Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone)

Menopause

Volumn 22, Issue 9, 2015, Pages 950-963

  Archer, David F ^a   Labrie, Fernand ^b   Bouchard, Céline ^c   Portman, David J ^d   Koltun, William ^e   Cusan, Leonello ^b   Labrie, Claude ^b   Côté, Isabelle ^b   Lavoie, Lyne ^b   Martel, Céline ^b   Balser, John ^f  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

^b Endoceutics Inc   (Canada)

^c Clinique de Recherche en Sante des Femmes   (Canada)

^d Columbus Center for Women's Health Research ^*  (United States)

^e Medical Center for Clinical Research   (United States)

^f Veristat Inc   (United States)

Author keywords

Dehydroepiandrosterone; Dryness; Dyspareunia; Intracrinology; Menopause; Prasterone; Vulvovaginal atrophy

Indexed keywords

PLACEBO; PRASTERONE; STEROID;

ADULT; AGED; ARTICLE; BOTHERSOMENESS; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DYSPAREUNIA; FEMALE; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MENOPAUSE; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; POSTMENOPAUSE; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; STEROID BLOOD LEVEL; THICKNESS; TREATMENT DURATION; VAGINA ATROPHY; VAGINA PH; VAGINAL DRYNESS; VAGINAL SECRETION; INTRAVAGINAL DRUG ADMINISTRATION; MIDDLE AGED; PAIN MEASUREMENT; PATHOLOGY; TREATMENT OUTCOME;

ADMINISTRATION, INTRAVAGINAL; ADULT; AGED; DEHYDROEPIANDROSTERONE; DOUBLE-BLIND METHOD; DYSPAREUNIA; FEMALE; HUMANS; MENOPAUSE; MIDDLE AGED; PAIN MEASUREMENT; PROSPECTIVE STUDIES; TREATMENT OUTCOME;

EID: 84928079792     PISSN: 10723714     EISSN: 15300374     Source Type: Journal    
DOI: 10.1097/GME.0000000000000428     Document Type: Article

References (51)

