|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Premarin® may be confused with Primaxin®, Provera®, Remeron®
Pronunciation
(ES troe jenz KON joo gate ed, EE kwine)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of moderate-to-severe vasomotor symptoms associated with menopause; treatment of vulvar and vaginal atrophy; hypoestrogenism (due to hypogonadism, castration, or primary ovarian failure); prostatic cancer (palliation); breast cancer (palliation); osteoporosis (prophylaxis, postmenopausal women at significant risk only); abnormal uterine bleeding; moderate-to-severe dyspareunia (pain during intercourse) due to vaginal/vulvar atrophy of menopause
Use: Unlabeled/Investigational
Uremic bleeding
Pregnancy Considerations
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. These products are contraindicated for use during pregnancy. Use of the vaginal cream may weaken latex found in condoms, diaphragms or cervical caps.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
The AAP considers ethinyl estradiol, an estrogen derivative, to be “usually compatible” with breast-feeding. Estrogen has been shown to decrease the quantity and quality of human milk. Use only if clearly needed. Monitor the growth of the infant closely.
Contraindications
Hypersensitivity to estrogens 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
Warnings/Precautions
Boxed warnings:
• Cardiovascular disease: See “Disease-related concerns” below.
• Dementia: See “Concerns related to adverse effects” below.
• Endometrial carcinoma: See “Concerns related to adverse effects” below.
• Risks vs benefits: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Breast cancer: Estrogens may increase the risk of breast cancer. An increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (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.
• Dementia: [U.S. Boxed Warning]: The risk of dementia may be increased in postmenopausal women; increased incidence was observed in women ?65 years of age taking CE alone or in combination with MPA.
• Endometrial carcinoma: [U.S. Boxed Warning]: Adequate diagnostic measures, including endometrial sampling (if indicated), should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding. Unopposed estrogens may increase the risk of endometrial carcinoma in postmenopausal women with an intact uterus. Risk appears to be associated with long-term use. The use of a progestin should be considered when administering estrogens to postmenopausal women with an intact uterus.
• Lipid effects: 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.
• Ovarian cancer: Postmenopausal estrogen therapy and combined estrogen/progesterone therapy may increase the risk of ovarian cancer; however, the absolute risk to an individual woman is small. Although results from various studies are not consistent, risk does not appear to be significantly associated with the duration, route, or dose of therapy. In one study, the risk decreased after 2 years following discontinuation of therapy.
• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.
• Vaginal bleeding: Presentation of irregular, unresolving vaginal bleeding warrants further evaluation including endometrial sampling, if indicated, to rule out malignancy
Disease-related concerns:
• Cardiovascular disease: [U.S. Boxed Warning]: Estrogens with or without progestin should not be used to prevent cardiovascular 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 CE alone or in combination with MPA. Nonfatal MI, PE, and thrombophlebitis have also been reported in males taking high doses of CE (eg, for prostate cancer).
• Cholestatic jaundice: Use caution with history of cholestatic jaundice associated with past estrogen use or pregnancy.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including asthma, epilepsy, migraine, diabetes, heart failure, or renal dysfunction.
• Endometriosis: Estrogens may exacerbate endometriosis. Malignant transformation of residual endometrial implants has been reported posthysterectomy with estrogen only therapy. Consider adding a progestin in women with residual endometriosis posthysterectomy.
• Gallbladder disease: Use with caution in patients with gallbladder disease.
• Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas.
• Hypocalcemia: Use with caution in patients with severe hypocalcemia.
• Porphyria: Use with caution in patients with porphyria.
• SLE: Use with caution in patients with SLE.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children. 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.
• Surgical patients: Whenever possible, estrogens should be discontinued at least 4 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Dosage form specific issues:
• Vaginal cream: Use of the vaginal cream may weaken latex found in condoms, diaphragms or cervical caps.
Other warnings/precautions:
• Osteoporosis use: When used solely for prevention of osteoporosis in women at significant risk, nonestrogen treatment options should be considered.
• Risks vs benefits: [U.S. Boxed Warning]: Estrogens with or without progestin should be used for shortest duration possible at the lowest effective dose consistent with treatment goals. 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.
• Vulvar and vaginal atrophy use: When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered. Use caution applying topical products to severely atrophic vaginal mucosa.
