Norinyl 1+35 Side Effects
Generic Name: ethinyl estradiol / norethindrone
Note: This page contains side effects data for the generic drug ethinyl estradiol / norethindrone. It is possible that some of the dosage forms included below may not apply to the brand name Norinyl 1+35.
For the Consumer
Applies to ethinyl estradiol / norethindrone: oral tablet, oral tablet chewable
Other dosage forms:
As well as its needed effects, ethinyl estradiol / norethindrone may cause unwanted side effects that require medical attention.
If any of the following side effects occur while taking ethinyl estradiol / norethindrone, check with your doctor immediately:Less common:
- Breast tenderness
- heavy non-menstrual vaginal bleeding
- irregular menstrual periods
- longer or heavier menstrual periods
- normal menstrual bleeding occurring earlier, possibly lasting longer than expected
- Chest pain
- clay-colored stools
- dark urine
- difficulty with speaking
- double vision
- fast or irregular heartbeat
- inability to move the arms, legs, or facial muscles
- inability to speak
- itching or rash
- loss of appetite
- pain, redness, or swelling in the arm or leg
- pains in the chest, groin, or legs, especially in the calves of the legs
- severe headaches of sudden onset
- severe nausea or vomiting
- slurred speech
- stomach pain
- sudden loss of coordination
- sudden onset of shortness of breath for no apparent reason
- sudden onset of slurred speech
- sudden vision changes
- tightness in the chest
- unpleasant breath odor
- unusual tiredness or weakness
- unusual warmth or flushing of the skin
- unusually heavy or unexpected menstrual bleeding
- vaginal bleeding or spotting
- vomiting of blood
- yellow eyes or skin
Some ethinyl estradiol / norethindrone side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:More common:
- blemishes on the skin
- heavy bleeding
- weight changes
For Healthcare Professionals
Applies to ethinyl estradiol / norethindrone: oral tablet, oral tablet chewable
A number of studies have suggested that use of oral contraceptives decreases the risk of ovarian cancer. Specifically, the risk of epithelial ovarian cancers is decreased by 40%. The protection against ovarian cancer may last for 10 to 15 years after discontinuation of oral contraceptives. After long term use (12 years), the risk of ovarian cancer is decreased by as much as 80%.
The risk of endometrial cancer is decreased by approximately 50%. Protection may last for 15 years after discontinuation and may be greatest for nulliparous women who may be at higher risk for endometrial carcinoma than other women.
The incidence of hospitalization for pelvic inflammatory disease is approximately 50% lower in women taking oral contraceptives. The reason for the decrease in the frequency (or severity) of pelvic inflammatory disease in women taking oral contraceptives has not been fully elucidated.
Some recent studies have suggested that the decrease in frequency of functional ovarian cysts reported with some older formulations may not occur in women taking newer low dose formulations.
One recent study (The Nurses' Health Study) has suggested that long term use of oral contraceptives is safe and does not adversely affect long term risk for mortality.[Ref]
Women taking oral contraceptive combinations may have experienced several non-contraceptive health benefits. These benefits include protection against two malignant neoplasms (endometrial carcinoma and ovarian cancer). In addition, use of oral contraceptive combinations has reportedly decreased the frequency of benign breast tumors, decreased the risk of ovarian cysts, decreased the risk of ectopic pregnancy, increased menstrual regularity, decreased the incidence of iron deficiency anemia, decreased the incidence of dysmenorrhea, and decreased the incidence of pelvic inflammatory disease.[Ref]
Gastrointestinal side effects have included nausea, which occurred in approximately 10% of treated women and was more frequent during the first cycles of therapy. Some early reports suggested an association between oral contraceptive use and gallbladder disease.[Ref]
Cases of oral contraceptive-induced esophageal ulceration and geographic tongue have been reported rarely.
