Before you begin using a medication, be sure to inform your doctor of any medical conditions or Allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use Divigel (Estradiol-topical).

Important information about estrogen:

• Divigel (Estradiol-topical) should be used at the lowest dose that relieves your menopausal symptoms for the shortest time period possible.
• Estrogens should not be used to prevent heart disease, heart attacks, or strokes.

Blood clotting disorders: Estrogens should not be used by people with active Thrombophlebitis (inflammation of a vein leading to a clot) or thromboembolic disorders (diseases of blood clotting and abnormal circulation). Some studies have suggested that there is an increased risk for healthy women to develop blood clots in the groin, legs, or lungs (conditions called deep vein thrombosis or pulmonary embolism) when taking hormone replacement therapy.

Women with severe varicose veins or severe Obesity (body mass index (BMI) more than 30 kg/m²), and those needing to stay in bed for 3 weeks or more, are generally considered to be at increased risk of blood clots.

If you have a family history of thromboembolic disorders (see above), or have experienced a blood clot either during pregnancy or while taking estrogens, inform your doctor so that you can be monitored closely. Women with cerebrovascular disease (such as stroke) or Coronary Artery Disease (such as Angina) should use estrogens with caution, and only if clearly needed.

Blood pressure: Increased blood pressure is not uncommon for women using Divigel (Estradiol-topical). Blood pressure should be monitored with estrogen use, especially if high doses are used.

Bone disease: Estrogen can change the way your body uses calcium and phosphorus. If you have bone disease due to cancer or a metabolic condition causing too much calcium in your body, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Breast Cancer: Studies indicate an increased risk of breast cancer with long-term use of estrogen replacement therapy. Women who have breast nodules, fibrocystic disease, abnormal mammograms, or a strong family history of breast cancer should approach the use of estrogens with caution. Women taking estrogens should have regular breast examinations and should be instructed in breast self-examination. Divigel (Estradiol-topical) must not be applied to the breasts, as it may have harmful effects on the breast tissue.

Diabetes: Estradiol may cause a change in blood sugar levels and glucose tolerance may change. People with diabetes may find it necessary to monitor their blood sugar more frequently while using Divigel (Estradiol-topical).

If you have diabetes or are at risk for developing diabetes, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Dementia: Recent studies have indicated that the use of estrogen, with or without a progestin may contribute to the development of dementia for women over the age of 65. If this is a concern, contact your doctor.

Endometrial cancer: There is evidence from several studies that estrogen replacement therapy, including estradiol, can increase the risk of cancer of the endometrium (lining of the uterus). Taking a progestin at the right time along with the estrogen reduces the risk of endometrial cancer to the same level as that of a woman who does not take estrogen. For this reason, all women who have not had their uterus removed should also take a progestin if they are using estrogens.

Endometriosis and fibroids: Divigel (Estradiol-topical) may worsen fibroids, causing sudden enlargement, pain, or tenderness. It may also cause worsening symptoms of endometriosis. If you have had endometriosis or fibroids in the past, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed. If you notice any abdominal tenderness or pain, contact your doctor as soon as possible.

Fluid retention: Estrogen may cause fluid retention, which may cause worsening symptoms of heart or kidney dysfunction, or Asthma. If you have any of these conditions, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Gall bladder disease: Estrogens may increase the risk of gall bladder disease. If you have a history of gall bladder disease, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Heart disease: There is evidence from recent studies that the use of estrogen plus progestin may cause an increase in the risk of heart disease. If you have heart disease or are at risk of heart disease, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

High Cholesterol or triglycerides: Estrogen may increase triglyceride levels in those who already have high levels. This has been observed particularly when estrogen is taken orally (by mouth); the risk is reduced with use of the gel. Ask your doctor to monitor your cholesterol levels.

Kidney function: Estrogen can affect how calcium and phosphorus are metabolized by your body, which may be a concern if you have Kidney Disease. If you have decreased kidney function or kidney disease, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Liver function: Estrogens may cause liver problems or make existing liver problems worse. If you have a history of reduced liver function or liver disease, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Migraine headaches: Estrogen can cause an increase in migraine headaches or cause migraine headaches to develop. If you have a history of migraine headaches, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed. If you develop worsening symptoms of migraine headaches or develop headaches with an aura (flashes of light, halos) contact your doctor as soon as possible.

Ovarian Cancer: There is evidence from several studies that the use of estrogen replacement therapy for a long period of time (particularly 5 or more years) may increase the risk of cancer of the ovaries.

Seizures: Estrogen can increase the frequency of seizures for people with Epilepsy. If you have a seizure disorder such as epilepsy, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Thyroid disease: Estrogen affects how your body uses thyroid hormone. If you take thyroid replacement therapy, discuss with your doctor how Divigel (Estradiol-topical) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Divigel (Estradiol-topical), and whether any special monitoring is needed.

Pregnancy: Estrogen should not be used during pregnancy as it may be harmful to the developing baby. If you become pregnant while taking Divigel (Estradiol-topical), contact your doctor immediately.

Breast-feeding: Taking estrogen while breast-feeding may decrease the amount and quality of breast milk. Estrogen is also passed through breast milk to your breast-feeding child. Breast-feeding is not advised while taking Divigel (Estradiol-topical).

Children: The safety and effectiveness of Divigel (Estradiol-topical) have not been established for use by children.