Ortho-Prefest Side Effects
Generic Name: estradiol / norgestimate
Note: This page contains side effects data for the generic drug estradiol / norgestimate. It is possible that some of the dosage forms included below may not apply to the brand name Ortho-Prefest.
For the Consumer
Applies to estradiol / norgestimate: tablets
Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Seek medical attention right away if any of these SEVERE side effects occur while taking estradiol / norgestimate:
Nausea; vomiting; weight change; bleeding between menstrual periods; breast tenderness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); calf/leg pain or swelling; changes in vision; chest pain; difficulty wearing contact lenses; dizziness or fainting; headache or sudden severe headache; lumps in the breast; missed menstrual period; numbness of an arm or leg; one-sided weakness; persistent or recurrent abnormal vaginal bleeding; severe stomach pain; slurred speech; swelling of fingers or ankles; trouble breathing or shortness of breath; yellowing skin or eyes.
For Healthcare Professionals
Applies to estradiol / norgestimate: oral tablet
Gastrointestinal side effects have included abdominal pain (12%), nausea (6%), and flatulence and tooth disorders (5%). Cholestatic jaundice, vomiting, and bloating have occurred. Some studies have demonstrated a 2 to 4 fold increase in gallbladder disease in postmenopausal women taking estrogen therapy.[Ref]
Oncologic side effects have included reports of increased risk of invasive breast cancer. A large study (n = 16,608 postmenopausal women) of conjugated equine estrogens and medroxyprogesterone was terminated in 2002 due to the increased risk of coronary heart disease, stroke, and pulmonary embolism. Other oncologic side effects of unopposed estrogen therapy have included an increased risk of endometrial carcinoma, and less persuasively, an increased risk of breast cancer. 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.[Ref]
The risk of breast cancer due to use of estrogens is controversial. Meta analysis of epidemiological data supports a modest risk increase associated with long-term hormone replacement therapy (HRT).
A 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 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 reported "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 doubling) could not be excluded."
Follow-up data 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 significant increase in the incidence of breast cancer in beagle dogs in addition to an apparent increase in the incidence of endometrial cancer in rhesus monkeys was noted in early animal carcinogenicity studies.
A prospective cohort study (11 years) of 37,105 women by Gapstur et al evaluated the histology of the breast cancer in women with ever HRT use. Little evidence of 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 <= and RR = 2.65, CI, 1.32 to 5.23 for HRT use > 5yrs, p = 0.005]. The relative risk 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 <= 5yrs and 2.63, CI 1.18 to 5.89 for > 5yrs). Risk of invasive ductal or lobular carcinoma for current users <= 5yrs was RR = 1.38, CI, 1.03 to 1.85.[Ref]
The effects of estrogen therapy in reducing cardiovascular risk have been related to beneficial alterations in lipid profiles in treated women.
Data from the Nurse's Heart Study involving postmenopausal women without coronary heart disease who received combined estrogen-progestin therapy reported a marked decrease in coronary heart disease during a 16 year follow-up. Data from the Heart and Estrogen/progestin Replacement Study (HERS) Research Group involving 2763 postmenopausal women with established coronary disease reported no reduction in the overall rate of coronary heart disease despite a 11% decrease in low density lipoproteins and a 10% increase in high density lipoproteins in patients receiving conjugated estrogen-medroxyprogesterone when compared to the placebo group after an average follow-up of 4.1 years.
Some investigators have suggested that estrogens may increase blood pressure, particularly in patients receiving high doses. Other investigators have suggested that decreases in blood pressure (or no change) occur. In addition, it has been suggested that noncontraceptive use of estrogens in young women (particularly smokers) may substantially increase the risk of nonfatal myocardial infarction. Conflicting data have concluded that no increased risk of myocardial infarction exists.
The majority of cases of thromboembolic disease during hormonal therapy have been attributed to estrogens and not to progestins.[Ref]
Cardiovascular side effects have included reports of increased risk coronary heart disease, stroke, and pulmonary embolism. A large study (n = 16,608 postmenopausal women) of conjugated equine estrogens and medroxyprogesterone was terminated in 2002 due to the increased risk of coronary heart disease. stroke, and pulmonary embolism. Earlier studies had suggested that unopposed estrogen therapy may decrease the risk of coronary heart disease by as much as 35% and that combination therapy with a progestin may also decrease coronary risk.[Ref]
Metabolic side effects of estrogens have included increased serum triglyceride levels resulting in pancreatitis in patients with familial lipoprotein metabolic defects. However, metabolic effects in patients treated with estrogens have included generally favorable alterations in plasma lipid profiles. Specifically, increased HDL and decreased cholesterol and LDL levels have occurred.
