livial /1 sex, quality of life at menopause and management elizabeth farrell head, menopause unit,...

Liv

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Sex, quality of life at menopause and management

Elizabeth Farrell Head, Menopause Unit, Monash

Medical Centre, Clayton, &

Director , Jean Hailes Foundation for Women’s Health, Clayton, Australia

March

2007 Taipei

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DISCLOSURES

• Educational and research grants

• Symposium or meeting speaker

• Organon

• Novo-Nordisk

• Schering

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Sexual well being & function

• Complex influences & changes in middle-aged women

• MWMHP ( 438 Australian woman aged 45-55 years)

• Relate to aging, psychosocial & physical factors– Prior level of sexual function– Losing or gaining a partner– Feelings towards partner – Oestradiol level – Mood– Age

• Incremental decline with menopause related to decreasing oestradiol level

(Dennerstein L, Lehert P, Burger H, Guthrie J, Am J Med 2005)

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Menopause & Sexual function

• MWMHP measured sexual function and distress– Sexual dysfunction increased from 42%-88% from the early to

late menopause transition– Decreasing scores correlated with decreasing oestradiol not

androgens– In the postmenopause phase

• Decline in sexual arousal and interest• Frequency of sexual activites• Total score• Increase in vaginal dryness• Dyspareunia• Increase in partner’s problems in sexual performance (Dennerstein L, Alexander JL, Kotz K Annu Rev Sex Res 2003)

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Androgen levels

• Cross sectional study of 1423 women aged 18-75 years

– Androgens decline steeply in the early reproductive years– Do not vary because of the menopause– Postmenopausal ovary continues to produce androgens– Over 55 years after BSO lower total T and free T level

(Davison S et al JCEM 2005)

– No single androgen level is predictive of low female sexual function

(Davis SR, Davison SL, Donath S, Bell R JAMA 2005)

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Total testosterone0

12

34

Tota

l tes

tost

eron

e, n

mol

/L

20 30 40 50 60 70 80age, years

01

23

4To

tal t

esto

ster

one,

nm

ol/L

18-24 25-34 35-44 45-54 55-64 65-75age group, years

Davison et al JCEM 2005

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Rymer, Gynecol Endocrinol 1998

Treats vaginal atrophy

Treats menopausal symptoms

No stimulation of breast tissue Low incidence of breast tenderness

No endometrial proliferation

Prevents postmenopausal bone loss

Enhances mood and sexual well-being

Livial (Tibolone) - STEAR(Selective Tissue estrogenic activity regulator)

Neutral effects on cardiovascular system

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Laan et al., Climacteric 2001

** P< 0.0001 between groups

(nmol) (nmol) (µmol) (nmol)

Livial: Effects on sexual well-being

Effects of Livial on endogenous androgen statusin post menopausal women

Livial

placebo

0

10

20

30

40

50

60

70

80

TT FAI A DHEAS SHBG

**

**

* P< 0.05 between groups

*

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-60

-40

-20

0

20

40

60

80

100

120

140

Total T SHBG T:SHBG A DHEAS

Livial (n = 50)

E2/NETA (n = 50)

% change at 12 months

Dören et al., Fertil Steril 2001

*

* *

p < 0.001 between groups

Effects on postmenopausal endogenous androgen status: Livial vs. EPT


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Genazzani et al., Maturitas 1987

Pre Post Before 1 2 6

Mean -endorphin (fmol/ml)

* *

0

4

8

12

16

menopausal treatment Months’ treatment

Livial (n = 16)

placebo (n = 14)

0

4

8

12

16**

The effect of Livial on endorphins

Livial: Effects on mood and sexual well-being

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Premenopausal

Postmenopausal+ LivialPostmenopausal+ Placebo

0

1

2

3

Erotic Fantasy

*

0

1

2

3

4

5

Vaginal Pulse Amplitude (mV)

Baseline

*

Laan et al., Climacteric 2001

* p < 0.05 between Livial and placebo for postmenopausal women

n = 37

The effects of Livial on vaginal blood flow, sexual desire and arousability


Vaginal Pulse Amplitude (mV)changes vs. baseline

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+3 = much improved; 0 = no change; –3 much decreased

Palacios et al., Maturitas 1995

-1

0

1

2Change in scale

Livial (n = 14)

Placebo (n = 14)

Aspects of sexual desire

Sexualattraction

libido

initiation

partner initiation

responsiveness

fantasies

excitement

activity

orgasm

pain

Livial significantly different for all values at 12 months (p <0.01)

Effect on libido: Livial vs. placebo


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Rymer et al., Maturitas 1994

Livial group (n = 46); control group (n = 45)*p < 0.05; **p < 0.001

Livial Controls

1

2

3

4

* *

Libido

Baseline

1 year

2 years

Livial Controls

1

2

3

4

Mean scores

** **

Sexual enjoyment

Mean scores

Effect on sexuality: Livial vs. control


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Frequency of orgasm

0

1

2

3

4

5

6

E 2+ A

(n = 23)

