Hormone replacement therapy continued

Hysterectomised patients

Oral

• Low dose – recommended as starting dose
• Higher dose – when symptoms are not controlled by the above

Non-oral

• Patches:
  • can be matrix or reservoir
  • matrix tend to cause less skin irritation and adhere better
  • patches can be changed once or twice weekly
• Gels – are useful if transdermal treatment is the preferred option but skin irritation occurs with patches
• Implants:
  • usually used as a last resort in patients post-hysterectomy when symptoms are not controlled by other means
• All estrogen only preparations can be used in non-hysterectomised patients, as long as an appropriate progestogen is given in addition

Testosterone

• Women who have had a hysterectomy and ovaries removed may benefit from testosterone replacement therapy along with estrogen, for improved libido. Testosterone implant 6 monthly or twice weekly patch in conjunction with systemic estrogen

Perimenopausal patients

• Sequential combined therapies are used in women with an intact uterus who are not yet postmenopausal, i.e. have some continuing ovarian function. Products contain daily estrogen and cyclical progestogen, causing a bleed each month in 85% of patients
• Side effects are often experienced during the progestogen phase of treatment and can be reduced by using a product containing a different type or route of progestogen
• Available as oral or patches
• Low dose – recommended as starting dose
• Long cycle treatment – useful in perimenopausal patients who are having infrequent periods, but may not be sufficiently post menopausal to offer continuous combined therapy to, and will confer a bleed every 3 months
• Tailor-made sequential combined therapy is useful in patients who develop PMS type symptoms on a fixed HRT, particularly if the regime contains a progestogen of testosterone derivation
• The following progestogens can be given with estrogen only regimes:
  • micronised progesterone – 200 mg daily at bedtime for 12 days per 28 days (days 15–26 inclusive)
  • medroxyprogesterone acetate – 10 mg daily for 14 days per 28 days
  • intra-uterine progestogen-only system – licensed for use for 4 years as the progestogen part of HRT
• Careful explanation is required as to the timing of administration of the separate progestogen, in order to synchronise it with the existing cycle

Hormone replacement therapy continued

Post menopausal patients

• Continuous combined therapies offer ‘period free’ therapy for patients who are ≥54 years, or more than 1 year post menopausal at any age
• The criteria should be fulfilled in order to offer such treatment to patients who no longer have a continuing ovarian cycle, so that steady levels of both estrogen and progestogen can be achieved
• Start with low dose preparations and increase as necessary for symptom control
• Continuous combined therapies are available as oral or patches
• Patients should be advised to expect some bleeding in the first few months of treatment, but should have settled by six months

Gonadomimetic (tibolone)

• Because of its androgenic component, tibolone can be particularly helpful for postmenopausal patients with reduced libido
• Current evidence suggests that tibolone does not increase mammographic breast density, as it may occur with other types of HRT
• Long-term use of tibolone is thought to be associated with a similar increased risk of breast cancer to that of estrogen alone, which is less than that of estrogen plus progestogen

Why and when to offer continuous combined therapy

• Why?
  • no physiological reason for menstrual bleeds if can be avoided
  • most women prefer a no-period option
  • cheaper for patient – one prescription charge instead of the two for sequential combined therapy
  • thought to be less risk of endometrial hyperplasia in the long term with continuous combined compared to sequential therapy
• When?
  • patient known to be post-menopausal at whatever age, ideally by having at least one year of amenorrhoea
  • if sequential therapy started whilst patient is still having periods, wait till age 54 years. At 54 years 80% of women will have cessation of ovarian function
  • change from sequential to continuous combined by advising patient to finish current sequential pack and start new therapy at the end of the expected bleed

Follow up

Initial follow up

• When commenced on HRT, or when HRT changed, see after 3 months to:
  • – assess effect of therapy
  • – enquire about side effects and bleeding pattern
  • – check blood pressure and weight

Annual review

• When settled on therapy see annually to:
  • check effectiveness of therapy and presence of side effects
  • update on best type of therapy for patients
  • discuss pros and cons of continuing HRT, in particular, discussing increased risk of breast cancer with long-term HRT
  • check blood pressure
  • encourage breast awareness
  • cervical smear 3 yearly
  • carry out pelvic examination (only if clinically indicated)

Management of side effects

• In all patients allow 3 months on treatment before making any changes as frequently side effects subside
• Estrogenic symptoms include breast tenderness/enlargement, leg cramps, bloating, nausea and headache. Consider the following:
  • try evening primrose oil
  • reduce estrogen dose, particularly in older patients
  • take medication with food
  • change route of administration
  • change type of oral estrogen
• Progestogenic symptoms include PMS type symptoms, breast tenderness, lower abdominal pain, backache, depressed mood, acne/greasy skin. Consider the following:
  • change progestogen
  • change route of administration
  • offer tailor-made combination (remember recommended dose and duration for endometrial protection)
  • if post menopausal, consider changing to continuous combined or tibolone to avoid symptoms related to progestogen fluctuation

Management of poor symptom control

• Poor symptom control:
  • check compliance
  • allow 3 to 6 months on therapy to ensure full effect
  • inadequate estrogen dosage – increase dose or change from oral to non-oral route
  • poor absorption due to bowel disorder – change to non-oral route
  • drug interactions e.g. barbiturates, phenytoin, carbamazepine – increase oral dose or change to non-oral route
  • poor patch adhesion – change delivery system
  • incorrect diagnosis – review indications
  • unrealistic expectations – counsel

Hormone replacement therapy continued

When to refer

• Persistent side effects following logical therapy changes as per side effect management
• Inadequate control despite logical changes in HRT as per poor symptom control
• Bleeding problems:
  • during sequential therapy – change in pattern of bleeding including increased duration, frequency and/or heaviness, and irregular bleeding
  • during continuous combined therapy or tibolone – if still bleeding after 6 months of therapy or if bleeding occurs after a spell of amenorrhoea
  • Selective estrogen receptor modulators (SERMs) – any bleeding whilst on therapy should be treated as a post menopausal bleed
• Complex medical history
• History of hormone dependent cancer
• Patient request

Management flowchart for patients with menopause

full guidelines available from…
http://www.menopausematters.co.uk

Menopause Matters. Hormone replacement therapy. May 2005, updated January 2011.