ATC Class:G03CA57
VA Class:HS300
Conjugated estrogens is a mixture of estrogens that is available either as preparations that meet current official USP standards (i.e., conjugated estrogens USP)101, 105, 107, 108, 109 or as nonofficial preparations (i.e., synthetic conjugated estrogens A and synthetic conjugated estrogens B, which are prepared synthetically from plant sources).106, 108, 109, 121, 122
In women, oral conjugated estrogens USP and synthetic conjugated estrogens A are used for the management of moderate to severe vasomotor symptoms associated with menopause and for the management of vulvar and vaginal atrophy (atrophic vaginitis).101, 106, 111 If estrogens are used solely for the management of vulvar and vaginal atrophy, use of topical vaginal preparations should be considered.101, 107 Synthetic conjugated estrogens B is used for the management of moderate to severe vasomotor symptoms and for the management of severe vaginal dryness, pain with sexual intercourse, and symptoms of vulvar and vaginal atrophy associated with menopause.121, 266 Oral conjugated estrogens USP also is used for the management of female hypoestrogenism secondary to hypogonadism, castration, or primary ovarian failure.101
Oral conjugated estrogens USP is used adjunctively with other therapeutic measures (e.g., diet, calcium, weight-bearing exercise [including walking, running], physical therapy) to retard further bone loss and the progression of osteoporosis associated with estrogen deficiency in postmenopausal women.100, 101, 107 While estrogen replacement therapy is effective for the prevention of osteoporosis in women and has been shown to reduce bone resorption and retard or halt bone loss in postmenopausal women, such therapy is associated with a number of adverse effects.100, 101, 107 (See Uses: Estrogen Replacement Therapy, in the Estrogens General Statement 68:16.04.) If prevention of postmenopausal osteoporosis is the sole indication for therapy with oral conjugated estrogens, alternative therapy (e.g., alendronate, raloxifene, risedronate) should be considered.101, 107, 112
Another therapeutic option involves use of conjugated estrogens in combination with an estrogen agonist-antagonist (bazedoxifene) for the management of moderate to severe vasomotor symptoms associated with menopause and for prevention of osteoporosis.262 The combination of conjugated estrogens with bazedoxifene is referred to as a tissue-selective estrogen complex (TSEC).263
While results from earlier observational studies indicated that estrogen replacement therapy (ERT) or combined estrogen/progestin therapy (hormone replacement therapy, HRT) was associated with cardiovascular benefit in postmenopausal women, results of the Heart and Estrogen/progestin Replacement Study (HERS) evaluating estrogen/progestin and the Women's Health Initiative (WHI) study evaluating estrogen alone and estrogen/progestin therapy indicate that hormone therapy does not decrease the incidence of cardiovascular disease.103, 112, 113, 114, 120 The American Heart Association (AHA), American College of Obstetricians and Gynecologists (ACOG), FDA, and manufacturers recommend that hormone therapy not be used to prevent heart disease in healthy women (primary prevention) or to protect women with preexisting heart disease (secondary prevention).111, 112, 115, 116, 117 (See Cardiovascular Risk Reduction under Uses: Estrogen Replacement Therapy, in the Estrogens General Statement 68:16.04.)
Oral conjugated estrogens USP is used for the palliative treatment of advanced, inoperable, metastatic carcinoma of the breast in postmenopausal women and in men. Estrogens are one of several second-line agents that can be used in certain postmenopausal women with metastatic breast cancer.
Oral conjugated estrogens USP is used for the palliative treatment of advanced carcinoma of the prostate in men; however, the risk of adverse cardiovascular effects of estrogens must be considered.
Conjugated estrogens USP may be administered IM or IV for the treatment of abnormal uterine bleeding caused by hormonal imbalance not associated with organic pathology.
Conjugated estrogens USP may be administered intravaginally for the management of atrophic vaginitis or kraurosis vulvae.
