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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.
Pronunciation
(ES troe jenz, KON joo gate ed, aye, sin THET ik)
Generic Available (U.S.)
No
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of moderate-to-severe vasomotor symptoms of menopause; treatment of vulvar and vaginal atrophy
Pregnancy Considerations
Use during pregnancy is contraindicated.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
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; estrogen-dependent tumor; hepatic dysfunction or disease; pregnancy
Warnings/Precautions
Boxed warnings:
• Breast cancer: See “Concerns related to adverse effects” below.
• 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: [U.S. Boxed Warning]: Based on data from the Women's Health Initiative (WHI) studies, an increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA). This risk may be associated with duration of use and declines once combined therapy is discontinued (Chlebowski, 2009). The risk of invasive breast cancer was decreased in postmenopausal women with a hysterectomy using CE only, regardless of weight. However, the risk was not significantly decreased in women at high risk for breast cancer (family history of breast cancer, personal history of benign breast disease) (Anderson, 2012). An increase in abnormal mammogram findings has also been reported with estrogen alone or in combination with progestin therapy. Estrogen use may also lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs. Use is contraindicated in patients with known or suspected breast cancer.
• Dementia: [U.S. Boxed Warning]: Estrogens with or without progestin should not be used to prevent dementia. In the Women's Health Initiative Memory Study (WHIMS), an increased incidence of dementia was observed in women ≥65 years of age taking CE alone or in combination with MPA.
• Endometrial carcinoma: [U.S. Boxed Warning]: The use of unopposed estrogen in women with an intact uterus is associated with an increased risk of endometrial cancer. The addition of a progestin to estrogen therapy may decrease the risk of endometrial hyperplasia, a precursor to endometrial cancer. Adequate diagnostic measures, including endometrial sampling if indicated, should be performed to rule out malignancy in postmenopausal women with undiagnosed abnormal vaginal bleeding. Estrogens may exacerbate endometriosis. Malignant transformation of residual endometrial implants has been reported posthysterectomy with unopposed estrogen therapy. Consider adding a progestin in women with residual endometriosis posthysterectomy.
• Inherited thrombophilia: Women with inherited thrombophilias (eg, protein C or S deficiency) may have increased risk of venous thromboembolism (DeSancho, 2010; van Vlijmen, 2011).
• 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 (Mørch, 2009). Although the risk of ovarian cancer is rare, women who are at an increased risk (eg, family history) should be counseled about the association (NAMS, 2012).
• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue if migraine, loss of vision, proptosis, diplopia, or other visual disturbances occur; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.
Disease-related concerns:
• Asthma: Use caution in patients with asthma; may exacerbate disease.
• Carbohydrate intolerance: May have adverse effects on glucose tolerance; use caution in women with diabetes.
• Cardiovascular disease: [U.S. Boxed Warning]: Estrogens with or without progestin should not be used to prevent cardiovascular disease. Using data from the Women's Health Initiative (WHI) studies, an increased risk of deep vein thrombosis (DVT) and stroke has been reported with CE and an increased risk of DVT, stroke, pulmonary emboli (PE) and myocardial infarction (MI) has been reported with CE with MPA in postmenopausal women. Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of venous thromboembolism (VTE). Risk factors should be managed appropriately; discontinue use if adverse cardiovascular events occur or are suspected.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.
• Epilepsy: Use caution with epilepsy; may exacerbate disease.
• Gallbladder disease: Use of postmenopausal estrogen may be associated with an increased risk of gallbladder disease requiring surgery.
• Hepatic dysfunction: Estrogens are poorly metabolized in patients with hepatic dysfunction. Use caution with a history of cholestatic jaundice associated with prior estrogen use or pregnancy. Discontinue if jaundice develops or if acute or chronic hepatic disturbances occur. Use is contraindicated with hepatic disease.
• Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas; may exacerbate disease.
• Hereditary angioedema: Exogenous estrogens may exacerbate angioedema symptoms in women with hereditary angioedema.
• Hypocalcemia: Use with caution in patients with severe hypocalcemia.
• Migraine: Use caution with migraine; may exacerbate disease.
• Porphyria: Use with caution in patients with porphyria; may exacerbate disease.
• SLE: Use with caution in patients with SLE; may exacerbate disease.
Concurrent drug therapy issues:
• Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.
Special populations:
• Elderly: May be inappropriate in this age group due to potential of increased risk of breast and endometrial cancers and lack of proven cardioprotection (Beers Criteria).
