HORMONE REPLACEMENT THERAPY

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HORMONE REPLACEMENT THERAPY

• An overview

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Menopause

• 12 months after the last period
• Mean age 51 years
• Perimenopausal symptoms 4 years before
• TAH women upto 5 years prematurely
• Signs/ symptoms in other conditions
• FSH gt 30iu/l diagnostic

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Choice of HRT preparations

• Unopposed oestrogens
• Sequential combined oestrogen/progestogens
• Continuous combined oestrogen/progestogens
• Local oestogen
• Tibolone (Livial)

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The Oestrogens

• Synthetic
• - ethinyl oestradiol
• - mestranol
• Natural or conjugated equine
• - 17b oestradiol
• - oestradiol valerate

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The Progestagens

• 19 norethisterone types (androgenic)
• - norethisterone
• - levo / norgestrol
• the Progesterone analogues
• Dihydrogesterone
• Medroxyprogesterone acetate (MPA)

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Tibolone (Livial)

• A synthetic steroid with weak androgenic,
  oestrogenic and progestogenic properties

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Disadvantages of HRT

• Increased risk of endometrial, breast cancer
  with unopposed oestrogen
• Risk increases with length of exposure
• Risk of breast cancer after 5 years use
• Thromboembolism RR x 3

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Advantages to HRT

• Vasomotor symptoms reduced (75 women)
• Psychological benefit
• Improves libido
• Urogenital symptoms improved

• Prevention of osteoporosis
• Cardiovascular prevention

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Prevention of osteoporosis

• 1/3 of life post menopausal as life expectancy
  for women 75 years
• High risk women e.g steroid use, smokers. Family
  history
• Bone loss continues after cessation of therapy
• Tibolone also licensed for this

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Cardio vascular protection

• oral HRT increases HDL reduces LDL
• 20 reduction in IHD
• 15 reduction in CVA
• Evidence shows reduction in Alzheimers disease

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Hypertension - myths

• Synthetic oral oestrogen (ethinyl oestradiol) in
  COCP can stimulate hepatic production of renin
  angiotensinogen leading to vasoconstriction
  hypertension
• But oestrogen also causes vasodilatation
• SO that there is no evidence that HRT affects BP

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Contraindications to HRT

• Unexplained genital tract bleeding
• Active liver disease
• Pregnancy
• Breast feeding
• Active VTE
• Familial risk VTE
• Active treatment for breast cancer

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Routes of administration

• Oral
• Transdermal patches
• Subcutaneous implants( testosterone)
• Transdermal gel
• Local forms e.g. creams, pessaries, ring(estring)
• Mirena in the future ( an oestrogen)

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Transdermal/subcutaneousoestrogens

• Avoid first pass metabolism therefore lower
  oestrogen dose
• Good for certain groups of women-
• vv, VTE, hypertension, smokers, obese,
  malabsorption syndromes, migraine, on enzyme
  inducing agents, with oestrogenic side effects,
  raised triglycerides, gallstone disease

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Drug related side effects

• oestrogenic
• Breast tenderness
• Vaginal discharge
• Leg cramps
• Headaches
• Eye irritation

• progestogenic
• PMS
• Acne / oily skin
• Depression
• Bloating
• Weight gain

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Contraception HRT

• Contraception should be continued after the
  menopause for 12 months if aged gt 50 and for 2
  years if under 50
• The POP can be used with HRT
• ? Mirena oestrogen in the future

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SERMS(selective oestrogen receptor modulators)

• Tamoxifen is anti-oestrogenic at the breast but
  oestrogenic to the endometrium and bone
• SERMS are oestrogenic to bone, cv system lipids
  but anti-oestrogenic to breast endometrium
• Raloxifene the first licensed in 1998

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Choice- patient/ doctor

• Symptoms
• Past and present medical history
• Risk factors for osteoporosis, IHD, VTE, breast
  cancer
• Medication
• Lifestyle
• To bleed or not to bleed
• HER CHOICE wins