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 Hormone Replacement Therapy

• Need progestagen to prevent endometrial hyperplasia if woman has uterus

• Cannot be used for Contraception

  • use alternative method for 2 years post-menopause as risk of fertility

Use

• menopausal women whose lives are inconvenienced by vasomotor instability or vaginal atrophy

• reducing risk of Osteoporosis

  • early natural / surgical menopause (<45) at greatest risk

  • multiple risk factors

• treatment of menopausal symptoms

•  

  • vasomotor

  • vaginitis

  • vaginal atrophy

• prophylaxis

  • Ischaemic Heart Disease

  • Osteoporosis

Benefits

• amelioration / reversal of menopausal effect

• reduced Osteoporosis

• reduction in Stroke

• reduction in Myocardial Infarction

  • ? reduced CVS mortality

• reduced risk of Alzheimer's Disease

Options

• Unopposed oestrogens - after hysterectomy

• Cyclic progestagens - bleeding every 1, 3 or 6 months

• Continuous progestagens - but not within one year of menopause, 10% get continuous spotting

Administration

• Oral - but large 1st pass effect on liver

• Transdermal patch

• Transdermal gel

• Implants

• Topical / Vaginal

Side-effects

Contra-indications

• Acute thromboembolism

• undiagnosed vaginal bleeding

• endometrial or breast cancer

• acute liver disease

Risks

• Breast Cancer

• Endometrial Cancer

• Venous thromboembolism / Pulmonary Embolism

Alternatives

• Raloxifen

  • selective oestrogen receptor modifier

  • no effect on endometrium

  • prevents osteoporosis

Disadvantages:

There is an increased risk of endometrial cancer. This risk can be reduced by use of a progestogen, however the use of a progestogen decreases risk reduction in stroke and MI.

The increased risk of breast cancer is related to the duration of HRT. Within about 5 years of stopping HRT the excess risk of breast cancer disappears. Women who use HRT for a short time around the menopause have a very low excess risk.

It is advised that women without predisposing factors for thromboembolism can continue      HRT without excessive risk. In women with predisposing factors the balance of the benefits of HRT need to be weighed against the risk of thromboembolism.

     The Vaginal atrophy for which HRT is prescribed can also be treated with vaginal oestrogen preparations for a few weeks (can be repeated if necessary) thereby avoiding the increased risks of endometrial and breast cancer and risks of venous thromboembolism. The Vaginal preparations, however, cannot alter systemic vasomotor effects of the menopause.

Contra-Indications:

Pregnancy, Oestrogen-dependent cancer, active thrombophlebitis or thromboembolic disorders, liver disease, undiagnosed vaginal bleeding, breast feeding

Cautions:

Migraine, history of breast nodules, fibrocystic disease, pre-existing uterine fibroids, endometriosis, risk factors for thromboembolic disease, porphyria

Side Effects:

Nausea and vomiting, abdominal cramps and bloating, weight changes, breast enlargement and tenderness, premenstrual-like syndrome, sodium and fluid retention, changes in liver function, changes in libido, depression, headache, migraine and dizziness.

Prescribing: 

Natural oestrogens (oestradiol, oestrone, and oestriol) and conjugated oestrogens are appropriate for use in hormone replacement.  Oestrogen therapy can be given continuously or cyclically.

Progestogen is also necessary if the patient has a uterus (eg: has not had a hysterectomy ) or is not on a combined therapy such as tibolone.

Oral preparations of oestrogens are subject to first pass metabolism.  Subcutaneous and transdermal administration more closely mimic endogenous hormone activity.  However, subcutaneous implants can cause rebound vasomotor symptoms reflecting supraphysiological plasma concentrations.  Prolonged endometrial stimulation occurs even after discontinuation and should be considered (as with all hormone replacement therapies) in the event of surgery which is an additional risk actor for venous thromboembolism.

Women with Uterus:

Therapies must include a progestogen.  The addition of a progestogen is essential to minimize the risk of cystic hyperplasia of the endometrium, which can lead to cancer.  Unfortunately, the addition of progestogen diminishes the benefits of oestrogens on MI and stroke risk.  

            Cyclical HRT involves progestogen taken for 10-14 days of each 28 day oestrogen cycle treatment. There is usually a resultant withdrawal bleed towards the end of the progestogen. Continuous combined HRT aims to avoid bleeding. Irregular bleeding can still occur in the beginning of treatment. Some examples are: Prempak-C, Climagest.

      Women without uterus:

These preparations do not include progestogens. Treatments can be in tablet form e.g: Premarin, harmogen; implants (Estradiol implants); patches (Menorest, FemSeven)  or as gels (Oestrogel)

Additional Therapys:

      Tibolone is a slight exception to the above categories. It is an oestrogen and progestogen combined pill with weak androgenic activity. It is given continuously (with no need for additional progestogen.)