Although in the past oral conjugated estrogens has been used for the prevention of postpartum breast engorgement†, the FDA has withdrawn approval of estrogen-containing drugs for this indication since estrogens have not been shown to be safe for use in women with postpartum breast engorgement.110 Data from controlled studies indicate that the incidence of substantial painful engorgement is low in untreated women, and the condition usually responds to appropriate analgesic or other supportive therapy.
Reconstitution and Administration
Conjugated estrogens USP is usually administered orally, but may also be administered intravaginally or by deep IM or slow IV injection. Synthetic conjugated estrogens A and synthetic conjugated estrogens B are administered orally.106, 121
When parenteral administration of conjugated estrogens USP is required, IV injection is preferred because of the more rapid response obtained following this route of administration compared to IM injection. For direct IV injection, the drug should be administered slowly to avoid the occurrence of a flushing reaction.
For parenteral administration, conjugated estrogens USP powder for injection is reconstituted with 5 mL of sterile water for injection. 104 Using aseptic technique, the diluent should then be slowly added, directing the flow against the inner wall of the vial (Secule®), while gently agitating the container to facilitate dissolution of the contents; vigorous shaking of the container should be avoided.104 Premarin® solutions should be used immediately after reconstitution.104
Oral dosage preparations containing medroxyprogesterone acetate in combination with conjugated estrogens USP as monophasic or biphasic regimens are commercially available in a mnemonic dispensing package that is designed to aid the user in complying with the prescribed dosage schedule.107 The monophasic combination (Prempro®) is available in a 28-day dosage preparation that contains 28 tablets of conjugated estrogens USP (0.625 mg) in fixed combination with medroxyprogesterone acetate (2.5 or 5 mg).107 The monophasic combination (Prempro®) also is available in a 28-day dosage preparation that contains 28 tablets of conjugated estrogens USP (0.3 or 0.45 mg) in fixed combination with medroxyprogesterone acetate (1.5 mg).107 The biphasic combination (Premphase®) is available in a 28-day dosage preparation that contains 14 tablets of conjugated estrogens USP (0.625 mg) and 14 tablets of conjugated estrogens USP (0.625 mg) in fixed combination with medroxyprogesterone acetate (5 mg).107
The oral dosage preparation containing conjugated estrogens in fixed combination with bazedoxifene acetate is commercially available in a 30-day package that includes 2 blister packs of 15 tablets each containing conjugated estrogens 0.45 mg in fixed combination with bazedoxifene acetate 22.6 mg (equivalent to 20 mg of bazedoxifene).262
Dosage of conjugated estrogens USP, synthetic conjugated estrogens A, and synthetic conjugated estrogens B must be individualized according to the condition being treated and the tolerance and therapeutic response of the patient. To minimize the risk of adverse effects, the lowest possible effective dosage should be used. Because of the potential increased risk of cardiovascular events, breast cancer, and venous thromboembolic events, therapy with estrogen, estrogen/progestin, or conjugated estrogens in fixed combination with bazedoxifene should be limited to the lowest effective doses and shortest duration of therapy consistent with treatment goals and risks for the individual woman.101, 107, 262 Therapy with estrogen, estrogen/progestin, or conjugated estrogens in fixed combination with bazedoxifene should be periodically reevaluated.101, 107, 262
Estrogen therapy is administered in a continuous daily dosage regimen or, alternatively, in a cyclic regimen. When estrogens are administered cyclically, the drugs usually are given once daily for 3 weeks followed by 1 week without the drugs or once daily for 25 days followed by 5 days off, and then the respective regimen is repeated as necessary.101
While estrogen therapy alone (estrogen replacement therapy, ERT) may be appropriate in women who have undergone a hysterectomy, a progestin generally is added to estrogen therapy (hormone replacement therapy, HRT) in women with an intact uterus.107 Addition of a progestin for 10 or more days of a cycle of estrogen or daily with estrogen in a continuous regimen reduces the incidence of endometrial hyperplasia and the attendant risk of endometrial carcinoma in women with an intact uterus.107 Morphologic and biochemical studies of the endometrium suggest that 10-13 days of progestin are needed to provide maximum maturation of the endometrium and to eliminate any hyperplastic changes. As an alternative to progestins, the use of bazedoxifene (an estrogen agonist-antagonist) in fixed combination with conjugated estrogens reduces the risk of endometrial hyperplasia.261, 262, 263
When estrogen therapy is used in conjunction with a progestin or in fixed combination with bazedoxifene, the usual precautions associated with progestins or bazedoxifene should be observed.262, 266, 267 Clinicians prescribing estrogens in conjunction with progestins or conjugated estrogens in fixed combination with bazedoxifene should be aware of the risks associated with these drugs and the manufacturers' labeling should be consulted.262, 266, 267 Clinical studies indicate that addition of a progestin to estrogen replacement therapy does not interfere with the efficacy of estrogen therapy in the management of vasomotor symptoms associated with menopause, treatment of vulvar and vaginal atrophy, or prevention of osteoporosis.107 The choice and dosage of a progestin may be important factors in minimizing potential adverse effects.
