4%). 6%). Apart from uterus-related adverse drug reactions, there was no other difference in the safety profile in women with or without a uterus. 9 mg continuously combined with P4 100 mg). Adverse drug reactions observed during clinical trials are listed in Table 1 and classified according to frequency and system organ class.
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) very rare (< 1/10 000) and not known (cannot be estimated from the available data).
Table 1:
Adverse drug reactions System organ class Very common Common Uncommon Infections and infestations Vulvovaginal candidiasis Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma Nervous system disorders Dizziness Vascular disorders Venous thromboembolism Gastrointestinal disorders Abdominal pain lowera, Abdominal pain, Abdominal distension, Nausea, Constipation Skin and subcutaneous tissue disorders Urticaria Musculoskeletal and connective tissue disorders Pain in extremity Reproductive system and breast disorders Vaginal haemorrhageb, Endometrial thickening Disordered proliferative endometrium, Breast pain, Breast tenderness, Nipple pain, Uterine spasm, Endometrial hyperplasia, Endometrial polypc, Adenomyosis, Breast massd, Breast swellinge, Ovarian cyst 10 Vaginal discharge, Vulvovaginal pruritus General disorders and administration site conditions Asthenia Peripheral swelling Investigations Weight increased a Includes pelvic pain b Includes uterine haemorrhage and intermenstrual bleeding c Includes cervical polyp and uterine polyp d Includes Phyllodes tumour, breast cyst, breast scan abnormal e Includes breast enlargement, breast engorgement Description of selected adverse reactions Breast cancer risk • An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined oestrogen-progestagen therapy for more than 5 years.
• The increased risk in users of oestrogen-only therapy is lower than that seen in users of oestrogen-progestagen combinations. 4). • Absolute risk estimations based on results of the largest randomised placebo-controlled trial (WHI-study) and the largest meta-analysis of prospective epidemiological studies are presented.
0 *Taken from baseline incidence rates in England in 2015 in women with BMI = 27 (kg/m2) Note: Since the background incidence of breast cancer differs by EU country, the number of additional cases of breast cancer will also change proportionately.
8 *Taken from baseline incidence rates in England in 2015 in women with BMI = 27 (kg/m2) 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) * WHI study in women with no uterus, which did not show an increase in risk of breast cancer ‡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.
Endometrial cancer risk • Postmenopausal women with a uterus The endometrial cancer risk is about 5 in every 1 000 women with a uterus not using HRT. 4). Depending on the duration of oestrogen-only use and oestrogen dose, the increase in risk of endometrial cancer in epidemiology studies varied from between 5 and 55 extra cases diagnosed in every 1 000 women between the ages of 50 and 65.
Adding a progestagen to oestrogen-only therapy for at least 12 days per cycle can prevent this increased risk. 2)). Ovarian cancer Use of oestrogen-only or combined oestrogen-progestagen HRT has been associated with a slightly […]