HRT - Follow-up Assessments

See also Hormone Replacement Therapy record.

Large studies (such as Women's Health Initiative¹ and the Million Women Study²) have cast concerns and controversy over the wide-spread use of HRT with evidence of increased risk of breast cancer, cardiovascular disease and thromboembolic disease and little evidence for supposed benefits such as maintained protection against osteoporosis and cognitive decline.³

However, many women still have significant and disabling symptoms associated with menopause and HRT continues to have an important clinical role in improving quality of life in symptomatic menopausal women, with many opting to remain on HRT despite the research findings.⁴ This is reflected by attitudes of UK women doctors to using HRT themselves: whilst uptake and continuation rates have declined since 1993 (reflecting general prescribing trends), many still intend to continue long term use of HRT.⁵

Components to a follow-up assessment:

• Check effectiveness: is the patient receiving adequate oestrogen?
  Where a patient remains symptomatic, consider:
  • Poor absorption - for example, due to bowel disorder.
  • Drug interactions reducing bio-available oestrogen - for example, carbamazepine and phenytoin.
  • Problems with patch adhesion.
  • Incorrect diagnosis - hypothyroidism or diabetes may mimic some features of menopause.
  • Patient expectations may also need to be addressed.
  Altering the HRT product or regimen may help address some of these problems.
• Check for side-effects, e.g. breast tenderness or enlargement, nausea, headaches or bleeding, and manage appropriately.
• Check BP and weight.
• Breast exam - only necessary if clinically indicated (based on symptomatic disease, personal or family history) but better to encourage breast awareness and participation in screening mammography if appropriate for age.
• Pelvic exam - as suggested by patient or family history and cervical smear if appropriate for age (20 - 64).
• A review and discussion of an individual's risk/benefit ratio concerning HRT should occur at least annually. Alternatives to continuing on HRT, including stopping or a trial of an alternative approach for symptom control, should be discussed.

Side-effects account for 35% of HRT discontinuations. These may be oestrogen related (occurring continuously or randomly through a cycle) or progestogen related (occurring cyclically during progestogen phase).

Oestrogen-related side effects

These are usually transient and resolve spontaneously with increasing duration of use. Encourage patients to persist with a particular therapy for at least 12 weeks. They are more likely to occur or be problematic where there has been a longer interval since ovarian failure.
Oestrogen-related side-effects include:

• Breast tenderness - try a low fat, high carbohydrate diet. Evening primrose oil is no longer recommended.
• Leg cramps - try exercise and calf stretching.
• Dyspepsia - adjust time of dose, administer with food.
• Migraine - try transdermal oestrogen as this may produce more stable levels.

For side-effects persisting beyond 12 weeks:

• Reduce the oestrogen dose (though this may limit original menopausal symptom control).
• Change the oestrogen type i.e. between estradiol and conjugated oestrogens.
• Change the route of delivery.

Progestogen-related side effects

These may be more problematic and are usually connected to the type, duration and dose of progestogen. They include:

• Fluid retention
• Headaches or migraine
• Breast tenderness
• Mood swings and depression
• Acne
• Lower abdominal and back pain

Again encourage perseverance as symptoms may improve over 3 months. If there is no improvement, strategies include:

• Change of progestogen type.
• Reduce dose (but not below recommended ceiling required for endometrial protection).
• Change route e.g. away from oral therapy if nausea is predominant.
• Reduce duration of therapy - change from a 14 day to a 12 day monthly sequential replacement regime.
• Reduce frequency using long-cycle HRT - progestogen for 14 days every 3 months (only suitable for women without natural regular cycles).
• Use of continuous combined therapy or tibolone often reduces progestogen-related side-effects with established use (only suitable for postmenopausal women).

Weight gain

This is often given as a major reason why women discontinue HRT but there is no RCT evidence of HRT-induced weight gain. Reassure that weight gain is common at this time of life and counter with dietary and life-style advice.

Bleeding

Monthly sequential preparations should produce regular predictable and acceptable bleeds starting towards the end or soon after the progestogen phase.
This pattern may be altered by:

• Non-concordance
• Drug interaction
• GI upset

Breakthrough bleeding is common in the first 3-6 months of continuous combined and long-cycle HRT regimens.