1. 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
2. Labrie F, Bélanger 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; 82: 2396-2402
3. Labrie F, Labrie C. DHEA and intracrinology at menopause, a positive choice for evolution of the human species. Climacteric 2013; 16: 205-213
4. 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
5. Chakraborty TR, Gore AC. Aging-related changes in ovarian hormones, their receptors, and neuroendocrine function. Exp Biol Med (Maywood) 2004; 229: 977-987
6. The Practice Committee of American Society of Reproductive Medecine. Estrogen and progestogen therapy in postmenopausal women. Fertil Steril 2004; 82(suppl 1): S70-S80
7. Archer DF, Furst K, Tipping D, Dain MP, Vandepol C. A randomized comparison of continuous combined transdermal delivery of estradiolnorethindrone acetate and estradiol alone for menopause. CombiPatch Study Group. Obstet Gynecol 1999; 94: 498-503
8. Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001; 75: 1065-1079
9. Labrie F, Archer D, 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
10. Hill K. The demography of menopause. Maturitas 1996; 23: 113-127
11. Kleinman NL, Rohrbacker NJ, Bushmakin AG, Whiteley J, Lynch WD, Shah SN. Direct and indirect costs of women diagnosed with menopause symptoms. J Occup Environ Med 2013; 55: 465-470
12. Santoro N, Komi J. Prevalence and impact of vaginal symptoms among postmenopausal women. J Sex Med 2009; 6: 2133-2142
13. Rossin-Amar B. [Vaginal dryness in the menopausal woman (physiological and psychological aspects)]. Gynecol Obstet Fertil 2000; 28: 245-249
14. Gass ML, Cochrane BB, Larson JC, et al. Patterns and predictors of sexual activity among women in the hormone therapy trials of the Womens Health Initiative. Menopause 2011; 18: 1160-1171
15. Mac Bride MB, Rhodes DJ, Shuster LT. Vulvovaginal atrophy. Mayo Clin Proc 2010; 85: 87-94
16. Palacios S, Castelo-Branco C, Cancelo MJ, Vazquez F. Low-dose, vaginally administered estrogens may enhance local benefits of systemic therapy in the treatment of urogenital atrophy in postmenopausal women on hormone therapy. Maturitas 2005; 50: 98-104
17. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women [Review]. Cochrane Database System Rev 2006; CD001500
18. Ponzone R, Biglia N, Jacomuzzi ME, Maggiorotto F, Mariani L, Sismondi P. Vaginal oestrogen therapy after breast cancer: is it safe? Eur J Cancer 2005; 41: 2673-2681
19. Trinkaus M, Chin S, Wolfman W, Simmons C, Clemons M. Should urogenital atrophy in breast cancer survivors be treated with topical estrogens? Oncologist 2008; 13: 222-231
20. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 2002; 94: 606-616
21. Labrie F, Cusan L, Gomez JL, et al. Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause 2009; 16: 30-36
22. Sturdee DW, Panay N. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13: 509-522
23. Labrie F. DHEA after menopause-sole source of sex steroids and potential sex steroid deficiency treatment. Menopause Manag 2010; 19: 14-24
24. Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone) a physiological and highly efficient treatment of vaginal atrophy. Menopause 2009; 16: 907-922
25. Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (DHEA, Prasterone), a highly efficient treatment of dyspareunia. Climacteric 2011; 14: 282-288
26. US Food and Drug Administration. 2003-Draft Guidance for Industry: Estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms-Recommendations for Clinical Evaluation. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM135338.pdf. Accessed August 19, 2014
27. Davila GW, Singh A, Karapanagiotou I, et al. Are women with urogenital atrophy symptomatic? Am J Obstet Gynecol 2003; 188: 382-388
28. US Food and Drug Administration. 2013-Bioanalytical Method Validation-Revision 1. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM). Division of Drug Information, WO51, Room 2201, Center for Drug Evaluation and Research, Food and Drug Administration. Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulator yinformation/guidances/ucm368107.pdf. Accessed August 19, 2014
29. Ke Y, Bertin J, Gonthier R, Simard JN, Labrie F. A sensitive, simple and robust LC-MS/MS method for the simultaneous quantification of seven androgen-And estrogen-related steroids in postmenopausal serum. J Steroid Biochem Mol Biol 2014; 144: 523-534
30. Dury AY, Ke Y, Gonthier R, Isabelle M, Simard JN, Labrie F. Validated LC-MS/MS simultaneous assay of five sex steroid/neurosteroid-related sulfates in human serum. J Ster Biochem Mol Biol 2015; 14: 1-10
31. Labrie F. Intracrinology. Mol Cell Endocrinol 1991; 78: C113-C118
32. Labrie F, Martel C, Berube 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: 359-367
33. 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: 178-194
34. Labrie F, Cusan L, Gomez JL, et al. Corrigendum to: effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol 2008; 112: 169
35. Labrie F. All sex steroids are made intracellularly in peripheral tissues by the mechanism of intracrinology after menopause. J Steroid Biochem Mol Biol 2015; 145: 133-138
36. Portman DJ, Labrie F, Archer DF, et al. Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Menopause 2015; In press
37. Bouchard C, Labrie F, Archer DF, et al. Decreased efficacy of twiceweekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy. Climacteric 2015; 18: 590-607
38. Kim HJ, McGuire DB, Tulman L, Barsevick AM. Symptom clusters: concept analysis and clinical implications for cancer nursing. Cancer Nurs 2005; 28: 270-282, quiz 83-84
39. Greenblum CA, Rowe MA, Neff DF, Greenblum JS. Midlife women: symptoms associated with menopausal transition and early postmenopause and quality of life. Menopause 2013; 20: 22-27
40. Chen L, Ng MJ, van der Vlugt TH, Price PH, Orencia A. Statistical considerations for the efficacy assessment of clinical studies of vulvar and vaginal atrophy. Drug Inf J 2010; 44: 581-588
41. Simon J, Nachtigall L, Gut R, Lang E, Archer DF, Utian W. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol 2008; 112: 1053-1060
42. Bachmann G, Lobo RA, Gut R, Nachtigall L, Notelovitz M. Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Obstet Gynecol 2008; 111: 67-76
43. Bachmann G, Bouchard C, Hoppe D, et al. Efficacy and safety of lowdose regimens of conjugated estrogens cream administered vaginally. Menopause 2009; 16: 719-727
44. Bulun SE, Yang S, Fang Z, et al. Role of aromatase in endometrial disease. J Steroid Biochem Mol Biol 2001; 79: 19-25
45. Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause 2009; 16: 897-906
46. Semmens JP, Wagner G. Estrogen deprivation and vaginal function in postmenopausal women. JAMA 1982; 248: 445-448
47. The North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause 2007; 14: 357-369
48. Eugster-Hausmann M, Waitzinger J, Lehnick D. Minimized estradiol absorption with ultra-low-dose 10 microg 17beta-estradiol vaginal tablets. Climacteric 2010; 13: 219-227
49. Pandit L, Ouslander JG. Postmenopausal vaginal atrophy and atrophic vaginitis. Am J Med Sci 1997; 314: 228-231
50. The North American Menopause Society. Estrogen and progestogen use in peri-And postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007; 14: 168-182
51. Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Womens VIews of Treatment Options for Menopausal Vaginal ChangEs) survey. J Sex Med 2013; 10: 1790-1799