ATC Class:G03CA07
VA Class:HS300
Estropipate and esterified estrogens have pharmacologic effects that are similar to those of other natural synthetic estrogens.
While results from earlier observational studies indicated that estrogen replacement therapy (ERT) or combined estrogen/progestin therapy (HRT) was associated with cardiovascular benefit in postmenopausal women, results from recent controlled studies indicate that hormone therapy does not decrease the incidence of cardiovascular disease. The American Heart Association (AHA), American College of Obstetricians and Gynecologists (ACOG), US Food and Drug Administration, 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). (See Cardiovascular Risk Reduction under Uses: Estrogen Replacement Therapy, in the Estrogens General Statement 68:16.04.)
Estropipate is used orally for the management of moderate to severe vasomotor symptoms associated with menopause. In addition, estropipate is used orally as an adjunct to 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. 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. (See Uses: Estrogen Replacement Therapy, in the Estrogens General Statement 68:16.04.) If prevention of postmenopausal osteoporosis is the sole indication for estrogen therapy, alternative therapy (e.g., alendronate, raloxifene, risedronate) should be considered. Estropipate also is used orally for the management of vulvar and vaginal atrophy, female hypogonadism and castration, and primary ovarian failure. If estrogens are used solely for the management of vulvar and vaginal atrophy, use of topical vaginal preparations should be considered.
In women, esterified estrogens is used for the management of moderate to severe vasomotor symptoms associated with menopause. Esterified estrogens also is used for the management of vulvar and vaginal atrophy, female hypogonadism and castration, and primary ovarian failure. If estrogens are used solely for the management of vulvar and vaginal atrophy, use of topical vaginal preparations should be considered.
Esterified estrogens in fixed combination with methyltestosterone is used for the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond adequately to estrogens alone. While estrogen/androgen combinations were found to be effective for the management of vasomotor symptoms associated with menopause under a determination made by the US Food and Drug Administration (FDA) in 1976, formal administrative proceedings were initiated by the FDA in April 2003 to examine the effectiveness of estrogen/androgen combinations for this indication.100, 101 FDA is undertaking this action because the agency does not believe there is substantial evidence available to establish the contribution of androgens to the effectiveness of estrogen/androgen combinations for the management of vasomotor symptoms in menopausal women who do not respond to estrogens alone.100, 101 The FDA will allow continued marketing of combination estrogen/androgen products while the matter is under study.101
Esterified estrogens 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.
Esterified estrogens 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.
Estropipate and esterified estrogens are administered orally.
Dosage of estropipate and esterified estrogens 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. When short-term estrogen therapy is indicated (e.g., for the management of vasomotor symptoms associated with menopause; vulvar and vaginal atrophy), therapy should be discontinued as soon as possible; attempts to reduce dosage or discontinue the drug should be made at 3- to 6-month intervals. Because of the potential increased risk of cardiovascular events, breast cancer, and venous thromboembolic events, estrogen and estrogen/progestin therapy should be limited to the lowest effective doses and shortest duration of therapy consistent with treatment goals and risks for the individual woman. Estrogen and estrogen/progestin therapy should be periodically reevaluated.
Estrogen therapy is administered continuously or cyclically. When estrogens are administered cyclically, the drugs are usually given once daily for 3 weeks, followed by 1 week without the drugs, and then this regimen is repeated as necessary. While estrogen therapy alone may be appropriate in women who have undergone a hysterectomy, many experts currently recommend that a progestin be added to estrogen therapy in women with an intact uterus. Addition of progestin therapy for 10 or more days of a cycle of estrogen administration or daily with estrogen in a continuous regimen has been associated with a decreased incidence of endometrial hyperplasia and the attendant risk of endometrial carcinoma in women with an intact uterus. 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. When a progestin is used in conjunction with an estrogen, the usual precautions associated with progestin therapy should be observed. Clinicians prescribing progestins should be aware of the risks associated with these drugs and the manufacturers' labeling should be consulted. The choice and dosage of a progestin may be important factors in minimizing potential adverse effects.
