DR FULVA DAVE 29th November 2016 Menopause & HRT DR FULVA DAVE 29th November 2016

‘Aging’ an unavoidable property of all living tissue.. - Charles Darwin

‘They thought I was a hypochondriac ‘They thought I was a hypochondriac. It’s taken me years to convince them that there was something else besides neurosis’ ‘I didn’t feel like a ‘real woman’. I felt inferior’ ‘I felt like a new person. I was reborn, even though they were brought on by tablets’ ‘Most people say; ‘At my age’, ‘I’m at the age’ and I think, ‘well, I’m not, not at all, I’m half the age’………………

Women’s one third of life in menopause Women make up almost half (47%) the workforce in the UK – occupational health issue 3.5 million women age 50 or over Research at University of Nottingham in 2011 - majority felt they were little preparted for this ‘change of life’ - need for further advice & support - some considered working part-time/alternatives - Issue about temperature control at workplace, poor toilet facilities, lack of access to cold drinking water, uniform etc

Objectives Refresh and strengthen the basics NICE update Clarify myths related to HRT

What is menopause? Meno-pause (cessation of periods) 12 months after last menstrual period Average age in UK - 51 years Perimenopause - symptoms + irregular periods (45-55 years) Early menopause < 45 years (around 5%) Premature menopause < 40 years (1%)

Menopause contd. DO NOT use FSH test to diagnose menopause if on women using hormones Consider using FSH test as a diagnostic test for menopause ONLY if: Age 40 - 45 years with menopausal symptoms including a change in menstrual cycle Age < 40 with a suspicion of early onset of menopause

Premature menopause Aetiology Elevated FSH levels > 30 IU/L (two samples 4-6 weeks apart) Fertility issues Osteoporosis - Increased risk Need HRT until 51 years Refer for expert opinion

Symptoms & effects Hot flushes Osteoporosis Night sweats Cardiovascular disease Sleep disturbances Dementia Joint pains, aches Degenerative/debilitating disease Headaches Incontinence Memory loss Anxiety, depression Vaginal dryness, low libido Oestrogen deficiency Bloating Increased urinary frequency

How does it affect? Not everyone suffers with symptoms 70% - vasomotor symptoms Varies - familial, ethnicity Duration : 6 months - 20 years After 60, requirement for oestrogen reduced

What to do? Awareness Coping mechanisms (Diet, lifestyle, Exercises) If severe, consider HRT

Diet, Exercise, Lifestyle Greatest impact on women’s life Balanced diet & optimum BMI Weight bearing exercise, brisk walking Smoking, alcohol, caffeine, excess salt & sugar

Hormone replacement therapy (HRT) Oestrogen (Main), Progestogens (Endometrial protection) and Testosterone (Rarely used) Truly effective to reduce symptoms and long term benefits for bones Women without uterus Women with uterus - Oestrogen only - Oestrogen & Progesterone Still having periods or within 1 year of LMP Cyclical/Sequential More than one year of LMP or after 54 years Continuous combined

HRT contd. Oestrogen preparations Progesterone preparations Ethinyl estradiol (synthetic) Norethisterone Estradiol Levonorgesterol Estriol Medroxyprogesterone acetate Estrone Mirena IUS Micronised Progesterone – Utrogesterone (natural)

Doses & routes Oral 0.5mg, 1mg, 2mg (once a day) Patches 25, 37.5, 50, 75, 100 mcg (twice weekly) – below waist Gel/Pessary/Cream Progestogens - variable Mirena (20mcg LNG/day) Natural progestogen (utrogestan) 100 or 200mcg Testosterone (gel, cream) Implants no longer available in UK

Side effects Fluid retention Headaches Breast tenderness Bloating Nausea Mood swings PMS like symptoms

Contraindications Oestrogen dependent malignant tumours - breast, endometrium Undiagnosed vaginal bleeding Current DVT/PE Pregnancy

Controversies…..

