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Testosterone Therapy for Hypoactive Sexual Desire Disorder
Slide source: Introduction Rationale for use Combination estrogen-testosterone therapy Testosterone use in women – Therapies available and under investigation – Dosing/administration issues – Clinical trials of testosterone use in women – Managing side effects Patient selection
Slide source: Rationale for Testosterone Therapy Testosterone levels in women decline with aging – Women in their 40s have approximately one-half the level of women in their 20s Women who undergo oophorectomy experience dramatic decreases in the level of testosterone – Level of testosterone decreases to one half of those prior to surgery Zumoff B, et al. J Clin Endocrinol Metab. 1995;80: Judd HL, et al. J Clin Endocrinol Metab. 1974;39:
Slide source: Rationale for Testosterone Therapy (cont’d) Testosterone has been linked to sexual desire and coital frequency in menopausal women Accumulating data indicate that testosterone therapy increases sexual function, including sexual desire, in postmenopausal women McCoy NL, et al. Maturitas. 1985;7: Shifren JL, et al. N Engl J Med. 2000;343: Lobo RA, et al. Fertil Steril. 2003;79:
Slide source: Combination Estrogen- Testosterone Therapy
Slide source: Impact of Estrogen Deficiency on Sexual Function Changes in urogenital anatomy – Shortening and loss of elasticity of the vagina – Diminished secretions – Increased pH – Thinning of vaginal epithelial layers Reduced blood flow Reduced nerve transmission and discharge Sleep disruption Mood alterations Sarrel PM. Obstet Gynecol. 1990;75:26S-30S. Bachmann GA, et al. Menopause. 2004;11:
Slide source: Low Estrogen Is Associated With Increased Prevalence of Sexual Problems Sarrel PM. J Womens Health Gend Based Med. 2000;9:S25-S32. Sarrel PM. Obstet Gynecol. 1990;75:26S-30S. Percentage of Women Reporting Problems N=93; significance not reported.
Slide source: Simon J, et al. Menopause. 1999;6: N=93; *P≤0.05 EE=esterified estrogens; MT=methyltestosterone Placebo Low-Dose EE High-Dose EE Low-Dose EE + MT High-Dose EE + MT Postplacebo run-in period Month 1 Month 3 * * * ** * * * Efecto de Terapia con Estrógenos and Estrógenos- Andrógenos sobre Síntomas menopaúsicos
Slide source: Testosterone Use in Women
Slide source: Testosterone Therapies Available and Under Investigation Testosterone Therapies Available and Under Investigation * Oral – Methyltestosterone – Testosterone undecanoate Intramuscular – Testosterone propionate – Testosterone cypionate – Testosterone enanthate Subcutaneous (implant) – Testosterone propionate pellets – Testosterone crystalline pellets Transdermal – Transdermal testosterone patch – Testosterone gel – Testosterone emulsion – Testosterone spray Other – Testosterone-containing vaginal ring – Sublingual testosterone in propylene glycol * Not approved by US Food and Drug Administration for use in women.
Slide source: Estrógenos y Enantato de Testosterona: Deseo sexual Sherwin BB, et al. Psychosom Med. 1987;49: Semanas B1234 Estrógeno + TE Control Estrógeno Inyeccion Niveles medios de Deseo Sexual N=65; TE=testosterona enantato
Slide source: Davis SR, et al. Maturitas. 1995;21: Estrogen Estrogen + testosterone Libido Activity Satisfaction Pleasure Fantasy Orgasm Relevancy Sexuality Score (Means of 6, 12, 18, and 24 Months) Summary Statistics N=34 Estradiol and Testosterone Implants: Sexual Function
Slide source: EEEE+MT Treatment difference Total Testosterone (ng/dL) Baseline Change from baseline (mean serum concentration) 20.8 6.8 P=0.02 Bioavailable Testosterone (pg/mL) Baseline Change from baseline (mean serum concentration) 3.1 2.0 P<0.010 Lobo RA, et al. Fertil Steril. 2003;79: EE=esterified estrogens; MT=methyltestosterone Estrogen and Methyltestosterone: Effect on Testosterone Levels N = 111 N = 107
