Estradiol-Progesterone

Estradiol-Progesterone is a prescription medication indicated for women with a uterus for moderate to severe vasomotor symptoms related to menopause.

• Estradiol-Progesterone is available under the following different brand names: Bijuva

Common side effects of Estradiol-Progesterone include:

• breast tenderness
• headache
• vaginal bleeding
• vaginal discharge
• pelvic pain

Serious side effects of Estradiol-Progesterone include:

• blood clots: trouble breathing, leg pain or swelling, skin that's warm to the touch
• heart attack: chest pain, arm pain, shortness of breath, cold sweat, lightheadedness
• stroke: sudden weakness on one side of your body, drooping face, changes in your speech or vision, confusion, headache
• unusual changes in breast shape, size, or color
• unusual vaginal bleeding, vaginal discharge, or pelvic pain

Rare side effects of Estradiol-Progesterone include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 0.5 mg/100 mg
• 1 mg/100 mg

Vasomotor symptoms

Adult dosage

• 1 capsule (1 mg/100 mg) orally each evening with food

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Estradiol-Progesterone has severe interactions with no other drugs
• Estradiol-Progesterone has serious interactions with no other drugs
• Estradiol-Progesterone has moderate interactions with no other drugs
• Estradiol-Progesterone has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Undiagnosed abnormal genital bleeding
• Known, suspected, or history of breast cancer
• Known or suspected estrogen-dependent neoplasia
• Active pulmonary embolism (PE) and deep vein thrombosis (DVT) or a history of these conditions
• Active arterial thromboembolic disease (eg, stroke, myocardial infarction [MI]) or a history of these conditions
• Known anaphylactic reaction, angioedema, or hypersensitivity to estradiol, progesterone, or any excipients
• Known liver impairment or disease
• Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Estradiol-Progesterone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Estradiol-Progesterone?”

Cautions

• Increased risk of PE, DVT, stroke, and MI with estrogen plus progestin hormone replacement therapy (HRT)
• A nonsignificant increased risk for ovarian cancer was reported in the WHI estrogen plus progestin substudy
• Risk for probable dementia increased in women aged 65-79 years taking estrogen plus progestin or estrogen alone
• A twofold to fourfold increase in risk for gallbladder disease requiring surgery was reported in postmenopausal women receiving estrogens
• Estrogen may lead to severe hypercalcemia in women with breast cancer and bone metastases; discontinue therapy if hypercalcemia occurs, and take appropriate measures to reduce serum calcium level
• Retinal vascular thrombosis reported in women receiving estrogens; discontinue therapy pending examination if there is a sudden partial or complete loss of vision or a sudden onset of proptosis, diplopia, or migraine; permanently discontinue therapy if examination reveals papilledema or retinal vascular lesions
• Adding progestin for more than 10 days of estrogen administration cycle or daily with an estrogen continuous regimen, a lowered incidence of endometrial hyperplasia was reported than would be induced by estrogen treatment alone
• In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens; in a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogens on blood pressure was not seen
• In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevated plasma triglycerides leading to pancreatitis
• Estrogens may be poorly metabolized with impaired liver function; caution with a history of cholestatic jaundice associated with past estrogen use or with pregnancy
• Estrogen administration leads to increased thyroid-binding globulin levels; women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require an increased thyroid replacement dose
• Estrogens and progestins cause some degree of fluid retention; caution with conditions that may be affected (eg, cardiac or renal dysfunction); monitor any woman with a condition(s) that might predispose her to fluid retention, such as cardiac or renal impairment; discontinue estrogen plus progestogen therapy, with evidence of medically concerning fluid retention
• Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism; consider whether the benefits of therapy outweigh the risks in such women
• Residual endometrial implants reported in women treated posthysterectomy with estrogen-alone therapy; consider the addition of progesterone for these women
• Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema; consider whether the benefits outweigh the risks in such women
• Estrogen therapy may cause an exacerbation of asthma, diabetes, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas; consider whether the benefits of estrogen therapy outweigh the risks in women with such conditions
• Serum follicle–stimulating hormone and estradiol levels are not useful in the management of moderate to severe vasomotor symptoms
• Manage appropriately any risk factors for arterial vascular disease (for example, hypertension, diabetes, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE; eg, personal history or family history of VTE, obesity, and systemic lupus erythematosus)
• Increase in risk for stroke demonstrated after the first year and persisted; immediately discontinue estrogen with or without progestogen therapy if a stroke occurs or suspected
• VTE reported with therapy; increase in VTE risk demonstrated during the first year and persisted; immediately discontinue estrogen plus progestogen therapy if a VTE occurs or is suspected; if feasible, discontinue estrogens at least 4-6 weeks before surgery of the type associated with an increased risk for thromboembolism or during periods of prolonged immobilization
• Breast cancer reported with therapy; all women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations; in addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results
• Studies of addition of a progestogen for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone; endometrial hyperplasia may be a precursor to endometrial cancer; there are, however, possible risks that may be associated with use of progestogens with estrogens compared with estrogen-alone regimens; these include an increased risk for breast cancer
• Estrogens may be poorly metabolized in women with hepatic impairment; exercise caution in any woman with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; in the case of recurrence of cholestatic jaundice, discontinue
• Exacerbation of hypothyroidism
• Estrogen administration leads to increased thyroid-binding globulin (TBG) levels; women with normal thyroid function can compensate for increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range
• Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy; monitor thyroid function in these women during therapy to maintain free thyroid hormone levels in an acceptable range
• Endometrial cancer
  • Increased risk for endometrial cancer reported with unopposed estrogen therapy in women with a uterus; endometrial cancer risk among unopposed estrogen users is about twofold to 12-fold greater than in nonusers and appears dependent on treatment duration and estrogen dose
  • Clinical surveillance of all women using estrogen-alone or estrogen plus progestogen therapy is important; perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding with unknown etiology
  • There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose; adding a progestogen to estrogen therapy in postmenopausal women has been shown to reduce the risk for endometrial hyperplasia, which may be a precursor to endometrial cancer
• Drug interaction overview
  • Estrogens and progestins are metabolized partially by CYP3A4
  • CYP3A4 inducers may reduce plasma estrogen/progestin concentration, possibly resulting in a decreased therapeutic effect
  • CYP3A4 inhibitors may increase plasma concentrations of estrogen/progestin, possibly resulting in increased adverse effects

Pregnancy and Lactation

• Not indicated for women who are premenopausal, pregnant, or lactating
• Pregnancy
  • There are no data on use in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk for genital or nongenital birth defects (including cardiac anomalies and limb reduction defects) after exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy
• Lactation
  • Estrogens plus progestogens are present in human milk and can reduce milk production in breast-feeding women; this reduction can occur at any time but is less likely to occur once breastfeeding is well-established; the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for therapy and any potential adverse effects on the breastfed child from therapy or an underlying maternal condition