For the management of moderate to severe vasomotor symptoms associated with menopause or for the management of vulvar and vaginal atrophy, the usual oral dosage of estropipate is 0.75-6 mg daily in a cyclic regimen. The lowest dosage that controls symptoms should be used. If estropipate is used in the management of vasomotor symptoms and the woman is menstruating, administration of the drug is started on the fifth day of the menstrual cycle; if the woman has not menstruated within the last 2 or more months prior to initiation of estropipate therapy, administration of the drug is started arbitrarily.
For the prevention of osteoporosis, the usual oral dosage of estropipate is 0.75 mg daily in a cyclic regimen. The drug usually is administered once daily for 25 consecutive days, followed by 6 days without the drug, and then this regimen is repeated as indicated.
For the management of female hypogonadism, the usual oral dosage of estropipate is 1.5-9 mg daily for 21 consecutive days, followed by 8-10 days without the drug; if menstruation does not occur by the end of the 8- to 10-day drug-free period, the same estropipate dosage schedule should be repeated. The lowest dosage that controls symptoms should be used. The number of courses of estropipate therapy required to induce menstruation varies, depending on the individual responsiveness of the endometrium. If satisfactory withdrawal bleeding does not occur, an oral progestin may be given concomitantly with estropipate during the third week of the cycle.
For the management of female castration or primary ovarian failure, the usual oral dosage of estropipate is 1.5-9 mg daily for 21 consecutive days, followed by 8-10 days without the drug. 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.
For the management of moderate to severe vasomotor symptoms associated with menopause, the usual dosage of esterified estrogens is 1.25 mg daily in a cyclic regimen. For the management of vulvar and vaginal atrophy, the usual dosage is 0.3-1.25 mg daily in a cyclic regimen. Esterified estrogens is usually administered once daily for 21 consecutive days, followed by 7 days without the drug, and then this regimen is repeated as necessary. If esterified estrogens is used in the management of vasomotor symptoms and the woman is menstruating, administration of the drug is started on the fifth day of the menstrual cycle.
For replacement therapy in female hypogonadism, the usual dosage of esterified estrogens is 2.5-7.5 mg given daily in divided doses for 20 consecutive days, followed by 10 days without the drug, and then this regimen may be repeated cyclically. The number of courses of esterified estrogens therapy required to induce menstruation in hypogonadal females varies, depending on the individual responsiveness of the endometrium. If menstruation does not occur in hypogonadal females by the end of the first complete cycle, the same dosage schedule should be repeated. If menstruation occurs before the end of the 10-day drug-free period, a 20-day estrogen-progestin regimen may be initiated with esterified estrogens 2.5-7.5 mg given daily in divided doses for 20 days; during the last 5 days of esterified estrogens administration, an oral progestin is administered. If menstruation begins before the estrogen-progestin regimen is completed, therapy should be discontinued and then reinstituted on the fifth day of menstruation.
For the management of female castration or primary ovarian failure, the usual oral dosage of esterified estrogens is 1.25 mg daily in a cyclic regimen. 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.
For the palliative treatment of inoperable, advanced, metastatic carcinoma of the breast in appropriately selected men and postmenopausal women, the usual dosage of esterified estrogens 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 dosage of esterified estrogens is 1.25-2.5 mg 3 times daily.
For the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond adequately to estrogens alone, esterified estrogens is administered in a daily dosage of 0.625 mg in conjunction with methyltestosterone in a daily dosage of 1.25 mg. Esterified estrogens also is given in a daily dosage of 1.25 mg in conjunction with methyltestosterone in a daily dosage of 2.5 mg. Esterified estrogens in fixed combination with methyltestosterone is given in a cyclic regimen; the drugs are administered once daily for 21 consecutive days, followed by 7 days without the drugs, and then the cycle is repeated.
Estropipate and esterified estrogens 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.)
The principal pharmacologic effects of estropipate and esterified estrogens are similar to those of other natural and synthetic estrogens. (See Pharmacology in the Estrogens General Statement 68:16.04.)
On a weight basis, 1.5 mg of estropipate is approximately equivalent to 0.9 mg of estrone or 1.25 mg of estrone sodium sulfate.
