Adult Dosing

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

• Start 1 g PV qd x 1 wk followed by 1 g PV x 2/wk

• In postmenopausal women with uterus, add progestin to the therapy to reduce the risk of endometrial cancer
• Use lowest effective dose of estrogen/progestin combination for shortest duration

Pediatric Dosing

• Not indicated

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of moderate to severe vaginal dryness and dyspareunia, a symptom of vulvar and vaginal atrophy, associated with menopause

• 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

• Use of unopposed 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. Adding a progestin to estrogen therapy reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
• 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 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
• Also, estrogen plus progestin therapy has been shown to increase the risk of invasive breast cancer
• Other doses of 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

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Contraindicated

See Supplemental Patient Information

• Estrogen conjugated vaginal cream is absorbed systemically; hence, the warnings, precautions, and adverse reactions associated with oral synthetic conjugated estrogen should be taken into account
• Estrogen alone or in combination with progestin therapy increases the risk of stroke, DVT, pulmonary embolism, and myocardial infarction [US Black Box Warning]. Discontinue therapy immediately if any of these symptoms occur
• 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 [US Black Box warning]. Advise patients to perform breast self-examinations every month
• Prolonged use of estrogen-plus progestin and estrogen-only therapy has been associated with an increased risk of ovarian cancer
• 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 progestins may cause fluid retention; use cautiously in patients with conditions like asthma, epilepsy, migraine, and cardiac or renal dysfunction
• 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
• Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism

Cautions: Use cautiously in

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

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 Category:X

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

• CNS: Headache, migraine, exacerbation of epilepsy, dementia, dizziness, exacerbation of chorea
• PSYCHIATRY: Mood changes, depression
• CV: Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, hypertension, hot flushes
• 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, dysmenorrhea
• GI: Nausea, vomiting, abdominal pain/bloating, cholestatic jaundice, gallbladder disease, pancreatitis, enlargement of hepatic hemangiomas, 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: URTI, 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: Anaphylactoid reactions
• MISC: Infection, fever, edema, flu syndrome

• 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)
• There is very little to no systemic accumulation during recommended dosing interval for this product
• Metabolized by liver; CYP450: 3A4. Also undergoes enterohepatic recirculation
• Renally excreted
• Half-life
• Estradiol: 22.1 hrs
• Estrone: 34.1 hrs
• Equilin: 15.7 hrs

US Trade Name(s)

• Only generic available

US Availability

estrogen conjugated A (Synthetic) (generic)

• CRE: 0.625 mg/g

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Endocrine/Metabolic

Sex Hormones

Estrogens

Obstetrics/Gynecology

Sex Hormones

Estrogens