estrogens, conjugated

estrogens, conjugated

(ess' troe jenz)

Oral, topical vaginal cream:

C.E.S. (CAN), Premarin

Parenteral:

Premarin Intravenous

Synthetic:

Cenestin

Pregnancy Category X

Drug classes

Hormone

Estrogen

Therapeutic actions

Estrogens are endogenous female sex hormones important in the development of the female reproductive system and secondary sex characteristics. They affect the release of pituitary gonadotropins; cause capillary dilatation, fluid retention, protein anabolism, and thin cervical mucus; conserve calcium and phosphorus; encourage bone formation; inhibit ovulation and prevent postpartum breast discomfort. They are responsible for the proliferation of the endometrium; absence or decline of estrogen produces signs and symptoms of menopause on the uterus, vagina, breasts, cervix. Their efficacy as palliation in male patients with androgen-dependentprostatic carcinoma is attributable to their competition with androgens for receptor sites, thus decreasing the influence of androgens.

Indications

Oral

·        Palliation of moderate to severe vasomotor symptoms, atrophic vaginitis, or kraurosis vulvae associated with menopause

·        Treatment of female hypogonadism; female castration; primary ovarian failure

·        Osteoporosis: To retard progression

·        Palliation of inoperable prostatic cancer

·        Palliation of metastatic breast cancer

·        Cenestin: Treatment of moderate to severe vasomotor symptoms associated with menopause

·        Unlabeled use: Postcoital contraceptive

Parenteral

·        Treatment of uterine bleeding due to hormonal imbalance in the absence of organic pathology

Vaginal cream

·        Treatment of atrophic vaginitis and kraurosis vulvae associated with menopause

Contraindications and cautions

·        Contraindicated with allergy to estrogens, breast cancer (with exceptions), estrogen-dependent neoplasm, undiagnosed abnormal genital bleeding, active or past thrombophlebitis or thromboembolic disorders from previous estrogen use, pregnancy (serious fetal defects; women of childbearing age should be advised of risks and birth control measures suggested).

·        Use cautiously with metabolic bone disease, renal insufficiency, CHF, lactation.

Available forms

Tablets—0.3, 0.45, 0.625, 0.9, 1.25 mg; injection—25 mg; vaginal cream—0.625 mg/g

Dosages

Oral drug should be given cyclically (3 wk on/1 wk off) except in selected cases of carcinoma and prevention of postpartum breast engorgement.

ADULTS

·        Moderate to severe vasomotor symptoms associated with menopause: 0.625 mg/day PO. If patient has not menstruated in 2 mo, start at any time. If patient is menstruating, start therapy on day 5 of bleeding; 0.625–1.25 mg (Cenestin).

·        Atrophic vaginitis, kraurosis vulvae associated with menopause: 0.3–1.25 mg/day PO or more if needed. 2–4 g vaginal cream daily intravaginally or topically, depending on severity of condition. Taper or discontinue at 3- to 6-mo intervals.

·        Female hypogonadism: 0.3–0.625 mg/day PO in divided doses for 20 days followed by 10 days of rest. If bleeding does not appear at the end of this time, repeat course. If bleeding does occur before the end of the 10-day rest, begin a 20-day 2.5–7.5 mg estrogen cyclic regimen with oral progestin given during the last 5 days of therapy. If bleeding occurs before this cycle is finished, restart course on day 5 of bleeding.

·        Female castration, primary ovarian failure: 1.25 mg/day PO. Adjust dosage by patient response to lowest effective dose.

·        Prostatic cancer (inoperable): 1.25–2.5 mg tid PO. Judge effectiveness by phosphatase determinations and by symptomatic improvement.

·        Osteoporosis: 0.625 mg/day PO given continuously or cyclically (25 days on/5 days off).

·        Breast cancer (inoperable, progressing): 10 mg tid PO for at least 3 mo.

·        Abnormal uterine bleeding due to hormonal imbalance: 25 mg IV or IM. Repeat in 6–12 hr as needed. IV route provides a more rapid response.

PEDIATRIC PATIENTS

Not recommended due to effect on the growth of the long bones.

Pharmacokinetics

Route	Onset	Peak
Oral	Slow	Days
IV	Gradual	Hours

Metabolism: Hepatic; T_1/2: Unknown

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

IV facts

Preparation: Reconstitute with provided diluent; add to normal saline, dextrose, and invert sugar solutions. Refrigerate unreconstituted parenteral solution; use reconstituted solution within a few hours. Refrigerated reconstituted solution is stable for 60 days; do not use solution if darkened or precipitates have formed.

Infusion: Inject slowly over 2–5 min.

Incompatibilities: Do not mix with protein hydrolysate, ascorbic acid, or any solution with an acid pH.