Estropipate is estrone solubilized as the sulfate and stabilized with piperazine. Conjugation of estrone with sulfate at the 3-hydroxy position on ring A of the steroid nucleus results in the formation of a water-soluble derivative; the pharmacologically inert piperazine moiety acts as a buffer to increase the stability and uniform potency of estrone sulfate.
Estropipate occurs as a white to yellowish white, fine crystalline powder and is odorless or may have a slight odor. The drug has solubilities of less than 0.5 mg/mL in water and in alcohol at 25°C.
Esterified estrogens is a mixture of the sodium salts of the sulfate esters of the estrogenic substances, principally estrone, that are of the type excreted in the urine of pregnant mares. Estrone sodium sulfate is the principal active ingredient in esterified estrogens. Esterified estrogens may be derived from natural sources and/or prepared synthetically.
Esterified estrogens occurs as a white or buff-colored, amorphous powder and is odorless or may have a slight, characteristic odor.
Commercially availableestropipate tablets should be stored at a temperature less than 25°C; esterified estrogens tablets should be stored at room temperature. Commercially available estropipate tablets and esterified estrogens tablets should be stored in well-closed containers.
Additional Information
For further information on chemistry, pharmacology, pharmacokinetics, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of estrone, estropipate, and esterified 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.
Most preparations containing androgenic anabolic steroid hormones are subject to control under the Federal Controlled Substances Act of 1970, as amended by the Anabolic Steroids Control Act of 1990 and 2004, as schedule III (C-III) drugs.102, 104 (See Uses: Misuse and Abuse, in Testosterone 68:08.) However, manufacturers of certain preparations containing androgenic anabolic steroids (principally combinations that also include estrogens) have applied for and obtained for their product(s) an exemption from the record-keeping and other regulatory requirements of the Federal Controlled Substances Act.103, 105 (See the introductory paragraph under Preparations, in Testosterone 68:08.) Because regulatory requirements for a given preparation containing an androgenic anabolic steroid may be subject to change under the provisions of the Act, the manufacturer should be contacted when specific clarification about a preparation's status is required.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 0.75 mg* | Estropipate Tablets | |
Ogen® (scored) | ||||
Ortho-Est® (scored) | ||||
1.5 mg* | Estropipate Tablets | |||
Ogen® (scored) | Pfizer | |||
Ortho-Est® (scored) | Sun Pharmaceuticals | |||
Estropipate Tablets | ||||
3 mg* | Estropipate Tablets | |||
Ogen® (scored) | Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions November 2, 2012. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
100. Food and Drug Administration. Certain estrogen-androgen combinations drugs; drugs for human use; drug efficacy study implementation; amendment and opportunity for hearing. [Docket nos. 78N-0377 and 98P-1041; DESI 7661] Fed Regist . 2003; 68:17953-7.
101. Food and Drug Administration. FDA revises finding on estrogen/androgen combination products in the treatment of hot flashes. FDA Talk Paper . Rockville, MD; 2003 Apr 10. Correction. 2003 Apr 11. From the FDA web site. Accessed 2003 Jun 9. [Web]
102. Drug Enforcement Administration (DEA), Department of Justice. Schedules of controlled substances: anabolic steroids. Final rule. [21 CFR Part 1308] Fed Regist . 1991; 56:5753-4.
103. Drug Enforcement Administration (DEA), Department of Justice. Schedules of controlled substances: exempt anabolic products. Final rule. [21 CFR Part 1308] Fed Regist . 1992; 57:55090-1.
104. Drug Enforcement Administration (DEA), Department of Justice. Implementation of the Anabolic Steroid Control Act of 2004. Fed Regist . 2005; 241:74653-8.
105. Drug Enforcement Administration (DEA), Office of Diversion Control. Exempt Anabolic Steroids (December 31, 2003). From the DEA web site. [Web]
106. Pfizer. Ogen® (estropipate) tablets prescribing information. New York, NY; 2005 Nov.
107. Monarch Pharmaceuticals. Menest® (esterified estrogens) tablets prescribing information. Bristol, TN; 2005 Jun.
108. Solvay Pharmaceuticals Inc. Estratest® and Estratest® H.S. (esterified estrogens and methyltestosterone) tablets prescribing information. Marietta, GA; 2005 Jan.