Esterified Estrogens and Methyltestosterone Risks, Warnings, and Complications

ENDOMETRIAL CANCER: Women taking estrogens are at a significantly increased risk of endometrial cancer (cancer of the uterine lining) by 2-12 fold. The risk depends both on the dose of estrogens and the duration of treatment. Your healthcare professional will prescribe the lowest dose of estrogens for the shortest duration consistent with your symptoms. There is some evidence that cyclic administration carries a lower risk than continuous administration of estrogens, and for this reason, your doctor may recommend 3 weeks on and 1 week off. If prolonged use of estrogens is necessary, your doctor will reevaluate you at 3-6 month intervals to see if you still need treatment. They will try to periodically taper medication or discontinue it.

If you are a postmenopausal woman and still have your uterus, tell your doctor without delay if you have undiagnosed abnormal genital bleeding. This includes undiagnosed persistent bleeding that does not go away or recurrent bleeding that keeps coming back. Your doctor will undertake adequate diagnostic measures to rule out endometrial cancer. 

NOT FOR USE IN PREGNANCY: Female sex hormones, including estrogens and progestogens, can cause severe damage to the fetus if used during early pregnancy. Exposure to these drugs is associated with an increased risk of vaginal and cervical cancers later in life in female fetuses. It is also linked to a significantly higher incidence of congenital anomalies, including heart defects and limb reduction defects. Even very short treatment for a few days can increase the risk of birth defects. Female sex hormones should not be used during pregnancy to treat a threatened abortion as they are ineffective for this purpose. Do not use esterified estrogens and methyltestosterone in case of a known or suspected pregnancy. If you become pregnant while on this medication, contact your doctor immediately. 

CARDIOVASCULAR RISK: Esterified estrogens and methyltestosterone is a combination of exogenous androgens and estrogens. The WHI clinical trials (Women’s Health Initiative Study) reported increased risks of myocardial infarction (heart attack), stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in women taking oral conjugated estrogens, with or without progestins such as medroxyprogesterone acetate.

Because of these risks, your doctor will prescribe the lowest effective dose for the shortest duration possible to control symptoms. They may recommend against taking esterified estrogens and methyltestosterone if you are at a high risk of cardiovascular disease. Risk factors for cardiovascular disease include high blood pressure, diabetes, high cholesterol, smoking, and obesity.

Note: Estrogen therapy has been linked to reduced coronary artery plaque in younger postmenopausal women. Talk about the risks and benefits of estrogen replacement therapy with your healthcare provider. 

BREAST CANCER RISK: Long-term continuous use of natural and synthetic estrogens is linked to a higher risk of cancers of the breast, cervix, vagina, uterine endometrium, and liver. Currently, there is no strong evidence that estrogen use by postmenopausal women increases breast cancer risk, but this is a possibility due to the presence of estrogen receptors on some types of breast cancer cells. Doctors are, therefore, cautious in prescribing estrogens to women with a strong family history of breast cancer or to women with breast nodules, breast lumps, fibrocystic disease, or abnormalities on mammograms.

Before starting treatment with esterified estrogens and methyltestosterone, tell your provider if you have a personal or family history of breast cancer. Talk to your healthcare provider about doing monthly self-breast exams. Your doctor may recommend close clinical surveillance with mammograms for early detection of breast cancer. Call your doctor right away if you develop any changes in your breasts, such as lumps, pain, or swelling.

GALLBLADDER DISEASE: Women receiving estrogens are at a 2- to 3-times higher risk of gallbladder disease. Tell your doctor if you have a history of gallbladder problems. Call your doctor immediately if you develop symptoms such as fatigue, right upper stomach pain that may spread to the back, nausea, vomiting, loss of appetite, light-colored stools, dark urine, or jaundice (yellowing of the skin or eyes).

BLOOD CLOTS: Taking estrogens is linked to a higher risk of blood clots in the heart (heart attack), lungs (pulmonary embolism), brain (stroke), legs (deep vein thrombosis), eye (retinal thrombosis), and gut (mesenteric thrombosis). These risks are dose-related. 

Long periods of immobility also increase the risk of blood clots in women receiving estrogens. You may need to discontinue estrogen therapy 4-6 weeks before surgery or anticipate prolonged immobilization due to the elevated risk of blood clots.

Seek emergency medical care if you develop signs of a blood clot in the legs (pain in one or both legs, cramps, swelling, or tightness); lungs (chest pain, trouble breathing, cough); heart (chest pain, chest tightness, fast heartbeat, difficulty breathing, nausea, dizziness, sweating); or brain (sudden numbness or weakness on one side of the body, trouble walking, loss of balance, lack of coordination, trouble speaking, difficulty understanding speech, confusion, vision problems).

HEPATIC ADENOMAS: Hepatic adenomas are benign tumors of the liver that appear to be linked to estrogen-containing oral contraceptive use. These benign tumors can rupture and cause death through intra-abdominal hemorrhage (bleeding). Malignant hepatocellular carcinoma has also been reported in women taking estrogen-containing oral contraceptives. 

Call your doctor immediately if you develop signs of liver dysfunction, such as abdominal pain or tenderness, a mass in the abdomen, or signs of hypovolemic shock due to hemorrhage (fast pulse, sweating, weakness, confusion, fainting). 

HYPERTENSION: Increased blood pressure is common in women using oral contraceptives and may also occur with the use of estrogen replacement therapy in menopause. Monitor your blood pressure at home while on esterified estrogens and methyltestosterone. Tell your doctor if you notice high readings. 

GLUCOSE TOLERANCE: Use of estrogen-containing oral contraceptives can lead to worsening of glucose tolerance. Tell your doctor if you have diabetes. Your doctor will monitor your blood glucose levels carefully while you are taking estrogens.

HYPERCALCEMIA: Estrogens can cause severely elevated blood calcium levels in people with breast cancer and bone metastases (cancer that has spread to the bones). Tell your doctor right away if you have symptoms such as stomach pain, nausea, vomiting, constipation, increased thirst, muscle weakness, bone pain, or confusion. You will need to stop taking estrogens if your blood calcium levels are high.

RISK OF DEVELOPING PROBABLE DEMENTIA: Taking esterified estrogens and methyltestosterone can increase the risk of developing probable dementia in women above 65 years of age. Talk with your doctor if this is a concern for you.

RISKS ASSOCIATED WITH EXOGENOUS ANDROGENS: In patients with breast cancer, taking androgens can stimulate osteolysis (bone breakdown) and lead to hypercalcemia (high calcium). High doses or prolonged use of androgens is linked to cholestatic jaundice, life-threatening liver problems, and hepatocellular carcinoma. Tell your doctor immediately if you develop right upper stomach pain, nausea, loss of appetite, or yellowing of the skin or eyes.