indication

For the treatment of urogenital symptoms associated with post-menopausal atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria).

pharmacology

Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level.

mechanism of action

Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.

toxicity

Can cause nausea and vomiting, and withdrawal bleeding may occur in females.

biotransformation

Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450.

absorption

43%

half life

36 hours

route of elimination

Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

drug interactions

Amobarbital: The enzyme inducer, amobarbital, decreases the effect of the hormone agent, estradiol.

Aprobarbital: The enzyme inducer, aprobarbital, decreases the effect of the hormone agent, estradiol.

Butabarbital: The enzyme inducer, butabarbital, decreases the effect of the hormone agent, estradiol.

Butalbital: The enzyme inducer, butalbital, decreases the effect of the hormone agent, estradiol.

Butethal: The enzyme inducer, butethal, decreases the effect of the hormone agent, estradiol.

Ethotoin: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, estradiol.

Fosphenytoin: The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, estradiol.

Griseofulvin: The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, estradiol.

Heptabarbital: The enzyme inducer, heptabarbital, decreases the effect of the hormone agent, estradiol.

Hexobarbital: The enzyme inducer, hexobarbital, decreases the effect of the hormone agent, estradiol.

Mephenytoin: The enzyme inducer, mephenytoin, decreases the effect of the hormone agent, estradiol.

Methohexital: The enzyme inducer, methohexital, decreases the effect of the hormone agent, estradiol.

Methylphenobarbital: The enzyme inducer, methylphenobarbital, decreases the effect of the hormone agent, estradiol.

Pentobarbital: The enzyme inducer, pentobarbital, decreases the effect of the hormone agent, estradiol.

Phenobarbital: The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, estradiol.

Phenytoin: The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estradiol.

Prednisolone: The estrogenic agent, estradiol, may increase the effect of the corticosteroid, prednisolone.

Prednisone: The estrogenic agent, estradiol, may increase the effect of corticosteroid, prednisone.

Primidone: The enzyme inducer, primidone, decreases the effect of the hormone agent, estradiol.

Raloxifene: Association not recommended

Secobarbital: The enzyme inducer, secobarbital, decreases the effect of the hormone agent, estradiol.

Talbutal: The enzyme inducer, talbutal, decreases the effect of the hormone agent, estradiol.

Tipranavir: Estradiol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Estradiol. Use an alternate form of contraception or monitor for estrogen deficiency if Estradiol is used for hormone replacement therapy.

Ursodeoxycholic acid: Estrogens decreases the effect of ursodiol