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TRANSCRIPT
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Testosterone Therapy for Testosterone Therapy for Hypoactive Sexual Desire Hypoactive Sexual Desire DisorderDisorder
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IntroductionIntroduction
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
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Rationale for Testosterone TherapyRationale 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;80:1429-1430.Judd HL, et al. J Clin Endocrinol Metab. 1974;39:1020-1024.
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Rationale for Testosterone Therapy (cont’d)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;7:203-210.Shifren JL, et al. N Engl J Med. 2000;343:682-688.Lobo RA, et al. Fertil Steril. 2003;79:1341-1352.
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Combination Estrogen-Combination Estrogen-Testosterone TherapyTestosterone Therapy
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Impact of Estrogen Deficiency Impact of Estrogen Deficiency on Sexual Functionon 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;11:120-130.
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Low Estrogen Is Associated With Low Estrogen Is Associated With Increased Prevalence of Sexual ProblemsIncreased Prevalence of Sexual Problems
Sarrel PM. J Womens Health Gend Based Med. 2000;9:S25-S32.Sarrel PM. Obstet Gynecol. 1990;75:26S-30S.
Per
cen
tag
e o
f W
om
en
Rep
ort
ing
Pro
ble
ms
0
10
20
30
40
50
60
70
VaginalDryness
Bothered byProblem
Dyspareunia(Intensity)
Pain WithPenetration
Burning
<50 pg/mL estradiol
>50 pg/mL estradiol
N=93; significance not reported.
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Simon J, et al. Menopause. 1999;6:138-146.
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-Efecto de Terapia con Estrógenos and Estrógenos-Andrógenos sobre Síntomas menopaúsicosAndrógenos sobre Síntomas menopaúsicos
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Testosterone Use in WomenTestosterone Use in Women
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Testosterone Therapies Available Testosterone Therapies Available and Under Investigationand 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.
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Estrógenos y Enantato de Testosterona: Estrógenos y Enantato de Testosterona: Deseo sexualDeseo sexual
Sherwin BB, et al. Psychosom Med. 1987;49:397-409.
SemanasB 1 2 3 4
Estrógeno + TEControl
EstrógenoInyeccion
1
2
3
0
4
5N
ivel
es
med
ios
de
Des
eo
S
exu
al
N=65; TE=testosterona enantato
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Davis SR, et al. Maturitas. 1995;21:227-236.
Estrogen
Estrogen + testosterone
Libido
Activity
Satisfaction
Pleasure
Fantasy
Orgasm
Relevancy
5 6 7 8 9 10Sexuality Score
(Means of 6, 12, 18, and 24 Months)
Summary Statistics
N=34
Estradiol and Testosterone Implants:Estradiol and Testosterone Implants:Sexual FunctionSexual Function
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EE EE+MT Treatment difference
Total Testosterone (ng/dL)
Baseline
Change from baseline (mean serum concentration)
20.8 1.1
-0.1 7.4
18.9 8.4
-3.7 6.8 P=0.02
Bioavailable Testosterone (pg/mL)
Baseline
Change from baseline (mean serum concentration)
3.1 2.7
-0.3 2.4
2.7 1.5
2.0 2.0 P<0.010
Lobo RA, et al. Fertil Steril. 2003;79:1341-1352.
EE=esterified estrogens; MT=methyltestosterone
Estrogen and Methyltestosterone:Estrogen and Methyltestosterone:Effect on Testosterone Levels Effect on Testosterone Levels
N = 111 N = 107
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Lobo RA, et al. Fertil Steril. 2003;79:1341-1352.
*P<0.02 vs baseline
*
EE+MT (n = 107)
0
0.3
0.6
0.9
4 8 12 16
Study Week
Mea
n C
han
ge EE (n = 111)
Estrogen and Methyltestosterone:Estrogen and Methyltestosterone:Sexual DesireSexual Desire
EE=esterified estrogens; MT=methyltestosterone
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Estrogen and Methyltestosterone:Estrogen and Methyltestosterone: Frequency of Interest/Desire Frequency of Interest/Desire
Lobo RA, et al. Fertil Steril. 2003;79:1341-1352.
*P<0.02 vs baseline; †P<0.01 vs baselineStudy Week
EE+MT (n = 107)
EE (n = 111)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
4 8 12 16
Mea
n C
han
ge
*
† †
EE=esterified estrogens; MT=methyltestosterone
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Estrogen and Methyltestosterone: Estrogen and Methyltestosterone: Sexual FunctioningSexual Functioning
Sarrel PM, et al. J Reprod Med. 1998;43:847-856.
