Estratest H.S. tablets

ESTRATEST Each dark green, capsule shaped, sugar-coated oral tablet contains: 1.25 mg of Esterified Estrogens, USP and 2.5 mg of Methyltestosterone.

ESTRATEST H.S. (Half-Strength):  Each light green, capsule shaped, sugar-coated oral tablet contains: 0.625 mg of Esterified Estrogens, USP and 1.25 mg of Methyltestosterone.

Esterified Estrogens

Esterified Estrogens, USP is a mixture of the sodium salts of the sulfate esters of the estrogenic substances, principally estrone, that are of the type excreted by pregnant mares. Esterified Estrogens contain not less than 75.0 percent and not more than 85.0 percent of sodium estrone sulfate, and not less than 6.0 percent and not more than 15.0 percent of sodium equilin sulfate, in such proportion that the total of these two components is not less than 90.0 percent.

Category: Estrogens

Methyltestosterone

Methyltestosterone, USP is an androgen. Androgens are derivatives of cyclopentano-perhydrophenanthrene. Endogenous androgens are C-19 steroids with a side chain at C-17, and with two angular methyl groups. Testosterone is the primary endogenous androgen. Fluoxymesterone and methyltestosterone are synthetic derivatives of testosterone.

Methyltestosterone is a white to light yellow crystalline substance that is virtually insoluble in water but soluble in organic solvents. It is stable in air but decomposes in light. Methyltestosterone structural formula:

ESTRATEST and ESTRATEST H.S. Tablets contain the following inactive ingredients:  acacia, calcium carbonate, citric acid, colloidal silicon dioxide, gelatin, lactose, magnesium stearate, methylparaben, propylparaben, microcrystalline cellulose, pharmaceutical glaze, povidone, sodium benzoate, sodium bicarbonate, carboxymethylcellulose sodium, sorbic acid, sucrose, starch, talc, titanium dioxide, tribasic calcium phosphate, alcohol denatured 3A and purified water.

ESTRATEST Tablets also contain:  FD&C Blue No. 1 Lake, FD&C Yellow No. 6 Lake, and D&C Yellow No. 10 Lake.

ESTRATEST H.S. Tablets also contain:  D&C Yellow No. 10 Lake, FD&C Blue No. 1 Lake, FD&C Blue No. 2 Lake, FD&C Yellow No. 6 Lake, and FD&C Red No. 40 Lake.

Estrogens:   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 esterified estrogens are similar to those of endogenous estrogens. They are soluble in water and are well absorbed from the gastrointestinal tract.

In responsive tissues (female genital organs, breasts, hypothalamus, pituitary) estrogens enter the cell and are transported into the nucleus. As a result of estrogen action, specific RNA and protein synthesis occurs.

Estrogen Pharmacokinetics

Metabolism and inactivation occur primarily in the liver. Some estrogens are excreted into the bile; however they are reabsorbed from the intestine and returned to the liver through the portal venous system. Water soluble esterified estrogens are strongly acidic and are ionized in body fluids, which favor excretion through the kidneys since tubular reabsorption is minimal.

Androgens:   Endogenous androgens are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as beard, pubic, chest, and axillary hair, laryngeal enlargement, vocal cord thickening, alterations in body musculature, and fat distribution. Drugs in this class also cause retention of nitrogen, sodium, potassium, phosphorus, and decreased urinary excretion of calcium. Androgens have been reported to increase protein anabolism and decrease protein catabolism. Nitrogen balance is improved only when there is sufficient intake of calories and protein. Androgens are responsible for the growth spurt of adolescence and for the eventual termination of linear growth which is brought about by fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rates, but may cause a disproportionate advancement in bone maturation. Use over long periods may result in fusion of the epiphyseal growth centers and termination of growth process. Androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietic stimulating factor.

Androgen Pharmacokinetics

Testosterone given orally is metabolized by the gut and 44 percent is cleared by the liver in the first pass. Oral doses as high as 400 mg per day are needed to achieve clinically effective blood levels for full replacement therapy. The synthetic androgens (methyltestosterone and fluoxymesterone) are less extensively metabolized by the liver and have longer half-lives. They are more suitable than testosterone for oral administration.

Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. Generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life.

About 90 percent of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6 percent of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Testosterone is metabolized to various 17-keto steroids through two different pathways. There are considerable variations of the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes.