Slide source: Lobo RA, et al. Fertil Steril. 2003;79: *P<0.02 vs baseline * EE+MT (n = 107) Study Week Mean Change EE (n = 111) Estrogen and Methyltestosterone: Sexual Desire EE=esterified estrogens; MT=methyltestosterone
Slide source: Estrogen and Methyltestosterone: Frequency of Interest/Desire Lobo RA, et al. Fertil Steril. 2003;79: *P<0.02 vs baseline; † P<0.01 vs baseline Study Week EE+MT (n = 107) EE (n = 111) * † † EE=esterified estrogens; MT=methyltestosterone
Slide source: Estrogen and Methyltestosterone: Sexual Functioning Sarrel PM, et al. J Reprod Med. 1998;43: EE=esterified estrogens; MT=methyltestosterone
Slide source: Estrogen and Testosterone Patch: Free and Bioavailable Testosterone Levels Shifren JL, et al. N Engl J Med. 2000;343: N=75; *P<0.001 for comparison with placebo Endocrine Sciences normal range for cycling women Placeb o Regimen (+CEE) 0 Regimen (+CEE) Free T (pg/mL) * * Bioavailable T (ng/dL) * * Baseline 300 mcg150 mcg CEE=conjugated equine estrogens; T=testosterone
Slide source: N=75; *P<0.05 for comparison with placebo Baseline 300 mcg 150 mcg Placebo Thoughts/ Desires Frequency Pleasure/ Orgasm Problems Percentage of Normative Mean * * Arousal Shifren JL, et al. N Engl J Med. 2000;343: Oral Estrogen and Testosterone Patch: Sexual Function
Slide source: Oral Estrogen and Testosterone Patch: Effect on Sexual Function Author (Year)Population (N) Treatment (Dose) Outcome (at 24 Weeks) Braunstein (2003) SM, HSDD (N=447) T patch (150, 300, 450 mcg/d) Placebo patch Desire Activity Davis (2003)SM, HSDD (N=77) T patch (300 mcg/d) Placebo patch Desire Activity Braunstein GD, et al. In: Program and abstracts of the 14th annual meeting of the North American Menopause Society; September 17-20, 2003; Miami Beach, Fla. Abstract 60. Davis S, et al. Fertil Steril. 2003;80(suppl 3):76. SM=surgically menopausal; HSDD=hypoactive sexual desire disorder; T=testosterone
Slide source: Oral Estrogen and Testosterone Patch: Effect on Sexual Function (cont’d) Author (Year)Population (N) Treatment (Dose) Outcome (at 24 Weeks) Simon (2004) SM, HSDD (N=562) T patch (300 mcg/d) Placebo patch Desire Activity Buster (2004) SM, HSDD (N=533) T patch (300 mcg/d) Placebo patch Desire Activity Simon JA, et al. Obstet Gynecol. 2004;103(suppl):64S. Buster J, et al. In: Program and abstracts of the 86th annual meeting of the Endocrine Society; June , 2004; New Orleans, La. Abstract OR44-6. SM=surgically menopausal; HSDD=hypoactive sexual desire disorder; T=testosterone
Slide source: Floter A, et al. Climacteric. 2002;5: N=50; EV-estradiol valerate; TU-testosterone undecanoate *P<0.05 vs EV at 24 weeks Estrogen and Testosterone Undecanoate: Sexual Function McCoy Sex Scale Score (Mean) * EV Baseline * * EV + TU Enjoyment of Sex Satisfaction With Frequency of Sex Interest in Sex
Slide source: Potential Side Effects With Testosterone Therapies Hirsutism Acne Voice deepening Alopecia Liver toxicity Negative effects on lipoproteins Clitoromegaly
Slide source: Side Effects in Studies With Testosterone Therapies Few side effects are reported in studies Increased doses are associated with – Facial hair – Acne/oily skin Oral preparations – Decreases in high-density lipoprotein Not seen with transdermal preparations
Slide source: N=75; *P<0.05 for comparison with placebo Hirsutism (Lorenzo Scale) Acne (Palatsi Scale) Facial Depilation (Times/Month) Mean Score (SEM) Baseline 300 mcg * 150 mcg Placebo Shifren JL, et al. N Engl J Med. 2000;343: Estrogen and Testosterone Patch: Safety
Slide source: Estrogen and Methyltestosterone: Safety EEEE+MT Hirsutism score (Lorenzo scale) Baseline score Change from baseline at week 2.2 Acne score (Palatsi scale) Baseline score Change from baseline at week 0.5 Lobo RA, et al. Fertil Steril. 2003;79: EE=esterified estrogens; MT=methyltestosterone
Slide source: Patient Selection Testosterone therapy, in conjunction with estrogen therapy, may be indicated in women with: – Surgical menopause – Decreased libido – Diminished sense of well-being