Intravaginal Testosterone Improves Sexual Satisfaction and Vaginal Symptoms Associated With Aromatase Inhibitors

Context Intravaginal testosterone (IVT) is a potential treatment of vulvovaginal atrophy (VVA) associated with aromatase inhibitor (AI) use. Objective To investigate the effects of IVT on sexual satisfaction, vaginal symptoms, and urinary incontinence (UI) associated with AI use. Design Double-blind, randomized, placebo-controlled trial. Setting Academic clinical research center. Participants Postmenopausal women taking an AI with VVA symptoms. Intervention IVT cream (300 μg per dose) or identical placebo, self-administered daily for 2 weeks and then thrice weekly for 24 weeks. Main Outcomes and Measures The primary outcome was the change in the sexual satisfaction score on the Female Sexual Function Index (FSFI). Secondary outcomes included vaginal symptoms and responses to the Profile of Female Sexual Function, the Female Sexual Distress Scale-Revised (FSDS-R), and the Questionnaire for UI Diagnosis. Serum sex steroids were measured. Results A total of 44 women were randomly assigned and 37 provided evaluable data, (mean age 56.4 years, SD 8.8 years). At 26 weeks, the mean between-group difference in the baseline-adjusted change in FSFI satisfaction scores was significantly greater for the IVT group than the placebo group (mean difference 0.73 units; 95% CI, 0.02 to 1.43; P = 0.043). IVT cream resulted in significant improvements, compared with placebo, in FSDS-R scores (P = 0.02), sexual concerns (P < 0.001), sexual responsiveness (P < 0.001), vaginal dryness (P = 0.009), and dyspareunia (P = 0.014). Serum sex steroid levels did not change. Few women had UI symptoms, with no treatment effect. Conclusion IVT significantly improved sexual satisfaction and reduced dyspareunia in postmenopausal women on AI therapy. The low reporting of UI among women on AI therapy merits further investigation.

[1]  E. Kreydin,et al.  The Association of Serum Testosterone Levels and Urinary Incontinence in Women , 2018, The Journal of urology.

[2]  Farwa Rizvi,et al.  A systematic review of intravaginal testosterone for the treatment of vulvovaginal atrophy , 2017, Menopause.

[3]  S. Davis,et al.  Aromatase Inhibitors Are Associated With Low Sexual Desire Causing Distress and Fecal Incontinence in Women: An Observational Study. , 2017, The journal of sexual medicine.

[4]  R. Santen,et al.  Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors , 2017, The Journal of clinical endocrinology and metabolism.

[5]  A. Zanesco,et al.  Micturition dysfunction in four‐month old ovariectomized rats: Effects of testosterone replacement , 2017, Life sciences.

[6]  Joscelyn N. Hoffmann,et al.  Prevalence and correlates of vaginal estrogenization in postmenopausal women in the United States , 2017, Menopause.

[7]  L. Esserman,et al.  Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial , 2017, JAMA oncology.

[8]  N. Panay,et al.  Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. , 2017, Fertility and sterility.

[9]  D. Portman,et al.  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 , 2014, Menopause.

[10]  S. Davis,et al.  Women's expectations and experiences of hormone treatment for sexual dysfunction , 2014, Climacteric : the journal of the International Menopause Society.

[11]  A. Pinto-Neto,et al.  Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on sexual function in postmenopausal women: a randomized controlled trial. , 2014, The journal of sexual medicine.

[12]  D. Travers-Gustafson,et al.  Breast Cancer, Aromatase Inhibitor Therapy, and Sexual Functioning: A Pilot Study of the Effects of Vaginal Testosterone Therapy , 2014, Sexual medicine.

[13]  F. Cardoso,et al.  Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[14]  S. Davis,et al.  Understanding discontinuation of oral adjuvant endocrine therapy by women with hormone receptor–positive invasive breast cancer nearly 4 years from diagnosis , 2013, Menopause.