• Heavy or prolonged bleeding - increase dose, duration or type of progestogen. Consider the use of the levonorgestrel-releasing intrauterine system (IUS) combined with oral or transdermal oestrogen.
• Bleeding early in progestogen phase - increase dose or change type of progestogen.
• Painful bleeding - change type of progestogen.
• Irregular bleeding - change regimen or increase progestogen.
• No bleeding - occurs in 5% women and reflects an atrophic endometrium. Need to exclude pregnancy in perimenopausal women and to ensure compliance with progestogen element of HRT regimen.

Refer to secondary care where:

• Breakthrough bleeding persists for longer than 4–6 months after starting HRT.
• A bleed following amenorrhoea.
• Multiple (3+) treatment failures.

Urgent referral where any persistent or unexplained bleeding continues beyond 6 weeks after stopping HRT.

Menopausal symptoms (hot flushes and sweats) last on average between 2-5 years⁹ but there is considerable individual difference and may last decades in some women.
A trial of withdrawal of HRT should be considered in:

• Those women symptom-free on HRT after 1-2 years.
• Women who have been on HRT for longer than 5 years.
• Women on HRT for premature menopause after the age of 50.

Abrupt cessation or gradual withdrawal of HRT?

Little good evidence to guide practice. Many women do not notice symptoms even with an abrupt cessation whilst others revert swiftly to their original problems with hot flushes and sweats and sleep disturbance.
Some experts suggest gradual reduction of HRT dose:⁶

• Oestrogen only tablets - decrease to 1 mg daily for 1-2 months and then alternate days for a further 1-2 months
• Oestrogen only patches - step down a patch strength daily to 25 micrograms daily for 1-2 months and then half a matrix patch of this dose for a further 1-2 months
• Cyclical combined tablets - step down to pack containing 1 mg estradiol daily for 1-2 months, then switch to alternate day dosing (use alternate tablets from calender pack to ensure receiving progestogen for part of cycle)
• Cyclical combined patches - as for oestrogen-only patches but ensure use oestrogen-only patches for 2 weeks of cycle and combined patches for further 2 weeks
• Continuous combined tablets and patches - reduce dose gradually to the lowest strength of tablets or patches and then use alternate day tablets or half a patch for a further 1-2 months.

Vasomotor symptoms frequently recur on stopping HRT and where severe, restarting treatment may be the most appropriate course of action.

Lifestyle measures

• There is some evidence that more active women suffer less from menopausal symptoms.
• The most effective activities appear to be regular aerobic exercise such as running or swimming.
• Avoiding possible triggers e.g. caffeine, alcohol, smoking, spicy food, also appears to reduce the severity and frequency of vasomotor symptoms.
• Wear lighter clothing and sleep in a cooler environment. Maintain good sleep hygiene.

Non-drug alternatives

Bioadhesive moisturiser gels such as Replens© rehydrate vaginal tissues more effectively than lubricant vaginal gels and offer an alternative to systemic or vaginal HRT where vaginal dryness is the primary symptom.

Pharmacological alternatives¹⁰

Complementary therapies¹⁰

There is an increasing demand for alternatives to manage menopausal symptoms.
There is little scientific evidence that complementary and alternative therapies can treat menopausal symptoms effectively or provide the same benefits as conventional therapies. However, many use them and believe them to be safer and more 'natural'. National guidance does not recommend the use of any complementary therapies.⁶

Women should be counselled regarding:

• The lack of scientific evidence regarding efficacy.
• The lack of regulation compared to conventional medicines - often little is known regarding active ingredient, safety, adverse effects or potential interactions. Severe adverse side-effects may occur e.g. liver toxicity with black cohosh or kava.
• Some products have oestogenic properties (e.g. ginseng, black cohosh, red clover) and are therefore unsuitable in women with contraindications to oestrogen. Long term safety, particularly effects on the breast and endometrium, are unknown.
• Concerns about contaminants such as mercury, arsenic or lead.