estrogens esterified/methyltestosterone (Covaryx, Estratest, Estratest H.S.)
Classes: Estrogen and Androgen Combos
Dosing and uses of Covaryx, Estratest (estrogens-esterified-methyltestosterone)
Adult dosage forms and strengths
estrogens esterified/methyltestosterone
tablet
- 0.625mg/1.25mg
- 1.25mg/2.5mg
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
Pediatric dosage forms and strengths
Not indicated
Covaryx, Estratest (estrogens-esterified-methyltestosterone) adverse (side) effects
Frequency not defined
Common
- Edema
- Headache
- Acne, alopecia
- Breast soreness, menstrual irregularities
- Bloating, nausea, vomiting
Less Common
- Anaphylaxis
- Suppression of clotting factors II, V, VII
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 w/ & 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
Dementia Risks
- Estrogens w/ & 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
Contraindications
Pregnancy, lactation
Estrogen-dependent neoplasia
Breast cancer
Liver dysfunction or dz
Undiagnosed abnl vaginal bleeding
Active/history of DVT/Pe
Active/recent thromboembolic dz
Hypersensitivity
Cautions
Cardiac dz, renal dz, DM, endometriosis, hyperlipidemias, HTN, hypothyroidism
Incr risk of VTe
Fluid retention may exacerbate asthma, epilepsy, migraines, & cardiac or renal dysfunction
Incr risk of endometrial cancer
Concomitant warfarin, oral anticoagulants: may need to incr anticoagulant dose
See also individual monographs:
- Estrogens, esterifed
- Methyltstosterone
Pregnancy and lactation
Pregnancy category: X
Lactation: excreted into breast milk, avoid
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 Covaryx, Estratest (estrogens-esterified-methyltestosterone)
Half-Life: methyltestosterone: PO: 10-100 min
Protein Bound: esterified estrogens: 50-80%; methyltestosterone: 98%
Metabolism:
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: less extensive first-pass hepatic metabolism than testosterone
Excretion:
Esterified estrogens: urine as conjugates, most estrogens are also excreted in bile & undergo enterohepatic recycling
Methyltestosterone:
- urine: 90%
- feces: 6%
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