Dosing & Uses
Dosage Forms & Strengths
Menopausal Vasomotor Symptoms
Treatment of moderate-to-severe vasomotor symptoms associated with menopause in patients not improved by estrogens alone
Use lowest dose that will control symptoms
Typical dosage range: 0.625 mg/1.25 mg PO qDay up to 1.25 mg/2.5 mg qDay
Administration should be cyclic (eg, 3 weeks on and 1 week off)
Attempts to discontinue or taper medication should be made at 3-6 month intervals
Serious - Use Alternative
Significant - Monitor Closely
Frequency Not Defined
Suppression of clotting factors II, V, VII
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
- Estrogens with & 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, & deep vein thrombosis (DVT) in postmenopausal women (aged 50-79 yr) during 5.6 yr of treatment w/ daily PO conjugated estrogens (CE 0.625 mg) combined w/ medroxyprogesterone acetate (MPA 2.5 mg) compared w/ placebo
- Estrogens alone: A substudy of the WHI Study reported increased risk for stroke & DVT in postmenopausal women (aged 50-79 yr) during 6.8 yr of treatment w/ oral conjugated estrogens (0.625 mg/day) alone compared w/ placebo
- Unopposed estrogen in women with intact uterus is assocated with increased risk of endometrial cancer
- Estrogens with & 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 w/ MPA 2.5 mg, compared w/ 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 w/ conjugated estrogens 0.625 mg alone compared w/ 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 & other combinations & dosage forms of estrogens & progestins
- Because of these risks, estrogens w/ or without progestins should be prescribed at lowest effective dose & for shortest duration consistent w/ treatment goals and individual risks
Estrogen dependent tumor
Liver dysfunction or disease
Undiagnosed abnormal vaginal bleeding
Active/history of DVT/PE
Active/recent thromboembolic disease
Cardiac disease, renal disease, DM, endometriosis, hyperlipidemias, HTN, hypothyroidism
Increased risk of VTE
Fluid retention may exacerbate asthma, epilepsy, migraines, & cardiac or renal dysfunction
Increased risk of ovarian and endometrial cancer
Concomitant warfarin, oral anticoagulants: may need to incr anticoagulant dose
Estrogen may cause retinal vascular thrombosis; discontinue if migraine, proptosis, loss of vision, diplopia, or other vision abnormalities occur
Women with thrombophilias may experience increased risk of venous thromboembolism
Use caution in patients with familial defects of lipoprotein metabolism; triglycerides and HDL cholesterol may increase while LDL cholesterol may decrease
See also individual monographs:
- Estrogens, esterifed
Pregnancy & Lactation
Pregnancy Category: X
Lactation: Excreted into breast milk; contraindicated
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.
Mechanism of Action
Esterified estrogen: reduces LHRH release from hypothalamus, reduces gonadotropin release from pituitary; incr synthesis of DNA, RNA, & various proteins in target tissues
Methyltestosterone: synthetic testosterone derivatives with predominantly anabolic & minor androgenic activity; promoting growth & development of male sex organs & maintaining secondary sex characteristics in androgen-deficient males
Half-Life: Methyltestosterone: 10-100 min (PO)
Protein bound: 50-80% (esterified estrogens); 98% (methyltestosterone)
- Esterified estrogens: Urine as conjugates, most estrogens are also excreted in bile & undergo enterohepatic recycling
- Methyltestosterone: Urine (90%); feces (6%)
- Esterified estrogens: Liver, undergoes extensive first-pass metabolism to less active products such as estriol; kidneys, gonads, & muscle tissues may be involved in metabolism to some extent
- Methyltestosterone: Hepatic
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.
|1||This drug is available at the lowest co-pay. Most commonly, these are generic drugs.|
|2||This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.|
|3||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.|
|4||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|5||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
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