Adverse Reactions
Note: Percentages reported in postmenopausal women following oral use.
>10%:
Central nervous system: Headache (26% to 32%; placebo 28%)
Endocrine & metabolic: Breast pain (7% to 12%; placebo 9%)
Gastrointestinal: Abdominal pain (15% to 17%)
Genitourinary: Vaginal hemorrhage (2% to 14%)
Neuromuscular & skeletal: Back pain (13% to 14%)
1% to 10%:
Central nervous system: Nervousness (2% to 5%)
Dermatologic: Pruritus (4% to 5%)
Gastrointestinal: Flatulence (6% to 7%)
Genitourinary: Vaginitis (5% to 7%), leukorrhea (4% to 7%), vaginal moniliasis (5% to 6%)
Neuromuscular & skeletal: Weakness (7% to 8%), leg cramps (3% to 7%)
Additional adverse reactions reported with injection or vaginal cream; frequency not defined:
Genitourinary: Cystis-like syndrome, genital pruritus, vulvovaginal discomfort
Local: injection site: Edema, pain, phlebitis
In addition, the following have been reported with estrogen and/or progestin therapy:
Cardiovascular: DVT, edema, hypertension, MI, stroke, superficial venous thrombosis
Central nervous system: Dementia, dizziness, epilepsy exacerbation, headache, irritability, mental depression, migraine, mood disturbances, nervousness
Dermatologic: Angioedema, chloasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, hirsutism, loss of scalp hair, melasma, pruritus, rash, urticaria
Endocrine & metabolic: Breast cancer, breast discharge, breast enlargement, breast tenderness, dysmenorrhea, fibrocystic breast changes, galactorrhea, glucose intolerance, HDL-cholesterol increased, hyper-/hypocalcemia, LDL-cholesterol decreased, libido (changes in), ovarian cancer, serum triglycerides/phospholipids increased, thyroid-binding globulin increased, total thyroid hormone (T4) increased
Gastrointestinal: Abdominal cramps, bloating, cholecystitis, cholelithiasis, gallbladder disease, ischemic colitis, nausea, pancreatitis, vomiting, weight gain/loss
Genitourinary: Abnormal uterine bleeding/spotting, changes in cervical ectropion, changes in cervical secretions, endometrial cancer, endometrial hyperplasia, increased size of uterine leiomyomata, vaginal candidiasis
Hematologic: Aggravation of porphyria, antithrombin III and antifactor Xa decreased; factors II, II-VII-X complex, VII, VIII, VII-X complex, IX, X, and XII increased; increased beta-thromboglobulin, fibrinogen levels, plasminogen/plasminogen activity, platelet aggregability, platelet count, and prothrombin
Hepatic: Cholestatic jaundice, hepatic hemangiomas enlarged
Neuromuscular & skeletal: Arthralgias, chorea, leg cramps
Local: Thrombophlebitis
Ocular: Contact lens intolerance, corneal curvature steepening, retinal vascular thrombosis
Respiratory: Asthma exacerbation, pulmonary thromboembolism
Miscellaneous: Anaphylactoid/anaphylactic reactions, benign meningioma growth potentiation
Metabolism/Transport Effects
Based on estradiol and estrone: Substrate of CYP1A2 (major), 2A6 (minor), 2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (minor), 2E1 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 2C8 (weak); Induces CYP3A4 (weak)
Drug Interactions
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Estrogenic Properties): May enhance the adverse/toxic effect of Estrogen Derivatives. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Ropinirole: Estrogen Derivatives may increase the serum concentration of Ropinirole. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Somatropin: Estrogen Derivatives may diminish the therapeutic effect of Somatropin. Shown to be a concern with oral hormone replacement therapy in postmenopausal women. Risk D: Consider therapy modification
Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Tipranavir: Estrogen Derivatives may enhance the dermatologic adverse effect of Tipranavir. The combination of tipranavir/ritonavir and ethinyl estradiol/norethindrone was associated with a high incidence of skin rash. Tipranavir may decrease the serum concentration of Estrogen Derivatives. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (routine use increases estrogenplasma concentrations and risk of breast cancer). Ethanol may also increase the risk of osteoporosis.
Food: Folic acid absorption may be decreased.
