03/18 BfArM Orders New Risk Statements for Medicinal Products for Hormone Replacement Therapy - Risk of Breast Cancer Considerably Increased by Estrogen-Progestogen Combinations
Press release 18/2003
Within a risk management action (Stufenplan) the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) has ruled that the product informations on medicinal products for hormone replacement therapy (HRT) are to include amplified and more strict statements on the risk of venous thromboembolism, coronary heart disease, stroke, breast cancer, and ovarian cancer. Several recently published studies, including the "Million Women Study" published a few days ago (see below), have demonstrated these risks. Medicinal products for HRT should only be administered for treatment of pronounced menopausal complaints. Furthermore, it is recommended that treatment be as short and at as low doses as possible.
The BfArM thus continues its re-evaluation of this class of medicinal products (cf. press releases 15/02, 03/03, 15/03, Urgent Drug Information of 2 September 2002) and also implements the measures agreed upon with other European drug regulatory agencies.
The benefit-risk ratio of long-term HRT for prevention of osteoporosis is considered to be unfavourable by the BfArM which has prompted its partners within the EU that a mutual evaluation be elaborated concerning this aspect as well. Therefore, the indication 'osteoporosis' is not included in the current risk management notification. However, the BfArM does reserve the right to initiate national measures.
The "Million Women Study" has now confirmed evidence that combinations of the two female hormones estrogen and progestogen considerably increase the risk of breast cancer as compared to estrogen alone. Such combinations are administered to women whose uterus was not removed, because estrogens can cause cancer of the uterus mucosa and the addition of progestogen prevents this. The authors of the study estimate that approximately 32 of 1000 women without HRT in industrialised countries can expect to be diagnosed with breast cancer between the ages of 50 and 65. Use of estrogen-only preparations for 5 years leads to ca. 1.5 extra cases of breast cancer in 1000 women. After 10 years of using such estrogen monopreparations approximately 5 extra cases of breast cancer occur. In the case of HRT with combination preparations of estrogens and progestogen the corresponding figures for extra cases of breast cancer are approximately four times as high (6 resp. 19). In addition, the study shows that women taking medicinal products for HRT also have a greater risk of dying from breast cancer than those not using HRT and that the risk of breast cancer is already increased during the first year of HRT with combined medicinal products. However, it is also confirmed that the risk of breast cancer returns to the same level as in women who have never taken HRT within a few years after discontinuation of HRT [Million Women Study 2003].
Whether, and if so which, further measures might become necessary in addition to the current risk management notification based on the "Million Women Study" and the other recent publications, will first be debated on a European level.
Doctors and women are advised that especially estrogen-progestogen combinations for treatment of pronounced symptoms of estrogen deficiency should only be prescribed or taken after extensive information of the patient as to the serious risks already to be expected during the first year of treatment. The individual health situation should also be borne in mind. Treatment should be as short-term and low-dose as possible. Women without a uterus should only receive estrogens and not estrogen-progestogen combination products.
Million women study collaborators. Breast Cancer and hormone-replacement therapy in the million women study. Lancet 2003;362:419-27.
Year of issue: 2003