• 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 4-6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• Risks vs benefits: [U.S. Boxed Warning]: Estrogens with or without progestin should be used for the 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. Patients should be reevaluated as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from Women's Health Initiative (WHI) studies, which evaluated oral CE 0.625 mg with or without MPA 2.5 mg relative to placebo in postmenopausal women. Other combinations and dosage forms of estrogens and progestins were not studied. Outcomes reported from clinical trials using CE with or without MPA should be assumed to be similar for other doses and other dosage forms of estrogens and progestins until comparable data becomes available.
• Vulvar and vaginal atrophy use: When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered.
Adverse Reactions
>10%:
Central nervous system: Headache (11% to 68%), dizziness (11%), pain (11%)
Endocrine & metabolic: Breast pain (29%), endometrial thickening (19%), metrorrhagia (14%)
Gastrointestinal: Abdominal pain (9% to 28%), nausea (9% to 18%)
Neuromuscular & skeletal: Paresthesia (8% to 33%), back pain (14%)
Respiratory: Upper respiratory tract infection (13%)
Miscellaneous: Infection (2% to 14%)
1% to 10%:
Central nervous system: Anxiety (6%), fever (1%)
Gastrointestinal: Dyspepsia (10%), vomiting (7%), constipation (6%), diarrhea (6%), weight gain (6%)
Genitourinary: Vaginitis (8%)
Neuromuscular & skeletal: Leg cramps (10%), hypertonia (6%)
Respiratory: Rhinitis (6% to 8%), cough (6%)
In addition, the following have been reported with estrogen and/or progestin therapy:
Cardiovascular: Edema, hypertension, MI, stroke, venous thromboembolism
Central nervous system: Epilepsy exacerbation, irritability, mental depression, migraine, mood disturbances, nervousness
Dermatologic: Angioedema, chloasma, erythema multiforme, erythema nodosum, hemorrhagic eruption, hirsutism, melasma, pruritus, rash, scalp hair loss, urticaria
Endocrine & metabolic: Breast cancer, breast enlargement, breast tenderness, glucose tolerance impaired, HDL-cholesterol increased, hyper-/hypocalcemia, LDL-cholesterol decreased, libido changes, serum triglycerides/phospholipids increased, thyroid-binding globulin increased, total thyroid hormone (T4) increased
Gastrointestinal: Abdominal cramps, bloating, cholecystitis, cholelithiasis, gallbladder disease, pancreatitis, weight gain/loss
Genitourinary: Alterations in frequency and flow of menses, cervical secretion changes, endometrial cancer, endometrial hyperplasia, uterine leiomyomata size increased, vaginal candidiasis
Hematologic: Aggravation of porphyria, antithrombin III and antifactor Xa decreased, fibrinogen levels increased, platelet aggregability and platelet count increased; prothrombin and factors VII, VIII, IX, X increased
Hepatic: Cholestatic jaundice, hepatic hemangiomas enlarged
Neuromuscular & skeletal: Arthralgias, chorea, leg cramps
Local: Thrombophlebitis
Ocular: Contact lens intolerance, retinal vascular thrombosis, corneal curvature steepening
Respiratory: Asthma exacerbation, pulmonary thromboembolism
Miscellaneous: Anaphylactoid/anaphylactic reactions, carbohydrate intolerance
Metabolism/Transport Effects
Substrate of CYP1A2 (major), CYP2A6 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (weak); Induces CYP3A4 (weak/moderate)
Drug Interactions
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double aripiprazole dose when initiating concomitant therapy with a CYP3A4 inducer (e.g., carbamazepine). Monitor response and adjust aripiprazole dose as clinically indicated. If CYP3A4 inducer is discontinued, reduce aripiprazole dose to 10-15 mg/day. Risk D: Consider therapy modification
Ascorbic Acid: May increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Axitinib: CYP3A4 Inducers (Weakly to Moderately Effective) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any estrogen derivative. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
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
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP2E1 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. Management: Monitor for reduced growth hormone efficacy. A larger somatropin dose may be required to reach treatment goal. This interaction does not appear to apply to non-orally administered estrogens (e.g., transdermal, vaginal ring). 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. Management: Women using hormonal contraceptives should consider alternative, non-hormonal forms of contraception. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (routine use increases estrogen plasma concentrations and risk of breast cancer).
Food: Grapefruit juice may increase estrogen plasma concentrations, leading to increased adverse effects.
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
Store at room temperature of 25°C (77°F).
