Mirena Blackwell Synergy, Mammary Carcinogenesis, Vascular Reactivity, Latter Hypothesis, Cholesterol Transport
****** Under the link I just mentioned you can find this: Sir, Kingman et al.'s success in controlling menorrhagia in women with inherited bleeding disorders (BJOG 111:1425–1428) echoes numerous reports in women without complicating haematological ... more »
Under the link I just mentioned you can find this:
Kingman et al.'s success in controlling menorrhagia in women with inherited bleeding disorders (BJOG 111:1425–1428) echoes numerous reports in women without complicating haematological conditions. However, they ignore the metabolic effects. The LNG-IUS is associated with high systemic absorption of the progestogen, and serum levels of levonorgestrel (LNG) have been recorded around 511 pmol/L.1 This is the equivalent of two LNG-containing minipill tablets daily continuously. LNG suppresses Apolipoprotein AI (Apo AI) formation by inhibiting the ABCA1 transporter protein.2 The synthesis of Apo AI is a fundamental step in the initiation of reverse cholesterol transport, which is enhanced by oestradiol and statins and when deficient, the ensuing atherosclerosis in animal models can be reversed by the administration of Apo AI.3
The epidemiological observation of the relationship of breast cancer with the use of progestogen only contraceptives goes to the 1980s,4 but these were mentally rejected by many physicians because it did not conform with the doctrine of ‘oestrogen induced’ mammary carcinogenesis. The validity of the latter hypothesis was challenged in a randomised clinical trial of oestrogen only treatment5 and a wealth of biological data show that progesterone and progestogens in general and LNG in particular being established mammary epithelial mitogens.
The LNG-IUS also suppresses oestrogen production, inducing a clinical situation not unlike a premature menopause in at least 50% of treated women. Oestrogen deprivation for the number of years such treatment is being administered will have a profound effect on bone mass and vascular reactivity. Similar concerns have recently been widely circulated regarding the use of depot MPA contraceptive preparations.
Given that it is unlikely that a randomised controlled trial of the size of the Women's Health Initiative one will ever be mounted to test the long term effects of the LNG-IUS, caution is required, particularly in treating older women, for whom treatment may bring forward the menopause.
The idea that LNG-IUS works entirely as a local progestogen should be revised, and patients and doctors should be warned about the metabolic and carcinogenic risks, whatever the marketing pressures.
May WahabaaObstetrics and Gynaecology, George Eliot Hospital, Nuneaton, Warwickshire, UK & Farook Al-AzzawibbObstetrics and Gynaecology, University Hospitals of Leicester, Leicestershire, UK