4. Adverse drug reactions (ADRs) The adverse reactions listed in the table are based on post-marketing spontaneous (reporting rate), clinical trials and class-effects. Breast pain is a very common adverse event reported in ≥ 10% of patients.
System Organ Class Common ADRs (>1/100, < 1/10) Uncommon ADRs (>1/1000, <1/100) Rare ADRs (>1/10000, <1/1000) Very Rare ADRs (<1/10000), isolated reports Infections and infestations Vaginitis Vaginal candidiasis Neoplasms benign and malignant (including cysts and polyps) Fibrocystic breast changes, Ovarian cancer Enlargement of hepatic hemangiomas Immune system disorders Anaphylactic/ anaphylactoid reactions, including urticaria and angioedema Metabolism and nutrition disorders Glucose intolerance Exacerbation of porphyria, Hypocalcaemia Psychiatric disorders Depression Changes in libido; Mood disturbances, Irritability Nervous system disorders Dizziness, Headache, Migraine, Anxiety Stroke, Exacerbation of epilepsy, Exacerbation of chorea Eye disorders Intolerance to contact lenses None Retinal vascular thrombosis Cardiac disorders Myocardial infarction Vascular disorders Pulmonary embolism, Deep vein thrombosis Superficial thrombophlebitis Respiratory, thoracic and mediastinal disorders Exacerbation of asthma Gastrointestinal disorders Nausea, Bloating, Abdominal pain Vomiting, Pancreatitis Hepatobiliary disorders Gallbladder disease Cholestatic jaundice Skin and subcutaneous tissue disorders Alopecia; Acne; Pruritus Chloasma/melas ma, Hirsutism, Pruritus; Rash Musculoskeletal , connective tissue and bone disorders Arthralgias, Leg cramps Reproductive system & breast disorders Breakthrough bleeding/ spotting Dysmenorrhea, Breast, tenderness / enlargement, Discharge Change in menstrual flow, Change in cervical ectropion and secretion Galactorrhoea, Increased size of uterine leiomyomata General disorders and administration site conditions Oedema Investigations Changes in weight (increase or decrease), Increased triglycerides Increase in blood pressure Breast cancer • An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined estrogen-progestogen therapy for more than 5 years.
• Any increased risk in users of estrogen-only therapy is substantially lower than that seen in users of estrogen-progestogen combinations. 4). • Results of the largest randomised placebo-controlled trial (WHI-study) and largest epidemiological study (MWS) are presented.
7 6 (5-7) #Overall risk ratio. The risk ratio is not constant but will increase with increasing duration on use Note: Since the background incidence of breast cancer differs by EU country, the number of additional cases of breast cancer will also change proportionately.
5) +4 (0 – 9) ‡When the analysis was restricted to women who had not used HRT prior to the study there was no increased risk apparent during the first 5 years of treatment: after 5 years the risk was higher than in non-users. *Taken from baseline incidence rates in developed countries **WHI study in women with no uterus, which did not show an increase in risk of breast cancer Endometrial Cancer Postmenopausal women with a uterus The endometrial cancer risk is about 5 in every 1000 women with a uterus not using HRT.
4). Depending on the duration of estrogen-only use and estrogen dose, the increase in risk of endometrial cancer in epidemiology studies varied from between 5 and 55 extra cases diagnosed in every 1000 women between the ages of 50 and 65.
Adding a progestogen to estrogen-only therapy for at least 12 days per cycle can prevent this increased risk. 2)). 4). 56). For women aged 50 to 54 years taking 5 years of HRT, this results in about 1 extra case per 2000 users. In women aged 50 to 54 who are not taking HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period.
e. deep vein thrombosis or pulmonary embolism. 4). 3) 5 (1 - 13) *Study in women with no uterus Risk of coronary artery disease • The risk of coronary artery disease is slightly […]