ESTROGENS, CONJUGATED

ESTROGENS, CONJUGATED
(ess'tro-jenz)
C.E.S.

, Cenestin, Enjuvia, Premarin, Progens
Classifications: hormone; estrogens;
Therapeutic: female hormone replacement therapy (hrt)
Prototype: Estradiol
Pregnancy Category: X

Availability

0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, 1.25 mg, 2.5 mg tablets; 25 mg injection; 0.625 mg vaginal cream

Action

Circulating estrogens modulate the pituitary secretion of the gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these gonadotropins seen in postmenopausal women.

Therapeutic Effect

Binds to intracellular receptors that stimulate DNA and RNA to synthesize proteins responsible for effects of estrogen.

Uses

Atrophic vaginitis, kraurosis vulvae, and abnormal bleeding (hormonal imbalance); also female hypogonadism, primary ovarian failure, vasomotor symptoms associated with menopause; to retard progression of osteoporosis and as palliative therapy of breast and prostatic carcinomas.

Unlabeled Uses

Postcoital contraceptive.

Contraindications

Breast cancer, except for palliative therapy; vaginal and cervical cancers; endometrial cancer; endometrial hyperplasia; abnormal vaginal bleeding; hepatic disease or cancer; hypercalcemia; ovarian cancer; history of thromboembolic disease; known or suspected pregnancy (category X).

Cautious Use

Hypertension; gallbladder disease; diabetes mellitus; heart failure; kidney dysfunction.

Route & Dosage

Menopause, Osteoporosis, Atrophic Vaginitis, Kraurosis Vulvae
Adult: PO 0.3–1.25 mg/d for 21 d each month, adjust to lowest level that gives symptom control (≤0.625 mg/d) IV/IM 25 mg, repeated in 6–12 h if needed Topical 2–4 g of cream/d

Female Hypogonadism
Adult: PO 2.5–7.5 mg/d in 1–3 divided doses for 20 d, followed by a 10 d rest period

Postcoital Contraception
Adult: PO 30 mg/d in divided doses for 5 consecutive days beginning within 72 h of coitus

Breast Cancer
Adult: PO 10 mg t.i.d. for at least 3 mo

Prostatic Cancer Palliation
Adult: PO 1.25–2.5 mg t.i.d.

Administration

Oral

Give cyclically except when used for treatment of postpartum breast engorgement and for palliation of cancer. Cyclic regimen is to dose for 3 wk followed by 1 wk off.

Topical

Use calibrated dosage applicator dispensed with the cream.

Intramuscular

Reconstitute by first removing approximately 5 mL of air from the dry-powder vial, then slowly inject the supplied diluent to the vial by aiming it at the side of the vial. Gently agitate to dissolve but DO NOT SHAKE.
Use within a few hours of reconstitution.

Intravenous

PREPARE: Direct: Reconstitute as for IM injection.

ADMINISTER: Direct: Give slowly at a rate of 5 mg/min. Estrogen solution is compatible with D5W and NS and may be added to IV tubing just distal to the needle if necessary.

INCOMPATIBILITIES Solution/additive: Ascorbic acid. Y-site: Pantoprazole.

Store ampule and reconstituted solution at 2°–8° C (38°–46° F) and protected from light; stable for 60 d. Discard precipitated or discolored solution.

Adverse Effects (≥1%)

CNS: Headache, dizziness, depression, libido changes. CV: Thromboembolic disorders, hypertension. GI: Nausea, vomiting, diarrhea, bloating, cholestatic jaundice. Urogenital: Mastodynia, spotting, changes in menstrual flow, dysmenorrhea, amenorrhea. Metabolic: Reduced carbohydrate tolerance, fluid retention. Other: Leg cramps, intolerance to contact lenses.

Interactions

Drug: barbiturates, carbamazepine, phenytoin, rifampin decrease estrogen effect by increasing its metabolism; oral anticoagulants may decrease hypoprothrombinemic effects; interfere with effects of bromocriptine; may increase levels and toxicity of cyclosporine, tricyclic antidepressants, theophylline; decrease effectiveness of clofibrate.

Pharmacokinetics

Absorption: Rapid absorption from GI tract; readily absorbed through skin and mucous membranes (including vaginal mucosa); slow absorption from IM injections. Distribution: Distributed throughout body tissues, especially in adipose tissue; crosses placenta, excreted in breast milk. Conjugated estrogens are bound primarily to albumin. Metabolism: Metabolized primarily in liver to glucuronide and sulfate conjugates of estradiol, estrone, and estriol. Elimination: In urine. Half-Life: 4–18 h.

Nursing Implications

Assessment & Drug Effects

See additional implications under estradiol.
Monitor for and report breakthrough vaginal bleeding.
Assess for relief of menopausal symptoms.
If depression develops, discontinue the drug.
Lab tests: Monitor serum phosphatase levels with prostate cancer.
Monitor bone density annually when used for osteoporosis prophylaxis.

Patient & Family Education

Be aware of importance of taking drug exactly as prescribed: Specifically, do not omit, increase, or decrease doses without advice of physician.
Intravaginal administration: For self-administration, wash hands well before and after application, and avoid contact of denuded areas with the cream. Do not use tampons while on vaginal cream therapy.
Notify physician promptly of adverse symptoms.
Risk of blood clot formation is high with morning after pill. Know signs of thrombophlebitis (see Appendix F).
Review package insert to ensure understanding of estrogen therapy.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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