Esterified estrogens Side Effects
For the Consumer
Applies to esterified estrogens: oral tablet
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using esterified estrogens and call your doctor at once if you have:
signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;
signs of a blood clot in your leg--pain, swelling, warmth, or redness in one or both legs;
heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
liver problems--severe stomach pain, fever, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
high levels of calcium in your blood--nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, confusion, lack of energy, or tired feeling;
a change in the pattern or severity of migraine headaches;
swelling in your hands, ankles, or feet;
a breast lump; or
severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.
Common side effects may include:
light vaginal bleeding or spotting;
breast pain or tenderness;
nausea, vomiting, bloating;
skin color changes, increased facial hair, thinning scalp hair;
headache, dizziness, mood changes, decreased sex drive;
vaginal itching or discharge, very light menstrual periods; or
problems with contact lenses.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.
For Healthcare Professionals
Applies to esterified estrogens: oral tablet
Rare cases of oral pigmentation and ischemic colitis have been reported.[Ref]
Gastrointestinal symptoms of nausea and vomiting have been the most frequently reported adverse effects. Some studies have demonstrated a 2 to 4 fold increase in gallbladder disease in postmenopausal women taking estrogen therapy.[Ref]
Oncologic side effects associated with unopposed estrogen therapy have included an increased risk of endometrial carcinoma in patients with an intact uterus and less persuasively, an increased risk of breast cancer.[Ref]
A number of studies have suggested that the risk of endometrial carcinoma is removed (or delayed) by the administration of progestins in combination with estrogen therapy.
The increased risk of breast cancer due to use of estrogens is controversial. Several studies have suggested that long-term estrogen therapy may be associated with a slightly increased risk of breast cancer. Meta analysis of 51 studies (epidemiological data) supports a modest risk increase associated with long-term hormone replacement therapy (HRT).
One study of Swedish women has reported that a 10% increase in the relative risk of breast cancer may occur and that the risk is related to increasing duration of estrogen therapy. In that study, women with more than nine years of estrogen use had a 70% greater relative risk of breast cancer than controls. That study, however, examined use of a variety of estrogen preparations of which estradiol was the most frequently prescribed. In addition, women who took progestins did not demonstrate a decreased risk of breast cancer and may even have been at higher risk.
The Toronto Breast Cancer Study has reported that women who receive unopposed conjugated estrogens for less than 15 years are not at increased risk of breast cancer. In that study, an increase in the risk of breast cancer for women who used conjugated estrogens for more than 15 years was not ruled out.
The Case-Control Surveillance Study has reported that there is "no evidence that the use of unopposed conjugated estrogens increases the risk of breast cancer, even after long duration of use or long latent intervals, but the possibility of a modest increase (less than a doubling) could not be excluded."
Follow-up to the Nurses' Health Study of 1992 concluded, however, that there is an increased risk of breast cancer in women taking estrogen replacement therapy and that the risk is not reduced by concurrent use of progestins. (In that study, greater risk was associated with advanced age and prolonged duration of hormonal therapy.)
A study of middle-aged women in the Puget Sound area concluded that "on the whole, the use of estrogen with progestin HRT [hormone replacement therapy] does not appear to be associated with an increased risk of breast cancer in middle-aged women."
A prospective cohort study (11 years) of 37105 women by Gapstur et al evaluated the histology of the breast cancer in women who ever used HRT. No association was found between duration of ever HRT use and the incidence of ductal carcinoma in situ or invasive ductal/lobular carcinoma. The duration of ever HRT use was associated with risk of invasive carcinoma with a favorable prognosis (relative risk (RR) = 1.81, 95% confidence interval (CI), 1.07 to 3.07 for HRT use less than or equal to 5yrs and RR = 2.65, CI, 1.32 to 5.23 for HRT use > 5yrs, p = 0.005). The relative risks of invasive carcinoma with a favorable prognosis for current users (adjusted for age and other risk factors) was 4.42, CI, 2.00 to 9.76 for less than or equal to 5yrs and 2.63, CI, 1.18 to 5.89 for > 5yrs. Risk of invasive ductal or lobular carcinoma for current users less than or equal to 5yrs was RR = 1.38, CI, 1.03 to 1.85.[Ref]
The effect of estrogen therapy in reducing cardiovascular risk is thought to be related to beneficial alterations in lipid profiles in treated women.
