. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule. Climacteric 2016;19:181–7
   PubMed Web of Science ®Google Scholar
• Nilsson K, Heimer G. Low-dose oestradiol in the treatment of urogenital oestrogen deficiency-a pharmacokinetic and pharmacodynamic study. Maturitas 1992;15:121–7
   PubMed Web of Science ®Google Scholar
• Shiongi Inc. Osphena (Ospemifene) Tablets. Prescribing Information. Florham Park, NJ; February 2015
   Google Scholar
• Simon JA. The Woman’s Health Initiative and one of many unintended consequences. Menopause 2016;23:1057–9
   PubMed Web of Science ®Google Scholar
• The North American Menopause Society. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 2017;24:728–53
   PubMed Web of Science ®Google Scholar
• United States Food and Drug Administration. 2018 Compounding policy priorities plan. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm592795.htm [last accessed 26 Mar 2018]
   Google Scholar
• United States Food and Drug Administration. Guidance for industry: estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms – recommendations for clinical evaluation. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071643.pdf) [last accessed 6 Dec 2017]; 2003
   Google Scholar
• AMAG Pharmaceuticals. Intrarosa (prasterone) vaginal insert. Prescribing Information. Waltham, MA; April 2017. Available from: http://www.intrarosahcp.com/wp-content/uploads/2017/07/INTRAROSA-PI-7-2017.pdf [last accessed 17 April 2018]; 2017
   Google Scholar
• Traish AM, Kang HP, Saad F, et al. Dehydroepiandrosterone (DHEA)-a precursor steroid or an active hormone in human physiology. J Sex Med 2011;8:2960–82; quiz 2983
   PubMed Web of Science ®Google Scholar
• Crawford S, Santoro N, Laughlin GA, et al. Circulating dehydroepiandrosterone sulfate concentrations during the menopausal transition. J Clin Endocrinol Metab 2009;94:2945–51
   PubMed Web of Science ®Google Scholar
• Belanger A, Pelletier G, Labrie F, et al. Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab 2003;14:473–9
   PubMed Web of Science ®Google Scholar
• Berman JR, Almeida FG, Jolin J, et al. Correlation of androgen receptors, aromatase, and 5-alpha reductase in the human vagina with menopausal status. Fertil Steril 2003;79:925–31
   PubMed Web of Science ®Google Scholar
• Bertin J, Dury AY, Ouellet J, et al. Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction. J Sex Med 2014;11:1949–61
   PubMed Web of Science ®Google Scholar
• Kennedy TG, Armstrong DT. Induction of vaginal mucification in rats with testosterone and 17beta-hydroxy-5alpha-androstan-3-one. Steroids 1976;27:423–30
   PubMed Web of Science ®Google Scholar
• Berger L, El-Alfy M, Martel C, et al. Effects of dehydroepiandrosterone, Premarin and Acolbifene on histomorphology and sex steroid receptors in the rat vagina. J Steroid Biochem Mol Biol 2005;96:201–15
   PubMed Web of Science ®Google Scholar
• Sourla A, Flamand M, Belanger A, et al. Effect of dehydroepiandrosterone on vaginal and uterine histomorphology in the rat. J Steroid Biochem Mol Biol 1998;66:137–49
   PubMed Web of Science ®Google Scholar
• 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;109:67–80
   PubMed Web of Science ®Google Scholar
• Mayo Clinic: Mayo Medical Laboratories. Test Definition: ESTF: Estrogens, Estrone (E1) and Estradiol (E2), Fractionated, Serum https://www.mayomedicallaboratories.com/test-catalog/Clinical%-C2%B1and%C2%B1Interpretive/84230 [last accessed 13 Mar 2018]; 2017
   Google Scholar
• Labrie F, Cusan L, Gomez JL, et al. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol 2008;111:178–94
   PubMed Web of Science ®Google Scholar
• Nakamoto J. Endocrine testing. In: Jameson JL, De Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric (Seventh Edition) [Internet]. Philadelphia: Elsevier Saunders; 2016: 2655–2688e1. Available from: https://www.sciencedirect.com/science/article/pii/B9780323189071010015
   Google Scholar
• Labrie F, Martel C, Bérube R, et al. Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol 2013;138:359–67
   PubMed Web of Science ®Google Scholar
• Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause 2009;16:897–906
   PubMed Web of Science ®Google Scholar
• Bouchard C, Labrie F, Archer DF, et al. Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy. Climacteric 2015;18:590–607
   PubMed Web of Science ®Google Scholar
• Archer DF, Labrie F, Bouchard C, et al. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause 2015;22:950–63
   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;23:243–56
   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 estrogens and 10μg estradiol on symptoms of vulvovaginal atrophy. J Steroid Biochem Mol Biol 2017;174:1–8
   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;81:46–56
   PubMed Web of Science ®Google Scholar
• Ke Y, Gonthier R, Simard JN, et al. Serum steroids remain within the same normal postmenopausal values during 12-month intravaginal 0.50% DHEA. Horm Mol Biol Clin Investig 2015;24:117–29
   PubMed Web of Science ®Google Scholar
• Nakamoto J, editor. Part 16 Endocrine Testing. Philadelphia, PA: Elsevier Saunders; 2016
   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;22:1289–95
   PubMed Web of Science ®Google Scholar
• Krychman M, Graham S, Bernick B, et al. The women’s EMPOWER survey: women’s knowledge and awareness of treatment options for vulvar and vaginal atrophy remains inadequate. J Sex Med 2017;14:425–33
   PubMed Web of Science ®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;25:837–47
   PubMed Web of Science ®Google Scholar