Herb/Nutraceutical: St John's wort may decrease levels. Herbs with estrogenic properties may enhance the adverse/toxic effect of estrogen derivatives; examples include alfalfa, black cohosh, bloodroot, hops, kudzu, licorice, red clover, saw palmetto, soybean, thyme, wild yam, yucca.
Storage
Injection: Refrigerate at 2°C to 8°C (36°F to 46°F) prior to reconstitution. Use immediately following reconstitution.
Tablets, vaginal cream: Store at room temperature 20°C to 25°C (68°F to 77°F).
Reconstitution
Injection: Reconstitute with sterile water for injection; slowly inject diluent against side wall of the vial. Agitate gently; do not shake violently.
Compatibility
Stable in D5W and NS.
Y-site administration: Compatible: Heparin with hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C.
Compatibility when admixed: Incompatible: Ascorbic acid.
Mechanism of Action
Conjugated estrogens contain a mixture of estrone sulfate, equilin sulfate, 17 alpha-dihydroequilin, 17 alpha-estradiol and 17 beta-dihydroequilin. Estrogens are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estradiol is the principle intracellular human estrogen and is more potent than estrone and estriol at the receptor level; it is the primary estrogen secreted prior to menopause. Following menopause, estrone and estrone sulfate are more highly produced. Estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone, and follicle-stimulating hormone through a negative feedback system; estrogen replacement reduces elevated levels of these hormones in postmenopausal women.
Pharmacodynamics/Kinetics
Absorption: Well absorbed
Protein binding: Binds to sex-hormone-binding globulin and albumin
Metabolism: Hepatic via CYP3A4; estradiol is converted to estrone and estriol; also undergoes enterohepatic recirculation (avoided with vaginal administration); estrone sulfite is the main metabolite in postmenopausal women
Half-life elimination: Total estrone: 27 hours
Time to peak, plasma: Total estrone: 7 hours
Excretion: Urine (primarily estriol, also as estradiol, estrone, and conjugates
Dosage
Adults:
Male: Androgen-dependent prostate cancer palliation: Oral: 1.25-2.5 mg 3 times/day
Female:
Prevention of postmenopausal osteoporosis: Oral: Initial: 0.3 mg/day cyclically* or daily, depending on medical assessment of patient. Dose may be adjusted based on bone mineral density and clinical response. The lowest effective dose should be used.
Moderate-to-severe vasomotor symptoms associated with menopause: Oral: Initial: 0.3 mg/day, cyclically* or daily, depending on medical assessment of patient. The lowest dose that will control symptoms should be used. Medication should be discontinued as soon as possible.
Moderate-to-severe dyspareunia: Intravaginal: Vaginal cream: 0.5 g twice weekly (eg, Monday and Thursday) or once daily cyclically*
Vulvar and vaginal atrophy:
Oral: Initial: 0.3 mg/day; the lowest dose that will control symptoms should be used. May be given cyclically* or daily, depending on medical assessment of patient. Medication should be discontinued as soon as possible.
Vaginal cream: Intravaginal: 0.5-2 g/day given cyclically*
Abnormal uterine bleeding:
Acute/heavy bleeding:
Oral (unlabeled route): 1.25 mg, may repeat every 4 hours for 24 hours, followed by 1.25 mg once daily for 7-10 days
I.M., I.V.: 25 mg, may repeat in 6-12 hours if needed
Note: Treatment should be followed by a low-dose oral contraceptive; medroxyprogesterone acetate along with or following estrogen therapy can also be given
Nonacute/lesser bleeding: Oral (unlabeled route): 1.25 mg once daily for 7-10 days
Female hypogonadism: Oral: 0.3-0.625 mg/day given cyclically*; dose may be titrated in 6- to 12-month intervals; progestin treatment should be added to maintain bone mineral density once skeletal maturity is achieved.
Female castration, primary ovarian failure: Oral: 1.25 mg/day given cyclically*; adjust according to severity of symptoms and patient response. For maintenance, adjust to the lowest effective dose.
