Menopause Management in 21st century - Amazon S3 · Diagnosing Menopause • DON’T –Check FSH,...

Menopause Management

in 21st century

Dr Elizabeth Farrell AM Hon LLD FRANZCOG FRCOG

Head, Menopause Unit, Monash Health

Acting Medical Director, Jean Hailes

Disclosure Statement

• Speakers bureau, Expert panel and Consultant:

− Bayer HealthCare

− Wyeth Pharmaceuticals (now Pfizer)

− Flordis

• Director:

− Jean Hailes for Women’s Health (a not-for-profit charity)

Stages of reproductive aging

• Average duration of peri-menopause 4-6 years (range 1-10 years)

• Average age of menopause is 51 years (range 45-55 years)

• Average duration of menopausal symptoms 5-8 years (range 0-13 years)

Harlow et al., Fertil & Steril, 2012

LOOP – double ovulation

Contraception required until 12 months or 2 years after FMP depending on age.

Symptoms across the transition

Perimenopause symptoms

-Mood changes

-Sore breasts

- Bloating

-Headaches/migraines

-Periods: irregular in flow & pattern & symptoms

Menopause symptoms

Vaginal dryness-

Low libido-

Urogenital symptoms-

-Hot flushes

-

-

disturbances

-

-

-

-

-Hot flushes

-Night sweats

-Sleep

disturbances

-Formication

-Joint pains

-Irritability

-Fatigue

80% some

80% some

symptoms

80 % mild to 80 % mild to

moderate

symptoms

80% have

symptoms

for < 5 years

Factors influencing menopausal

symptoms

Menopausal symptoms

Cause of menopause

Other health issues

Cancer treatments

Psychological issues

Socioeconomic/ education

Age Ethnicity

and culture

Lifestyle

Climate

Attitude to menopause/

aging

Diagnosing Menopause • DON’T

– Check FSH, LH, oestradiol or testosterone levels in a woman

with symptoms around the expected age of menopause (over 45

years)

• these results are unlikely to change your management. The indications for

intervention are clinical.

• DO

– Take a good history of menopausal symptoms, preferably using

a standardised symptom measurement system

– Record personal and family medical history and risk factors incl.

breast cancer, thromboembolic disease and osteoporosis

– Investigate appropriately

Because you will offer help to the woman with symptoms and

these factors will influence what treatments you advise!

Management is about an holistic approach to improving

health and wellbeing

Hormone Replacement Therapy (Menopause Hormone Therapy)

• The appropriate time to initiate HRT is at the onset of symptoms, i.e. near the menopause.

• HRT should be part of an overall strategy • including lifestyle recommendations regarding diet,

• smoking cessation,

• exercise and

• safe alcohol consumption to maintain health of peri and post menopausal women.

• The option of HRT is an individual decision in terms of: – Quality of life and health priorities as well as

– Personal risk factors such as age, time since menopause and

– The risk of venous thromboembolism, stroke, ischemic heart disease and breast cancer.

Vasomotor Symptoms

* Global Consensus Statement on Menopausal Hormone Therapy de Villiers TJ. Climacteric 2013;16:203–204.

• HRT/MHT is the most effective

treatment for vasomotor symptoms

associated with menopause at any age,

with:

– Benefits more likely to outweigh risks for

symptomatic women before the age of 60

years or within 10 years after menopause.

Osteoporosis

• HRT/MHT is effective and appropriate

for the prevention of osteoporosis-related

fractures in at-risk women before age 60

years or within 10 years after menopause.

• (Treatment of osteoporosis in under 60

years)

* Global Consensus Statement on Menopausal Hormone Therapy de Villiers TJ. Climacteric 2013;16:203–204.

Oestrogen only

• RCTs, observational data and meta-analyses show that standard-dose estrogen-alone HRT/MHT: may decrease

– coronary heart disease and

– all-cause mortality in women younger than 60 years of age and within 10 years of menopause.

• Oestrogen as a single systemic agent in women after hysterectomy

– but additional progestogen is required in the presence of a uterus.

* Global Consensus Statement on Menopausal Hormone Therapy de Villiers TJ. Climacteric 2013;16:203–204.

