Menopause and HRT

Definitions

• The ‘menopause’ is the final menstrual period of a woman’s life
• However, to diagnose the ‘final menstrual period’, the woman must have been amenorrheic for a minimum of 12 months
• The ‘climacteric‘ is the time leading up to the menopause when the woman’s fertility is waning

Physiology

• As the number of follicles decrease, the ovarian sensitivity to GnRH and LH is reduced and there is falling levels of oestrogen
  • There is a consequential rise in LH and FSH levels
    • This also stimulates stromal tissue to increase levels of oestrone (the production of its precursor from ovarian stromal tissue and adrenals is stimulated by LH/FSH and then converted in the periphery.  This is also now unapposed from luteal progesterone) (NB still dramatically reduced levels of oestradiol since no follicular production)
• The real measure of menopause (hormonally) is elevated FSH (LH also rises but is more quickly cleared by the kidney)

A premenopausal woman’s risk of coronary artery disease is one fifth of a man’s of the same age

Signs/Symptoms

• Menstrual irregularity (as number of recruitable follicles decrease)
• Vasomotor symptoms
  • ‘Hot flushes’; sweats; palpitations
  • Usually last a few minutes
  • May disrupt sleep and cause cognitive/lethargy problems
• Vaginal atrophy predisposes to UTI/dyspareunia/traumatic bleeding/stress incontinence/prolapse
• Osteoporosis due to decreased oestrogen and subsequent increased osteoclastic activity- may predispose to fractures (particularly colles/neck of femur)

Investigations

Although the menopause is a physiological process, care and the appropriate investigations should be taken in those with suspicious histories.

• An FSH>30IU/l on >2 occasions suggests the menopause has passed

Management

• Lifestyle advice
  • For hot flushes, taking regular exercise and losing weight may be beneficial.  Also wearing lighter clothing, sleeping in cooler room, avoiding triggers etc
  • Getting into a good sleep routine may be helpful for other symptoms
• HRT (see below)
• (Hot flushes may also respond to paroxetine or clonidine- used in patients who may be unsuitable for HRT)

Hormone Replacement Therapy

• Indications for HRT
  • Vasomotor symptoms (main indication) and urogenital symptoms
    • NB For urogenital sx alone, vaginal oestrogen may be an alternative
  • It is rare for HRT to be prescribed for mood and/or sexual function alone (unless influenced by sweats/urogenital symptoms), although it will possibly improve both
• Types of HRT
  • Can either come as oestrogen only or with progesterone; and may be prescribed cyclically (with bleeds: oestrogen taken daily and progesterone given at the end of the cycle for 10-14 days- mimicking the natural cycle- OR progesterone is only taken for 14 days every 13 weeks (3-monthly cycle) which may be more beneficial in patients with irregular cycles) or continuously
  • HRT can be taken orally or given as a patch (transdermally)
• Risks and contraindications
  • With combined HRT, there is a small increased risk of breast cancer, coronary event, VTE and stroke.
    • A past medical history and/or significant family history of any of the above (including angina) are contra-indications to HRT
    • Other contraindications include pregnancy/breast feeding, undiagnosed abnormal vaginal bleeding, endometrial cancer, uncontrolled hypertension (BP > 160/110 mmHg is an indication to stop HRT)
• For perimenopausal patients with a uterus
  • Offer cyclical combined HRT at the lowest effective dose and for the shortest duration possible (maximal benefit is usually ~3 months and tx can be continued for up to 5 years (in reality- more))
    • AVOID oestrogen only preparations- risk of endometrial cancer
    • Advise re: contraception (patient can still get pregnant if perimenopausal)
  • After 1 year of cyclical HRT, consider switching to continuous HRT
    • Also discuss advantages of switching to local HRT
• For patients without a uterus (i.e. menopausal symptoms following hysterectomy)
  • Unapposed oestrogen can be given in these patients
• For postmenopausal patients with a uterus
  • Offer continuous combined HRT as you would for perimenopausal patients  
  • Alternatively, tibolone can be used instead
    • Tibolone is a selective oestrogen receptor modulator (SERM)
    • It has a similar risk profile to conventional HRT but the risk of stroke seems to be greater (rarely used in patients >60)

All of the above (risks, duration of use, types of HRT etc) should be explained to the patient prior to prescribing.

• NB For patients with poor symptom control or side effects, consider switching preparations or changing the dose