Amena Mechanism of Action

Pharmacology: Pharmacodynamic: Tibolone is a synthetic steroid compound characterized as a selective tissue estrogenic activity regulator (STEAR). Tibolone itself has no biological activity; its effects are the result of the activity of its metabolites on various tissues. The 3αOH and 3βOH metabolites of tibolone act like estrogen in the thermoregulatory centers in the brain (preventing hot flushes), bone (preventing bone loss) and vaginal tissue (preventing dryness and soreness). In endometrial tissue, the △4-isomer acts like progesterone in the womb to prevent overgrowth of the endometrium and subsequent bleeding.
In breast tissue, the main action of progestogenic △4-isomer of tibolone are strong inhibition of sulfatase activity and weak inhibition of 17α-hydroxysteroid dehydrogenase activity which result in clocking the conversion of estrone sulfate to the active hormone estrone and 17β-estradiol. Tibolone inhibits human breast cell proliferation and stimulate apoptosis. Unlike classical hormone replacement, therapy, the incidence of breast tenderness is low and mammographic density dose not increase with tibolone.
Tibolone has androgenic effects on certain metabolic and hematologic parameters such as decrease in plasma high density lipoprotein cholesterol, triglycerides and lipoprotein(a), and may increase blood fibrinolytic activity.
Tibolone improves vaginal dryness and vaginal atrophy. Tibolone has testoterone-like activity that appears to play a role in enhancing women's mood and libido, although response is variable.
Pharmacokinetic: Tibolone is rapidly and extensively absorbed after oral administration. It is rapidly metabolized by the liver into two estrogenic metabolites (3α- and 3β-OH-tibolone), which bind to the estrogen receptor, and a third metabolite, the △4-isomer, which binds to the progesterone and androgen receptors. Some of the pharmacokinetic parameters of tibolone cannot be determined due to its very low plasma levels. There is no significant effect on the extent of absorption when taken with food.
Peak concentrations of tibolone and its metabolites occur about 1 to 1.5 hours after oral administration; two mainmetabolites have an elimination half-life of about 7 hours. Metabolites are excreted in the bile and eliminated in the feces. About 30% of a dose is excreted in the urine.
The pharmacokinetic parameters for tibolone and its metabolites were found to independent of renal function.