indication

Estropipate is used for the treatment of moderate to severe vasomotor symptoms associated with the monopause, and moderate to severe symptoms of vulval and vaginal atrophy associated with the menopause. It is also used to treat hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and prevent postmenopausal osteoporosis.

pharmacology

Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

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.

biotransformation

Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.

absorption

Estropipate is well absorbed through the skin and gastrointestinal tract. When applied for a local action, absorption is usually sufficient to cause systemic effects.

route of elimination

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

drug interactions

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

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

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

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

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

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

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

Raloxifene: Association not recommended