medrogestone and tibolone

INDIRECT MECHANISM OF ACTION: Tibolone (OD 14) is the precursor of its active principles that are its metabolites: 3 alpha and 3 beta hydroxylated derivatives. In vivo, the latter behave like estrogens. Certain tissues (liver, endometrium) may metabolize the 3 beta ol derivative into the delta 4 isomer with progestagenic and androgenic activity. The metabolism of the product in other tissues such as the breast and brain is unknown.. At the dose of 2.5 mg/day, the product expresses an estrogen activity equivalent to that observed with classical doses of estrogens in the brain, genito-urinary tract, vascular endothelium and bone. In the brain and muscle, it also has a slightly androgenic effect and in the breast an antiestrogenic effect. ON METABOLIC LEVEL: The product acts like a minor androgen (lowering triglycerides and HDL cholesterol without interfering in the cholesterol cell flow) and it stimulates fibrinolysis. ON CLINICAL LEVEL: Tibolone treats the symptoms of estrogen privation and protects against bone loss, without inducing bleeding or mastodynia. There is a lack of large epidemiological studies on prevention of fracture risks, cardiovascular effects and breast. Tolerance in the population studied was excellent (healthy population). However, tolerance remains to be assessed in particular sub-groups (populations at risk of certains pathologies).

Topics: Adult; Aged; Animals; Blood Coagulation; Breast; Cardiovascular Diseases; Controlled Clinical Trials as Topic; Double-Blind Method; Endometrium; Estradiol; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Humans; Hysterectomy; Lipid Metabolism; Lipids; Medrogestone; Menopause; Middle Aged; Norethindrone; Norethindrone Acetate; Norpregnenes; Osteoporosis, Postmenopausal; Ovariectomy; Placebos; Postmenopause; Progesterone Congeners; Prospective Studies; Rabbits; Rats; Risk Factors; Surveys and Questionnaires; Time Factors

To investigate the effects of tibolone on carbohydrate metabolism, and to compare these effects with those of a sequential regimen of conjugated equine estrogens and medrogestone.. This was an open-label, multicentre, comparative study. Seventy-two postmenopausal women were randomized to receive either tibolone 2.5 mg/day or conjugated equine estrogens 0.6 mg plus sequential medrogestone 5 mg (CEE/M) for six 28-day cycles. Carbohydrate metabolism was evaluated at baseline and after three and six cycles of treatment by an oral glucose tolerance test (OGTT). A blood sample was taken at 30, 60, 90 and 120 mm after glucose 75 mg dosing for determination of plasma glucose, insulin and connecting peptide (C-peptide) levels.. The changes from baseline of glucose, insulin and C-peptide area-under-the-curve (AUC) values were not statistically significant after 3 and 6 months of tibolone or CEE/M treatment. There was a small transitory decrease in HbA(1C) after three cycles of treatment with tibolone.. The effects of tibolone and CEE/M on carbohydrate metabolism were considered to have no clinical significance.

Topics: Blood Glucose; C-Peptide; Drug Administration Schedule; Estrogen Receptor Modulators; Estrogens, Conjugated (USP); Female; Glucose Tolerance Test; Hormone Replacement Therapy; Humans; Insulin; Medrogestone; Middle Aged; Netherlands; Norpregnenes; Postmenopause