Applies to ethinyl estradiol / ethynodiol: oral tablet.

Serious side effects

Along with its needed effects, ethinyl estradiol/ethynodiol may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ethinyl estradiol/ethynodiol:

Incidence not known

• Absent, missed, or irregular menstrual periods
• anxiety
• bloody stools
• blurred vision
• breast tenderness, enlargement, discharge
• changes in skin color, pain, tenderness, or swelling of the foot or leg
• chest pain or discomfort
• chills
• clay-colored stools
• confusion
• cough
• dark or cloudy urine
• decrease in urine output or decrease in urine-concentrating ability
• diarrhea
• difficulty in speaking
• dizziness or lightheadedness
• double vision
• fainting
• fast heartbeat
• fever
• headache, severe and throbbing
• inability to move the arms, legs, or facial muscles
• inability to speak
• itching of the vagina or outside the genitals
• loss of appetite
• nausea
• nervousness
• pain during sexual intercourse
• pain or discomfort in the arms, jaw, back or neck
• pounding in the ears
• slow or fast heartbeat
• slow speech
• stomach pain and tenderness
• stopping of menstrual bleeding
• sweating
• swelling
• swelling, pain, or tenderness in the upper abdominal area
• tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area
• thick, white curd-like vaginal discharge without odor or with mild odor
• troubled breathing
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting
• vomiting of blood
• yellow eyes or skin

Other side effects

Some side effects of ethinyl estradiol / ethynodiol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• Acne
• changes in appetite
• changes in weight
• decreased interest in sexual intercourse
• decreased milk production
• light vaginal bleeding between regular menstrual periods
• loss in sexual ability, desire, drive, or performance
• mental depression
• patchy brown or dark brown discoloration of the skin

For Healthcare Professionals

Applies to ethinyl estradiol / ethynodiol: oral tablet.

General

The more commonly reported adverse events with combined oral contraceptives include nausea, vomiting, and headache.^[Ref]

Cardiovascular

Combined Oral Contraceptives:

Frequency not reported: Increased risk of thrombophlebitis, thrombosis, arterial thromboembolism, myocardial infarction and coronary thrombosis; hypertension, edema^[Ref]

Nervous system

Combined Oral Contraceptives:

Frequency not reported: Migraine, headache, dizziness, cerebral hemorrhage, cerebral thrombosis^[Ref]

Genitourinary

Combined Oral Contraceptives:

Frequency not reported: Breakthrough bleeding and spotting, especially during the first several cycles; change in menstrual flow; amenorrhea during or after use; vaginal candidiasis; cystitis-like syndrome; vaginitis; hemolytic uremic syndrome; changes in cervical erosion or secretion; oligomenorrhea and amenorrhea following termination of oral contraceptive use^[Ref]

Gastrointestinal

Combined Oral Contraceptives:

Frequency not reported: Nausea, vomiting abdominal cramps, bloating, mesenteric thrombosis, colitis, gallbladder disease^[Ref]

Respiratory

Combined Oral Contraceptives:

Frequency not reported: Pulmonary embolism,

Endocrine

Combined Oral Contraceptives:

Frequency not reported: Temporary infertility after discontinuation of use; breast changes including tenderness, enlargement, and secretion; premenstrual syndrome; diminution in lactation when given immediately postpartum^[Ref]

Hepatic

Combined Oral Contraceptives:

Frequency not reported: Benign and malignant liver tumors, and other hepatic lesions; cholestatic jaundice, Budd-Chiari syndrome^[Ref]

Dermatologic

Combined Oral Contraceptives:

Frequency not reported: Chloasma or melasma (which may persist), rash (allergic), hirsutism, loss of scalp hair, erythema multiforme, erythema nodosum, acne, porphyria, hemorrhagic eruption

Psychiatric

Combined Oral Contraceptives:

Frequency not reported: Nervousness, mental depression, changes in libido^[Ref]

Oncologic

Combined Oral Contraceptives:

Frequency not reported: Breast cancer, hepatocellular carcinoma, endocervical hyperplasia^[Ref]

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."

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.

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]

Ocular

Combined Oral Contraceptives:

Frequency not reported: Retinal thrombosis, optic neuritis, changes in contact lens tolerance, cataracts, change in corneal curvature (steepening), ectropion^[Ref]

Metabolic

Combined Oral Contraceptives:

Frequency not reported: Changes in appetite, increased/decreased weight, reduced tolerance to carbohydrates

Renal

Combined Oral Contraceptives:

Frequency not reported: Impaired renal function