Menopause and HRT

Maureen Mc Farland

October 2006

Consultation

Ascertain menopausal status (LMP, symptoms, contraception)

Risk factors for CVD / VTE Risk factors for osteoporosis / breast Ca Woman’s personal views on the menopause

itself and on any interventions It is a woman’s evidence-based patient

choice to take or not to take HRT/ therapy Her decision recorded

Menopause in perspective

Average age – 52 Average life expectancy – 81 and increasing women can expect to live around 30 years in

the postmenopausal state More women will live to be 100 Can now be considered to be a mid-life event

Symptoms: vasomotor

About 70% in Western cultures will experience vasomotor symptoms

Prevalence highest in 1st year after FMP Sympathetic nervous control of blood flow to

the skin is impaired No reflex constriction to ice stimulus Serotonin and its receptors implicated

Symptoms : psychological

While many symptoms have been associated with menopause

General population studies show most women do not experience major changes in mood

Likely to be associated with past problems and current life stresses

Symptoms: sexual dysfunction

US National Health & Social Life Survey :

- SD is more prevalent for women (43%) than men (31%)

Population studies: numbers with FSD rise from 42% to 88% during early to late perimenopause (before FMP)

Underlying reasons for FSD are commonly multifactorial – hormonal and non-hormonal

Long term complications of oestrogen deficiency

Greater bearing on women’s QOL Clinically silent for years Far greater problem in terms of morbidity,

mortality and economic burden

- Osteoporosis- CVD - Dementia- Urogenital atrophy

Osteoporosis

1 in 3 women, 1 in 12 men National Institute of Health definition: -

skeletal disorder characterized by compromised bone strength predisposing to increased risk of fracture

Bone strength: integration of bone density and bone quality

Determinants of bone mass:

Age – peaks mid 20s,

- begins to decline mid-40s

- accelerated rate of loss for 6-10 yrs after menopause

- slower rate of loss

- Seems sensible to encourage good diet in childhood, with exercise and no smoking – little evidence of efficacy of these

Determinants of bone mass

Ethnicity and genetic factors – greater role than environmental influences

DMPA – relationship complex:- Amenorrhoea is associated with a 5-10% loss

of bone – not progressive- Patient’s own risk factors for OP- Should be stopped around 40- Long term effects on teenagers uncertain

Risk factors for osteoporosis

Genetic – FH esp 1° relative with hip Constitutional – low BMI, early menopause Environmental – smoking, alcohol, diet,

sedentary Drugs – steroids Diseases – RA, neuromuscular,liver disease,

malabsorption, hyperparathyroid, hyperthyroid, hypogonadism

Cardiovascular disease

Most common cause of death in women over 60yrs

Stroke – major cause of long term disability Oophorectomized women are at 2-3 fold

increase risk of CHD

WHI (nearly 4 yrs ago)

Reported no beneficial effect and may increase the risk of CHD

BUT >20% of these women were >70yrs, mean age 63yrs

NOT age of typical menopausal woman with symptoms

WHI data overall cannot be used to discuss women <60yrs

WHI 50-59 – less CHD, CABG, PCTA, angina

Danish Study

30% decrease in mortality from CHD

Interpretation: there may be a window of opportunity for CVD protection

No comment from regulating authorities

Dementia

One of the major causes of disability world-wide

Women have a central role providing care and support to people with dementia

Swedish twin study 2005 (6604) Length of reproductive period and age at

menopause were inversely associated with risk of cognitive decline

Use of HT -> 40% decline in risk

Urogenital Atrophy

Oestrogen deficiency after menopause cause atrophic changes in urogenital tract -> urinary symptoms eg frequency, nocturia, incontinence, recurrent infection.

These may co-exist with symptoms of genital atrophy – dyspareunia, itching, burning, dryness

Smoking decreases bioavailability of oestrogen -> inc symptoms

Timing of symptoms varies

Vaginal atrophy

Pre-menopausal vaginal epithelium pH <4 Post-menopausal – glycogen depletion ->

loss of lactic acid-> vaginal more easily colonised by other bacteria

Changes in collagen in pelvic floor -> pelvic floor atrophy and shortened urethra

