Drug reference
PREMARIN ® TABLETS Menopausal symptoms ▶BY MOUTH ▶Adult: 0.3–1.25 mg daily continuously; with cyclical progestogen for 12–14 days of each cycle in women with a uterus Postmenopausal osteoporosis prophylaxis ▶BY MOUTH ▶Adult: 0.625–1.25 mg daily continuously; with cyclical progestogen for 12–14 days of each cycle in women with a uterus
PDF page 819
Active arterial thromboembolic disease (e.g. angina or myocardial infarction). history of breast cancer. history of venous thromboembolism. liver disease (where liver function tests have failed to return to normal). oestrogen-dependent cancer. recent arterial thromboembolic disease (e.g. angina or myocardial infarction). thrombophilic disorder. undiagnosed vaginal bleeding. untreated endometrial hyperplasia
PDF page 819
Acute porphyrias p. 1120. diabetes (increased risk of heart disease). factors predisposing to thromboembolism. history of breast nodules (closely monitor breast status—risk of breast cancer). history of endometrial hyperplasia. history of fibrocystic disease (closely monitor breast status—risk of breast cancer). hypophyseal tumours. increased risk of gall-bladder disease reported. migraine. migraine-like headaches. presence of antiphospholipid antibodies (increased risk of thrombotic events). risk factors for oestrogen-dependent tumours (e.g. breast cancer in first-degree relative). risk of breast cancer. symptoms of endometriosis may be exacerbated. uterine fibroids may increase in size CAUTIONS, FURTHER INFORMATION ▶Risk of breast cancer HRT use is associated with an increased risk of breast cancer—see Important safety information. Radiological detection of breast cancer can be made more difficult as mammographic density can increase with HRT use. ▶Risk of endometrial cancer The increased risk of endometrial cancer depends on the dose and duration of oestrogen- only HRT. Endocrine system In women with a uterus, the addition of a progestogen cyclically (for at least 10 days per 28-day cycle) reduces the additional risk of endometrial cancer; this additional risk is eliminated if a progestogen is given continuously. However, this should be weighed against the increased risk of breast cancer. ▶Risk of ovarian cancer Long-term use of combined HRT or oestrogen-only HRT is associated with a small increased risk of ovarian cancer. This excess risk disappears within a few years of stopping. ▶Risk of venous thromboembolism Women using combined or oestrogen-only HRT are at an increased risk of deep vein thrombosis and of pulmonary embolism especially in the first year of use. In women who have predisposing factors (such as a personal or family history of deep vein thrombosis or pulmonary embolism, severe varicose veins, obesity, trauma, or prolonged bed-rest) it is prudent to review the need for HRT, as in some cases the risks of HRT may exceed the benefits. Travel involving prolonged immobility further increases the risk of deep vein thrombosis. ▶Risk of stroke Risk of stroke increases with age, therefore older women have a greater absolute risk of stroke. Combined HRT or oestrogen-only HRT increases the risk of stroke. ▶Risk of coronary heart disease HRT does not prevent coronary heart disease and should not be prescribed for this purpose. There is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause. Although very little information is available on the risk of coronary heart disease in younger women who start HRT close to the menopause, studies suggest a lower relative risk compared with older women.
PDF pages 819, 820
MHRA/CHM ADVICE: HORMONE REPLACEMENT THERAPY (HRT): FURTHER INFORMATION ON THE KNOWN INCREASED RISK OF BREAST CANCER WITH HRT AND ITS PERSISTENCE AFTER STOPPING (SEPTEMBER 2019) Data from a meta-analysis of more than 100 000 women with breast cancer have confirmed that the risk of breast cancer is increased with the use of all forms of systemic HRT, except vaginal oestrogens, for longer than 1 year. Findings have shown that the risk increases further with longer duration of use, is higher for combined oestrogen-progestogen HRT than with oestrogen-only HRT, and persists for more than 10 years after stopping HRT. Healthcare professionals are advised to only prescribe HRT for the relief of postmenopausal symptoms that adversely affect quality of life, and to regularly review patients to ensure that it is used for the shortest time and at the lowest dose. Patients currently and previously on HRT should be informed of the risk and to be vigilant for signs of breast cancer; they should also be encouraged to attend breast screening appointments.
PDF page 819
→Appendix 1: hormone replacement therapy
PDF page 820
▶Common or very common Alopecia. arthralgia. breast abnormalities. depression. leg cramps. menstrual cycle irregularities. vaginal discharge. weight changes ▶Uncommon Anxiety. cervical abnormalities. contact lens intolerance. dizziness. embolism and thrombosis. gallbladder disorder. gastrointestinal discomfort. headaches. hirsutism. libido disorder. mood altered. nausea. oedema. skin reactions. vulvovaginal candidiasis ▶Rare or very rare Angioedema. asthma exacerbated. cerebrovascular insufficiency. chorea exacerbated. colitis ischaemic. epilepsy exacerbated. galactorrhoea. glucose tolerance impaired. hypocalcaemia. jaundice cholestatic. myocardial infarction. neoplasms. pancreatitis. pelvic pain. vomiting ▶Frequency not known Endometrial hyperplasia. erythema nodosum SIDE-EFFECTS, FURTHER INFORMATION Cyclical HRT (where a progestogen is taken for 12–14 days of each 28-day oestrogen treatment cycle) usually results in regular withdrawal bleeding towards the end of the progestogen. Continuous combined HRT commonly produces irregular breakthrough bleeding in the first 4–6 months of treatment. Bleeding beyond 6 months or after a spell of amenorrhoea requires further investigation to exclude serious gynaecological pathology.
PDF page 820
HRT does not provide contraception and a woman is considered potentially fertile for 2 years after her last menstrual period if she is under 50 years, and for 1 year if she is over 50 years. A woman who is under 50 years and free of all risk factors for venous and arterial disease can use a low-oestrogen combined oral contraceptive pill to provide both relief of menopausal symptoms and contraception; it is recommended that the oral contraceptive be stopped at 50 years of age since there are more suitable alternatives. If any potentially fertile woman needs HRT, non-hormonal contraceptive measures (such as condoms) are necessary. Measurement of follicle-stimulating hormone can help to determine fertility, but high measurements alone (particularly in women aged under 50 years) do not necessarily preclude the possibility of becoming pregnant.
PDF page 820
Manufacturer advises avoid—not indicated during pregnancy.
PDF page 820
Avoid until weaning or for 6 months after birth (adverse effects on lactation).
PDF page 820
Manufacturer advises caution; avoid in acute or active disease.
PDF page 820
There can be variation in the licensing of different medicines containing the same drug. Tablet ▶Premarin (Pfizer Ltd) Conjugated oestrogens 300 microgram Premarin 0.3mg tablets | 84 tablet P £6.07 DT = £6.07 Conjugated oestrogens 625 microgram Premarin 0.625mg tablets | 84 tablet P £4.02 DT = £4.02 Conjugated oestrogens 1.25 mg Premarin 1.25mg tablets | 84 tablet P £3.58 DT = £3.58 Combinations available: Conjugated oestrogens with medroxyprogesterone, p. 803
PDF page 820
Information sheet The MHRA has provided a patient information sheet to aid healthcare professionals when counselling women on the risk of breast cancer with HRT use.
PDF page 820
0.3–1.25 mg daily continuously; with cyclical
First-line fragment. Read the complete Indications and Dose section above.
PDF page 819
0.625–1.25 mg daily continuously; with cyclical
First-line fragment. Read the complete Indications and Dose section above.
PDF page 819