In many tissues the activity of testosterone appears to depend on reduction to dihydrotestosterone, which binds to cytosol receptor proteins. The steroid-receptor complex is transported to the nucleus where it initiates transcription events and cellular changes related to androgen action.

ESTRATEST and ESTRATEST H.S. are indicated in the treatment of:

Moderate to severe vasomotor symptoms associated with the menopause in those patients not improved by estrogens alone. (There is no evidence that estrogens are effective for nervous symptoms or depression without associated vasomotor symptoms, and they should not be used to treat such conditions.)

ESTRATEST and ESTRATEST H.S. HAVE NOT BEEN SHOWN TO BE EFFECTIVE FOR ANY PURPOSE DURING PREGNANCY AND ITS USE MAY CAUSE SEVERE HARM TO THE FETUS (See BOXED WARNINGS ).

Estrogens should not be used in women with any of the following conditions:

1. Known or suspected cancer of the breast except in appropriately selected patients being treated for metastatic disease.
2. Known or suspected estrogen-dependent neoplasia.
3. Known or suspected pregnancy (See BOXED WARNINGS ).
4. Undiagnosed abnormal genital bleeding.
5. Active thrombophlebitis or thromboembolic disorders.
6. A past history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when in treatment of breast malignancy).

Methyltestosterone should not be used in:

1. The presence of severe liver damage.
2. Pregnancy and in breast-feeding mothers because of the possibility of masculinization of the female fetus or breast-fed infant.

Associated with Estrogens

(See WARNINGS regarding induction of neoplasia, adverse effects on the fetus, increased incidence of gallbladder disease, and adverse effects similar to those of oral contraceptives, including thromboembolism). The following additional adverse reactions have been reported with estrogenic therapy, including oral contraceptives:

1. Genitourinary system:   Breakthrough bleeding; spotting; change in menstrual flow; dysmenorrhea; premenstrual-like syndrome; amenorrhea during and after treatment; increase in size of uterine fibromyomata; vaginal candidiasis; change in cervical erosion and in degree of cervical secretion; cystitis-like syndrome.
2. Breasts:   Tenderness; enlargement; secretion.
3. Gastrointestinal:   Nausea; vomiting; abdominal cramps; bloating; cholestatic jaundice.
4. Skin:   Chloasma or melasma which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism.
5. Eyes:   Steepening of corneal curvature; intolerance to contact lenses.
6. Central Nervous System:   Headache, migraine, dizziness; mental depression; chorea.
7. Miscellaneous:   Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; changes in libido.

Associated with Methyltestosterone

Endocrine and Urogenital.

1. Female:   The most common side effects of androgen therapy are amenorrhea and other menstrual irregularities, inhibition of gonadotropin secretion, and virilization, including deepening of the voice and clitoral enlargement. The latter usually is not reversible after androgens are discontinued. When administered to a pregnant woman androgens cause virilization of external genitalia of the female fetus.
2. Skin and Appendages:   Hirsutism, male pattern of baldness, and acne.
3. Fluid and Electrolyte Disturbances:   Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates.
4. Gastrointestinal:   Nausea, cholestatic jaundice, alterations in liver function test, rarely hepatocellular neoplasms, and peliosis hepatis (see WARNINGS ).
5. Hematologic:   Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia.
6. Nervous System.   Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.
7. Metabolic:   Increased serum cholesterol.
8. Miscellaneous:   Inflammation and pain at the site of intramuscular injection or subcutaneous implantation of testosterone containing pellets, stomatitis with buccal preparations, and rarely anaphylactoid reactions.

ESTRATEST (Imprinted "SOLVAY 1026")

Bottles of 100............................................NDC 0032-1026-01

Bottles of 1000..........................................NDC 0032-1026-10

ESTRATEST (dark green, capsule shaped, sugar-coated oral tablets) contains: 1.25 mg of Esterified Estrogens, USP and 2.5 mg of Methyltestosterone, USP.

ESTRATEST H.S. (Imprinted "SOLVAY 1023")

Bottles of 100............................................NDC 0032-1023-01

ESTRATEST H.S. "Half-Strength" (light green, capsule shaped, sugar-coated oral tablets) contains: 0.625 mg of Esterified Estrogens, USP and 1.25 mg of Methyltestosterone, USP.

Store at controlled room temperature 15° to 30°C (59° to 86°F).

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