Estrace (Premarin)

• Type of Drug: Estrogen
• Prescribed for: Moderate to severe menopausal symptoms and preventing postmenopausal osteoporosis. Estrogen drugs are also prescribed for ovarian failure, breast cancer (in selected women and men), advanced cancer of the prostate, osteoporosis, abnormal bleeding of the uterus, vaginal irritation, female castration, and Turner’s syndrome. Estrogens may also be prescribed for birth control. Diethylstilbestrol is an effective “morning after” contraceptive, but should only be used as an emergency treatment because of the damage it causes to developing fetuses.
  There is no evidence that Estrogens work for nervous symptoms or depression occurring during menopause. They should not be used to treat these conditions; they should be used only to replace estrogen that is naturally absent after menopause.

Estrace (Premarin) General Information

Six different estrogenic substances have been identified in women, but only three are actually present in large amounts: estradiol, estrone, and estriol. Estradiol is the most potent of the three and is the major estrogen produced by the ovaries. Estradiol is naturally modified to estrone, which is then turned into estriol, the least potent of the three. All of the Estrogens listed in this section will produce equal effects and side effects when their doses are equal, taking their various potencies into account. More potent medicines require a smaller dose to produce the same effect.

Estrogens are natural body substances with specific effects on the human body, including growth and maintenance of the female reproductive system and all female sex characteristics. They promote growth and development of all parts of the reproductive system and breasts; they affect the release of hormones from the pituitary (master) gland that controls the opening of the capillaries (the smallest blood vessels); they can cause fluid retention; they affect protein breakdown in the body; they prevent ovulation and breast engorgement, in women after giving birth; and they continue in the shaping and maintenance of the skeleton through their influence on calcium in the body.

The differences between the various products lie in the specific estrogenic substances they contain, their dose, and, in some cases, the fact that they affect one part of the body more than another. For the most part, however, estrogen products are interchangeable, as long as differences in dosage are taken into account.

Estrace (Premarin) Cautions and Warnings

Estrogens have been reported to increase the risk of endometrial cancer in postmenopausal women taking them without a progestin for prolonged periods of time by a factor of 5 to 10 times; the risk depends upon the duration of treatment and the dose of the Estrogen being taken. When long-term Estrogen therapy is needed for the treatment of menopausal symptoms, taking a Progestin product such as Medroxyprogesterone reduces the chance of endometrial cancer and other problems. In women who have had a hysterectomy, there is no need for Progestin treatment.

Estrogens have been prescribed as “morning-after” contraceptives, primarily in emergencies such as rape or incest, but they are dangerous because of the way they affect the developing fetus. Combination oral contraceptives containing Norgestrel and Ethinyl Estradiol are more commonly prescribed for this use. Postmenopausal women taking Estrogens have a 2 to 3 times greater chance of developing gallbladder disease.

If you are taking an Estrogen product and experience recurrent, abnormal, or persistent vaginal bleeding, contact your doctor immediately. If you have active thrombophlebitis or any other disorder associated with the formation of blood clots, you probably should not take this drug. If you feel that you have a disorder associated with blood clots, and you are taking an Estrogen or a similar product, contact your doctor immediately.

Estrogens should not be used to treat painful breast engorgement with milk that sometimes develops after giving birth. This condition usually responds to pain relievers and other treatments.

Animal studies have shown that prolonged continuous administration of Estrogen substances can increase the frequency of cancer (breast, cervix, testis, uterus, vagina, kidney, and liver). The question of whether Estrogens increase the risk of breast cancer has not been answered. Some studies have reported an increased risk, but others have not verified that result. Estrogens should be taken with caution by women with a strong family history of breast cancer and by those who have breast nodules, fibrocystic disease of the breast, or abnormal mammograms.

It is possible that women taking Estrogens for extended periods of time may experience some of the same long-term side effects as women who have taken oral contraceptives for extended periods of time. These long-term problems may include the development of blood-clotting disorders, liver cancer or other liver tumors, high blood pressure, glucose intolerance (symptoms similar to diabetes) or worsening of the disease in diabetic patients, unusual sensitivity to the sun, and high blood levels of calcium.

Vaginal Estrogen creams may stimulate bleeding of the uterus. They can also cause breast tenderness, vaginal discharge, and withdrawal bleeding (if the product is suddenly stopped). Women with endometriosis may experience heavy vaginal bleeding.

Estrace (Premarin) Possible Side Effects

• Most common: breast enlargement or tenderness (both sexes), ankle and leg swelling, loss of appetite, weight changes, retention of water, nausea, vomiting, abdominal cramps, and feeling of bloatedness. The estrogen patch can cause skin rash, irritation, and redness at the patch site.
• Less common: bleeding gums, breakthrough vaginal bleeding, vaginal spotting, changes in menstrual flow, painful menstruation, premenstrual syndrome, no menstrual period during and after Estrogen use, enlargement of uterine fibroids, vaginal infection with Candida, a cystitis-like syndrome, mild diarrhea, jaundice or yellowing of the skin or whites of the eyes, rash, loss of scalp hair, and development of new hairy areas. Lesions of the eye and contact-lens intolerance have also been associated with estrogen therapy. You may experience migraine headache, mild dizziness, depression, and increased sex drive (women) or decreased sex drive (men).
• Rare: stroke, blood-clot formation, dribbling or sudden passage of urine, loss of coordination, chest pains, leg pains, difficulty breathing, slurred speech, and vision changes. Men who receive large Estrogen doses as part of the treatment of prostate cancer are at a greater risk for heart attack, phlebitis, and blood clots in the lungs.

