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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