Exposure to conjugated estrogens USP vaginal cream has been reported to weaken latex condoms.105 The potential for conjugated estrogens USP vaginal cream to weaken and contribute to the protective failure of latex or rubber condoms, diaphragms, or cervical caps should be considered.105
For the management of moderate to severe vasomotor symptoms and/or for the management of vulvar and vaginal atrophy associated with menopause, the usual initial oral dosage of conjugated estrogens USP is 0.3 mg daily.101 Subsequent dosage adjustment should be based on the patient's response.101 The drug may be administered in a continuous daily regimen or in a cyclic regimen (25 days on drug followed by 5 days off drug, then this regimen is repeated as necessary).101 Alternatively, for the management of vulvar and vaginal atrophy, 0.5-2 g of conjugated estrogens USP vaginal cream may be administered intravaginally once daily in the usual cyclic regimen.105
When conjugated estrogens USP is used in conjunction with medroxyprogesterone for the management of moderate to severe vasomotor symptoms associated with menopause or for the management of vulvar and vaginal atrophy, conjugated estrogens USP is administered in a continuous daily dosage regimen while medroxyprogesterone may be administered in a continuous daily dosage regimen (Prempro®) or cyclically (Premphase®).107 When both drugs are administered in a continuous daily dosage regimen, conjugated estrogens is administered in a daily dosage of 0.3 mg in conjunction with oral medroxyprogesterone acetate in a daily dosage of 1.5 mg.107 Alternatively, conjugated estrogens is administered in a daily dosage of 0.45 mg in conjunction with medroxyprogesterone acetate in a daily dosage of 1.5 mg, or conjugated estrogens is administered in a daily dosage of 0.625 mg in conjunction with medroxyprogesterone acetate in a daily dosage of 2.5 or 5 mg.107 When conjugated estrogens USP is administered in a continuous daily dosage regimen and medroxyprogesterone is administered cyclically (Premphase®), conjugated estrogens USP is administered in a daily dosage of 0.625 mg, while oral medroxyprogesterone acetate is administered in a daily dosage of 5 mg on days 15-28 of the cycle.107 Therapy with conjugated estrogens in conjunction with medroxyprogesterone generally should be initiated with the lowest dosage (i.e., conjugated estrogens 0.3 mg in conjunction with medroxyprogesterone acetate 1.5 mg).107 Subsequent dosage should be adjusted based on the patient's therapeutic response and should be reevaluated periodically.107 If spotting or bleeding is problematic and has been appropriately evaluated, dosage can be adjusted.107
When conjugated estrogens is used in conjunction with bazedoxifene for the treatment of moderate to severe vasomotor symptoms associated with menopause, conjugated estrogens is administered in a daily dosage of 0.45 mg in fixed combination with bazedoxifene 20 mg.262
Synthetic Conjugated Estrogens A
For the management of moderate to severe vasomotor symptoms associated with menopause, the usual oral dosage of synthetic conjugated estrogens A is 0.45-1.25 mg daily.106 The usual initial oral dosage of synthetic conjugated estrogens A is 0.45 mg daily; subsequent dosage adjustment should be based on the patient's response.106 For the management of vulvar and vaginal atrophy, the usual oral dosage of synthetic conjugated estrogens A is 0.3 mg daily.106
Synthetic Conjugated Estrogens B
