What are the potential side effects of continuous oral contraception and how are they managed?

Side Effects of Continuous Oral Contraception

The most common side effect of continuous oral contraceptive use is unscheduled breakthrough bleeding and spotting, particularly during the first 3-6 months, which is generally not harmful and decreases with continued use. 1, 2

Common Transient Side Effects

Minor side effects that typically resolve within the first few months include:

• Irregular bleeding and spotting – the most frequent adverse effect, expected during the initial 3-6 months of continuous use 1, 2
• Headache – common transient complaint 1
• Nausea – typically improves with persistent use 1
• Breast tenderness – may occur initially 1
• Vaginal discharge or discomfort (particularly with vaginal ring formulations) 1

Serious Adverse Effects

The most serious risk is venous thromboembolism (VTE), which increases from 1 per 10,000 to 3-4 per 10,000 woman-years during COC use 1. This risk is substantially lower than the 10-20 per 10,000 woman-years associated with pregnancy and postpartum 1.

Other serious cardiovascular risks include:

• Arterial thromboembolism and pulmonary embolism 3
• Myocardial infarction – risk increases 2-6 fold, primarily in smokers or women with underlying cardiovascular risk factors 3
• Cerebrovascular events (thrombotic and hemorrhagic strokes) – risk greatest in women >35 years who smoke 3
• Hypertension – COCs may increase blood pressure 3

Additional serious but rare complications:

• Hepatic adenomas or benign liver tumors 3
• Gallbladder disease 3
• Cervical cancer – risk increases with duration of use (≥5 years), but declines after discontinuation 1

Metabolic and Hormonal Effects

• Fluid retention – may occur due to estrogen component, though formulations with drospirenone (which has antimineralcorticoid activity) may actually prevent water retention 3, 4
• Weight changes (increase or decrease) – reported but not consistently demonstrated 3
• Glucose intolerance – progestogens may affect glucose tolerance 3
• Lipid changes – some progestogens may decrease HDL cholesterol and elevate LDL levels 3

Bone Health Considerations

Concern exists regarding low-dose estrogen COCs in young adolescents (<14 years or within 2 years of menarche), as peak bone mass development occurs during adolescence 1. However, definitive evidence of clinically significant osteopenia with COC use has not been demonstrated 1.

Breast Cancer Risk

Current or recent COC use (<6 months since last use) is associated with a modestly increased relative risk of 1.19-1.33 for breast cancer 3. This risk is greatest in women <34 years of age, when baseline breast cancer incidence is lowest 1. The risk increases with longer duration of current use (up to approximately 1.4 with >8-10 years of use) 3.

Other Reported Side Effects

Additional adverse effects with uncertain causation include 3:

• Mood changes and depression – association neither confirmed nor refuted
• Decreased libido or changes in sexual desire
• Migraine (contraindicated if migraines with aura) 1
• Contact lens intolerance – visual changes may occur 3
• Vaginal candidiasis 3
• Acne or hirsutism (though COCs often improve these conditions) 3
• Cholestatic jaundice 3

Management of Breakthrough Bleeding (Most Common Complaint)

For persistent breakthrough bleeding during continuous use:

1. First 3-6 months: Reassure patient this is expected and generally not harmful; continue regimen without interruption 1, 2

2. Rule out other causes: Evaluate for pregnancy, STIs, smoking, or new gynecological pathology 2

3. If bleeding persists and is unacceptable:

   • Advise a 3-4 day hormone-free interval (not during first 21 days of use, and not more than once per month) 1, 2
   • Consider switching to a COC with higher estrogen content (30-35 μg ethinyl estradiol) 2
   • If still unacceptable, counsel on alternative contraceptive methods 1, 2

Drug Interactions

Medications that decrease COC effectiveness include 1:

• Rifampin – significant interaction requiring alternative contraception 1, 3
• Anticonvulsants (phenytoin, carbamazepine, phenobarbital) 1, 3
• Some antiretroviral drugs (efavirenz, nevirapine, ritonavir-boosted protease inhibitors) 1

Important: Most broad-spectrum antibiotics do NOT affect COC effectiveness (rifampin is the exception) 1. Tetracyclines specifically do not reduce COC effectiveness 1.

COCs may affect other medications:

• Lamotrigine levels decrease significantly when co-administered with COCs, potentially reducing seizure control 3
• Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir are contraindicated due to risk of liver enzyme elevations 3

Contraindications (When COCs Should NOT Be Used)

Absolute contraindications include 1:

• Severe uncontrolled hypertension (≥160/100 mm Hg)
• Migraines with aura or focal neurologic symptoms
• Current or history of thromboembolism or thrombophilia
• Complicated valvular heart disease
• Ongoing hepatic dysfunction
• Complications of diabetes (nephropathy, retinopathy, neuropathy)
• Complicated solid organ transplantation

Note: Smoking is NOT a contraindication in women <35 years old, though it should be discouraged 1.

Follow-Up Recommendations

Schedule a routine follow-up visit 1-3 months after initiating continuous COCs to address adverse effects, adherence issues, and assess for mood changes or worsening depression 1, 5.