The reported effects of estrogens on cardiovascular activity are variable. Alterations in lipid profiles in treated women are thought to be responsible for reducing cardiovascular risks. Data suggest estrogen use may increase blood pressure, particularly in patients receiving high doses, decrease blood pressure, or result in no change. In addition, noncontraceptive use of estrogens in young women (particularly smokers) may substantially increase the risk of nonfatal myocardial infarction. Other studies have concluded that no increased risk of myocardial infarction exists.[Ref]
Cardiovascular risks are thought to be reduced with estrogen therapy. Studies suggest that unopposed estrogen therapy may decrease the risk of coronary heart disease by as much as 35%. Combination therapy with a progestin may also decrease coronary risk. However, the extent of risk reduction with combination therapy has not been determined. Data are available that suggest combination therapy does not reduce the overall rate of coronary heart disease in postmenopausal women with established coronary disease.[Ref]
While HDL, LDL and total cholesterol levels are generally "improved" during estrogen therapy, triglyceride levels may be significantly increased. Some dramatic elevations in triglyceride levels and to a lesser extent, cholesterol levels, have been reported.[Ref]
Metabolic side effects generally have been favorable alterations in plasma lipid profiles. Specifically, increased HDL and decreased cholesterol and LDL levels have occurred. Estrogen therapy may lead to an increase in serum triglyceride levels resulting in pancreatitis in patients with familial lipoprotein metabolic defects.
Hypercalcemia has occurred in patients with breast cancer and bone metastases. Aggravation of porphyria has been reported.[Ref]
Estrogens may cause some degree of fluid retention and mastodynia.[Ref]
Genitourinary side effects may include abnormal uterine bleeding which must be carefully distinguished from bleeding related to endometrial carcinoma. In addition, estrogens may increase the size of preexisting uterine leiomyomata.
Several cases of pseudoincontinence (excessive vaginal discharge perceived by patients as urinary incontinence) have been reported in premenopausal who have undergone hysterectomy-oophorectomy and received post-operative estrogens.[Ref]
Hematologic side effects of hypercoagulability have been reported, although the clinical significance of such hypercoagulability in postmenopausal women taking estrogens has not been determined.[Ref]
Many of the reports of hepatic tumors occurred in women taking long-term oral contraceptives. However, some tumors have been reported in women taking isolated estrogen therapy.[Ref]
Hepatic side effects have included rare cases of focal nodular hyperplasia, liver cell adenomas, hepatic hemangiomas and well-differentiated hepatocellular carcinomas.[Ref]
Hypersensitivity reactions including anaphylaxis have been reported in association with estrogens and the dyes contained in some conjugated estrogen formulations.[Ref]
Nervous system side effects associated with estrogen therapy have included migraine, dizziness, and mental depression. A case of chorea has been reported in association with conjugated estrogen therapy. Alterations in libido have occurred.[Ref]
Ocular side effects of estrogen therapy have included alterations in corneal curvature and contact lens discomfort.[Ref]
Some investigators have suggested that estrogen therapy may increase the risk of "fibrocystic breast disease" by as much as two-fold.[Ref]
Psychiatric effects of estrogen use have included case reports of rapid mood cycling in patients with severe depression.[Ref]
Dermatologic effects have included chloasma or melasma. Resolution has not occurred in all cases following discontinuation of estrogen therapy. Scalp hair loss, hirsutism, erythema nodosum, and hemorrhagic eruptions have occurred.[Ref]
Endocrine effects of estrogen use have included decreased fasting plasma glucose. Estrogen use may result in increased levels of thyroxin-binding globulin leading to increased total thyroid serum levels and decreased resin uptake of T3. Free thyroid hormone levels have remained unchanged.[Ref]
1. "Product Information. Estratab (esterified estrogens)" Solvay Pharmaceuticals Inc, Marietta, GA.
