Andrea R. Genazzani

Menopause symptoms and

quality of life

University of Pisa, Italy

Disclosure of Interest: Nothing to Disclose

SEX STEROIDS INFLUENCE THE FUNCTION OF MULTIPLE TISSUES, ORGANS AND SYSTEMS. NEARLY EVERY HUMAN CELL IS SENSITIVE TO THESE HORMONES.

SEX STEROIDS IN WOMEN

MENOPAUSE IS ABOUT THE WOMAN IN FRONT OF US

MENOPAUSE AND A WOMAN’S BODY

THE MAIN CHALLENGE

THE MAIN MEDICAL NEEDS

ISSUES IN MENOPAUSAL MEDICINE

A WOMAN’S PERSONAL AND SOCIAL IDENTITY

MOTHERHOOD BEAUTY

MOTHERHOOD BEAUTY

EROTICISM CAREER

MENOPAUSE IS ABOUT QUALITY OF LIFE

THAT IS WHAT LEARNING IS.

YOU SUDDENLY UNDERSTAND

SOMETHING YOU'VE

UNDERSTOOD ALL YOUR LIFE,

BUT IN A NEW WAY.

DORIS LESSING

Qol after Menopause depends on:

general health, lifestyle

physical functioning and integrity

psychological/emotional stability

positive partnership (incl. sexual life)

education, professional activity

religion, cultural environment

social integration before menopause

PROBLEMS WITH QOL ASSESSMENT

• Minimal definitional agreement

• Objective measurement difficult

• QOL often oversimplified as health status (symptom inventory vs. measure of sense of well-being)

IMPORTANCE OF QUALITY OF LIFE MEASUREMENT

Accurate appraisal of Quality of Life:

• Critical to enhancing treatment adherence

• Enhances clinician interactions with patients

• Helps assess and optimize treatment effectiveness

• Improves overall patient satisfaction with treatment

Qol instruments vary based on the domain investigated

GLOBAL QOL

• A reflection of a person’s beliefs about

functioning and achieving in various

aspects of life

• A spectrum that ranges from perceived

distress at one end to the absence of

distress and a sense of well-being at the

other

HEALTH-RELATED QOL

• The domains of physical and

psychological functioning

• The patients’ perception of their physical,

cognitive and mental health

Fol 20-100 pg/mL Ovu 300-500 pg/mL Lut 100-300 pg/mL

10-20 pg/mL

I tr. 1.000-5.000 pg/mL II tr. 5.000-15.000 pg/mL III tr. 10.000-40.000 pg/mL

ESTROGENS DURING A WOMAN’S LIFE

Age – healthy women

100

50

0.0 20 years 40 years

50%

reduction

DHEA

DHEAS

TESTOSTERONE

Androgens decline between 20 and 40 years

%

Cl- channel

b

a

g

g

a

PREG(S)

General anesthetics

GABA

Benzodiazepines Imidazopyridines

Pyrazolopyrimidines

Barbiturates

Ethanol

Neurosteroids and GABA-A

Cellular excitability

Network synchronization

Synaptic plasticity

MOOD

EMOTIONAL STATE

AFFECTIVITY

ALLOPREGNANOLONE 3-DIOL

DHEA(S)

The Brain-Steroids Aging A Multisignaling process

TIME – LIFE EVENTS

GENETIC

FACTORS DURING AGING

ENVIRONMENT

BRAIN

HORMONES

BODY Function/ Activities

AR Genazzani et al, Hum Rep Update

SEXUAL PROBLEMS & DISTRESS IN US WOMEN

Shifren et al, 2008

0

5

10

15

20

18-44 45-64 >64 years

Desire

Arousal

Orgasm

Any

%

HOT FLUSHES AND QOL

• Interfere with daily activities

• Impact on other members of family

• Interfere with sleep cycle

• Impair sexual function

• Result in :

– fatigue

– Loss of concentration

– Depression

Estradiol

DOSE RESPONSE TO ESTROGEN THERAPY Number of Moderate-Severe Hot Flushes

0

10

20

30

40

50

60

70

80 Placebo

0.25mg E

0.5mg E

1mg E

2mg E

Notelovitz et al, OG 2000, 95:726

Nu

mb

er

significantly (p < 0.05)

different from placebo

*

*

*

*

0 1 4 5 6 7 8 9 10 11 12 3

Weeks

2

J Clin Endocrinol Metab, July 2010, 95(Suppl 1):S7–S66

RISKS AND BENEFITS OF HRT

J Clin Endocrinol Metab, July 2010, 95(Suppl 1):S7–S66

RISKS AND BENEFITS OF HRT

6543210-1-2-3-4-5-6

Total Number of Objective Hot Flashes during Sleeping Hours

6

5

4

3

2

1

0

-1

-2

-3

-4

-5

-6

De

laye

d P

ara

gra

ph

Rec

all

(sc

ore

ad

jus

ted

fo

r o

the

r s

ign

ific

an

t p

red

icto

rs)

6543210-1-2-3-4-5-6

Total Number of Objective Hot Flashes during Sleeping Hours

6

5

4

3

2

1

0

-1

-2

-3

-4

-5

-6

De

laye

d P

ara

gra

ph

Rec

all

(sc

ore

ad

jus

ted

fo

r o

the

r s

ign

ific

an

t p

red

icto

rs)

HF AND COGNITIVE FUNCTION

Objective hot flashes are negatively related to verbal memory performance in midlife women.