For the management of moderate to severe vasomotor symptoms associated with menopause, the usual oral dosage of synthetic conjugated estrogens B is 0.3-1.25 mg daily.266 The usual initial oral dosage of synthetic conjugated estrogens B for this condition is 0.3 mg daily.121, 266 Subsequent dosage adjustment should be based on the patient's response.121, 266
For the management of severe vaginal dryness, pain with sexual intercourse, and vulvar and vaginal atrophy associated with menopause, the usual oral dosage of synthetic conjugated estrogens B is 0.3 mg daily.266
For the prevention of osteoporosis, the usual initial oral dosage of conjugated estrogens USP is 0.3 mg once daily.101 Subsequent dosage should be adjusted based on the patient's clinical and bone mineral density responses.101 The drug may be administered in a continuous daily regimen or in a cyclic regimen (25 days on drug followed by 5 days off drug, then this regimen is repeated as necessary).101
When conjugated estrogens USP is used in conjunction with medroxyprogesterone, conjugated estrogens USP is administered in a continuous daily dosage regimen while medroxyprogesterone may be administered in a continuous daily dosage regimen (Prempro®) or cyclically (Premphase®).107 When both drugs are administered in a continuous daily dosage regimen, conjugated estrogens USP is administered in a daily dosage of 0.3 mg in conjunction with oral medroxyprogesterone acetate in a daily dosage of 1.5 mg.107 Alternatively, conjugated estrogens is administered in a daily dosage of 0.45 mg in conjunction with medroxyprogesterone acetate in a daily dosage of 1.5 mg, or conjugated estrogens is administered in a daily dosage of 0.625 mg in conjunction with medroxyprogesterone acetate in a daily dosage of 2.5 or 5 mg.107 When conjugated estrogens USP is administered in a continuous daily dosage regimen and medroxyprogesterone is administered cyclically, conjugated estrogens USP is administered in a daily dosage of 0.625 mg, while oral medroxyprogesterone acetate is administered in a daily dosage of 5 mg on days 15-28 of the cycle.107 Therapy with conjugated estrogens in conjunction with medroxyprogesterone generally should be initiated with the lowest dosage (i.e., conjugated estrogens 0.3 mg in conjunction with medroxyprogesterone acetate 1.5 mg).107 Subsequent dosage should be adjusted based on the patient's clinical and bone mineral density responses.107 If spotting or bleeding is problematic and has been appropriately evaluated, dosage can be adjusted.107
When conjugated estrogens is used in conjunction with bazedoxifene for the prevention of osteoporosis, conjugated estrogens is administered once daily at a dosage of 0.45 mg in fixed combination with bazedoxifene 20 mg.262
For replacement therapy in female hypoestrogenism, the usual oral dosage of conjugated estrogens USP is 0.3-0.625 mg daily in a cyclic regimen (3 weeks on drug, 1 week off).101 Dosage may be adjusted based on symptom severity and responsiveness of the endometrium.101
For the management of female castration or primary ovarian failure, the usual initial oral dosage of conjugated estrogens USP is 1.25 mg daily in a cyclic regimen.101 Subsequent dosage should be adjusted according to the severity of the symptoms and the patient's therapeutic response, using the lowest possible effective maintenance dosage.101
Inoperable Carcinoma of the Breast
For the palliative treatment of inoperable, advanced, metastatic carcinoma of the breast in appropriately selected men and postmenopausal women, the usual oral dosage of conjugated estrogens USP is 10 mg 3 times daily. Estrogen therapy is usually continued in these patients for at least 3 months.
