Estrogens (Esterified) and Methyltestosterone

Pronunciation

(ES troe jenz es TER i fied & meth il tes TOS te rone)

U.S. Brand Names

Estratest®; Estratest® H.S.; Syntest D.S.; Syntest H.S.

Synonyms

Conjugated Estrogen and Methyltestosterone; Esterified Estrogen and Methyltestosterone

Generic Available

Yes

Canadian Brand Names

Estratest®

Use

Vasomotor symptoms of menopause

Pregnancy Risk Factor

X

Pregnancy Implications

Refer to Estrogens (Esterified) monograph.

Contraindications

Hypersensitivity to estrogens, methyltestosterone, or any component of the formulation; undiagnosed abnormal vaginal bleeding; history of or current thrombophlebitis or venous thromboembolic disorders (including DVT, PE); active or recent (within 1 year) arterial thromboembolic disease (eg, stroke, MI); carcinoma of the breast, except in appropriately selected patients being treated for metastatic disease; estrogen-dependent tumor; hepatic dysfunction or disease; pregnancy; breast-feeding

Warnings/Precautions

Cardiovascular-related considerations: Estrogens with or without progestin should not be used to prevent coronary heart disease. Use caution with cardiovascular disease or dysfunction. May increase the risks of hypertension, myocardial infarction (MI), stroke, pulmonary emboli (PE), and deep vein thrombosis; incidence of these effects was shown to be significantly increased in postmenopausal women using conjugated equine estrogens (CEE) in combination with medroxyprogesterone acetate (MPA). Nonfatal MI, PE, and thrombophlebitis have also been reported in males taking high doses of CEE (eg, for prostate cancer). Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; use with caution in patients with familial defects of lipoprotein metabolism. Whenever possible, estrogens should be discontinued at least 4-6 weeks prior to surgeries associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Neurological considerations: The risk of dementia may be increased in postmenopausal women; increased incidence was observed in women 65 years of age taking CEE in combination with MPA.

Cancer-related considerations: Unopposed estrogens may increase the risk of endometrial carcinoma in postmenopausal women. Estrogens may increase the risk of breast cancer. An increased risk of invasive breast cancer was observed in postmenopausal women using CEE in combination with MPA; a smaller increase in risk was seen with estrogen therapy alone in observational studies. An increase in abnormal mammograms has also been reported with estrogen and progestin therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs.

Estrogens may cause retinal vascular thrombosis; discontinue permanently if papilledema or retinal vascular lesions are observed on examination. Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes or renal dysfunction. Use with caution in patients with a history of severe hypocalcemia, SLE, hepatic hemangiomas, porphyria, endometriosis, and gallbladder disease. Use caution with history of cholestatic jaundice associated with past estrogen use or pregnancy. Safety and efficacy in pediatric patients have not been established. Prior to puberty, estrogens may cause premature closure of the epiphyses, premature breast development in girls or gynecomastia in boys. Vaginal bleeding and vaginal cornification may also be induced in girls.

Before prescribing estrogen therapy to postmenopausal women, the risks and benefits must be weighed for each patient. Women should be informed of these risks and benefits, as well as possible effects of progestin when added to estrogen therapy. Estrogens with or without progestin should be used for shortest duration possible consistent with treatment goals. Conduct periodic risk:benefit assessments.

Adverse Reactions

1% to 10%:

Cardiovascular: Increase in blood pressure, edema, thromboembolic disorder

Central nervous system: Depression, headache

Dermatologic: Chloasma, melasma

Endocrine & metabolic: Breast tenderness, change in menstrual flow, hypercalcemia

Gastrointestinal: Nausea, vomiting

Hepatic: Cholestatic jaundice

Drug Interactions

Based on estrone: Substrate of CYP1A2 (major), 2B6 (minor), 2C8/9 (minor), 2E1 (minor), 3A4 (major)

Also see individual agents.

Mechanism of Action

Conjugated estrogens: Activate estrogen receptors (DNA protein complex) located in estrogen-responsive tissues. Once activated, regulate transcription of certain genes leading to observed effects.

Testosterone: Increases synthesis of DNA, RNA, and various proteins in target tissues

Pharmacodynamics/Kinetics

See individual agents.

Dosage

Adults: Female: Oral: Lowest dose that will control symptoms should be chosen, normally given 3 weeks on and 1 week off

Monitoring Parameters

Yearly physical examination that includes blood pressure and Papanicolaou smear, breast exam, mammogram. Monitor for signs of endometrial cancer. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

Menopausal symptoms: Assess need for therapy at 3- to 6-month intervals

Dietary Considerations

Should be taken with food at same time each day.

Patient Education

Women should inform their physicians if signs or symptoms of any of the following occur: thromboembolic or thrombotic disorders including sudden severe headache or vomiting, disturbance of vision or speech, loss of vision, numbness or weakness in an extremity, sharp or crushing chest pain, calf pain, shortness of breath, severe abdominal pain or mass, mental depression or unusual bleeding; women should discontinue taking the medication if they suspect they are pregnant or become pregnant.

Nursing Implications

Women should inform their physicians if signs or symptoms of any of the following occur: thromboembolic or thrombotic disorders including sudden severe headache or vomiting, disturbance of vision or speech, loss of vision, numbness or weakness in an extremity, sharp or crushing chest pain, calf pain, shortness of breath, severe abdominal pain or mass, mental depression or unusual bleeding; women should discontinue taking the medication if they suspect they are pregnant or become pregnant.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause depression

Mental Health: Effects on Psychiatric Treatment

Barbiturates and carbamazepine may decrease the effects of estrogens; estrogens may affect metabolism of benzodiazepines; monitor for clinical effect

Dosage Forms

Tablet:

Estratest®: Esterified estrogen 1.25 mg and methyltestosterone 2.5 mg [contains sodium benzoate]

Estratest® H.S.: Esterified estrogen 0.625 mg and methyltestosterone 1.25 mg [contains sodium benzoate]

Syntest D.S.: Esterified estrogen 1.25 mg and methyltestosterone 2.5 mg

Syntest H.S.: Esterified estrogen 0.625 mg and methyltestosterone 1.25 mg

References

Shumaker SA, Legault C, Rapp SR, et al, "WHIMS Investigators. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial,"JAMA, 2003, 289(20):2651-62.

U.S. Food and Drug Administration, Department of Health and Human Services, "FDA Approves New Labels for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Following Review of Women's Health Initiative Data," January 8, 2003. Available at: http://www.fda.gov/medwatch/SAFETY/2003/safety03.htm#prempr. Accessed April 17, 2003.

"Writing Group for the Women's Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principle Results From the Women's Health Initiative Randomized Controlled Trial,"JAMA, 2002, 288:321-33.

International Brand Names

Estratest® (CA)