Adverse effects

·        CNS: Steepening of the corneal curvature with a resultant change in visual acuity and intolerance to contact lenses, headache, migraine, dizziness, mental depression, chorea, seizures

·        CV: Increased BP, thromboembolic and thrombotic disease

·        Dermatologic: Photosensitivity, peripheral edema, chloasma, erythema nodosum or multiforme, hemorrhagic eruption, loss of scalp hair, hirsutism,urticaria, dermatitis

·        GI: Gallbladder disease (in postmenopausal women), hepatic adenoma, nausea, vomiting, abdominal cramps, bloating, cholestatic jaundice, colitis,acute pancreatitis

·        GU: Increased risk of endometrial cancer in postmenopausal women, breakthrough bleeding, change in menstrual flow, dysmenorrhea, premenstrual-like syndrome, amenorrhea, vaginal candidiasis, cystitis-like syndrome, endometrial cystic hyperplasia

·        Hematologic: Hypercalcemia, decreased glucose tolerance

·        Local: Pain at injection site, sterile abscess, postinjection flare

·        Other: Weight changes, reduced carbohydrate tolerance, aggravation of porphyria, edema, changes in libido, breast tenderness

Topical vaginal cream

Systemic absorption may cause uterine bleeding in menopausal women and serious bleeding of remaining endometrial foci in sterilized women with endometriosis.

Interactions

Drug-drug

·        Increased therapeutic and toxic effects of corticosteroids

·        Decreased serum levels of estrogen with drugs that enhance hepatic metabolism of the drug: Barbiturates, phenytoin, rifampin, carbamazepine

Drug-lab test

·        Increased prothrombin and factors VII, VIII, IX, and X; thyroid-binding globulin with increased PBI, T₄, increased uptake of free T₃ resin (free T₄ is unaltered), serum triglycerides and phospholipid concentration

·        Decreased antithrombin III, pregnanediol excretion, response to metyrapone test, serum folate concentration

·        Impaired glucose tolerance

Nursing considerations

Assessment

·        History: Allergy to estrogens; breast cancer, estrogen-dependent neoplasm; undiagnosed abnormal genital bleeding; active or previous thrombophlebitis orthromboembolic disorders; pregnancy; lactation; metabolic bone disease; renal insufficiency; CHF

·        Physical: Skin color, lesions, edema; breast examination; injection site; orientation, affect, reflexes; P, auscultation, BP, peripheral perfusion; R, adventitious sounds; bowel sounds, liver evaluation, abdominal examination; pelvic examination; serum calcium, phosphorus; LFTs, renal function tests; Pap smear; glucose tolerance test

Interventions

·        Arrange for pretreatment and periodic (at least annual) history and physical, which should include BP, breasts, abdomen, pelvic organs, and a Pap smear.

·        Do not use to prevent CV events or dementia; may increase risk.

·        Caution patient of the risks involved with estrogen use, the need to prevent pregnancy during treatment, for frequent medical follow-up, and periodic rests from drug treatment.

·        WARNING: Give cyclically for short term only when treating postmenopausal conditions because of the risk of endometrial neoplasm; taper to the lowest effective dose, and provide a drug-free week each month.

·        Refrigerate unreconstituted parenteral solution; use reconstituted solution within a few hours.

·        Refrigerated reconstituted solution is stable for 60 days; do not use solution if darkened or precipitates have formed.

·        WARNING: Arrange for the concomitant use of progestin therapy during long-term estrogen therapy in women; this will mimic normal physiologic cycling and allow for cyclic uterine bleeding, which may decrease the risk of endometrial cancer. Women without a uterus do not need progestin.

Teaching points

·        Use this drug cyclically or short term; prepare a calendar of drug days, rest days, and drug-free periods.

·        Use vaginal cream properly.

·        Potentially serious side effects can occur: Cancers, blood clots, and liver problems; it is very important that you have periodic medical examinations throughout therapy.

·        This drug cannot be given to pregnant women because of serious toxic effects to the baby.

·        You may experience these side effects: Nausea, vomiting, bloating; headache, dizziness, mental depression (use caution if driving or performing tasks that require alertness); sensitivity to sunlight (use a sunscreen and wear protective clothing); rash, loss of scalp hair, darkening of the skin on the face; changes in menstrual patterns.

·        Report pain in the groin or calves of the legs, chest pain or sudden shortness of breath, abnormal vaginal bleeding, lumps in the breast, sudden severe headache, dizziness or fainting, changes in vision or speech, weakness or numbness in the arm or leg, severe abdominal pain, yellowing of the skin or eyes, severe mental depression, pain at injection site.

Adverse effects in Italic are most common; those in Bold are life-threatening.