Livial(n=23)

E2

(n=26)

Control(n = 24)

Initial values

Final values

* p < 0.05 compared with E2 and Control

Castelo-Branco et al., Maturitas 2000

**

Score

Effects on sexuality of postmenopausal women: Livial vs. estrogen plus androgen


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Initial values

Final values

Sexual responsiveness

* p < 0.05 compared with E2 and Control

Castelo-Branco et al., Maturitas 2000

0

2

4

6

8

10* *

Score

E2 + A

(n = 23)

Livial(n=23)

E2

(n=26)

Control(n = 24)

Effects on the sexuality of postmenopausal women: Livial vs. estrogen plus androgen


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*E2/NETA, 17-estradiol (2 mg/day)/norethisterone acetate (1 mg/day)p < 0.05 between groups

Nathorst-Böös and Hammar, Maturitas 1997

0

1

2

3

4McCoy sex scale Livial

E2/NETA

*

*

*

Frequency Enjoyment Satisfaction Total score

n = 437

Effect on sexuality: Livial vs. EPT


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Effects on sexual function

Egarter C. et al, Acta Obstet Scan 2002


Results from Sexual Functioning Inventory


Ability tohave orgasm

Coitalpain

Vaginalrelaxation

Vaginaldryness

Strongsexual desire

Contentmentwith sex life

Littlesexual desire

10

20

30

40

50

60

0

*

*

*

*

*

n.s.

n.s.

% Baseline

After 4 months

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Egarter C. et al, Acta Obstet Scan 2002


Results of the questionnaire about sexual desire (VAS)

Effects on sexual function


55

110

0

%

Sexual attraction

Sexual desire

Frequency

taking initiative

Partner in

itiative

Sexual fantasies

Sexual excitement

Change in behaviour

Coital activity

Intensity & frequency

of orgasmCoital pain

* * * **

* ** * *

Baseline

After 4 months

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Effect of tibolone and ccCE/MPA on Sexual Function

-4

-2

0

2

4

Points

Livial (N=24)

Prempro 5 (N=24)

Wu et al. Climacteric 2001;4:314-319

* P<0.05 vs. baseline† P<0.05 tibolone vs. ccCE/MPA

*† *† *† *† *†

*† *†

* * * * *

* *Interest Fantasies Arousal Satisfaction Frequency

of orgasmFrequencyof vaginaldryness

Frequencyof painful

intercourse

Change on the modified McCoy Scale items at 3 monthsChange on the modified McCoy Scale items at 3 months

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2.5

2.7

2.9

3.1

3.3

3.5

Baseline 3 months 6 months 12 months

Points

Livial (N=250)

Prempro 5 (N=251)

Effect of tibolone and ccCE/MPA on Sexual Function

Sexual drive, interest and/or performance

Huber et al. Br J Obstet Gynaecol 2002;109:886-893

Change on the Qualiy of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)

* P = 0.017 tibolone vs. ccCE/MPA

*

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40

42

44

46

48

50

Baseline week 12 week 24 week 48

Total

Tibolone 2.5 mg (N=242) E2/NETA (N=263)

TOTAL study – effect on total score of the McCoy’s Sexuality Questionnaire

MFSQ total sum score

*p<0.05 between treatment groups

*

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14.5

15

15.5

16

16.5

17

17.5

18

18.5

19

Baseline week 12 week 24 week 48

Mean

Tibolone E2/NETA

TOTAL Study – Sexual Interest

*p<0.05 between treatment groups, **p=0.003 between treatment groups

*

**

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Conclusions


• Livial improves mood and libido in postmenopausal women

• Livial improves sexual well-being by increasing sexual desire, frequency of arousability, sexual fantasies and vaginal lubrication

• Livial produces significant improvement in sexual enjoyment compared to EPT with regard to intercourse frequency and satisfaction

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Hormone therapy

• Treat menopausal symptoms – Hot flushes– Night sweats– Vaginal dryness– Dyspareunia

– Use of oestrogens may improve sexual function and in some studies further with addition of androgens

(Davis SR et al Maturitas 1995)

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Managementof Sexual Dysfunction

• History and examination to exclude physical factors– Vaginal dryness, atrophic vagina, introital narrowing

• Psychosocial factors– Life stress, relationship issues, previous sexual difficulties

• Medications

• Illness either in women or partner

• Investigation when appropriate

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Managementof Sexual Dysfunction

• Hormone therapy– E +/- P initially or Livial

– If no improvement when testosterone low add T (off label use)

• If no improvement in sexual function– Search for other causes– Counselling– Couple therapy

livial /1 sex, quality of life at menopause and management elizabeth farrell head, menopause unit,...

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