Estrogens (Conjugated / Equine, Systemic)

• C.E.S.
• CE
• CEE
• Conjugated Estrogen
• Estrogenic Substances, Conjugated

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Premarin: 25 mg (1 ea) [contains benzyl alcohol]

Tablet, Oral:

Premarin: 0.3 mg [contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]

Premarin: 0.45 mg [contains fd&c blue #2 (indigotine)]

Premarin: 0.625 mg [contains fd&c blue #2 (indigotine), fd&c red #40]

Premarin: 0.9 mg

Premarin: 1.25 mg [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]

• Premarin

Uremic bleeding

Data from one small randomized, double blind, placebo-controlled, crossover study in patients with chronic renal failure receiving hemodialysis and a history of bleeding, one small randomized, double blind, placebo-controlled, single center, crossover study in end-stage renal disease receiving hemodialysis without a history of bleeding, and one prospective, controlled single center study support the use of conjugated estrogens as an alternative treatment in the management of uremic bleeding due to the ability to shorten bleeding time [Heistinger 1990], [Livio 1986], [ Viganò 1988]. Clinical experience also suggests the utility of conjugated estrogens in the management of uremic bleeding [Hedges 2007]. Additional trials may be necessary to further define the role of conjugated estrogens in this setting.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use is contraindicated with hepatic dysfunction or disease.

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be taken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal genital bleeding.

Estrogen-alone therapy should not be used for the prevention of cardiovascular disease. The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens 0.625 mg alone, relative to placebo.

Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo.

The WHI estrogen-plus-progestin substudy demonstrated an increased risk of invasive breast cancer.

Estrogen-alone therapy should not be used for the prevention of dementia. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily conjugated estrogens (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

Estrogen plus progestin therapy should not be used for the prevention of dementia. The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens (with or without medroxyprogesterone acetate) and other dosage forms of estrogens (with or without progestins). Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Routine physical examination that includes blood pressure and Papanicolaou smear, breast exam, mammogram. Monitor for signs of endometrial cancer in female patients with uterus. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal genital bleeding. Monitor for loss of vision, sudden onset of proptosis, diplopia, migraine; signs and symptoms of thromboembolic disorders; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias; thyroid function in patients on thyroid hormone replacement therapy.

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

Prevention of osteoporosis: Bone density measurement

Uremic bleeding: Bleeding time

Note: Monitoring of FSH and serum estradiol is not useful when managing vasomotor symptoms associated with menopause or vulvar and vaginal atrophy.

These products are contraindicated for use during pregnancy. Estrogens are not indicated for use during pregnancy or immediately postpartum. In general, the use of estrogen and progestin as in combination hormonal contraceptives have not been associated with teratogenic effects when inadvertently taken early in pregnancy.