• Oestrogen-related adverse effects (e.g. fluid retention, bloating, breast tenderness or enlargement, nausea, headaches, leg cramps, and dyspepsia) may occur continuously or randomly throughout the cycle.
• Advise to persist with treatment for 3 months (as adverse effects may resolve):
• Leg cramps: lifestyle changes (e.g. exercise and stretching of the calf muscles) may be helpful.
• Nausea/gastric upset: adjust the timing of the oestrogen dosage or take with food.
• Breast tenderness: low-fat, high-carbohydrate diet may be helpful.
• Migraine: transdermal therapy as this produces more stable oestrogen levels.
• For persistent adverse effects, consider:
• Reducing the dosage or
• Changing the oestrogen type (i.e. swap between the two main forms of oestrogen, that is, estradiol and conjugated oestrogens) or
• Changing the route of delivery (e.g. tablets may cause nausea, but patches and gels generally do not).

In depth

• Progestogen-related adverse effects (e.g. fluid retention, breast tenderness, headaches/migraine, mood swings, depression, acne, lower abdominal pain, and backache) tend to occur in a cyclical pattern during the progestogen phase of cyclical HRT.
• Advise the woman to persist with therapy for 3 months (adverse effects may resolve).
• For persistent symptoms, consider:
• Changing froma a more androgenic progestogen (e.g. norethisterone and norgestrel) to a less androgenic progestogen (e.g. medroxyprogesterone or dydrogesterone).
• Changing from oral to transdermal, vaginal, or intrauterine progestogen.
• Reducing the duration of progestogen administration: swap from a 14 day to a 12 day product.
• Changing to a product with a lower dose of progestogen (dosages are preparation dependent).
• Switching to a long-cycle regimen, where progestogen is given for 14 days every 3 months (only suitable for women without natural regular periods).
• Changing to continuous combined therapy or tibolone (only suitable if postmenopausal).
• Many of these strategies are the opposite of what may be needed to give better bleeding control.

In depth

• Before changing treatment, visualize the cervix, check smears are up to date, and refer for transvaginal ultrasound to exclude pelvic abnormalities.
• Check compliance, drug interactions (e.g. anticonvulsants), or gastrointestinal upset.
• Altering the progestogen part of the regimen may improve bleeding problems:
• Heavy or prolonged bleeding: increase the duration or dosage of the progestogen, or change the type of progestogen. Idiopathic menorrhagia may be helped by using the levonorgestrel-releasing intrauterine system combined with an oestrogen delivered orally or transdermally.
• Bleeding early in the progestogen phase: increase dosage or change the type of progestogen.
• Irregular bleeding: change regimen or increase the dosage of progestogen.
• No bleeding whilst taking a cyclical regimen reflects an atrophic endometrium and occurs in 5% of women. Pregnancy needs to be excluded in perimenopausal women. Check compliance if the progestogen component is taken separately.

In depth

• Irregular breakthrough bleeding or spotting is common in the first 3–6 months.
• Bleeding beyond 6 months or after a spell of amenorrhoea requires further investigation or referral.

In depth

• Reassure the woman that HRT does not cause significant weight gain.

In depth