estrogen conjugated A (Synthetic) [Oral]

Adult Dosing

Moderate to severe vasomotor symptoms due to menopause

Start 0.45 mg PO qd; adjust the dose based on individual patient's response
Usual dose: 0.45-1.25 mg/day

Moderate to severe symptoms of vulvar and vaginal atrophy due to menopause

0.3 mg PO qd

Notes:

In postmenopausal women with intact uteri, add progestin for at least 12-14 days every 28-day cycle to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
Use the lowest effective dose for the shortest duration consistent with treatment goals and risks for the individual woman

Pediatric Dosing

Not indicated

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

Treatment of moderate to severe vasomotor symptoms due to menopause [0.45, 0.625, 0.9, 1.25 mg]
Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause [0.3 mg]

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredients of the product
Undiagnosed abnormal genital bleeding
Known, suspected, or history of breast cancer
Known or suspected estrogen-dependent neoplasia
Active or history of deep vein thrombosis or pulmonary embolism
Active or recent (within past 1 yr) arterial thromboembolic disease
Liver dysfunction or disease
Known or suspected pregnancy
Protein C or S deficiency
Thrombophilic disorder

Black Box Warnings ⬆ ⬇

Estrogen increases the risk of endometrial cancer; closely monitor all women taking estrogen therapy. Use adequate diagnostic measures, like endometrial sampling, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of natural estrogens, at equivalent estrogen doses, results in a different endometrial risk profile than synthetic estrogens
Do not use estrogens with or without progestins for the prevention of cardiovascular disease or dementia. As per the study conducted by Women’s Health Initiative (WHI), daily oral conjugated estrogens (CE) 0.625 mg alone increased the risk of stroke and deep vein thrombosis (DVT) in postmenopausal women (50-79 years of age) during 6.8 yrs and 7.1 yrs of treatment, respectively; also an increased risk of stroke, deep vein thrombosis (DVT), pulmonary embolism, and myocardial infarction was reported in postmenopausal women (50-79 yrs of age) during 5.6 years of treatment with daily oral CE 0.625 mg in combination with medroxyprogesterone acetate (MPA) 2.5 mg, relative to placebo
As per the WHI Memory Study (WHIMS), oral CE alone (0.625 mg) or in combination with MPA (2.5 mg) increased the risk of developing probable dementia in postmenopausal women 65 years of age during 5.2 and 4 years of treatment respectively, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women
Other doses of oral CE and MPA and other combinations and dosage forms of estrogens and progestins are not studied; however, these risks should be assumed to be similar. Use the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

Hepatic impairment: Contraindicated

Warnings/Precautions ⬆ ⬇

See Supplemental Patient Information

Estrogen alone or in combination with progestin therapy increases the risk of stroke, DVT, pulmonary embolism, and myocardial infarction [US Black Box Warning]
Risk factors for arterial vascular disease and/or venous thromboembolism should be managed appropriately
Estrogen alone or in combination with progestin therapy increases the risk of venous thromboembolism. Discontinue estrogen therapy 4-6 wks before surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization
Use of unopposed estrogens in women with intact uteri increases the risk of endometrial cancer 2-12 times greater than in non-users [US Black Box warning]
Use of estrogens and progestins in postmenopausal women has been reported to increase the risk of breast cancer. Perform regular breast examinations and mammograms based on patient age, risk factors, and prior mammogram results; advise patients to perform breast self-examinations every month
Estrogen and estrogen/progestin therapy has been reported to increase the risk of dementia in postmenopausal women 65 years of age and older [US Black Box warning]
Increased risk of gallbladder disease by 2 to 4 fold has been reported in postmenopausal women receiving estrogen therapy
Estrogen therapy may cause severe hypercalcemia in women with breast cancer and bone metastases. Discontinue therapy and provide appropriate measures if hypercalcemia occurs
Retinal vascular thrombosis may occur in women receiving estrogens. Discontinue the drug if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia or migraine. Permanently discontinue therapy if papilledema or retinal vascular lesions are seen on examination
Use of progestin with estrogen in a continuous regimen may lower the incidence of endometrial hyperplasia than would be induced by estrogen-alone treatment. However, there is possible increased risk of breast cancer, adverse effects on lipoprotein metabolism and impairment of glucose tolerance with the use of progestins along with estrogens compared to estrogen-alone regimens
Estrogen use may cause substantial increases in blood pressure; monitor BP at regular intervals
Estrogen therapy may elevate plasma triglycerides in women with preexisting hypertriglyceridemia, leading to pancreatitis and other complications; discontinue therapy if pancreatitis occurs
Use cautiously in patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy; discontinue the drug in case of recurrence
Estrogen administration may cause increased thyroid-binding globulin (TBG) levels. Patients on thyroid hormone replacement therapy receiving estrogens may require increased doses of their thyroid replacement therapy. Monitor thyroid function regularly to maintain free thyroid hormone levels in an acceptable range
Estrogen plus progestin may cause fluid retention; use cautiously in patients with conditions like asthma, epilepsy, migraine, and cardiac or renal dysfunction
Prolonged use of estrogen-plus progestin and estrogen-only therapy has been associated with an increased risk of ovarian cancer
Administration of estrogen therapy in women treated post-hysterectomy may exacerbate endometriosis; consider adding progestin to the therapy for women known to have residual endometriosis post-hysterectomy