*Cyclic administration: Either 3 weeks on, 1 week off or 25 days on, 5 days off
Male and Female:
Breast cancer palliation, metastatic disease in selected patients: Oral: 10 mg 3 times/day for at least 3 months
Uremic bleeding (unlabeled use): I.V.: 0.6 mg/kg/day for 5 days
Elderly: Refer to adult dosing; a higher incidence of stroke and invasive breast cancer was observed in women >75 years in a WHI substudy.
Administration: Oral
Administer at bedtime to minimize adverse effects. May be administered without regard to meals.
Administration: I.M.
May be administered intramuscularly.
Administration: I.V.
Administer I.V. doses slowly to avoid a flushing reaction.
Administration: Other
Vaginal cream: Administer at bedtime to minimize adverse effects. To clean applicator, remove plunger from barrel. Wash with mild soap and warm water; do not boil or use hot water.
Monitoring Parameters
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 vaginal 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
Reference Range
Children: <10 mcg/24 hours (SI: <35 ?mol/day) (values at Mayo Medical Laboratories)
Adults:
Male: 15-40 mcg/24 hours (SI: 52-139 ?mol/day)
Female:
Menstruating: 15-80 mcg/24 hours (SI: 52-277 ?mol/day)
Postmenopausal: <20 mcg/24 hours (SI: <69 ?mol/day)
Test Interactions
Pathologist should be advised of estrogen/progesterone therapy when specimens are submitted. Reduced response to metyrapone test.
Dietary Considerations
Ensure adequate calcium and vitamin D intake when used for the prevention of osteoporosis. Powder for reconstitution for injection (25 mg) contains lactose 200 mg.
Patient Education
Do not take any new medication during therapy without consulting prescriber. Use/apply exactly as directed and maintain prescribed cycles or term as prescribed. Routine use of alcohol may increase estrogen level and risk of breast cancer. Annual gynecologic exams and regular self-breast exams are important. If you have diabetes, monitor glucose levels closely (may impair glucose tolerance). You may experience nausea, vomiting, bloating, or abdominal pain (small, frequent meals may help); dizziness or mental depression (use caution when driving); rash; hair loss; headache; breast pain, increased/decreased libido, or enlargement/tenderness of breasts; or difficult/painful menstrual cycles. Report significant swelling of extremities; sudden acute pain in legs, chest, or abdomen; shortness of breath; severe headache or vomiting; CNS changes (dementia, mood disturbances, irritability, nervousness); sudden blindness; weakness or numbness of arm or leg; unusual vaginal bleeding; yellowing of skin or eyes; unusual bruising or bleeding; or other persistent adverse reactions. You may become intolerant to wearing contact lenses; notify prescriber if this occurs. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant while taking this medication. Consult prescriber for appropriate contraceptive measures. Consult prescriber if breast-feeding.
Geriatric Considerations
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 side effects and the return of menstrual bleeding (when cycled with a progestin), and be involved in the decision to prescribe. A higher incidence of stroke and invasive breast cancer was observed in women >75 years in a WHI substudy. Oral therapy may be more convenient for vaginal atrophy and urinary incontinence.
Cardiovascular Considerations
It is important to recognize that estrogens may induce or worsen hypertension. These problems are less severe with lower doses. Furthermore, estrogens may precipitate thromboembolic events, particularly in women who smoke. It is important that patients on long-term estrogens undergo monitoring of blood pressure and avoid cigarette use.
Conjugated estrogens (alone or in combination with a progestin) should not be used to prevent coronary heart disease. The HERS trial found that women with coronary disease derived no cardiovascular protection compared to those treated with placebo. In the Women's Health Initiative trial, a conjugated estrogen/progestin combination did not offer protection against heart disease. No cardiovascular benefits were seen; in fact, more coronary heart disease was observed in the treatment group. Substantial evidence suggests that estrogen therapy increases bone mineralization and therefore may be of added benefit in patients with osteoporosis. Estrogen also has a favorable effect on lipids (decreases total cholesterol and LDL, increases HDL) but increases triglycerides. Therapy should be initiated after careful evaluation of risk:benefit for therapy.