For the palliative treatment of advanced carcinoma of the prostate, the usual oral dosage of conjugated estrogens USP is 1.25-2.5 mg 3 times daily.
For the emergency treatment of abnormal uterine bleeding caused by hormonal imbalance, the usual IV or IM dose of conjugated estrogens USP is 25 mg. If necessary, the dose may be repeated in 6-12 hours. The use of conjugated estrogens USP for this condition does not preclude the use of other appropriate measures.
Conjugated estrogens USP, synthetic conjugated estrogens A, and synthetic conjugated estrogens B share the toxic potentials of other estrogens, and the usual cautions, precautions, and contraindications associated with estrogen therapy should be observed. (See Cautions in the Estrogens General Statement 68:16.04.)
Conjugated estrogens is contraindicated in patients who are hypersensitive to the drug or any ingredient in the respective formulation.
The principal pharmacologic effects of conjugated estrogens are similar to those of other natural and synthetic estrogens. (See Pharmacology in the Estrogens General Statement 68:16.04.)
Conjugated estrogens is a mixture of estrogens that is available either as preparations that meet current official USP standards (i.e., conjugated estrogens USP)101, 105, 107, 108, 109 or as nonofficial preparations (i.e., synthetic conjugated estrogens A, synthetic conjugated estrogens B).106, 108, 109, 121
Conjugated estrogens obtained from natural sources occurs as a buff-colored, amorphous powder and is odorless or has a slight, characteristic odor. Conjugated estrogens that is prepared synthetically occurs as a white to light buff, crystalline or amorphous powder and is odorless or has a slight odor. Conjugated estrogens is soluble in water.
Conjugated estrogens USP is a mixture containing the sodium salts of the water-soluble sulfate esters of estrone and equilin derived wholly or in part from equine urine or may be prepared synthetically from estrone and equilin. Conjugated estrogens USP also contains conjugated estrogenic substances of the type excreted by pregnant mares including 17α-dihydroequilin, 17α-estradiol, 17β-dihydroequilin, equilenin, 17α-dihydroequilenin, 17β-dihydroequilenin, δ8,9-dehydroestrone, and 17β-estradiol. Conjugated estrogens USP contains 52.5-61.5% sodium estrone sulfate and 22.5-30.5% sodium equilin sulfate. Conjugated estrogens contains, as sodium sulfate conjugates, 13.5-19.5% 17α-dihydroequilin, 2.5-9.5% 17α-estradiol, and 0.5-4% 17β-dihydroequilin.
Conjugated estrogens USP currently is commercially available as preparations (Premarin®, Premphase®, Prempro®) containing mixtures of estrogens obtained exclusively from natural sources and which are present in the formulations as the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mare urine; according to USP standards, the formulations include a mixture of sodium estrone sulfate and sodium equilin sulfate as well as the concomitant components 17α-dihydroequilin, 17α-estradiol, and 17β-dihydroequilin as sodium sulfate conjugates.101, 107
Conjugated estrogens USP injection is commercially available as a sterile, lyophilized cake. 104 The lyophilized cake also contains lactose, sodium citrate, and simethicone; in addition, sodium hydroxide and/or hydrochloric acid may be added during manufacture of the powder for injection to adjust the pH.104 A sterile diluent containing water for injection and benzyl alcohol as a preservative is provided for reconstitution.104
Synthetic Conjugated Estrogens A
Synthetic conjugated estrogens A is a mixture of conjugated estrogens prepared synthetically from plant sources (i.e., soy and yams).109 Synthetic conjugated estrogens A is commercially available as preparations (Cenestin®) containing a mixture of 9 of the 10 known conjugated estrogenic substances106, 109 present in currently available commercial preparations of conjugated estrogens USP.109 However, unlike currently available preparations of conjugated estrogens USP, the conjugated estrogenic substances present in synthetic conjugated estrogens A are prepared entirely synthetically.106, 109