Cautions: Use cautiously in

Risk of cardiovascular disease
Hypertension
Hypertriglyceridemia
History of cholestatic jaundice with estrogens or pregnancy
Hypothyroidism
Severe hypocalcemia
Diabetes mellitus
Surgery or prolonged immobilization
Porphyria
Systemic lupus erythematosus
Hepatic hemangiomas
Endometriosis
Smoking
Obesity
Chorea
Seizure disorder
Geriatric patients >65 yrs

Supplemental Patient Information

Explain postmenopausal women of the importance of reporting abnormal vaginal bleeding to their physician as early as possible
Inform postmenopausal women of possible serious and common adverse reactions of estrogen plus progestin therapy such as cardiovascular disorders, malignant neoplasms, probable dementia, headache, breast tenderness, nausea and vomiting

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:X

Breastfeeding: Estrogen administration during breastfeeding interferes with lactation by decreasing the quantity and quality of the milk. Detectable amounts have been secreted in breast milk. Manufacturer advises caution.

Adverse Reactions ⬆ ⬇

CNS: Headache, migraine, exacerbation of epilepsy, dementia, dizziness, chorea exacerbation
PSYCHIATRY: Mood changes, depression
CV: Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, hypertension
GU: Breast pain, vaginal hemorrhage/spotting, vaginitis, vaginal candidiasis, ovarian cancer, endometrial cancer, breast cancer, endometrial hyperplasia, abnormal uterine bleeding/spotting, uterine fibroid enlargement, cervical secretion changes, changes in libido, metrorrhagia, dysmenorrhea
GI: Nausea, vomiting, abdominal pain/bloating, cholestatic jaundice, gallbladder disease, pancreatitis, enlargement of hepatic hemangiomas, flatulence, ischemic colitis
DERM: Chloasma or melasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, hirsutism, pruritus, rash, acne, hair loss, urticaria, angioedema
EENT: Retinal thrombosis, contact lens intolerance, vision changes
RESP: Sinusitis, pharyngitis, rhinitis, exacerbation of asthma
METABOLIC: Hypocalcemia, severe hypercalcemia (metastatic breast cancer), fluid retention, glucose intolerance, weight changes
MUSC: Arthralgia, leg cramps
HEMA: Porphyria exacerbation
IMMU: SLE exacerbation
LABTESTS: Increased triglycerides
HYPERSENSITIVITY: Anaphylaxis, anaphylactoid reactions
MISC: Infection, asthenia, fever, flu syndrome, edema

Clinical Pharmacology ⬆ ⬇

Estrogen; binds to estrogen receptors and is responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. By negative feedback mechanism, it regulates the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH)
Well absorbed from GI tract
Metabolized by liver; CYP450: 3A4. Also undergoes enterohepatic recirculation
Renally excreted
Half-life
Equilin: 9.7 hrs
Estrone: 10.6 hrs

Brands and Availability ⬆ ⬇