Side Effects of Menest (esterified estrogens)

Menest (esterified estrogens) are a mixture of several estrogens, a type of female hormone used to treat common symptoms of menopause, dysfunctional uterine bleeding, female castration, female hypogonadism, prostate cancer, and breast cancer.

Estrogens cause growth and development of female sex organs and the maintenance of sex characteristics, including growth of underarm and pubic hair and shaping of body contours and skeleton. Estrogens also increase secretions from the cervix and promote growth of the inner lining of the uterus (endometrium).

Common side effects of Menest include

• breakthrough bleeding or spotting,
• loss of periods,
• excessively prolonged periods,
• breast pain,
• breast enlargement, and
• changes in sex drive.

Serious side effects of Menest include

• gallstones,
• hepatitis,
• migraine headaches, and
• fluid retention (swelling of the lower legs).

Melasma (tan or brown patches) may develop on the forehead, cheeks, or temples. These may persist even after the Menest is stopped. Menest may cause an increase in the curvature of the cornea, and patients with contact lenses may develop intolerance to their lenses.

Drug interactions of Menest include warfarin, because Menest increases the liver's ability to manufacture proteins that are required for blood to clot.

• Patients receiving warfarin, which reduces clotting by inhibiting the production of proteins required for clotting, should receive clotting tests if an estrogen is added to their treatment.
• Rifampin, barbiturates, carbamazepine, griseofulvin, phenytoin, and primidone can increase the elimination of Menest by enhancing the liver's ability to metabolize it. Use of these drugs may result in a reduction of the beneficial effects of Menest.
• Conversely, drugs such as erythromycin, ketoconazole, itraconazole, and ritonavir may reduce the elimination of Menest by the liver and lead to increased levels of estrogens in the blood.
• Grapefruit juice also may increase levels of Menest by increasing the absorption of estrogens from the intestine.
• Increased levels of estrogens in the blood may result in more estrogen-related side effects.

Menest should not be used during pregnancy because of an increased risk of fetal abnormalities. Menest is secreted in milk and causes unpredictable effects in the infant. Menest generally should not be used during breastfeeding.

The most common endocrine side effects are

• breakthrough
• bleeding or spotting,
• loss of periods, or
• excessively prolonged periods,
• breast pain,
• breast enlargement, and
• changes in sexuality (increase or decrease in libido).

Other important side effects include:

• gallstones,
• hepatitis,
• migraine headaches, and
• fluid retention (swelling of the lower legs).

Melasma (tan or brown patches) may develop on the forehead, cheeks, or temples. These may persist even after the estrogen is stopped. Estrogens may cause an increase in the curvature of the cornea, and, therefore, patients with contact lenses may develop intolerance to their lenses.

See BOX WARNING, WARNINGS and PRECAUTIONS .

The following additional adverse reactions have been reported with estrogens and/or progestin therapy.

Genitourinary System

Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer; premenstrual like syndrome, amenorrhea during and after treatment; cystitis like syndrome.

Breasts

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

Cardiovascular

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.

Gastrointestinal

Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gall bladder disease; pancreatitis, enlargement of hepatic hemangiomas.

Skin

Chloasma or melasma, that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.

Eyes

Retinal vascular thrombosis; steepening of corneal curvature; intolerance to contact lenses.

Central Nervous System

Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia.

Miscellaneous

Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.

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 antifactor 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 triglycerides levels.
5. Impaired glucose tolerance.
6. Reduced response to metyrapone test.