Synthetic conjugated estrogens A is commercially available as preparations containing mixtures of estrogens prepared exclusively synthetically as the sodium salts of water-soluble estrogen sulfates blended into a 9-component mixture of estrone sulfate and sodium equilin sulfate as well as the concomitant components 17α-dihydroequilin, 17α-estradiol, 17β-dihydroequilin, 17α-dihydroequilenin, 17β-dihydroequilenin, equilenin, and 17β-estradiol as sodium sulfate conjugates.106
Synthetic Conjugated Estrogens B
Synthetic conjugated estrogens B is a mixture of conjugated estrogens prepared synthetically from plant sources.121, 122 Synthetic conjugated estrogens B is commercially available as preparations (Enjuvia®) containing a mixture of the 10 conjugated estrogenic substances present in currently available commercial preparations of conjugated estrogens USP.121 Unlike currently available preparations of conjugated estrogens USP, the conjugated estrogenic substances present in synthetic conjugated estrogens B are prepared entirely synthetically.121
Synthetic conjugated estrogens B is commercially available as preparations containing mixtures of estrogens prepared exclusively synthetically as the sodium salts of water-soluble estrogen sulfates blended into a 10-component mixture of estrone sulfate and sodium equilin sulfate as well as the concomitant components 17α-dihydroequilin, 17α-estradiol, 17β-dihydroequilin, 17α-dihydroequilenin, 17β-dihydroequilenin, equilenin, 17β-estradiol, and δ8,9-dehydroestrone as sodium sulfate conjugates.121
Commercially available conjugated estrogens USP tablets, synthetic conjugated estrogens A tablets, synthetic conjugated estrogens B tablets, and conjugated estrogens USP vaginal cream should be stored at controlled room temperature (20-25°C).101, 105, 106, 107, 121 Conjugated estrogens USP powder for injection should be stored at a temperature of 2-8°C prior to reconstitution.104 Following reconstitution, solutions of the drug should be used immediately.104
Conjugated estrogens USP injection is physically and chemically compatible with the following IV solutions: 5% dextrose, 0.9% sodium chloride, and invert sugar solutions; the injection is physically and/or chemically incompatible with protein hydrolysate, ascorbic acid, or any solution with an acid pH.104 Specialized references should be consulted for specific compatibility information.
Additional Information
For further information on chemistry, pharmacology, pharmacokinetics, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of conjugated estrogens, see the Estrogens General Statement 68:16.04.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 0.45 mg with Bazedoxifene Acetate 20 mg (of bazedoxifene) | Pfizer | |
Tablets, monophasic regimen | 0.3 mg with Medroxyprogesterone Acetate 1.5 mg (28 tablets) | Pfizer | ||
0.45 mg with Medroxyprogersterone Acetate 1.5 mg (28 tablets) | Prempro® | Pfizer | ||
0.625 mg with Medroxyprogesterone Acetate 2.5 mg (28 tablets) | Prempro® | Pfizer | ||
0.625 mg with Medroxyprogesterone Acetate 5 mg (28 tablets) | Prempro® | Pfizer | ||
Tablets, biphasic regimen | 0.625 mg (14 tablets Premarin®) and 0.625 mg with Medroxyprogesterone Acetate 5 mg (14 tablets) | Pfizer |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 0.3 mg | Teva | |
0.45 mg | Enjuvia® | Teva | ||
0.625 mg | Enjuvia® | Teva | ||
0.9 mg | Enjuvia® | Teva | ||
1.25 mg | Enjuvia® | Teva |
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101. Wyeth. Premarin® (conjugated estrogens) USP tablets prescribing information. Philadelphia, PA; 2007 Jan.
