Many HRT preparations are available, providing choice of route of administration, dose, and type of regimen. Oral regimens are generally well tolerated by most women and remain the first choice treatment. The indication, severity of symptoms, age of the woman and tolerability determine the optimum dose of oestrogen. Patients who develop unexpected bleeding patterns should be referred for investigation.

Starting treatment

Hormone replacement therapy (HRT) can be used short term (one to two years) to relieve menopausal symptoms and long term (more than seven years) for the prevention of osteoporosis. The benefits and risks associated with treatment are discussed in an accompanying document.

Dose of oestrogen

Table 1. Bone conserving doses of oestrogen
Conjugated equine oestrogens 0.625 mg daily
Oestrogen sulphate  1.5 mg daily
Oestrodiol - oral 1-2 mg daily
Oestrodiol - transdermal 0.05 mg daily
Implant  50 mg six monthly

There is a dose-dependent relationship between oestrogen dose and suppression of hot flushes. If the patient is being treated for menopausal symptoms only, the lowest effective dose of oestrogen should be used.1 In general, younger women have a higher oestrogen requirement than older women e.g. up to two 100mcg patches per day may be necessary to control symptoms after premature menopause (age<45).2 Topical vaginal therapy may be useful for local symptoms and may be added in patients who have not responded adequately to usual systemic doses of oestrogens. Doses required to prevent osteoporosis are shown in table 1.3 These are often higher than the doses of oestrogen needed to relieve menopausal symptoms.

Route of delivery

Delivery systems include tablets, patches, implants, nasal sprays and vaginal creams, pessaries and rings. Patient preference and cost largely affect the route of delivery.

Both oral and transdermal routes have the advantage that treatment can be administered and stopped easily. The oral route is significantly cheaper than the transdermal route so is preferred unless gastrointestinal side effects are a problem. Transdermal routes avoid first pass metabolism and raise high density lipoprotein and triglyceride concentrations less than oral oestrogen; the clinical importance of these differences is not known.3

Types of HRT regimen

Cyclical HRT

continuous oestrogen, either oral or transdermal may be given along with a progestogen for 10-14 days per month to give a monthly withdrawal bleed. Alternatively a progestogen may be given for 14 days at the end of a three monthly cycle (to produce a quarterly withdrawal bleed). Some women have erratic bleeding on the 3-monthly regime, and may prefer to return to regular monthly bleeds.4

Continuous HRT

These regimes are restricted to women who are at least one year post menopause, or who are over 54 years old and consequently have low levels of circulating oestradiol. Earlier administration may result in unscheduled bleeding.2 With continuous oestrogen and progestogen regimens, bleeding is light to moderate in amount but the timing may be erratic and unpredictable. After 1 year bleeding stops in 90% of individuals.1 These regimens are well tolerated but patients must be counselled that irregular bleeding may occur during the first 4-6 months of treatment. Any bleeding that develops subsequently should be investigated.

Managing common unwanted effects

Side effects can be minimised or prevented by starting with a low dose and increasing it slowly. Short-term side-effects such as breast tenderness, headaches, slight nausea and bloating are due to raised levels of oestrodiol, and often resolve within three months. There is limited data comparing adverse effects in the different hormones and route of administration.

All progesterone can cause bloating, weight gain and symptoms similar to the premenstrual syndrome. They occur before a withdrawal bleed. If this causes a problem, changing to a different class of progestogen, or a three monthly cycle may help.4

Treatment alternatives

For women who are unable or disinclined to take HRT, alternatives are available. Tibolone could be used for vasomotor symptoms and osteoporosis prophylaxis. Raloxifene is licensed for the treatment and prevention of postmenopausal osteoporosis.

Other agents such as phyto-oestrogens and oil of primrose are claimed to relieve menopausal symptoms, but there is limited evidence to support their use.

Who should take HRT and for how long?

For the treatment of vasomotor symptoms, HRT can be started without waiting for persistent amenorrhoea as symptoms often start before periods finally stop. It remains unclear if and when HRT should be stopped in women who remain well. It has been suggested that HRT should be used for at least one year and then withdrawn. If symptoms return, treatment should be restarted for a further 3-6 months, then withdrawn again.5

Patients who are at high risk of osteoporotic fractures in the future should be considered for early treatment with HRT, which should continue for at least seven years. These include patients with premature menopause, early onset osteoporotic fracture and long term steroid treatment.

References

  1. Greendale GA, Lee NP, Arriola ER. The menopause. Lancet 1999;353:571-80. (R)
  2. Purdie D, Craword I. The menopause (2) Management of the symptomatic menopause. The Pharmaceutical Journal 1999;263:750-3.(R)
  3. Barrett-Connor E. Hormone replacement therapy. British Medical Journal 1998;317:457-61. (R)
  4. Anon. Hormone replacement therapy. Drug and Therapeutics Bulletin. 1996;34:81-4 (R)
  5. Anon. Hormone replacement therapy 1: new evidence MeReC bulletin 1997;8:9-12. (R)

KEY RCT - randomised controlled trial, CT - controlled trial, O - open study, MA - meta analysis, R - review, U - unpublished, Abs - abstract, E - editorial