Estrace (Premarin) Drug Interactions

• Phenytoin, Ethotoin, and Mephenytoin may interfere with Estrogen effects. Estrogens may reduce your requirement for oral anticoagulant (blood-thinning) drugs, an adjustment your doctor can make after a simple blood test.
• Estrogens increase the amount of calcium absorbed from the stomach. This interaction is used to help women with osteoporosis to increase their calcium levels.
• Estrogens may increase the side effects of antidepressants and Phenothiazine tranquilizers. Low estrogen doses may increase Phenothiazine effectiveness.
• Estrogens may increase the amount of Cyclosporine and adrenal corticosteroid drugs in your blood. Dosage adjustments of the nonEstrogen drugs may be needed.
• Estrogen increases the toxic effects of other drugs on the liver, especially in women over 35 and people with preexisting liver disease.
• Rifampin, barbiturates, and other drugs that stimulate the liver to break down drugs may reduce the amount of Estrogen in the blood.
• Estrogens may interfere with the actions of Tamoxifen and Bromocriptine.
• Women, especially those over 35, who smoke cigarettes and take an Estrogen have a much greater chance of developing stroke, hardening of the arteries, or blood clots in the lungs. The risk increases as age and tobacco use increase.
• Estrogens interfere with many diagnostic tests. Make, sure your doctor knows that you are taking an Estrogen before doing any blood tests or other diagnostic procedures.

Estrace (Premarin) Food Interactions

Estrogens may be taken with food to reduce nausea and stomach upset. Avoid drinking grapefruit juice if you are taking this medicine.

Usual Dose

Estrogen dosage depends on the condition being treated and the individual’s response. All of these products, including the Estradiol skin patch, can be taken continuously or on a cyclic schedule of 3 weeks on, 1 week off.

Tablet

• Chlorotrianisene: 12 to 200 mg.
• Conjugated Estrogens: 0.3 to 7.5 mg.
• Diethylstilbestrol: 1 to 15 mg.
• Esterified Estrogens: 0.3 to 30 mg.
• Estradiol: 1 to 60 mg.
• Estropipate: 0.625 to 7.5 mg.
• Ethinyl Estradiol: 0.02 to 2.0 mg.
• Quinestrol: 100 micrograms once per day for 7 days, then 100 to 200 micrograms per week.

Skin Patches

• Estradiol: 1 (0.05 or 0.1 mg) patch twice a week for 3 weeks; stop for 1 week, then start again. May be used continuously in some cases.

Vaginal Cream

Use the lowest possible dosage. Your doctor should reevaluate your need for an Estrogen vaginal cream every 3 to 6 months. Don’t stop using the medicine suddenly, because this can increase your chance of developing unpredicted or breakthrough vaginal bleeding.

• Conjugated Estrogens: 2 to 4 grams per day for 3 weeks; stop for 1 week, then start again.
• Dienestrol: 1 applicatorful 1 or 2 times per day for 1 to 2 weeks, then half the original dose for 1 or 2 weeks, then 1 applicatorful 1 to 3 times per week.
• Estradiol: 2 to 4 grams per day for 2 weeks, half the starting dose for another 2 weeks, then 1 gram 1 to 3 times per week.
• Estropipate: 2 to 4 grams per day for 3 weeks; stop for 1 week, then start again.

Estrace (Premarin) Overdosage

Overdose may cause nausea and withdrawal bleeding in adult women. Accidental overdoses in children have not resulted in serious adverse side effects. Call your local poison control center or hospital emergency room for information. ALWAYS bring the medicine container with you if you go to a hospital emergency room for treatment.

Estrace (Premarin) Special Information

Call your doctor if you develop breast pain or tenderness, swelling of the feet and lower legs, rapid weight gain, chest pain, difficulty breathing, pain in the groin or calves, unusual vaginal bleeding, missed menstrual period, lumps in the breast, sudden severe headaches, dizziness or fainting, disturbances in speech or vision, weakness or numbness in the arms or legs, abdominal pains, depression, yellowing of the skin or whites of the eyes, or jerky or involuntary muscle movements. Call your doctor if you think you are pregnant.

Women using a vaginal Estrogen cream who start to bleed or develop breast tenderness or other vaginal discharge should contact their doctors at once.

Women who smoke cigarettes and take Estrogens have a greater chance of cardiovascular side effects, including stroke and blood clotting.

Estrogen skin patches should be applied to a clean, dry, nonoily, hairless area of intact skin, preferably on the abdomen. Do not apply to your breasts, waist, or other area where tight-fitting clothes can loosen the patch from your skin. The application site should be rotated to prevent irritation, and each site should have a 7-day patch-free period.

It is important to maintain good dental hygiene while taking Estrogen products, and to use extra care when using your toothbrush or dental floss because of the chance that your Estrogen will make you more susceptible to some infections. Dental work should be completed prior to starting on any Estrogen medication.

Vaginal Estrogen creams should be inserted high into the vagina, about two-thirds of the length of the applicator.

Some of these products contain Tartrazine, a dye widely used to color pharmaceutical products. Avoid Tartrazine-containing products if you are allergic to it or have asthma. Check with your pharmacist to find out if your Estrogen product contains Tartrazine.

If you forget your Estrogen, take it as soon as you remember. If it is almost time for your next dose, skip the forgotten dose and continue with your regular schedule. Do not take a double dose.

Estrace (Premarin) Special Populations

Pregnancy/Breast-feeding
Estrogens should not be used during pregnancy to prevent a possible miscarriage; they don’t work for this purpose and are dangerous to the fetus.
Estrogens may reduce the flow of breast milk. The effects of Estrogens on nursing infants are not predictable. Either avoid the drug while breast-feeding or bottle-feed your baby.

Seniors
Estrogens may be taken without special precaution by most seniors, but the risk of some side effects increases with age, especially if you smoke.