Dosing and uses of Ortho Est (estropipate)
Adult dosage forms and strengths
tablet
- 0.75mg
- 1.5mg
- 3mg
- 6mg
Menopause
0.75-6 mg PO qDay; taper at 3-6 month intervals
Cream: 2-4 g intravaginal 3 weeks on, 1 week off
Ovarian Failure
1.5-9 mg PO qDay for 3 weeks, then off for 8 days; repeat if necessary
Osteoporosis, Prevention
0.75 mg PO qDay for 25 days, then off for 6 days; repeat
Other Indications & Uses
Vasomotor symptoms associated with menopause; ovarian failure; osteoporosis, treatment of female hypogonadism due to castration, or primary ovarian failure, menopausal atrophic vaginitis (vaginal cream) daily
Pediatric dosage forms and strengths
Safety & efficacy not established
Geriatric dosage forms and strengths
Osteoporosis, prevention
0.75 mg PO qDay for 25 days, then off for 6 days; repeat
Ortho Est (estropipate) adverse (side) effects
Frequency not defined
Peripheral edema
Depression
Headache
Melasma
Bloating
Nausea & vomiting
Breast enlargement & tenderness
Amenorrhea
Breakthrough bleeding
Spotting
Weight changes
Corneal curvation change
Warnings
Black box warnings
Estrogens increase risk of endometrial cancer
- Close clinical surveillance of all women taking estrogens is important
- Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding
- There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses
Cardiovascular risks
- Estrogens with and without progestins should not be used to prevent cardiovascular disease
- Estrogens plus progestins: Women’s Health Initiative (WHI) Estrogen Plus Progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis (DVT) in postmenopausal women (aged 50-79 yr) during 5.6 yr of treatment with daily PO conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) compared with placebo
- Estrogens alone: A substudy of the WHI Study reported increased risk for stroke and DVT in postmenopausal women (aged 50-79 yr) during 6.8 yr of treatment with oral conjugated estrogens (0.625 mg/day) alone compared with placebo
Dementia risks
- Estrogens with and without progestins should not be used to prevent dementia
- Women's Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 4 yr of treatment w/ daily CE 0.625 mg combined with MPA 2.5 mg, compared with placebo
- Estrogens alone: A substudy of the WHIMS reported an increased risk of developing probable dementia in postmenopausal women aged 65 yr or older during 5.2 yr of treatment with conjugated estrogens 0.625 mg alone compared with placebo
- Unknown whether these findings apply to younger postmenopausal women
Dose & duration
- In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins
- Because of these risks, estrogens with or without progestins should be prescribed at lowest effective dose and for shortest duration consistent with treatment goals and individual risks
Contraindications
Documented hypersensitivity
Active or history of breast cancer
Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
Estrogen-dependent neoplasia, liver disease, liver tumors
Undiagnosed abnormal vaginal bleeding
Uncontrolled hypertension
Diabetes mellitus with vascular involvement
Jaundice with prior oral contraceptive use
Cautions
Diabetes mellitus, endometriosis, hyperlipidemias, HTN, hypothyroidism, elderly, hepatic/renal impairment, uterine leiomyomata, porphyria, patients with defects of lipoprotein metabolism, hypertriglyceridemia, ovarian cancer, exacerbation of endometriosis or other conditions, smoking and >35 years old, SLE, depression
Fluid retention may exacerbate asthma, epilepsy, migraines, & cardiac or renal dysfunction
Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significang blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery.
Hypercalcemia may occur in patients with breast cancer and bone metastases
Increased risk of endometrial and ovarian cancer in postmenopausal women
Long-term postmenopausal estrogen treatment has been associated with increased risk of breast cancer, MI, stroke, DVT, PE, and dementia
May increase risk of thromboembolic disorders, may need to increase anticoagulant dose when administering concomitantly with anticoagulants
Pregnancy and lactation
Pregnancy category: X
Lactation: Controversial; estrogens are excreted into breast milk in small quantities, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ortho Est (estropipate)
Mechanism of action
Semisynthetic conjugate of estrone with piperazine; reduces the release of gonadotropin-releasing hormone from hypothalamus, reduces release of LH and FSH from pituitary gland; increases synthesis of DNA, RNA, and various proteins in target tissues
Pharmacokinetics
Half-Life: IM: 1.5-5 hr
Bioavailability: Readily absorbed through GI tract, skin, mucous membrane
Protein bound: 50-80%
Metabolism: Undergoes rapid and extensive first-pass metabolism in liver to less active products such as estriol; kidneys, gonads, and muscle tissues may be involved in metabolism to some extent
Metabolites: EstrioL
Excretion: Mainly in urine as conjugates with small amount of unchanged drug, most estrogens are also excreted in bile and undergo enterohepatic recycling
