Conjugated Estrogens

Conjugated estrogens is a prescription medication used to treat certain types of abnormal uterine bleeding due to hormonal imbalance when your doctor has found no other cause of bleeding or to treat painful intercourse caused by menopausal changes of the vagina. Additionally, it may be used to reduce moderate to severe hot flashes, treat menopausal changes in and around the vagina, help reduce your chances of getting osteoporosis, treat certain conditions in women before menopause if their ovaries do not make enough estrogen naturally, and ease symptoms of certain cancers that have spread through the body, in men and women.

Conjugated estrogens belong to a group of drugs called estrogen derivatives, which help raise your estrogen levels.

This medication comes in tablet form and is taken 1 to 3 times a day everyday or in cycles.

This medication also comes in cream form to be applied vaginally using an applicator either twice weekly or in cycles.

This medication is available in an injectable form to be given directly into a vein (IV) or muscle (IM) by a healthcare professional.

Common side effects of conjugated estrogens include headache, breast pain, and irregular vaginal bleeding.

Conjugated estrogens is a prescription medication used to treat a variety of conditions:

• To treat certain types of abnormal uterine bleeding due to hormonal imbalance when your doctor has found no other cause of bleeding
• To treat painful intercourse caused by menopausal changes of the vagina.
• To reduce moderate to severe hot flashes
• To treat menopausal changes in and around the vagina.
• To help reduce your chances of getting osteoporosis
• To treat certain conditions in women before menopause if their ovaries do not make enough estrogen naturally.
• To ease symptoms of certain cancers that have spread through the body, in men and women.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Conjugated Estrogens may be found in some form under the following brand names:

• Duavee

• Pmb

• Premarin

• Premarin with MethylTESTOSTERone

• Prempro

Oral/Topical/Injectable:

Serious, but less common side effects include:

• Heart attack
• Stroke
• Blood clots
• Dementia
• Breast cancer
• Cancer of the lining of the uterus (womb)
• Cancer of the ovary
• High blood pressure
• High blood sugar
• Gallbladder disease
• Liver problems
• Enlargement of benign tumors of the uterus ("fibroids")
• Severe allergic reaction

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

• New breast lumps
• Unusual vaginal bleeding
• Changes in vision or speech
• Sudden new severe headaches
• Severe pains in your chest or legs with or without shortness of breath, weakness and fatigue
• Swollen lips, tongue or face

Less serious, but common side effects include:

• Headache
• Breast pain
• Irregular vaginal bleeding or spotting
• Stomach or abdominal cramps, bloating
• Nausea and vomiting
• Hair loss
• Fluid retention
• Vaginal yeast infection
• Reactions from inserting conjugated estrogens, such as vaginal burning, irritation, and itching

These are not all the possible side effects of this medication. For more information, ask your healthcare provider or pharmacist for advice about side effects.

What can you do to lower your chances of getting a serious side effect with conjuaged estrogens?

• Talk with your healthcare provider regularly about whether you should continue using this medication.
• If you have a uterus, talk with your healthcare provider about whether the addition of a progestin is right for you.
  The addition of a progestin is generally recommended for a woman with a uterus to reduce the chance of getting cancer of the uterus. See your healthcare provider right away if you get vaginal bleeding while using conjugated estrogens.
• Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else.
  • If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
• If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. Ask your healthcare provider for ways to lower your chances for getting heart disease.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take:

• other medicines that are used vaginally
• St. John's Wort (Hypericum perforatum)
• phenobarbital (Luminal) (and other barbiturate medications)
• carbamazepine (Carbatrol, Epitol, Tegretol)
• rifampin (Rifadin, Rimactane, in Rifamate)
• erythromycin (E.E.S, Erythrocin)
• clarithromycin (Biaxin)
• ketoconazole (Nizoral)
• itraconazole (Sporanox)
• ritonavir (Norvir, in Kaletra)

This is not a complete list of drug interactions. Ask your healthcare provider or pharmacist for more information.

Important information you should know about conjugated estrogens (an estrogen mixture):

• Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Report any unusual vaginal bleeding right away while you are using this medication. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia (decline in brain function)
• Using estrogen-alone may increase your chances of getting strokes or blood clots,
• Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older
• Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes or dementia.
• Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots
• Using estrogens with progestins may increase your chance of getting dementia, based on a study of women age 65 years of age or older.
• You and your healthcare provider should talk regularly about whether you still need treatment with conjugated estrogens.

Do not start using conjugated estrogens if you:

• Have unusual vaginal bleeding
• Currently have or have had certain cancers
  • Estrogens may increase the chance of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use conjugated estrogens.
• Had a stroke or heart attack
• Currently have or have had blood clots
• Currently have or have had liver problems
• Have been diagnosed with a bleeding disorder
• Are allergic to conjugated estrogens or any of its other ingredients
• Think you may be pregnant

Grapefruit and grapefruit juice may interact with conjugated estrogens and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Tell your healthcare provider:

• If you have unusual vaginal bleeding. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• About all of your medical problems. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, or problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
• About all the medicines you take. This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how conjugated estrogens works. This medication may also affect how your other medicines work.
• If you are going to have surgery or will be on bedrest. You may need to stop using conjugated estrogens.
• If you are breast feeding. The estrogen hormones in conjugated estrogens can pass into your breast milk.

Tell your healthcare provider if you are pregnant or plan to become pregnant. Conjugated estrogens should not be used during pregnancy.

If you become pregnant while using conjugated estrogens, contact your healthcare provider right away.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. The estrogen hormones in conjugated estrogens can pass into your breast milk. Estrogen has been shown to decrease the quantity and quality of breast milk when given to breastfeeding women.

Oral:

• Take one tablet at the same time each day
• If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time
• Estrogens should be used at the lowest dose possible for your treatment only as long as needed. You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are taking and whether you still need treatment with this medication.
• If you see something that resembles a tablet in your stool, talk to your healthcare provider.

Topical:

Conjugated estrogens is a cream that you place in your vagina with the applicator provided with the cream.

• Step 1. Remove cap from tube.
• Step 2. Screw nozzle end of applicator onto tube.
• Step 3. Gently squeeze tube from the bottom to force sufficient cream into the barrel to provide the prescribed dose. Use the marked stopping points on the applicator to measure the correct dose, as prescribed by your healthcare provider.
• Step 4. Unscrew applicator from tube.
• Step 5. Lie on back with knees drawn up. To deliver medication, gently insert applicator deeply into vagina and press plunger downward to its original position.
• Step 6. TO CLEANSE: Pull plunger to remove it from barrel. Wash with mild soap and warm water. DO NOT BOIL OR USE HOT WATER.

Injectable:

• This medication is available in an injectable form to be given directly into a vein (IV) or muscle (IM) by a healthcare professional.

If you take too much conjugated estrogens or if you swallow the cream form, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If conjugated estrogens is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Oral:

• Store at room temperature.
• Dispense in a well-closed container.
• Keep out of the reach of children.

Topical:

• Keep out of the reach of children.
• Store at room temperature [15° to 30°C (59° to 86°F)].
• Latex or rubber condoms, diaphragms and cervical caps may be weakened and fail when they come into contact with the cream form.

Injectable:

• Store package in refrigerator, 2° to 8°C (36° to 46°F).

WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA

Estrogen-Alone Therapy

Endometrial Cancer

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Cardiovascular Disorders and Probable Dementia

Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.

The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo.

The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) -alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estrogen Plus Progestin Therapy

Cardiovascular Disorders and Probable Dementia

Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.

The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.

The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

Breast Cancer

The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.