Women using systemic HT may need additional vaginal oestrogen

Identify the “at risk” patients

Young women with premature menopause hormone profile in all hysterectomised

women women with fragility fractures Integrated care within a practice - include

Practice nurses doing “well-woman” clinics discharge letters from hospital

examination

BMI BP Breast and pelvic examination ONLY if

clinically indicated (as with OCP) Encourage cervical and breast screening

HRT Prescribing

Risk / benefit analysis

Follow-up

3 months - symptom relief,

- persistence of s/es

- abnormal bleeding

- (BP) Yearly - risk / benefit discussion

- BP

- abnormal bleeding

Investigations

FSH levels are only helpful if diagnosis is in doubt FSH not a guide to fertility status FSH no help in monitoring HRT Measure FSH if suspected premature Ov

failure Sample FSH ASAP after day 1 Oestradiol levels only useful for monitoring

non-oral HRT

Investigations

TFT – abnormalities can be confused with menopausal symptoms

Urinary catecholamines – rare cause of hot flushes

Total testosterone unhelpful (Most bound to SHBG [2/3] or albumin [1/3] )

Free testosterone index not available routinely

Investigations

Mammography: no evidence supports routine, over and above NHSBSP

Only 1 in 4 women on combined HRT showed increase breast density

Increase was 3%-6% MWS – observational data from uncontrolled

trials – increase interval cancers WHI O-only arm – NO increased Ca risk

Side effects and Risks

Oestrogen-related: fluid retention, bloating, breast tenderness, nausea, headaches, leg cramps, dyspepsia

Progestogen-related: fluid retention, breast tenderness, headaches or migraine, mood swings, depression, acne, lower abdominal pain, backache

Weight gain?

Major reason given why women are reluctant to try HRT

BUT Randomized placebo-controlled trials

repeatedly show no evidence of HRT – induced weight gain!

Oestrogen deficiency alters fat metabolism -> increased male distribution of fat deposition

Abnormal vaginal bleeding

With sequential – change in pattern or BTB CCT – persists > 4-6 months Concordance, other medication Examine, cervical cytology / Chlamydia TVS – endometrium > 4 mm – endometrial

biopsy / hysteroscopy

HRT and risk of VTE

HRT is associated with significant (but small ) increased risk of thrombosis & stroke

Possibly worse in first years of treatment No increase with transdermal oestrogen If high risk for VTE – consider transdermal

eg women with BMI >30,

WHI data (average age 63yrs)

Extra 7 CHD events per 10,000 Extra 8 strokes per 10,000 Extra 8 breast cancers per 10,000 Extra 18 VTE per 10,000 5 less hip fractures per 10,000 6 less colorectal Ca per 10,000 total mortality - no significant difference

Breast Cancer data

Breast cancers from age 50 - 70 /1000 women

time on HRT Breast Cancers extra Ca

never 45 per 1000 -

5 years use 47 per 1000 2 / 1000

10 yrs. use 51 per 1000 6 / 1000

15 yrs. use 57 per 1000 12 / 1000Beral et al Lancet 1997

WHI breast Ca risk data for 5 years use per 1000 women

Increase only seen in combined therapy

Age absolute difference in risk (death)

50-59 +3 (+1.4)

60-69 +4 (+1.5)

70-79 +7 (+2.2)

All +4 (+1.8)

Osteoporosis Clear evidence of reduced hip and spinal

fracture risk with lower doses Long-term treatment needed for ongoing

fracture prevention Regulatory authorities Dec 2003: HRT not

to be used as a first line prevention Alternatives are available for prevention

and treatment in older women Oestrogen - best option in women who are

younger or symptomatic or both

Osteoporosis

NICE guidelines next year Calculation of 10 year fracture risk Cost of achieving gain in QALY Focus is moving away from prevention, and

towards older age groups (GP contract has failed to reward OP

management)

Osteoporosis

Anti-resorptive agents – oestrogen, SERMs, Bisphosphonates, calcitrol, calcitonin

Anabolic agents – Teriparatide ( pulsed subcutaneous administration parathyroid hormone)

Dual action – strontium (Protelos) Women >65 who show unsatisfactory response to

bisphosphonates – PTH (osteonecrosis of jaw – seen in high dose

bisphosphonates used to treat Ca)

Summary

Decision making is based on Negotiation indication should dictate the duration HRT remains treatment of choice for relief

of symptoms and early prevention of Osteoporosis

Switch to period - free once clearly postmenopausal

Lower dose preparations are better tolerated

Summary

indications for longterm (> 10 yrs.)HRT:

-continuing symptoms

- benefits outweigh risks

-no alternative for osteoporosis reassess individual risks regularly in light of

changing personal circumstances and new data

Women in the Autumn of their lives deserve an Indian Summer, rather than a Winter of Discontent

Robert Greenblatt