estrogens esterified/methyltestosterone (Covaryx, Estratest, Estratest H.S.)

Dosing and uses of Covaryx, Estratest (estrogens-esterified-methyltestosterone)

• Adult
• Pediatric

 

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