2. Boston Collaborative Drug Surveilance Program "Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy." N Engl J Med 290 (1974): 15-9
3. Thomas DB, Persing JP, Hutchinson WB "Exogenous estrogens and other risk factors for breast cancer in women with benign breast diseases." J Natl Cancer Inst 69 (1982): 1017-25
4. Spengler RF, Clarke EA, Woolever CA, Newman AM, Osborn RW "Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases." Am J Epidemiol 114 (1981): 497-506
5. Gordon J, Reagan JW, Finkle WD, Ziel HK "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate." N Engl J Med 297 (1977): 570-1
6. Palmer JR, Rosenberg L, Clarke EA, Miller DR, Shapiro S "Breast cancer risk after estrogen replacement therapy: results from the Toronto Breast Cancer Study." Am J Epidemiol 134 (1991): 1386-95
7. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
8. Colditz GA, Hankinson SE, Hunter DJ, et al. "The use of estrogens and progestins and the risk of breast cancer in postmenopausal women." N Engl J Med 332 (1995): 1589-93
9. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9
10. Kaufman DW, Palmer JR, de Mouzon J, Rosenberg L, Stolley PD, Warshauer ME, Zauber AG, Shapiro S "Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study." Am J Epidemiol 134 (1991): 1375-85
11. Antunes CM, Strolley PD, Rosenshein NB, Davies JL, Tonascia JA, Brown C, Burnett L, Rutledge A, Pokempner M, Garcia R "Endometrial cancer and estrogen use. Report of a large case-control study." N Engl J Med 300 (1979): 9-13
12. The Writing Group for the PEPI Trial "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA 275 (1996): 370-5
13. Gapstur SM, Morrow M, Sellers TA "Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa women's health study." JAMA 281 (1999): 2091-7
14. Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C "The risk of breast cancer after estrogen and estrogen-progestin replacement." N Engl J Med 321 (1989): 293-7
15. The Writing Group for the PEPI Trial "Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial." JAMA 273 (1995): 199-208
16. Schwartz J, Freeman R, Frishman W "Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women." J Clin Pharmacol 35 (1995): 1-16
17. Crane MG, Harris JJ "Estrogens and hypertension: effect of discontinuing estrogens on blood pressure, exchangeable sodium, and the renin-aldosterone system." Am J Med Sci 276 (1978): 33-55
18. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
19. Stampfer MJ, Colditz GA, Willett WC, et al. "Postmenopausal estrogen and cardiovascular disease. Ten-year follow-up from the Nurses' Health Study." N Engl J Med 325 (1991): 756-62
20. Wren BG, Routledge DA "Blood pressure changes: oestrogens in climacteric women." Med J Aust 2 (1981): 528-31
21. Grady D, Rubin SM, Petiti DB, et al. "Hormone therapy to prevent disease and prolong life in postmenopausal women." Ann Intern Med 117 (1992): 1016-36
22. Jick H, Dinan B, Rothman KJ "Noncontraceptive estrogens and nonfatal myocardial infarction." JAMA 239 (1978): 1407-8
23. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
24. Rosenberg L, Slone D, Shapiro S, Kaufman D, Stolley PD, Miettinen OS "Noncontraceptive estrogens and myocardial infarction in young women." JAMA 244 (1980): 339-42
25. Collins P, Beale CM, Rosano GMC "Oestrogen as a calcium channel blocker." Eur Heart J 17 ( Suppl (1996): 27-31
26. Barrett-Connor E, Wingard DL, Criqui MH "Postmenopausal estrogen use and heart disease risk factors in the 1980s. Rancho Bernardo, Calif, revisited." JAMA 261 (1989): 1095-2100
27. Molitch ME, Oill P, Odell WD "Massive hyperlipemia during estrogen therapy." JAMA 227 (1974): 522-5
28. Julian TM "Pseudoincontinence secondary to unopposed estrogen replacement in the surgically castrate premenopausal female." Obstet Gynecol 70 (1987): 382-3
29. Auerbach R, Mittal K, Schwartz PE "Estrogen and progestin receptors in an ovarian ependymoma." Obstet Gynecol 71 (1988): 1043-5
30. Devor M, Barrett-Connor E, Renvall M, Feigal D, Ramsdell J "Estrogen replacement therapy and the risk of venous thrombosis." Am J Med 92 (1992): 275-81
31. Aldinger K, Ben-Menachem Y, Whalen G "Focal nodular hyperplasia of the liver associated with high-dosage estrogens." Arch Intern Med 137 (1977): 357-9
32. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9
33. Oppenheim G "A case of rapid mood cycling with estrogen: implications for therapy." J Clin Psychiatry 45 (1984): 34-5
Not all side effects for esterified estrogens may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
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- Drug class: estrogens
Other brands: Menest
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