Everything you need to know about HRT

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Everything you need to know about HRT

• Urvi Vyas

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Menopause

• The last menstrual period
• gt12 months amennorhoea with no other cause in
  women gt50 years
• Occurs earlier in smokers
• High production of FSH and LH as the negative
  feedback from oestrogen diminishes

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Clinical Features

• Vasomotor- hot flushes
• Urogenital- vaginal dryness and atrophy,
  recurrent UTIs and incontinence
• Psychological- irritability, confusion, loss of
  libido, depression
• CVS- increased risk of ischaemic heart disease
• Osteoporosis- decreased bone density

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Management

• Oral tablets- oestrogen only, opposed oestrogen,
  continuous combined oestrogen and progesterone
  therapy
• Patches
• Creams
• implants

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Indications for HRT

• Early menopause, continue until age 50
• Hysterectomy before the menopause, even if the
  ovaries are conserved
• Relief of symptoms during the menopause
• 2nd line treatment of osteoporosis for women gt51
  years

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Choice of preparation

• For women without a uterus i.e had hysterectomy-
  give oestrogen alone
• Premarin, Progynova, Harmogen
• For women with an intact uterus- progesterone is
  required for the last 12-14 days of the cycle to
  prevent endometrial proliferation
• Prempack, Nuvelle, Trisequens
• Continuous combined oestrogen and progesterone
  therapy-
• Kliofem, Premique, Climesse

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contraindications

• Oestrogen-dependent cancer i.e. endometrial
  cancer
• History of breast cancer
• Active or recent arterial thromboembolic disease
  (angina or MI)
• VTE
• Liver disease
• Dubin-Johnson and Rotor syndromes

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Evidence regarding risks

• The womens health initiative (WHI) (JAMA
  2002288321) RCT of 16000 asymptomatic post
  menopausal women aged 50-79, randomised to
  continuous combined HRT or placebo.
• A small increase in the rates of
• breast cancer (from 30 to 38)
• coronary heart disease (from 30 to 37)
• stroke (from 21 to 29)
• VTE (from 16 to 34)

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• A decrease in
• colorectal cancer (from 16 to 10)
• hip fractures (from 15 to 10)
• Overall global risk was 15 higher in the HRT
  group
• Compounding factors were that the average age was
  63, older than the UK average, and continuous
  combined HRT rather than cyclical HRT was used

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The Million Women Study

• Epidemiological cohort study looking at womens
  HRT use when invited for breast screening, and
  then followed up to look at breast cancer
  development (Lancet 2003362419)
• All women on HRT had a higher breast cancer risk
  than never users
• The risk was highest with combined preparations
• The absolute risk remains small eg for 1 000
  women taking combined HRT for 5 years there would
  be 6 extra cases of breast cancer

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• Oestrogen-only HRT and tibolone are associated
  with small increases in endometrial cancer
• Combined HRT decreases endometrial cancer risk
• But combined HRT is associated with a greater
  increase in breast cancer risk than
  oestrogen-only or tibolone
• Because breast cancer is more common, overall
  there is greater overall risk of cancer with
  combined HRT

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HRT and breast cancer risk

• Your pt aged 50, has a 6.1 risk of getting
  breast cancer in the next 30 year.
• If she takes combined HRT for 3 years the risk
  rises to 6.41
• For 5 years, to 6.7
• For 10 years, to 7.69
• With oestrogen only HRT, after 5 year the risk is
  6.28
• (BMJ 2005331347)

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• The risk/benefit ratio is favourable to treat
  menopausal symptoms, in fully-informed women,
  using the lowest possible doses for the shortest
  possible time

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When Long term HRT needed

• Long term combined preparations are less safe
  than oestrogen alone
• Consider using oestrogen alone with an IUS
• Consider Tibolone

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Tibolone

• 1st line treatment for menopausal sx
• 2nd line therapy for prevention of osteoporosis
• 2.2 times inc risk of stroke
• Inc risk of endometrial cancer, risk increases
  with duration of use
• Increased risk of having breast cancer diagnosed,
  lower than for combined HRT, risk returned to
  baseline within a few years of stopping treatment
• Decreases HDL

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Topical creams

• Deliver oestrogen locally to vaginal tissues
  pessaries, creams, rings
• No progesterone is needed but use is limited to 3
  months if uterus is present

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Alternatives

• Clonidine may reduce flushing symptoms but has
  many side effects
• Beta-blockers may be used for palpitations and
  tachycardia
• Antidepressants and sedatives can be used if
  symptoms persist
• Calcium, vitamin D, Bisphosphonates for
  osteoporosis

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Complementary treatments

• Black cohosh-seems to ease hot flushes but long
  term effects are unknown
• Red Clover-conflicting evidence, some species
  contain coumarins so unsuitable for women who
  take anticoagulants such as warfarin
• Dong quai, evening primrose oil, vitamin E and
  ginseng are no better than placebo
• Kava has been linked to cases of serious liver
  damage and so should be avoided