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
Sensationand Desire
Sensation Desire Frequency VaginalChanges
EEEE+MT
Ch
an
ge
in R
aw
Sco
re F
rom
P
revi
ou
s H
orm
on
e T
he
rap
y
*
*
†
N=20; *P<0.01; †P≤0.05 EE=esterified estrogens; MT=methyltestosterone
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Estrogen and Testosterone Patch: Estrogen and Testosterone Patch: Free and Bioavailable Testosterone LevelsFree and Bioavailable Testosterone Levels
Shifren JL, et al. N Engl J Med. 2000;343:682-688.
N=75; *P<0.001 for comparison with placebo
Endocrine Sciences normal range for cycling women
Placebo
Regimen (+CEE) 0
Regimen (+CEE)
1 2 3 4 5 6 7 8
Fre
e T
(p
g/m
L)
*
*
0
2
4
6
8
10
12
14
Bio
ava
ilab
le T
(n
g/d
L)
*
*
Baseline 300 mcg150 mcg
CEE=conjugated equine estrogens; T=testosterone
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N=75; *P<0.05 for comparison with placebo
Baseline
300 mcg
150 mcg
Placebo
Thoughts/Desires
Frequency Pleasure/Orgasm
Problems
Per
cen
tag
e o
f N
orm
ativ
e M
ean
40
50
60
70
80
90
100
110
120
*
*
Arousal
Shifren JL, et al. N Engl J Med. 2000;343:682-688.
Oral Estrogen and Testosterone Patch: Oral Estrogen and Testosterone Patch: Sexual FunctionSexual Function
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Oral Estrogen and Testosterone Patch: Oral Estrogen and Testosterone Patch: Effect on Sexual Function 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
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Oral Estrogen and Testosterone Patch: Oral Estrogen and Testosterone Patch: Effect on Sexual Function (cont’d)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 16-19, 2004; New Orleans, La. Abstract OR44-6.
SM=surgically menopausal; HSDD=hypoactive sexual desire disorder; T=testosterone
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Floter A, et al. Climacteric. 2002;5:357-65.
N=50; EV-estradiol valerate; TU-testosterone undecanoate*P<0.05 vs EV at 24 weeks
Estrogen and Testosterone Undecanoate: Estrogen and Testosterone Undecanoate: Sexual FunctionSexual Function
0
2
4
6
Mc
Co
y S
ex S
cale
Sc
ore
(M
ean
)
* EV
Baseline
**
EV + TU
Enjoyment of Sex
Satisfaction With Frequency of Sex
Interest in Sex
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Potential Side Effects With Testosterone Potential Side Effects With Testosterone TherapiesTherapies
Hirsutism
Acne
Voice deepening
Alopecia
Liver toxicity
Negative effects on lipoproteins
Clitoromegaly
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Side Effects in Studies With Side Effects in Studies With Testosterone Therapies 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
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N=75; *P<0.05 for comparison with placebo
0.0
0.5
1.0
1.5
2.0
2.5
Hirsutism
(Lorenzo Scale)
Acne
(Palatsi Scale)
Facial Depilation
(Times/Month)
Me
an
Sc
ore
(S
EM
)
Baseline 300 mcg
*
150 mcgPlacebo
Shifren JL, et al. N Engl J Med. 2000;343:682-688.
Estrogen and Testosterone Patch: SafetyEstrogen and Testosterone Patch: Safety
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Estrogen and Methyltestosterone: Safety Estrogen and Methyltestosterone: Safety
EE EE+MT
Hirsutism score
(Lorenzo scale)
Baseline score
Change from baseline at week 162.3 2.5
0.0 1.9
2.9 3.3
-0.4 2.2
Acne score
(Palatsi scale)
Baseline score
Change from baseline at week 160.1 0.4
0.2 0.5
0.2 0.5
0.1 0.5
Lobo RA, et al. Fertil Steril. 2003;79:1341-1352.
EE=esterified estrogens; MT=methyltestosterone
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Patient Selection Patient Selection
Testosterone therapy, in conjunction with estrogen therapy, may be indicated in women with:
– Surgical menopause
– Decreased libido
– Diminished sense of well-being