More recent studies have suggested that the risk of gallbladder disease is minimal.[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. A number of studies have examined a possible relationship between the use of oral contraceptives and the development of breast cancer. Many of the studies have reported conflicting results. A committee of the World Health Organization evaluated these studies and the risks of breast cancer and concluded that: "Numerous studies have found no overall association between oral contraceptive use and risk of breast cancer." In addition, the same committee also examined a possible relationship between oral contraceptive use and neoplasms of the uterine cervix and concluded that: "There are insufficient data to draw any firm conclusions regarding the effects of combined oral contraceptives on the risk of cervical adenocarcinoma."[Ref]
The World Health Organization committee also noted that some studies "have found a weak association between long-term use of oral contraceptives and breast cancer diagnosed before the age of 36, and perhaps up to the age 45....It is unclear whether this observed association is attributable to bias, the development of new cases of cancer, or accelerated growth of existing cancers."
The World Health Organization committee further concluded that there is no increased risk of breast cancer in women over the age of 45 who have previously taken oral contraceptives. In addition, studies suggest that use of oral contraceptives does not place specific groups of women (like those with a family history of breast cancer) at higher or lower risk, and variations in the hormonal content of oral contraceptives do not influence the risk of breast cancer.
In general, studies evaluating the potential risk of cervical cancer in patients taking oral contraceptives have been complicated by the large number of confounding factors which make investigations into the epidemiology of this neoplasm difficult. Some studies have suggested that women taking oral contraceptives are at increased risk of dysplasia, epidermoid carcinoma, and adenocarcinoma of the cervix. However, other studies have not found such an association.[Ref]
Detailed information concerning the effects of oral contraceptive therapy on lipid metabolism is available in the Endocrine paragraph of this side effect monograph.
Some early investigations of women taking high dose estrogen combinations (50 mcg or more of ethinyl estradiol or equivalent daily) suggested that such women may be at increased risk of cardiovascular complications (myocardial infarction, stroke, and vascular thrombosis, including venous thromboembolism). However, more recent large investigations of women taking low dose estrogen combinations have suggested that oral contraceptive use is not associated with an increased risk of serious cardiovascular complications in healthy non smoking women up to the age of 45. (For women aged 35 to 44 who smoke or who have preexisting systemic diseases that may affect the cardiovascular system, use of oral contraceptives is not recommended.)
However, some investigators have suggested that even the new low dose products may result in adverse effects on lipid metabolism and should prompt careful review of a woman's cardiovascular risk factors before a decision to use oral contraceptive combinations is made.
The frequency of both subarachnoid hemorrhage and thrombotic stroke has been reported by some investigators to be higher in women taking oral contraceptive hormones. However, other investigators have suggested that the risk of these effects for women using newer low dose formulations are very small for young women without underlying cardiovascular disease or other risk factors.[Ref]
Cardiovascular side effects have included reports of increased risk of 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. Cardiovascular side effects of the estrogen component of this combination have also included reports of hypertension. However, significant blood pressure increases generally occur only in women receiving high-dose estrogen products (50 mcg or more of ethinyl estradiol or equivalent daily). Estrogens have also been associated with edema. In addition, exogenous estrogens may exert cardioprotective effects by causing favorable changes in lipid profiles. These beneficial effects, however, may be partially or completely offset by alterations in lipid profiles induced by exogenous progestins.[Ref]
Endocrine side effects have included reports of complex alterations in plasma lipid profiles and carbohydrate metabolism. In addition, oral contraceptive use has been reported to cause conception delay.[Ref]
All the progestins which occur in commercially available oral contraceptive combinations have adverse effects on lipid profiles. Specifically, these progestins exert antiestrogen and androgen effects and decrease HDL (and HDL2) cholesterol levels and increase LDL cholesterol levels. However, the estrogens in oral contraceptive combinations exert opposing effects. Consequently, alterations in lipid profiles are related to the relative amount and potency of the specific estrogen and progestin in a given product. (Norethindrone exerts a moderate androgen effect and weak progestin and antiestrogen effects.)
A number of investigations have suggested that oral contraceptive combinations may decrease glucose tolerance. However, some recent studies with low dose preparations have suggested that decreases in glucose tolerance due to oral contraceptive combinations are generally minimal.