[15]  A. Perrone,et al.  Androgen receptor expression in the human vagina under different physiological and treatment conditions , 2013, International Journal of Impotence Research.

[16]  S. Davis,et al.  The use of hormone therapy for the maintenance of urogynecological and sexual health post WHI , 2012, Climacteric : the journal of the International Menopause Society.

[17]  M. Dowsett,et al.  Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator. , 2012, Journal of oncology practice.

[18]  B. Littenberg,et al.  Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. , 2011, The oncologist.

[19]  I. Tuğlu,et al.  The effect of testosterone treatment on urodynamic findings and histopathomorphology of pelvic floor muscles in female rats with experimentally induced stress urinary incontinence , 2011, International Urology and Nephrology.

[20]  F. Cardoso,et al.  Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  S. Davis,et al.  Sexual function after breast cancer. , 2011, The journal of sexual medicine.

[22]  J. Griggs,et al.  American society of clinical oncology clinical practice guideline update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. , 2010, Journal of oncology practice.

[23]  P. Dubey,et al.  A comparative study of the effects of local estrogen with or without local testosterone on vulvovaginal and sexual dysfunction in postmenopausal women. , 2010, The journal of sexual medicine.

[24]  David Handelsman,et al.  Development and validation of a sensitive liquid chromatography-tandem mass spectrometry assay to simultaneously measure androgens and estrogens in serum without derivatization. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[25]  C. Labrie,et al.  Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy , 2009, Menopause.

[26]  S. Shortreed,et al.  Age-specific prevalence of, and factors associated with, different types of urinary incontinence in community-dwelling Australian women assessed with a validated questionnaire. , 2009, Maturitas.

[27]  G. Braunstein,et al.  Testosterone for low libido in postmenopausal women not taking estrogen. , 2008, The New England journal of medicine.

[28]  L. Derogatis,et al.  Validation of the female sexual distress scale-revised for assessing distress in women with hypoactive sexual desire disorder. , 2008, The journal of sexual medicine.

[29]  C. Gazzaruso,et al.  Endogenous testosterone and endothelial function in postmenopausal women , 2007, Coronary artery disease.

[30]  J. Heiman,et al.  Genital and subjective measurement of the time course effects of an acute dose of testosterone vs. placebo in postmenopausal women. , 2007, The journal of sexual medicine.

[31]  E. Tsai,et al.  A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women , 2006, Menopause.

[32]  J. Wouda,et al.  ORIGINAL RESEARCH—ENDOCRINOLOGY: Vaginal Application of Testosterone: A Study on Pharmacokinetics and the Sexual Response in Healthy Volunteers , 2006 .

[33]  J. Cuzick,et al.  Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  C. McHorney,et al.  Profile of Female Sexual Function: a patient-based, international, psychometric instrument for the assessment of hypoactive sexual desire in oophorectomized women , 2004, Menopause.

[35]  E. Briganti,et al.  Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women , 2003, Menopause.

[36]  G. Chaudhuri,et al.  Correlation of androgen receptors, aromatase, and 5-alpha reductase in the human vagina with menopausal status. , 2003, Fertility and sterility.

[37]  S. Davis,et al.  Minireview: Aromatase and the Regulation of Estrogen Biosynthesis-Some New Perspectives. , 2001, Endocrinology.

[38]  H. Teede,et al.  Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodilation in postmenopausal women already receiving estrogen. , 2001, The Journal of clinical endocrinology and metabolism.

[39]  Candace S. Brown,et al.  The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. , 2000, Journal of sex & marital therapy.

[40]  U. Ulmsten,et al.  The prevalence of urogenital symptoms in postmenopausal women. , 1995, Maturitas.

[41]  S. Salinger.  Proliferative effect of testosterone propionate on human vaginal epithelium. , 1950, Acta endocrinologica.

[42]  R. Greenblatt.  TESTOSTERONE PROPIONATE PELLET IMPLANTATION IN GYNECIC DISORDERS , 1943 .