Review of Hormonal replacement therapy

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Review of Hormonal replacement therapy

• BMJ 1998317457-461
• Hospital Practice 20015

2
Introduction

• More women live half of their life after
  menopause
• how should they be counseled about HRT
• is the present protocol evidence based?

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Menopausal symptoms

• Improved the vasomotor symptoms like hot flush
  and night sweats immediately
• without treatment, these disappear in 1-2 years
• useful in urogenital symptoms but not incontinence

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Coronary heart disease

• Observation studies found a decreased in heart
  disease of RR 0.70 for women who used oestrogen
• bias occur because of higher social class, no DM,
  HT, more health conscious
• the cardioprotection is by increasing the
  concentration of HDL, decreasing LDL
• but raised triglycerides.

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• No effect of body weight, fat distribution, BP,
  fasting glucose or insulin concentration
• antioxidant
• calcium channel blocker

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Stroke

• Not associated with a reduced risk of stroke

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Osteoporosis

• Observational studies and clinical trials showed
  a decreased risk of hip fracture by 30 and
  spine fracture by 50
• 10 years after stopping the bone density and
  fracture risk were similar in untreated women.
• Calcium supplement potentiates the effect of
  oestrogen on bone mass.

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Endometrial cancer

• Unopposed oestrogen increased the risk of
  endometrial cancer
• entirely prevented by giving progesterone

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Breast cancer

• Collaborative reanalysis of 51 studies showed
  increase risk of breast cancer with long term
  use.
• For HRT 5 years or more, the RR was 1.35
• however the actual no. of women was small
• bias are expected to reduce the association
• e.g.. No family history, negative mammogram
  prior, premature menopause

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• Higher social class, thinner
• bias in diagnosis more mammogram
• increased breast density in some studies showed
  twofold increase risk of breast cancer

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Other risk and benefits

• Risks increased risk of gallbladder surgery,
  increased DVT and pulmonary embolism.( the
  absolute risk in low)
• benefits ? Decreased risk of colorectal cancer,
  ? Decreased Alzheimers disease

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Mortality

• Associate with longer survival
• not fully explained by a reduced cardiovascular
  death
• may reflect the multiple biological effects of
  oestrogen OR selective use of HRT by healthy women

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Who to treat?

• Indications menopause symptoms and osteoporosis.
• Bone densiometry can be a predictor of fracture
  risk, and identify those who should receive
  prophylactic HRT

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Absolute Contraindications

• Liver disease
• vaginal bleeding
• history of DVT, pulmonary embolism
• oestrogen dependent cancer

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Women at high risk

• Dyslipidemia HRT decrease LDL and increased HDL
• HMG coA reductase (statin) decreased LDL more
  than HRT and shown to prevent heart disease

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• Heart disease not clear for secondary prevention
  of heart disease
• the heart and oestrogen/progestin replacement
  therapy study(HERS) showed no protective effect
  and during the first year, there was 52
  increased risk of clinical event in treatment
  group

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• The risk of recurrence of breast cancer is unknown

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How to treat?

• Poor compliance
• Side effects are mastalgia, bloating,
  bleeding,premenstrual tension and depression
• minimized by half the dose
• transdermal cause less side effect than oral

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• New studies suggest that many women need only
  0.3mg conjugated equinine oestrogen plus 1000mg
  Calcium to preserve bone
• this regime causes minimal mastalgia, bleeding,
  or endometrial hyperplasia

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• Lipoprotein changes are similar with large or
  small doses, but transdermal raised HDL less
• uterine protection requires 12 days of cyclical
  progestogens or combined continuous treatment

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When to treat?

• Later or at the age of menopause?
• Most women develop osteoporosis after 65
• so starting late can reduce the duration of
  treatment and presumably the risk of breast
  cancer while still protecting bone
• facilitate the identification of women at high
  risk because 60 us a better predictor of bone
  density than perimenopausal.

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Delay treatment...

• Not recommended in those of a premature menopause
  , symptoms, or osteoporosis.
• Asymptommatic women of no particular risk for
  fracture can still wait for more evidence.

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Case presentation

• 62 year old women, request HRT for vaginal
  dryness, protect VS cardiovascular disease.
• Three months earlier, she had chest pain and lead
  to the diagnosis of coronary heart disease.
• She was given statin and on low fat diet
• 190lb cholesterol 240mg/dL, LDL 160, HDL 40

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treatment

• Latest evidence does not support the use of HRT
  in women with CHD
• measure bone density at 65 and given vaginal
  estrogen for the vaginal symptoms which has no
  systemic effect.

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Case 2

• 55 yr old woman with history of breast cancer
  request HRT for the management of hot flushes and
  prevention of osteoporosis
• her mother had osteoporosis and broken hip at 65.
• The tumor was estrogen receptor positive,
  diagnosed 5 yrs ago, treated with lumpectomy,
  node excision and radiation,
• followed by 5 years of tamoxifen
• hot flush began after tamoxifen

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Treatment

• Lack of conclusive data regarding the use of HRT
  in breast cancer, unknown recurrence rate.
• Paroxetine 20mg QD for hot flash
• alendronate for osteoporosis
• ? Other selective estrogen receptor modulators
  like raloxifene

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Summary

• Five or more years of postmenopausal oestrogen is
  the standard of care for the prevention or
  treatment of osteoporosis
• continuous use
• May increased risk of breast cancer
• may reduce risk of heart disease
• routine treatment should not be recommended until
  more evidence available