Despite the potentially adverse effects of oral contraceptives on lipid levels and glucose tolerance, some investigators have suggested that young diabetic women without existing vascular disease or severe lipidemias may be candidates for low dose oral contraceptive combinations provided that they receive close monitoring for adverse metabolic effects.[Ref]
Hepatic side effects have included focal nodular hyperplasia, intrahepatic cholestasis, liver cell adenomas, hepatic granulomas, hepatic hemangiomas and well-differentiated hepatocellular carcinomas, which have been reported rarely in association with estrogen therapy and therapy with oral contraceptive combinations.[Ref]
The rate of death due to hepatocellular carcinoma in the United States has not changed during the last 25 years (a time during which use of oral contraceptive hormones has increased dramatically).
A committee of the World Health Organization has reported that in developing countries where hepatitis B virus infection and hepatocellular carcinoma are common, "short term use of oral contraceptives does not appear to be associated with an increased risk. Data on the effects of long term use are scarce."
A recent Italian case-control study of women with hepatocellular carcinoma has suggested that the relative risk of hepatocellular carcinoma is 2.2 for oral contraceptive users compared to women who never used oral contraceptives.
A similar American case-control study from 1989 also reported a strong association between oral contraceptive use and hepatocellular carcinoma but concluded that: "If this observed association is causal, the actual number of cases of liver cancer in the United States attributable to oral contraceptive use is small. Therefore, these findings do not have public health importance in the United States and other Western nations."[Ref]
Cases of venous thrombosis, pulmonary embolism (sometimes fatal), and arterial thrombosis have been reported rarely.
Previous thrombotic disease is considered a contraindication to use of oral contraceptive combinations.[Ref]
Hematologic side effects have included the risk of thromboembolism that is associated with the use of exogenous estrogens. However, because the dose of exogenous estrogens is low in most commercially available preparations, the risk of thromboembolism is minimal for most women (except women who are over age 35 and smoke and women with a history of previous thrombotic diseases).[Ref]
Genitourinary side effects have commonly included breakthrough bleeding and spotting, especially during the first several cycles of oral contraceptive use. Non-hormonal causes of such bleeding should be excluded. Additional side effects reported with estrogen and/or progestin therapy include changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow, increase in size of uterine leiomyomata, vaginal candidiasis, change in amount of cervical secretion, change in cervical ectropion, ovarian cancer, endometrial hyperplasia, endometrial cancer and vaginitis.[Ref]
Some women experience oligomenorrhea and amenorrhea following termination or oral contraceptive use.[Ref]
Psychiatric side effects have included depression and precipitation of panic disorder.[Ref]
Immunologic side effects have included rare cases of oral contraceptive-induced systemic lupus erythematosus.[Ref]
Nervous system side effects have included chorea, which has been reported once in association with oral contraceptives.[Ref]
Ocular side effects have included rare cases of retinal thrombosis. In addition, the manufacturers of oral contraceptive products report that some patients develop changes in contact lens tolerance.
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.
A case of fatal pulmonary venooclusive disease has been associated with oral contraceptive therapy.
1. Gross TP, Schlesselman JJ "The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer." Obstet Gynecol 83 (1994): 419-24
2. Grimes DA "The safety of oral contraceptives: epidemiologic insights from the first 30 years." Am J Obstet Gynecol 166 (1992): 1950-4
3. Friedman AJ, Wheeler JM "Incidence of ovarian cyst formation in women taking ethynodiol diacetate, 1mg, with ethinyl estradiol, 35 micrograms." J Reprod Med 36 (1991): 345-9