Oestrogen/Progestogen

• Oestrogen plus progestogen HRT/MHT in this

population show:

– a similar trend for mortality

– most randomized clinical trials no significant increase

or decrease in coronary heart disease

• The increased risk of breast cancer/ VTE risk is

primarily associated with the addition of a progestogen

to estrogen therapy and related to the duration of

use. • Breast cancer /VTE risk is greater in women using medroxyprogesterone

acetate (Provera) than in those receiving other progestins,

• Progesterone appears safest.

* Global Consensus Statement on Menopausal Hormone Therapy de Villiers TJ. Climacteric 2013;16:203–204.

The risk of breast cancer with MHT

The risk of breast cancer in women over 50

years associated with MHT is a complex issue.

• The increased risk of breast cancer is primarily

associated with the addition of a progestogen to

estrogen therapy and related to the duration of

use.

• The risk of breast cancer attributable to MHT is

small and the risk decreases after treatment is

stopped.

Risk of VTE

• The risk of venous thromboembolism and ischaemic stroke increases with oral MHT – but the absolute risk is rare below age 60 years.

• Observational studies point to a lower risk with transdermal therapy. – MHT-related risk for VTE depends on the route of

oestrogen administration and type of progestogen. • Transdermal oestrogens have a minimal effect on haemostasis.

• Tibolone no increase in VTE risk

• The combination of oral oestrogen use with other VTE risk factors dramatically enhances VTE risk.

Hormone Replacement Therapy

• Perimenopause & first 2 years postmenopausal – Cyclic therapy E+P

• Post menopausal (> 2 – 3 years) – Continuous therapy E+P

– Tibolone

• Post hysterectomy – Continuous E

– Tibolone

• Premature or Early – High dose till age 50

– Surgical menopause E only +/- Testosterone

Duration of Therapy

The dose and duration of MHT should be consistent

with treatment goals and safety issues and should be

individualised.

• In women with premature menopause,

– Systemic high dose HRT is recommended at least

until the average age of expected menopause.

• The use of custom-compounded bioidentical

hormone therapy is not recommended.

• Current safety data do not support the use of MHT

in breast cancer survivors.

* Global Consensus Statement on Menopausal Hormone Therapy de Villiers TJ. Climacteric 2013;16:203–204.

HRT after 60 years

• Vasomotor symptoms persist on average of 7.4 years and >10 years in 10% of women.

• Moderate to severe vasomotor symptoms documented in 42% of women aged 60 to 65 years.

• Many women will continue to have vasomotor symptoms after age 65,

• Disrupt sleep and adversely affect health and quality of life.

• The decision to continue or discontinue HRT should be made jointly by the woman and her healthcare provider.

NAMS position statement 2015

Resources

AMS Guide to Equivalent HRT Doses

http://www.menopause.org.au/images/stories/infosheets/docs/AMS_

Guide_to_Equivalent_HRT_Doses_2015.pdf

Jean Hailes

Menopause Management

GP Tool

• Phases of Menopause

• Common Symptoms

• Routine Checks

• Hormone Replacement Therapy

• Special Conditions

• Bone Health

• Emotional Health

Genitourinary syndrome of the menopause

Genitourinary Syndrome of

Menopause

• Symptoms and signs due to low oestrogen and other sex steroids – changes to the labia majora/minora, clitoris,

vestibule/introitus, vagina, urethra and bladder.

– may include • genital symptoms of dryness, burning, and irritation;

• sexual symptoms of lack of lubrication, discomfort or pain, loss of libido and impaired function; and

• urinary symptoms of urgency, dysuria and recurrent urinary tract infections.

– may present with some or all of the signs and symptoms,

» Portman D. 2014,

Oestrogen only

• Local/Vaginal

• low-dose oestrogen

therapy

– Oestriol cream

– Low dose 10mcg oestradiol tablet

Vaginal Oestradiol

• Oestradiol 10ug vaginal tablet

• with an annual estrogen exposure of only 1.14

mg.