Maki P., Menopause 2008

MENOPAUSE SYMPTOMS AND DEPRESSION

Brown et al., Maturitas 2008

OR v

s.

asym

pto

matic w

om

en

HF Irritability

5

4

3

1

2

Risk of depression

HF ARE ASSOCIATED WITH LOWER BMD Study of Women's Health Across the Nation

2,213 participants aged 42 to 52 years; 5-year follow-up

Crandall, Carolyn J.et al., Menopause 2009

POST MEN

PERI MEN

0.01

0

0.005

BM

D (

g/c

m2)

PRE MEN

Difference in SPINE BMD (HF vs. no HF)

HF AND CV RISK FACTORS

Gast et al., Hypertension 2008

5523 women aged 46-57 years, of whom 38 % reported night sweats and 39 % hot flashes

1.20 (1.07-1.34)

1.52 (1.25-1.84)

HTN HIGH cholesterol

1.5

1.2

0.9

0.3

0.6

OR v

s.

wom

en w

ithout

HF

WOMEN MAY BE DIFFERENTLY VULNERABLE TO MENOPAUSAL CHANGES

E2

VASODILATATION

INFLAMMATION

LESION PROGRESSION

E2

VASODILATATION

INFLAMMATION

PLAQUE INSTABILITY

PLAQUE THROMBOSIS

ESTROGENS AND CVD

30 70 60 40 50 80

WHI

HERS

PHASE

NHS

secondary prevention

ERA

yr

primary prevention

CLINICAL TRIALS

HRT: IS THERE A WINDOW OF OPPORTUNITY TO START?

CEE + MPA

YEARS SINCE MENOPAUSE

0 1.0 2.5

Hazard Ratio (95% CI)

0.5 1.5 2.0

0 1.0 2.5

Hazard Ratio (95% CI)

0.5 1.5 2.0

0.56 <10

0.92 10-19

1.04 > 20

0.89 <10

1.22 10-19

1.71 > 20

HAZARD RATIOS

CEE

Figure 5. Cumulative Annualized Incidence Rates for Clinical Outcomes in the Women's

Health Initiative Estrogen-Alone Trial According to 10-Year Age Groups at Enrollment

LaCroix, A. Z. et al. JAMA 2011;305:1305-1314

Copyright restrictions may apply.

WHI SUB-STUDY (CEE-ALONE) ONLY WOMEN 50-59 Y AT ENROLLMENT CT SCAN OF THE HEART – CORONARY CALCIFICATIONS MEAN CORONARY-ARTERY CALCIUM SCORE WAS LOWER AMONG WOMEN RECEIVING ESTROGEN (83.1) THAN AMONG THOSE RECEIVING PLACEBO (123.1) (P=0.02).

JA Manson et al. N Engl J Med. 2007

Schierbeck L L et al. BMJ 2012;345:bmj.e6409

©2012 by British Medical Journal Publishing Group

Schierbeck L L et al. BMJ 2012;345:bmj.e6409

©2012 by British Medical Journal Publishing Group

Schierbeck L L et al. BMJ 2012;345:bmj.e6409

©2012 by British Medical Journal Publishing Group

Primary Prevention of CHD with HRT in Clinical Perspective

*Women <60 years old and/or <10 years since menopause when randomized

1Salpeter S, et al. J Gen Intern Med 2004;19:791-804. 2Salpeter S, et al. J Gen Intern Med 2006;21:363-366. 3Walsh JME, et al. JAMA 2004;21:363-366. 4Ridker PM, et al. N Engl J Med 2005;352:1293-1304.

Hormone Lipid Outcome Therapy1,2* Lowering3 Aspirin4

CHD 0.68 (0.48-0.96) 0.89 (0.69-1.09) 0.91 (0.80-1.03)

Total Mortality 0.61 (0.39-0.95) 0.95 (0.62-1.46) 0.95 (0.85-1.06)

Lindsay. Clin Obstet Gynecol. 1987;30:847-859.

44

42

40

38

36

34

Meta

carp

al BM

C

(m

g/m

m)

Blue area represents placebo-treated population of oophorectomized women

Years

From oophorectomy

From 3 years after oophorectomy

From 6 years after oophorectomy

0 2 4 6 8 10 12 14 16

ERT AND BONE LOSS

Zandi PP et al, JAMA. 2002;288:2123-2129

HRT and Alzheimer’s Disease

The Cache County Study

65 70 75 80 85 90 95 100

Women

Men

year

65 70 75 80 85 90 95 100

year

HRT non user

HRT use <3y

HRT use 3-10y

HRT use >10y

0.12

0.10

0.08

0.06

0.04

0.02

0

0.12

0.10

0.08

0.06

0.04

0.02

0

A wise man ought to realize that health is his

most valuable possession and learn how to treat

his illnesses by his own judgment.

Hippocrates

A wise menopause physician ought to realize that

health and quality of life are largely to be defined

based on each patient’s judgment.

Everything possible should be enacted to maintain QoL

after menopause, including, but not limited to, use of

HRT when indicated. Personalization is the key to

success.

Behavioral interventions (such as dietary education,

promotion of a healthy lifestyle, physical activity) or

medical treatments that improve QoL, will likely result

in the long term in reduced incidence of degenerative

disorders.

CONCLUSIONS