Effects of hormone treatment on hemostasis variables.
A survey was made of the changes in hemostasis and related inflammatory biomarkers for hormone treatments (HT) of women. Treatments included were oral and non-oral estrogens combined or not with progestogens, raloxifene, tamoxifene, tibolone and ethinylestradiol in oral contraceptives with non-androgenic progestogens. Special attention was given to dosages lower than the present standard dose and we explored how treatment variants approached a situation of minimal changes in biomarkers. For oral unopposed estrogens, dose reduction effectively reduced the changes in some hemostasis markers, but not in a specific set of anticoagulant variables (antithrombin, protein S, tissue factor pathway inhibitor, and the endogenous thrombin potential assay for resistance to activated protein C). Inflammation markers from the liver showed a dose-dependent reduction but effects were not nullified at the lowest dose tested. It was concluded that adequate reduction of estrogen dose for these effects will coincide with the dose-range of efficacy. Androgenic progestogens may be suitable for further reducing the impact of estrogens on some of the anticoagulant variables; reductions of estrogen-induced C-reactive protein increases appear possible with specific progestogens (medroxyprogesterone actate, nomegestrol acetate). For non-oral unopposed estrogens, all variables except inflammation biomarkers from the vascular wall showed minimal changes. Reduction in vascular inflammatory biomarkers, considered to mark anti-inflammatory effects, is augmented by medroxyprogesterone actate or norethisterone acetate. It was concluded that unopposed, non-oral estrogen treatment is the present best available option approaching minimal effects of treatment on biomarkers. Progestogen selection requires more data. We postulated that minimal effects on all cardiovascular biomarkers should define the HT with maximal safety for venous and arterial vascular events. The survey has identified specific biomarkers sensitive to low-dose unopposed and opposed estrogen which can be used to characterize future preparations for HT.
Kluft
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Center for Human Drug Research, Leiden, The Netherlands.
D000284:Administration, Oral; D000287:Administration, Topical; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D009652:Norpregnenes / Q000009:adverse effects; D011372:Progestins / Q000009:adverse effects; D020849:Raloxifene Hydrochloride / Q000009:adverse effects; D013629:Tamoxifen / Q000009:adverse effects; D054556:Venous Thromboembolism / Q000139:chemically induced
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D011372:Progestins; D013629:Tamoxifen; D004997:Ethinyl Estradiol; D020849:Raloxifene Hydrochloride; C027385:tibolone