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Findings from randomized controlled trials of"...
(esterified estrogens and methyltestosterone) Tablets
1. Estrogens Have Been Reported To Increase The Risk Of Endometrial Carcinoma
Three independent case control studies have reported an increased risk of endometrial cancer in postmenopausal women exposed to exogenous estrogens for prolonged periods.1-3 This risk was independent of the other known risk factors for endometrial cancer. These studies are further supported by the finding that incidence rates of endometrial cancer have increased sharply since 1969 in eight different areas of the United States with population-based cancer reporting systems, an increase which may be related to the rapidly expanding use of estrogens during the last decade.4
The three case control studies reported that the risk of endometrial cancer in estrogen users was about 4.5 to 13.9 times greater than in nonusers. The risk appears to depend on both duration of treatment1 and on estrogen dose.3 In view of these findings, when estrogens are used for the treatment of menopausal symptoms, the lowest dose that will control symptoms should be utilized and medication should be discontinued as soon as possible. When prolonged treatment is medically indicated, the patient should be reassessed on at least a semiannual basis to determine the need for continued therapy. Although the evidence must be considered preliminary, one study suggests that cyclic administration of low doses of estrogen may carry less risk than continuous administration, it therefore appears prudent to utilize such a regimen.
Close clinical surveillance of all women taking estrogens is important. In all cases of undiagnosed persistent or recurring abnormal vaginal bleeding, adequate diagnostic measures should be undertaken to rule out malignancy.
There is no evidence at present that “natural” estrogens are more or less hazardous than “synthetic” estrogens at equiestrogenic doses.
2. Estrogens Should Not Be Used During Pregnancy
The use of female sex hormones, both estrogens and progestogens, during early pregnancy may seriously damage the offspring. It has been shown that females exposed in utero to diethylstilbestrol, a non-steroidal estrogen, have an increased risk of developing in later life a form of vaginal or cervical cancer that is ordinarily extremely rare.5,6 This risk has been estimated as not greater than 4 per 1000 exposures.7 Furthermore, a high percentage of such exposed women (from 30 to 90 percent) have been found to have vaginal adenosis,8-12 epithelial changes of the vagina and cervix. Although these changes are histologically benign, it is not known whether they are precursors of malignancy. Although similar data are not available with the use of other estrogens, it cannot be presumed they would not induce similar changes. Several reports suggest an association between intrauterine exposure to female sex hormones and congenital anomalies, including congenital heart defects and limb reduction defects.13-16 One case control study16 estimated a 4.7 fold increased risk of limb reduction defects in infants exposed in utero to sex hormones (oral contraceptives, hormone withdrawal tests for pregnancy, or attempted treatment for threatened abortion). Some of these exposures were very short and involved only a few days of treatment. The data suggest that the risk of limb reduction defects in exposed fetuses is somewhat less than 1 per 1000.
In the past, female sex hormones have been used during pregnancy in an attempt to treat threatened or habitual abortion. There is considerable evidence that estrogens are ineffective for these indications, and there is no evidence from well controlled studies that progesterones are effective for these uses.
IF ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE FULL STRENGTH or ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE HALF STRENGTH is used during pregnancy, or if the patient becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus, and the advisability of pregnancy continuation.
ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE FULL STRENGTH: Each light green, capsule-shaped, film-coated oral tablet contains: 1.25 mg of Esterified Estrogens, USP and 2.5 mg of Methyltestosterone, USP.
ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE HALF STRENGTH: Each light blue, capsule-shaped, film-coated oral tablet contains: 0.625 mg of Esterified Estrogens, USP and 1.25 mg of Methyltestosterone, USP.
Esterified Estrogens, USP is a mixture of the sodium salts of the sulfate esters of the estrogenic substances, principally estrone, that are of the type excreted by pregnant mares. Esterified Estrogens contain not less than 75.0 percent and not more than 85.0 percent of sodium estrone sulfate, and not less than 6.0 percent and not more than 15.0 percent of sodium equilin sulfate, in such proportion that the total of these two components is not less than 90.0 percent.
Methyltestosterone is an androgen. Androgens are derivatives of cyclopentano-perhydrophenanthrene. Endogenous androgens are C-19 steroids with a side chain at C-17, and with two angular methyl groups. Testosterone is the primary endogenous androgen. Fluoxymesterone and methyltestosterone are synthetic derivatives of testosterone.
Methyltestosterone is a white to light yellow crystalline substance that is virtually insoluble in water but soluble in organic solvents. It is stable in air but decomposes in light.
Methyltestosterone structural formula:
Androst-4-en-3-one, 17-hydroxy-17-methyl-, (17B)-. Category: Androgen.
ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE FULL STRENGTH TABLETS and ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE HALF STRENGTH TABLETS contain the following inactive ingredients: lactose, magnesium stearate, microcrystalline cellulose, titanium dioxide, and other minor ingredients.
ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE FULL STRENGTH TABLETS also contain: FD&C Blue No. 1 and D&C Yellow No. 10 and PEG.
ESTERIFIED ESTROGENS AND METHYLTESTOSTERONE HALF STRENGTH TABLETS also contain: D&C Yellow No. 10, FD&C Blue No. 1.
1. Ziel, H.K. et al.: N. Engl. J. Med. 293: 1167-1170,
2.Smith, D.C., et al.: N. Engl. J. Med. 293: 1164-1167, 1975.
3. Mack, T.M., et al.: N. Engl. J. Med. 294: 1262-1267, 1976.
4. Weiss, N.S. et al.: N. Engl. J. Med. 294: 1259-1262, 1976.
5. Herbst, A.L. et al.: N. Engl. J. Med. 284: 878-881, 1971.
6. Greenwald, P., et al.: N. Engl. J. Med. 285: 390-392, 1971.
7.Lanier, A., et al.: Mayo Clin. Proc. 48: 793-799, 1973.
8. Herbst, A., et al.: Obstet. Gynecol. 40: 287-298, 1972.
9. Herbst, A., et al.: Am. J. Obstet. Gynecol. 118: 607-615, 1974.
10. Herbst, A., et al.: N. Engl. J. Med. 292: 334-339, 1975.
11. Stafl, A., et al.: Obstet. Gynecol. 43: 118-128, 1974.
12. Sherman, A.I., et al.: Obstet. Gynecol. 44: 531-545, 1974.
13. Gal, I., et al.: Nature 216: 83, 1967.
14. Levy, E.P., et al.: Lancet 1: 611, 1973.
15. Nora, J., et al.: Lancet 1: 941-942, 1973.
16. Janerich, D.T., et al.: N. Engl. J. Med. 291: 697-700, 1974.
Last reviewed on RxList: 3/20/2017
This monograph has been modified to include the generic and brand name in many instances.
Additional EEMT Information
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