medrogestone and Cardiovascular-Diseases

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

Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia.. To study the effects of HRT on the lipid profile and the low density lipoprotein subclass distribution in women with type 2 diabetes under satisfactory and non-satisfactory glycemic control.. Fifty-four postmenopausal women after a 6 week run-in diet were randomized to receive either placebo (HbA1c < 8%, n = 13; HbA1c > 8%, n = 17) or HRT (HbA1c < 8%, n = 11; HbA1c > 8%, n = 13) for 12 weeks. HRT consisted of cyclical conjugated estrogens 0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each treatment period the LDL subclass distribution was estimated by density gradient ultracentrifugation.. At the baseline and during the study, the HbA1c level was significantly higher in hyperglycemic patients than in the near-normoglycemic controls (baseline 10.2 +/- 2.9 vs. 6.5 +/- 0.7%, P < 0.01). They showed a trend for higher total and LDL cholesterol, triglycerides and lower high density lipoprotein-cholesterol compared to near-normoglycemic controls, as well as significantly higher triglyceride concentrations in very low density lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups. In the normoglycemic patients a small increase in HbA1c was observed (6.5 +/- 0.7 vs. 7.4 +/- 1%, P = 0.04). In all cases, HRT did not modify the proportion of LDL represented by denser LDLs.. HRT did not modify the LDL subclass distribution, even in the presence of moderate chronic hyperglycemia in women with type 2 diabetes.

Topics: Aged; Apolipoproteins B; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Hormone Replacement Therapy; Humans; Hyperglycemia; Lipoproteins, LDL; Medrogestone; Middle Aged; Postmenopause; Probability; Reference Values; Treatment Outcome

Recent studies have shown that estrogens alone or in association with progestins can exert an antioxidant effect on Low-Density Lipoprotein (LDL) and lipids of platelet membranes. It has been demonstrated that the oxidative modification of LDLs also involving the formation of lipid peroxides, exerts several biological effects that may contribute to the onset and progression of cardiovascular diseases. Therefore, the aim of our study was to evaluate the effect of short-term treatment with oral estrogens alone and estrogens plus progestin on endogenous and copper-induced serum levels of lipid peroxides in postmenopausal women.. Thirty-nine postmenopausal women were randomly divided into three groups: group I was treated with oral conjugated equine estrogens (CEE) for 21 days; group II received oral CEE for 21 days and, after 14 days of this treatment, 5 mg/day of medrogestone was added for 7 days; group III did not receive any therapy (controls). Endogenous and copper-induced serum levels of lipid peroxides were determined before and after 21 days of treatment in the two treated groups and in the control group.. The serum endogenous levels of lipid peroxides in postmenopausal women did not change after short-term treatment with hormone replacement therapy. Moreover, copper-induced serum levels of lipid peroxides significantly decreased after therapy in both groups I and II.. Our data show that hormone replacement therapy (HRT) inhibits lipid peroxidation and may play a role in preventing cardiovascular diseases.

Topics: Cardiovascular Diseases; Copper Sulfate; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Humans; Lipid Peroxidation; Medrogestone; Middle Aged; Postmenopause

This study was designed in order to evaluate the effect of conjugated equine estrogens (CEE) on internal carotid and middle cerebral artery blood flow in postmenopausal women.. Thirty-four healthy postmenopausal women with intact uteri were randomly divided into two groups of 17 subjects each. The first group was treated for 24 weeks with continuous CEE medication (0.625 mg daily) and cyclical supplementations of 5 mg/day of medrogestone acetate, given on the last 12 days of every 4-week period (Prempak, Wyeth, Italy). The second group received no treatment. The pulsatility indices (PI) of both the internal carotid artery and middle cerebral artery were measured.. In the treated group, the PI of the interior carotid artery and MCA was reduced from respectively 0.736 (0.016) and 0.745 (0.009) at baseline, to 0.669 (0.021) and 0.670 (0.011) after 24 weeks (p = 0.01); in the control group, the PI values remained unchanged. The between-group difference for both arteries was significant (p < 0.01).. The administration of CEE with cyclical medrogestone supplementation to postmenopausal women induces a statistically significant reduction in the PI of cerebral arteries.

Topics: Administration, Oral; Aged; Analysis of Variance; Animals; Cardiovascular Diseases; Carotid Artery, Internal; Cerebrovascular Circulation; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Estrogens, Conjugated (USP); Female; Hormone Replacement Therapy; Horses; Humans; Linear Models; Medrogestone; Middle Aged; Postmenopause; Progesterone Congeners; Regional Blood Flow; Treatment Outcome