Estratest Side Effects, and Drug Interactions - Esterified Estrogens and Methyltestosterone

Estratest Side Effects, and Drug Interactions - Esterified Estrogens and Methyltestosterone

SIDE EFFECTS

(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.

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.

1. Anticoagulants: C-17 substituted derivatives of testosterone, such as methandrostenolone, have been reported to decrease the anticoagulant requirements of patients receiving oral anticoagulants. Patients receiving oral anticoagulant therapy require close monitoring, especially when androgens are started or stopped.

2. Oxyphenbutazone: Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.

3. Insulin: In diabetic patients, the metabolic effects of androgens may decrease blood glucose and insulin requirements.

Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Animal Data: Testosterone has been tested by subcutaneous injection and implantation in mice and rats. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Human Data: There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases.

Geriatric patients treated with androgens may be at increased risk for the development of prostatic hypertrophy and prostatic carcinoma.

Teratogenic Effects: Pregnancy Category X (see CONTRAINDICATIONS).

It is not known whether androgens are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from androgens, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.