Women’s Health Initiative (WHI) Million Women Study (MWS) - USA (1993-2002) - UK (1996 – 2003) - 16000 (50-79) - One million women attending NHS - Randomised HRT Vs placebo breast screening clinic over 50 years old - Increase in breast cancer, coronary - Screening women already high risk events, stroke, DVT in HRT group - Study methodology criticised - Study stopped early in 2002 - Oestrogen only increases risk of breast, - HRT in under 60 - Protective uterine and ovarian cancer - Risk is duration dependent, more risk - Combined more risk than oestrogen only with combined than oestrogen only

HRT - risks Breast cancer risk - 4 extra cases /1000 women after 5 years (This is less risk than smoking 10 cigs/day) 45/1000 – population risk 49/1000 – HRT (5 years) 51/1000 – HRT (10 years) Combined HRT more risk than with Oestrogen only Safe for receptor negative cancers SSRIs should not be offered to patients with breast cancer on tamoxifen Risk reduces after stopping HRT

HRT risks contd. Ovarian cancer - No increased risk Endometrial cancer - Adding progestogen decreases risk

HRT risks contd. Venous thromboembolism Risk of VTE is increased with oral HRT compared to baseline population risk Risk of VTE associated with transdermal preparations given at the standard therapeutic dose is no greater than the baseline population risk Risk of VTE is greater in oral HRT compared with transdermal preparations Patients with high risk of VTE (strong FH of VTE or hereditary thrombophilia) refer to menopause specialist or haematologist for assessment before considering HRT

HRT risks contd. Risk of heart disease not increased if started between 50 and 59 Stroke - not increased if started under 60. More risk with smoking and over weight Weight gain - RCT no evidence Osteoporosis - Useful more in Premature menopause, but not a first line for prevention in older Do not use HRT In Breast or Endometrial cancer, Stroke or DVT, Severe liver disease.

Review At 3 months to assess efficacy and tolerability Annually thereafter unless treatment becomes ineffective or side effects from HRT

Referral Ongoing troublesome side effects Treatment does not improve their menopausal symptoms Ongoing troublesome side effects Menopausal symptoms & contraindication to HRT Uncertainty about the most suitable treatment options

Criteria for ultrasound Any bleeding after 6 months of continuous combined HRT even in low risk women Bleeding after amenorrhoea has been established Any bleeding in the first 6 months if any risk factors present

Alternative options Tibolone (Livial) – oestrogenic, progestogenic & androgenic properties SERM - Raloxifene SSRI/SNRI - Venlafaxine/Fluoxetine/Paroxetine Clonidine - not very effective Complementary - soya, red clover, black cohosh, evening primrose, acupuncture, homeotherapy Insufficient data for safety & effectiveness

Alternative options contd. Bio-identical hormones - not enough evidence for safety - same risk and benefit as traditional - unregulated Cognitive behavioural therapy

To summarise…. Premature menopause Peri menopause and Post menopause Totally safe until 51 years, then review Peri menopause and Post menopause Benefits Vs Risk (Individualised) Symptom control & long term benefits (Bones, Heart) Lowest effective dose Sooner the better Not advisable to start after 60 years

Do not use FSH test routinely to diagnose menopause Contraception after last menstrual period – 2 years if < 50 years 1 year if > 50 years Consider referral to appropriate health professional expert for complex cases

Where to refer?

Menopause clinic at QMC, NUH (every Thursday am) Miss Anita Juliana – RCOG & BMS accredited Menopause specialist Staff awareness session quarterly - NUH 14000+ workers 10500 women 4000 > 45 years old

Case discussion

Case study 52 year old secondary school teacher No relevant medical history Always calm and organised Recently irritable and struggling to cope with minor challenges Exploited by school children of her weakness Unable to sleep, asking GP for more sleeping tablets

How to approach? Relevant history LMP 6/12 ago, before that 3/12 ago Night sweats with severe chills sometimes, occasional day time flushes Often wakes up then sweats No interest in sex, often it hurts

She would like to try some HRT Where in menopause transition is she? What are the symptoms? What is her main concern? What is her risk profile?

What do we choose now? Elleste duet 1mg Estradiol 1mg plus NET 1mg from day 17-28 NHS cost £9.72 for 3 months

Review in 3 months Persistence of symptoms Any new symptoms/side effects? When do they occur in the cycle? Bleeding pattern BP Review of risk analysis

3 months later Symptoms and sleep better in the first 2 weeks of the pack Not so good and tearful when pill colour changes Bleeding is fine Would like to improve things

Modify treatment Increase estrogen Change progestogen preparation Femoston 2:10 ( 17B estradiol 2mg plus 10mg dydrogesterone) Cost £13.47 for 3 months

Additional resources NICE guideline 2015 British menopause society www.menopausematters.co.uk www.womens-health-concern.org.uk www.menopause-health-concern.org.uk www.daisynetwork.org.uk TOG article by Dr Dave et al…!

Thank you