indication

For the treatment of moderate to severe vasomotor symptoms associated with the menopause, atrophic vaginitis, osteoporosis, hypoestrogenism due to hypogonadism, castration, primary ovarian failure, breast cancer (for palliation only), and Advanced androgen-dependent carcinoma of the prostate (for palliation only)

pharmacology

Conjugated estrogens, a mixture of the water soluble salts of sulfate esters from estrone, equilin, 17 α-dihydroequilin, and other related steroids, may be derived from pregnant equine urine or yam and soy plants. Estrogens are important in the development and maintenance of the female reproductive system and secondary sex characteristics. They promote growth and development of the vagina, uterus, and fallopian tubes, and enlargement of the breasts. Indirectly, they contribute to the shaping of the skeleton, maintenance of tone and elasticity of urogenital structures, changes in the epiphyses of the long bones that allow for the pubertal growth spurt and its termination, growth of axillary and pubic hair, and pigmentation of the nipples and genitals. Decline of estrogenic activity at the end of the menstrual cycle can bring on menstruation, although the cessation of progesterone secretion is the most important factor in the mature ovulatory cycle. However, in the preovulatory or nonovulatory cycle, estrogen is the primary determinant in the onset of menstruation. Estrogens also affect the release of pituitary gonadotropins. The pharmacologic effects of conjugated estrogens are similar to those of endogenous estrogens.

mechanism of action

Estrogens enter the cells of responsive tissues (e.g., female organs, breasts, hypothalamus, pituitary) where they interact with a protein receptor, subsequently increasing the rate of synthesis of DNA, RNA, and some proteins. Estrogens decrease the secretion of gonadotropin-releasing hormone by the hypothalamus, reducing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary.

toxicity

Nausea and vomiting

biotransformation

Hepatic

absorption

Well absorbed

half life

7.4 hours

route of elimination

Estradiol, estrone, and estriol are excreted in the urine, along with glucuronide and sulfate conjugates. Exogenous estrogens are metabolized in the same manner as endogenous estrogens.

drug interactions

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Raloxifene: Association not recommended

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

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

Tipranavir: Conjugated estrogens may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Conjugated estrogens. Monitor for estrogen deficiency during concomitant therapy.

Ursodeoxycholic acid: Estrogens decreases the effect of ursodiol