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 dizziness, headache, depression, insomnia, nervousness, irritability, and mood disturbances
Mental Health: Effects on Psychiatric Treatment
Barbiturates and carbamazepine may decrease estrogen levels. The Women's Health Initiative (WHI) Memory Study reported an increased risk of developing dementia in postmenopausal women ?65 years of age during 4 years of treatment with oral conjugated equine estrogens and medroxyprogesterone acetate relative to placebo (1.8% vs 0.9%). Relative risk was 2.05 (95% CI 1.21-3.48). Therefore, estrogens and progestins should not be used for the prevention of dementia. The WHI also reported an increased risk of stroke (29 vs 21 per 10,000 women-years) compared to women receiving placebo. The increase in risk was observed after the first year and persisted. May cause hypertriglyceridemia; monitor in patients receiving antipsychotics especially clozapine, olanzapine, and quetiapine.
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (eg, increased potential for decreased levels/effects or increased potential for toxicity or thrombolic events). Assess results of annual gynecological exam, therapeutic effectiveness (dependent on rationale for use), need for continued therapy, and adverse effects (eg, thromboembolism, hypertension, edema, CNS changes) on a regular basis during therapy. Note: 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 and periodic assessment of risk:benefit should be made. Caution patients with diabetes to monitor glucose levels closely (may impair glucose tolerance). Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report. Remind patient about the importance of frequent self-breast exams and the need for annual gynecological exam. Determine that patient is not pregnant before starting therapy. Do not give to females of childbearing age unless patient is capable of complying with contraceptive use. Advise patient about appropriate contraceptive measures as appropriate.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, vaginal:
Premarin®: 0.625 mg/g (42.5 g)
Injection, powder for reconstitution:
Premarin®: 25 mg [contains benzyl alcohol (in diluent), lactose 200 mg]
Tablet:
Premarin®: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, 1.25 mg
Pricing: U.S. (www.drugstore.com)
Cream (Premarin)
0.625 mg/g (42.5): $115.99
Tablets (Premarin)
0.45 mg (30): $55.99
0.625 mg (30): $57.99
0.9 mg (30): $55.99
1.25 mg (30): $57.99
References
Belchetz PE, “Hormonal Treatment of Postmenopausal Women,” N Engl J Med, 1994, 330 (15):1062-71.
Cust MP, Ganagar KF, Hillard TC, et al, “A Risk-Benefit Assessment of Estrogen Therapy in Postmenopausal Women,” Drug Saf, 1990, 5(5):345-58.
Ettinger B, Friedman GD, Bush T, et al, “Reduced Mortality Associated with Long-Term Postmenopausal Estrogen Therapy,” Obstet Gynecol, 1996, 87(1):6-12.
“Effects of Estrogen or Estrogen/Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for PEPI Trial,” JAMA, 1995, 273(3):199-208.
Grodstein F, Stampfer MJ, Colditz GA, et al, “Postmenopausal Hormone Therapy and Mortality,” N Engl J Med, 1997, 336(25):1769-75.
Hulley S, Grady D, Bush T, et al, “Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women. Heart and Estrogen/Progestin Replacement Study (HERS) Research Group,” JAMA, 1998, 280(7):605-13.
Livio M, Mannucci PM, Vigano G, et al, “Conjugated Estrogens for the Management of Bleeding Associated With Renal Failure,” N Engl J Med, 1986, 315(12):731-5.
McCarthy ML and Stoukides CA, “Estrogen Therapy of Uremic Bleeding,” Ann Pharmacother, 1994, 28(1):60-2.
Mørch LS, Løkkegaard E, Andreasen AH, et al, “Hormone Therapy and Ovarian Cancer,” JAMA, 2009, 302(3):298-305.
Neistein LS, Adolescent Health Care - A Practical Guide, 2nd ed, Baltimore: Urban & Schwarzenberg, 1991, 661-6.
Rossouw JE, Anderson GL, Prentice RL, et al, “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(3):321-33.
Shumaker S, Legault C, Thal L, et al, “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, 289:2651-62.
The Writing Group for the PEPI Trial, “Effects of Estrogen or Estrogen/Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women,” JAMA, 1995, 273(3):199-208.
U.S. Food and Drug Administration, Department of Health and Human Services, “WHIMS Study on Estrogen/Progestin,” May 27, 2003. Available at http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm135318.htm.
Wassertheil-Smoller S, Hendrix S, Limacher M, et al, “Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women: The Women's Health Initiative: A Randomized Trial,” JAMA, 2003, 289:2673-84.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2009
Content last modified October 2009
| 