Mechanism of Action
Conjugated A/synthetic estrogens contain a mixture of 9 synthetic estrogen substances, including sodium estrone sulfate, sodium equilin sulfate, sodium 17 alpha-dihydroequilin, sodium 17 alpha-estradiol and sodium 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 over a period of several hours
Protein-binding: Sex hormone-binding globulin (SHBG) and albumin
Metabolism: Hepatic via CYP3A4; estradiol is converted to estrone and estriol; also undergoes enterohepatic recirculation; estrone sulfate is the main metabolite in postmenopausal women
Excretion: Urine (primarily estriol, also as estradiol, estrone, and conjugates)
Dosage
The lowest dose that will control symptoms should be used; medication should be discontinued as soon as possible. Oral:
Adults:
Moderate-to-severe vasomotor symptoms: 0.45 mg/day; may be titrated up to 1.25 mg/day. Attempts to discontinue medication should be made at 3- to 6-month intervals.
Vulvar and vaginal atrophy: 0.3 mg/day
Elderly: Refer to adult dosing. A higher incidence of stroke and invasive breast cancer were observed in women >75 years in a WHI substudy using conjugated equine estrogen.
Monitoring Parameters
Yearly 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
Test Interactions
Pathologist should be advised of estrogen/progesterone therapy when specimens are submitted. Reduced response to metyrapone test observed with conjugated estrogens (equine).
Patient Education
Annual gynecologic and regular self-breast exams are important. If you have diabetes, monitor glucose levels closely (may impair glucose tolerance). You may experience nausea, vomiting, abdominal pain, dizziness, mental depression, rash, headache, breast pain, or enlargement/tenderness of breasts. Report significant swelling of extremities; sudden acute pain in legs or calves, chest, or abdomen; shortness of breath; severe headache; sudden blindness; weakness or numbness of arm or leg; unusual vaginal bleeding; yellowing of skin or eyes; or unusual bruising or bleeding. You may become intolerant to wearing contact lenses; notify prescriber if this occurs.
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 were observed in women >75 years in a WHI substudy using conjugated equine estrogen.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: Low).
Additional Information
Not biologically equivalent to conjugated estrogens from equine source. Contains 9 unique estrogenic compounds (equine source contains at least 10 active estrogenic compounds).
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
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 results of annual gynecological exam. Monitor for thromboembolism, hypertension, edema, and CNS changes on a regular basis during therapy. 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). Remind patient about the importance of frequent self-breast exams and the need for annual gynecological exam.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Cenestin®: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, 1.25 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Cenestin)
0.3 mg (30): $103.99
0.45 mg (30): $101.20
0.625 mg (30): $102.99
0.9 mg (30): $104.49
References
Anderson GL, Chlebowski RT, Aragaki AK, et al, "Conjugated Equine Oestrogen and Breast Cancer Incidence and Mortality in Postmenopausal Women With Hysterectomy: Extended Follow-Up of the Women's Health Initiative Randomised Placebo-Controlled Trial," Lancet Oncol, 2012 [epub ahead of print].
Anderson GL, Limacher M, Assaf AR, et al, "Effects of Conjugated Equine Estrogen In Postmenopausal Women With Hysterectomy: The Women's Health Initiative Randomized Controlled Trial." JAMA, 2004, 291(14):1701-12.
Chlebowski RT, Kuller LH, Prentice RL, et al, "Breast Cancer After Use of Estrogen Plus Progestin in Postmenopausal Women," N Engl J Med, 2009, 360(6):573-87.
DeSancho MT, Dorff T, and Rand JH, "Thrombophilia and the Risk of Thromboembolic Events In Women on Oral Contraceptives and Hormone Replacement Therapy," Blood Coagul Fibrinolysis, 2010, 21(6):534-8.
Grodstein F, Stampfer MJ, Colditz GA, et al, “Postmenopausal Hormone Therapy and Mortality,” N Engl J Med, 1997, 336(25):1769-75.
Hsia J, Langer RD, Manson JE, et al, "Conjugated Equine Estrogens and Coronary Heart Disease: The Women's Health Initiative," Arch Intern Med, 2006, 166(3):357-65.
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.
Mørch LS, Løkkegaard E, Andreasen AH, et al, “Hormone Therapy and Ovarian Cancer,” JAMA, 2009, 302(3):298-305.
North American Menopause Society [NAMS], "The 2012 Hormone Therapy Position Statement of The North American Menopause Society," Menopause, 2012, 19(3):257-71.
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 SA, Legault C, Rapp SR, 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(20):2651-62.
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
van Vlijmen EF, Veeger NJ, Middeldorp S, et al, "Thrombotic Risk During Oral Contraceptive Use and Pregnancy in Women With Factor V Leiden or Prothrombin Mutation: A Rational Approach to Contraception," Blood, 2011, 118(8):2055-61.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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