Active ingredient: Conjugated Estrogens - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Estrogens

Dosage Forms

• Tablet
• Injection
• Vaginal cream
• Topical gel

Brands / Synonyms

Conestoral; Estrogens; Estrone Estrone Hydrogen Sulfate; Estrone Hydrogen Sulfate; Estrone Sodium Sulfate; Estrone Sulfate; Estrone Sulfate Sodium; Estrone Sulphate; Estrone-sulfate; Evex; Hyhorin; Morestin; Oestrone Sulphate; Par Estro; Premarin; Premarin I.V.; Prempro; Prempro/Premphase; Sodium Estrone Sulfate

Indications

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.

Absorption

Well absorbed

Toxicity

Nausea and vomiting

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

ENJUVIA tablets should not be used in individuals with any of the following conditions:

1. Undiagnosed abnormal genital bleeding.

2. Known, suspected, or history of cancer of the breast.

3. Known or suspected estrogen-dependent neoplasia.

4. Active deep vein thrombosis, pulmonary embolism or a history of these conditions.

5. Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).

6. Liver dysfunction or disease.

7. ENJUVIA tablets should not be used in patients with known hypersensitivity to its ingredients.

8. Known or suspected pregnancy. There is no indication for ENJUVIA in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy.

Drug Interactions

DRUG/LABORATORY TEST INTERACTIONS

1. Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.

2. Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T₄ levels (by column or by radioimmunoassay) or T₃ levels by radioimmunoassay. T₃ resin uptake is decreased, reflecting the elevated TBG. Free T₄ and free T₃ concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.

3. Other binding proteins may be elevated in serum, (i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG)) leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

4. Increased plasma HDL and HDL₂ cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglyceride levels.

5. Impaired glucose tolerance.

6. Reduced response to metyrapone test.