Metabolic side effects of progestin therapy have included weight changes (increases and decreases), impaired glucose tolerance, and changes in serum cholesterol concentrations.[Ref]
Hepatic side effects have included cases of focal nodular hyperplasia, liver cell adenomas, hepatic hemangiomas, and rarely, well-differentiated hepatocellular carcinomas.[Ref]
Hematologic side effects have included hypercoagulability, although the clinical significance of such hypercoagulability in postmenopausal women taking estrogens has not been determined.[Ref]
Endocrine side effects of estrogens have included increased levels of thyroxin-binding globulin, leading to an increase in total thyroid serum levels and a decrease in resin uptake of T3. Free thyroid hormone levels remain unchanged. Other endocrine effects may include a decrease on fasting plasma glucose.
Endocrine side effects of progestins have included breast tenderness, galactorrhea with or without hyperprolactinemia, prevention of lactation, hirsutism, and Cushing's syndrome.[Ref]
Genitourinary side effects have included breast pain (16%) and vaginal bleeding (9%). Dysmenorrhea (8%) and vaginitis (7%) have been reported. 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 women who have undergone hysterectomy-oophorectomy and received postoperative estrogens.[Ref]
Dermatologic side effects have included chloasma or melasma which may persist following discontinuation of therapy, reduced scalp hair growth, hirsutism, erythema multiforme, and erythema nodosum.[Ref]
Musculoskeletal side effects have included arthralgias and myalgias in 9% and 5% of patients, respectively.[Ref]
Other side effects have included reports that estrogen therapy may increase the risk of "fibrocystic breast disease" by as much as twofold.[Ref]
Respiratory side effects have included reports of increased risk of pulmonary embolism. A large study (n = 16,608 postmenopausal women) of conjugated equine estrogens and medroxyprogesterone was terminated in 2002 due to the increased risk of coronary heart disease. stroke, and pulmonary embolism. Other respiratory side effects have included infections of the upper respiratory tract in 21% of patients. Pharyngitis (7%), sinusitis (8%), and coughing (5%) have been reported.[Ref]
Nervous system side effects have included headaches in 23% of patients. Dizziness was reported in 5% of patients.[Ref]
Psychiatric side effects have included symptoms of depression in 5% of patients.[Ref]
Ocular side effects of estrogen therapy have included alterations in corneal curvature and contact lens discomfort.[Ref]
1. 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
2. "Product Information. Ortho-Prefest (estradiol-norgestimate)" Ortho McNeil Pharmaceutical, Raritan, NJ.
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. "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial." JAMA 288 (2002): 321-33
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. Gray LA Sr, Christopherson WM, Hoover RN "Estrogens and endometrial carcinoma." Obstet Gynecol 49 (1977): 385-9
8. 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
9. 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
10. 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
11. Obrink A, Bunne G, Collen J, Tjernberg B "Endometrial cancer and exogenous estrogens." Acta Obstet Gynecol Scand 58 (1979): 123
12. 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
13. "Hormone replacement therapy." Med Lett Drugs Ther 44 (2002): 78
14. The Writing Group for the PEPI Trial "Effects of hormone replacement therapy on endometrial histology in postmenopausal women." JAMA 275 (1996): 370-5
15. 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
16. 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
17. Crane MG, Harris JJ, Winsor W 3d "Hypertension, oral contraceptive agents, and conjugated estrogens." Ann Intern Med 74 (1971): 13-21
18. Wren BG, Routledge DA "Blood pressure changes: oestrogens in climacteric women." Med J Aust 2 (1981): 528-31
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. 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
21. Barrett-Connor E, Bush TL "Estrogen and coronary heart disease in women." JAMA 265 (1991): 1861-7
22. 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
23. 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
24. 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
25. Belchetz PE "Hormonal treatment of postmenopausal women." N Engl J Med 330 (1994): 1062-71
26. Collins P, Beale CM, Rosano GMC "Oestrogen as a calcium channel blocker." Eur Heart J 17 ( Suppl (1996): 27-31
27. Molitch ME, Oill P, Odell WD "Massive hyperlipemia during estrogen therapy." JAMA 227 (1974): 522-5
28. 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
29. Conter RL, Longmire WP Jr "Recurrent hepatic hemangiomas. Possible association with estrogen therapy." Ann Surg 207 (1988): 115-9
30. Boschetti C, Cortellaro M, Nencioni T, Bertolli V, Della Volpe A, Zanussi C "Short- and long-term effects of hormone replacement therapy (transdermal estradiol vs oral conjugated equine estrogens, combined with medroxyprogesterone acetate) on blood coagulation factors in postmenopausal women." Thromb Res 62 (1991): 1-8
31. 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
32. Julian TM "Pseudoincontinence secondary to unopposed estrogen replacement in the surgically castrate premenopausal female." Obstet Gynecol 70 (1987): 382-3
33. Auerbach R, Mittal K, Schwartz PE "Estrogen and progestin receptors in an ovarian ependymoma." Obstet Gynecol 71 (1988): 1043-5
34. Steiger MJ, Quinn NP "Hormone replacement therapy induced chorea." BMJ 302 (1991): 762
It is possible that some side effects of Ortho-Prefest may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.
More about Ortho-Prefest (estradiol / norgestimate)
- Other brands: Prefest
Related treatment guides
Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.