Diabetes: Diabetes mellitus: are amputation rates falling in England?

Abstract

have felt a bit like waiting for Godot. By contrast, minor and transient trans aminase elevations were found to occur in about 4% of women (35 of 790) receiving flutamide in daily doses between 250 mg and 500 mg. the view that flutamide hepatotoxicity is dose-dependent, rather than idio syncratic, is currently supported by P-values <0.00000001 (table 1). Cyproterone acetate and spironolactone are the main antiandrogenic alternatives for low-dose flutamide. Cyproterone acetate, a progestogen, is currently not available in the us, but still marketed in europe, mostly in a contraceptive combination with ethinylestradiol. spironolactone, a steroidal aldosterone antagonist, is marketed as a diuretic, but can serve as an antiandrogen if given in high dose. in the us, spironolactone has long been the antiandrogen of choice, given the prevailing, but mistaken, belief that flutamide had to be given in high doses, thus being hepatotoxic and also more expensive. an updated comparison with low-dose flutamide shows that spironolactone (200 mg daily) is about fivefold more costly than flutamide (62.5 mg daily). in addition, treatment with high-dose spironolactone is often associated with menstrual irregularities which, in turn, are usually masked by adding an oral contraceptive. thus, when either cyproterone acetate or spironolactone is used, even young adoles cents (<16 years) are prescribed a contra ceptive that silences their gonadotropic axis, augments their body adiposity, confers risk of venous thrombosis and, more generally, shifts their endocrine metabolic state further away from normalcy. By contrast, therapy with low-dose flutamide (and metformin, if needed) aims at restoring a physiological state, especially in young girls who may still be in an adolescent window of epigenetic programming and who are not yet at risk of pregnancy.8 in conclusion, hirsutism treatment with low-dose flutamide has—against all odds— evolved from the absence of evidence on efficacy and safety to evidence of absence of hepatotoxicity and also to evidence of presence of antiandrogenic efficacy. low-dose flutamide (about 1 mg/kg daily) now seems to offer a first-choice balance between antiandrogenic efficacy and hepatic safety for women and adolescent girls with androgenrelated symptoms including hirsutism. the safety of low-dose flutamide remains to be confirmed in the presence of comorbidities, such as obesity or steatohepatitis. low-dose flutamide is finally entering into the limelight of hirsutism therapy, thanks to the longstanding commitment of independent investigators, some of whom may have experienced the feeling that winston Churchill expressed in 1946: “i give my faithful counsel, as i did in bygone years, when i was always in a minority, and sometimes almost alone”.

DOI: 10.1038/nrendo.2010.106

Cite this paper

@article{Hinchliffe2010DiabetesDM, title={Diabetes: Diabetes mellitus: are amputation rates falling in England?}, author={Robert J. Hinchliffe and William J. Jeffcoate}, journal={Nature Reviews Endocrinology}, year={2010}, volume={6}, pages={422-424} }