8. After stopping treatment, the excess risk will decrease with time and the time needed to return to baseline depends on the duration of prior HRT use. When HRT was taken for more than 5 years, the risk may persist for 10 years or more.
No data for persistence of risk after stopping are available for tibolone, but a similar pattern cannot be ruled out. HRT, especially oestrogen-progestagen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.
Ovarian cancer Ovarian cancer is much rarer than breast cancer. Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women taking oestrogen-only or combined oestrogen-progestagen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping.
8). In the Million Women Study it was shown that the relative risk for ovarian cancer with use of tibolone was similar to the risk associated with use of other types of HRT. e. deep vein thrombosis or pulmonary embolism. 8). In an epidemiological study using a UK database, the risk of VTE in association with tibolone was lower than the risk associated with conventional HRT, but only a small proportion of women were current users of tibolone and a small increase in risk compared with non-use cannot be excluded.
− Patients with known thrombophilic states have an increased risk of VTE and HRT or tibolone may add to this risk. 3). − Generally recognized risk factors for VTE include use of oestrogens, older age, major surgery, prolonged immobilization, obesity (BMI > 30 kg/m2), pregnancy/postpartum period, systemic lupus erythematosus (SLE) and cancer.
There is no consensus about the possible role of varicose veins in VTE. As in all postoperative patients, prophylactic measures need to be considered to prevent VTE following surgery. If prolonged immobilisation is to follow elective surgery temporarily stopping HRT or tibolone 4 to 6 weeks earlier is recommended, if possible.
Treatment should not be restarted until the woman is completely mobilised. − In women with no personal history of VTE but with a first degree relative with a history of thrombosis at young age, screening may be offered after careful counselling regarding its limitations (only a proportion of thrombophilic defects are identified by screening).
g, antithrombin, protein S, or protein C deficiencies or a combination of defects) HRT or tibolone is contraindicated. − Women already on chronic anticoagulant treatment require careful consideration of the benefit-risk of use of HRT or tibolone.
− If VTE develops after initiating therapy, the drug should be discontinued. g. painful swelling of a leg, sudden pain in the chest, dyspnea). Risk of coronary artery disease − There is no evidence from randomised controlled trials of protection against myocardial infarction in women with or without existing CAD who received combined oestrogen-progestogen or oestrogen-only HRT.
In an epidemiological study using the GPRD no evidence was found of protection against myocardial infarction in postmenopausal women who received tibolone. 8). The baseline risk of stroke is strongly age-dependent and so the effect of tibolone is greater with older age.
5 mg tablets is not intended for contraceptive use. 5 mg dose after 2 years). Total triglycerides and lipoprotein(a) levels were also reduced. The decrease in total cholesterol and VLDL- cholesterol levels was not dose-dependent. Levels of LDL- cholesterol were unchanged.
The clinical implication of these findings is not yet known. − Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed. − Women with pre-existing hypertriglyceridaemia should be followed closely during oestrogen replacement or HRT, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition.
5 mg tablets results in a very minor decrease of thyroid binding globulin (TBG) and total T4. Levels of total T3 are unaltered. 5 mg tablets decreases the level of sex hormone-binding globulin (SHBG), whereas the levels of corticoid binding globulin (CBG) and circulating cortisol are unaffected.
− HRT does not improve cognitive function. There is some evidence of increased risk of probable dementia in women who start using continuous combined or oestrogen-only HRT after the age of 65. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
5 Interaction with other medicinal products and other forms of interaction As tibolone may increase blood fibrinolytic activity, it may enhance the effect of anticoagulants. This effect has been observed with warfarin. Consequently, women simultaneously treated with […]