Endometrial cancer 2 ; 3 50–59

6 Endometrial cancer 2 ; 3 50–59

2 4 4 32 NS NS 60–69

3 6 6 48 NS NS Ovarian cancer

3 6 < 1 2 < 1 2 Venous thromboembolism 4 ; 5 50–59

9 3 3 Coronary heart disease 7 ; 8 70–79

Note Where background incidence or additional cases have not been included in the table, this indicates a lack of available data. NS indicates a non-significant difference Taken from MHRA/CHM (Drug Safety Update 2007;

1 (2): 2–6 available at www.mhra.gov.uk/mhra/drugsafetyupdate

1. Tibolone increases the risk of breast cancer but to a lesser extent than with combined HRT. 2. Evidence suggests an increased risk of endometrial cancer with tibolone. After 2.7 years of use (in women of average age 68 years), 1 extra case of endometrial hyperplasia and 4 extra cases of endometrial cancer were diagnosed compared with placebo users. 3. The risk of endometrial cancer cannot be reliably estimated in those using combined HRT because the addition of progestogen for at least 10 days per 28-day cycle greatly reduces the additional risk, and addition of a daily progestogen eliminates the additional risk. The risk of endometrial cancer in women who have not used HRT increases with body mass index (BMI); the increased risk of endometrial cancer in users of oestrogen-only HRT or tibolone is more apparent in women who are not overweight. 4. Limited data does not suggest an increased risk of thromboembolism with tibolone compared to combined HRT or women not taking HRT. 5. Although the level of risk of thromboembolism associated with non-oral routes of administration of HRT has not been established, it may be lower for the transdermal route. 6. Tibolone use increases the risk of stroke about 2.2 times from the first year of treatment; risk of stroke is age-dependent and therefore the absolute risk of stroke with tibolone increases with age. 7. Increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause. 8. There is insufficient data to draw a conclusion on the risk of coronary heart disease with tibolone.

BNF 57

6.4.1 Female sex hormones 397

any potentially fertile woman needs HRT, non-hormonal rashes and chloasma, changes in libido, depression, contraceptive measures (such as condoms) are neces-

mood changes, headache, migraine, dizziness, leg sary.

cramps (rule out venous thrombosis), vaginal candi- Measurement of follicle-stimulating hormone can help

diasis, contact lenses may irritate; transdermal deliv- to determine fertility, but high measurements alone

ery systems may cause contact sensitisation (possible (particularly in women aged under 50 years) do not

severe hypersensitivity reaction on continued expo- necessarily preclude the possibility of becoming preg-

sure), and headache has been reported on vigorous nant.

exercise Withdrawal bleeding Cyclical HRT (where a progestogen

Surgery Major surgery under general anaesthesia,

is taken for 12–14 days of each 28-day oestrogen treatment cycle) usually results in regular withdrawal bleeding towards

including orthopaedic and vascular leg surgery, is a the end of the progestogen. The aim of continuous combined predisposing factor for venous thromboembolism and

HRT (where a combination of oestrogen and progestogen is it may be prudent to stop HRT 4–6 weeks before

taken, usually in a single tablet, throughout each 28-day surgery (see Risk of Venous Thromboembolism,

treatment cycle) is to avoid bleeding, but irregular bleeding may occur during the early treatment stages (if it continues

above); it should be restarted only after full mobilisation. endometrial abnormality should be excluded and consid- If HRT is continued or if discontinuation is not possible

eration given to cyclical HRT instead) (e.g. in non-elective surgery), prophylaxis with heparin

Dose

and graduated compression hosiery is advised. Oestro- . See under preparations genic activity may persist after removing an estradiol

Counselling on patches Patch should be removed after 3– implant (see above).

4 days (or once a week in case of 7-day patch) and replaced with fresh patch on slightly different site; recommended

Reasons to stop HRT For circumstances in which

sites: clean, dry, unbroken areas of skin on trunk below HRT should be stopped, see p. 440.

waistline; not to be applied on or near breasts or under waistband. If patch falls off in bath allow skin to cool before applying new patch