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105. Wyeth. Premarin® (conjugated estrogens) vaginal cream prescribing information. Philadelphia; PA; 2006 Jul 31.
106. Duramed. Cenestin® (synthetic conjugated estrogens A) tablets prescribing information. Cincinnati, OH; 2004 Feb.
107. Wyeth. Prempro® (conjugated estrogens/medroxyprogesterone acetate) tablets and Premphase® (conjugated estrogens/medroxyprogesterone acetate) tablets prescribing information. Philadelphia, PA. 2007 Jan.
108. The United States pharmacopeia, 29th rev, and The national formulary, 24th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2006;849.
109. Anon. A new conjugated estrogen. Med Lett Drugs Ther . 1999; 41:67-8. [PubMed 10445019]
110. Food and Drug Admnistration. Estrogens for postpartum breast engorgement; withdrawal of approval of the labeled indication for postpartum breast engorgement in estrogen-containing drug products; final order. Notice. [Docket No. 78N-0280; DESI Nos. 740, 1543, and 7661] Fed Regist . 1998; 63:69631-70.
111. U.S. Preventive Services Task Force. Postmenopausal hormone replacement therapy for primary prevention of chronic conditions: recommendations and rationale. Ann Intern Med . 2002; 137:834-9.
112. American College of Obstetricians and Gynecologists. Questions and answers on hormone replacement therapy. Washington DC; August 2002. From the American College of Obstetricians and Gynecologists web site ([Web]).
113. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled study. JAMA . 2002; 288:321-33. [PubMed 12117397]
114. Grady D, Herrington D, Bittner V et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA . 2002; 288:49-57. [PubMed 12090862]
115. American Heart Association. Q & A about hormone replacement therapy. November 20, 2002. From the American Heart Association web site. [Web]
116. US Food and Drug Administration. FDA approves new labels for estrogen and estrogen with progestin therapies for postmenopausal women following review of Women's Health Initiative data. FDA News . From FDA web site ([Web]). 2003 Jan 8.
117. Kusiak V. Dear health care professional letter: FDA approves prescribing information for postmenopausal hormone therapies. Philadelphia, PA: Wyeth. 2003 Jan 6.
120. The Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in post menopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA . 2004; 291:1701-12. [PubMed 15082697]
121. Duramed. Enjuvia® (synthetic conjugated estrogens B) tablets prescribing information. (dated 2005 Sep). In: Physicians' Desk Reference. 60th ed. Montvale, NJ: Thompson PDR; 2006 (Suppl A): A13-17.
122. Utian WH, Lederman SA, Williams BM et al. Relief of hot flushes with new plant-derived 10-component synthetic conjugated estrogens. Obstet Gynecol . 2004; 103:245-53. [PubMed 14754691]
261. . ACOG Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol . 2014; 123:202-16. [PubMed 24463691]
262. Pfizer. Duavee® (conjugated estrogens/bazedoxifene) tablets prescribing information. Philadelphia, PA; 2015 Sep.
263. Komm BS, Mirkin S, Jenkins SN. Development of conjugated estrogens/bazedoxifene, the first tissue selective estrogen complex (TSEC) for management of menopausal hot flashes and postmenopausal bone loss. Steroids . 2014; 90:71-81. [PubMed 24929044]
264. Pfizer. Premarin® (conjugated estrogens) USP tablets prescribing information. Philadelphia, PA; 2014 Dec.
265. Pfizer. Prempro® (conjugated estrogens/medroxyprogesterone acetate) tablets and Premphase® (conjugated estrogens/medroxyprogesterone acetate) tablets prescribing information. Philadelphia, PA. 2015 Mar.
266. Teva Pharmaceuticals. Enjuvia® (synthetic conjugated estrogens, B) tablets prescribing information. North Wales, PA; 2015 Jun.
267. Teva Pharmaceuticals. Cenestin® (synthetic conjugated estrogens, A) tablets prescribing information. North Wales, PA; 2015 Aug.