4. Lanes SF, Birmann B, Walker AM, Singer S "Oral contraceptive type and functional ovarian cysts." Am J Obstet Gynecol 166 (1992): 956-61
5. Waltimo J "Geographic tongue during a year of oral contraceptive cycles." Br Dent J 171 (1991): 94-6
6. Olsson H, Moller TR, Ranstam J "Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden." J Natl Cancer Inst 81 (1989): 1000-4
7. Rettig BA, Lemon HM "Cancers related to contraceptive use." Br J Cancer 74 (1996): 1509-10
8. Sillero-Arenas M, Rodriguez-Contreras R, Delgado-Rodriguez M, Bueno-Cavanillas A, Galvez-Vargas R "Patterns of research. Oral contraceptives and cervical cancer." Acta Obstet Gynecol Scand 70 (1991): 143-8
9. Brinton LA "Oral contraceptives and cervical neoplasia." Contraception 43 (1991): 581-95
10. Ewertz M "Oral contraceptives and breast cancer risk in Denmark." Eur J Cancer 28A (1992): 1176-81
11. Zondervan KT, Carpenter LM, Painter R, Vessey MP "Oral contraceptives and cervical cancer - further findings from the oxford family planning association contraceptive study." Br J Cancer 73 (1996): 1291-7
12. "Oral contraceptives and neoplasia. WHO Scientific Group." World Health Organ Tech Rep Ser 817 (1992): 1-46
13. Rosenberg L, Palmer JR, Clarke EA, Shapiro S "A case-control study of the risk of breast cancer in relation to oral contraceptive use." Am J Epidemiol 136 (1992): 1437-44
14. Leaf DA, Bland D, Schaad D, Neighbor WE, Scott CS "Oral contraceptive use and coronary risk factors in women." Am J Med Sci 301 (1991): 365-8
15. Speroff L "Oral contraceptives and venous thromboembolism." Int J Gynaecol Obstet 54 (1996): 45-50
16. Poulter NR, Chang CL, Farley TMM, Meirik O, Marmot MG, Debertribeiro M, Medina E, Artigas J, Shen H, Zhong YH, Zhang DW, "Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study." Lancet 348 (1996): 498-505
17. Williams RS "Benefits and risks of oral contraceptive use." Postgrad Med 92 (1992): 155-7
18. Piegsa K, Guillebaud J "Oral contraceptives and the risk of DVT." Practitioner 240 (1996): 544
19. Gillum LA, Mamidipudi SK, Johnston SC "Ischemic stroke risk with oral contraceptives: a meta-analysis." JAMA 284 (2000): 72-8
20. Derman R "Oral contraceptives: a reassessment." Obstet Gynecol Surv 44 (1989): 662-8
21. "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
22. Farmer R, Lewis M "Oral contraceptives and mortality from venous thromboembolism." Lancet 348 (1996): 1095
23. Thorneycroft IH "Oral contraceptives and myocardial infarction." Am J Obstet Gynecol 163 (1990): 1393-7
24. Stubblefield PG "Choosing the best oral contraceptive." Clin Obstet Gynecol 32 (1989): 316-28
25. Bracken MB, Hellenbrand KG, Holford TR "Conception delay after oral contraceptive use: the effect of estrogen dose." Fertil Steril 53 (1990): 21-7
26. Garg SK, Chase HP, Marshall G, Hoops SL, Holmes DL, Jackson WE "Oral contraceptives and renal and retinal complications in young women with insulin-dependent diabetes mellitus." JAMA 271 (1994): 1099-102
27. Janaud A, Rouffy J, Upmalis D, Dain MP "A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel." Acta Obstet Gynecol Scand Suppl 156 (1992): 33-8
28. Le Bail B, Jouhanole H, Deugnier Y, Salame G, Pellegrin JL, Saric J, Balabaud C, Bioulac-Sage P "Liver adenomatosis with granulomas in two patients on long-term oral contraceptives." Am J Surg Pathol 16 (1992): 982-7
29. Mishell DR "Contraception." N Engl J Med 320 (1989): 777-85
30. Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S "Oral contraceptive use and liver cancer." Am J Epidemiol 130 (1989): 878-82
31. Gyorffy EJ, Bredfeldt JE, Black WC "Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use." Ann Intern Med 110 (1989): 489-90
32. "Product Information. Ortho-Novum (oral contraceptive combination pill)." Ortho Pharmaceutical Corporation, Raritan, NJ.
33. Deci PA, Lydiard RB, Santos AB, Arana GW "Oral contraceptives and panic disorder." J Clin Psychiatry 53 (1992): 163-5
34. Iskander MK, Khan M "Chorea as the initial presentation of oral contraceptive related systemic lupus erythematosus." J Rheumatol 16 (1989): 850-1
35. Thorogood M "Risk of stroke in users of oral contraceptives." JAMA 281 (1999): 1255-6
It is possible that some side effects of Norinyl 1+35 may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.
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