• displays minimal systemic E2 absorption,

• has no increased risk of endometrial

hyperplasia or carcinoma and

• improved management of the symptoms of

estrogen deficiency-induced vaginal atrophy

Non hormonal therapies

Medication Reduction in HF (versus placebo)

Duration of studies

Additional benefits

Adverse effects

SNRI

Desvenlafaxine 100mg/day

64% (vs 51%) 1 year Improved sleep GIT, sexual dysfunction, Discontinuation syndrome

Venlafaxine SR 75mg/day

60% (vs 27%) 8 weeks

SSRI

Escitalopram 10-20mg/day

55% (vs 38%) 8 weeks Improved sleep, mood, QOL. No effect on sexual function

No discontinuation syndrome at 10mg

Citalopram 10-40mg/day

49% (vs23%) 6 weeks-9 months

Fluoxetine 20 mg/day

6 weeks-9 months

Interferes with tamoxifen GIT, insomnia

Paroxetine 7.5- 12.5mg

40-56% (vs 28-37%)

6-24 weeks Improved mood Improved sleep with low dose

Interferes with Tamoxifen GIT, insomnia No discontinuation syndrome at 7.5mg dose

Nelson et al., JAMA 2006; Rada et al., Cochrane review 2009; Loprinzi et al., JCO 2009

Medication Reduction in HF (versus placebo)

Duration of studies

Additional benefits

Adverse effects

Gabapentin 900-2400mg/day in divided doses

50-80% (vs 20-40 %)

8 weeks Improved sleep Decreased pain at week 4 Improved sleep, mood, QOL

Dizziness, drowsiness Weight gain with higher dose?

Pregabalin 75-150mg bd

60% (vs 36%) 6 weeks

Clonidine 25mg bd to 50mgbd

40% (vs 38%) 4-8 weeks Only agent listed on PBS

Dry mouth

Nelson et al., JAMA 2006; Rada et al., Cochrane review 2009; Loprinzi et al., JCO 2009

Treatment: Vasomotor symptoms:

Effective non- drug treatments

Therapy Effectiveness

Cognitive behavioural therapy Reduction in bothersomeness of VMS by 30-40% at 6 months. Improved mood, sleep, sexual function, QOL 1

Acupuncture 40% reduction in VMS 2

Hypnosis Limited evidence of benefit 3

1. Ayers et al., Menopause 2013; 2. Chui et al., Menopause 2014; 3. Elkins et al., Menopause 2013.

Treatment: Vasomotor symptoms: Watch this space…..

Therapy Effectiveness

Stellate ganglion block Pilot study: 50% reduction in VMS

Magnesium Pilot study- promising

Folic acid Pilot study- promising

Paced respiration Conflicting evidence

Weight loss Pilot study- promising

Yoga Pilot study -promising

No proven benefit and/or safety unknown

SOY

HERBS

HOMEOPATHY

VITAMIN E OMEGA-3

New Therapies

New therapies

• Gynoflor • Low dose oestriol /lactobacillus combined vaginal preparation,

improved symptoms in Breast cancer patients on AIs • Donders et al 2014

• Ospemifene • non-steroidal oral estrogen receptor agonist/antagonist, (ERAA)

• oestrogen agonist effect in the vaginal epithelium

• improved the vaginal maturation index (decreased parabasal cells and increased superficial cells),

• decreased vaginal pH, and

• decreased severity of the self-identified most bothersome symptom (dyspareunia or vaginal dryness) compared to placebo.

• Side effect hot flushes 13% • Simon J Climacteric 2013

New therapies

• Prasterone • Daily intravaginal prasterone (DHEA) (0.50%; 6.5

mg) treatment.

• Significant beneficial effects

– Lower percentage of vaginal parabasal cells, higher

percentage of vaginal superficial cells, vaginal pH,

– Reduction in moderate to severe dyspareunia

• No significant drug-related adverse effect

– Archer D et al 2015

New Therapies

• Conjugated oestrogens/ bazedoxifene

– TSEC tissue-selective estrogen complex – CE+ BZA (SERM))

– Approved in the United States and Europe

– Indicated for management of menopausal symptoms in women with intact uteri

• Neutral effects on the uterus and on breast tissue (SERM effect)

• Potential for skeletal benefit as CE and BZA are effective for fracture risk reduction

Menopause 2014

• HRT in healthy women

50-59 years who are

symptomatic is low risk

• Duration of therapy

depends on duration of

symptoms and an

annual risk /benefit

analysis

Menopause 2014

• Complex hormonal

changes as

periods cease.

• Quality of

life/Symptoms

– Management strategies • Knowledge

• Self help strategies

• HRT

• Non hormonal therapies