Is desogestrel safe?

Is Desogestrel Safe?

Desogestrel is generally safe and effective for contraception in healthy women, but carries an approximately doubled risk of venous thromboembolism (VTE) compared to second-generation progestins, and should be avoided in women with specific contraindications including current/history of VTE, breast cancer, or liver disease. 1, 2

Safety Profile Overview

Desogestrel is a third-generation progestin with established contraceptive efficacy and generally good tolerability 2, 3. The FDA-approved formulations containing desogestrel have been extensively studied, with the most widely used combination being 150 mcg desogestrel with 30 mcg ethinyl estradiol 3.

Key Safety Considerations

Cardiovascular Risk:

• The most significant safety concern is VTE risk, which is approximately doubled compared to second-generation progestins (levonorgestrel, norgestrel) 2
• The absolute VTE risk remains relatively low in reproductive-aged women without additional risk factors 4
• Arterial thrombosis risk (myocardial infarction, stroke) increases particularly in women over 35 who smoke or have hypertension, diabetes, or migraines 4, 1

Absolute Contraindications (Category 4 - Unacceptable Health Risk):

• Current or history of deep venous thrombosis/pulmonary embolism 4, 1
• Current or history of breast cancer 1
• Active liver disease or hepatic tumors 1
• Undiagnosed abnormal uterine bleeding 1
• Known or suspected pregnancy 1

Hepatic Concerns:

• Desogestrel-containing combined oral contraceptives are contraindicated with hepatitis C treatment regimens containing ombitasvir/paritaprevir/ritonavir due to significant ALT elevations (>5 times upper limit of normal) 1
• Must discontinue before starting such HCV therapy and can restart approximately 2 weeks after completion 1

Clinical Tolerability

Common Side Effects:

• Irregular bleeding patterns (most common reason for discontinuation) 1
• Headache, emotional lability, weight changes, acne 1
• Nausea, breast tenderness 1

Metabolic Effects:

• Generally favorable lipid profile: increases HDL cholesterol, minimal effect on LDL cholesterol 3
• Minimal impact on glucose tolerance or insulin resistance 3
• Little to no adverse effect on blood pressure in most women 3

Special Populations

Breastfeeding:

• Category 3 (risks usually outweigh benefits) if <1 month postpartum 4
• Category 2 (advantages generally outweigh risks) if 1-6 months postpartum 4
• Small amounts pass into breast milk and may decrease milk quantity and quality 1

HIV-Positive Women:

• No restriction for use (Category 1) in women at high risk for HIV or with HIV infection 4
• Potential drug interactions with antiretroviral therapy require monitoring 4

Adolescents:

• Safe and effective for postpubertal adolescents 4, 1
• Same safety profile expected as in adult women 1

Drug Interactions

Reduced Efficacy With:

• Rifampin or rifabutin (significant interaction) 4, 1
• Anticonvulsants (phenytoin, carbamazepine, barbiturates) 1
• Some antibiotics (though evidence is mixed for most) 1

Important Interaction:

• Combined hormonal contraceptives significantly decrease lamotrigine levels, potentially reducing seizure control 1

Cancer Risk

Breast Cancer:

• No consistent association between ever-use of combined oral contraceptives and breast cancer risk overall 1
• Some studies show small increased risk among current or very recent users (<6 months since last use) 1
• Contraindicated in women with current or history of breast cancer 1

Cervical Cancer:

• Possible association with cervical intraepithelial neoplasia, though confounded by sexual behavior and HPV exposure 1

Hepatic Tumors:

• Rare association with benign hepatic adenomas, risk increases after 4+ years of use 1

Clinical Bottom Line

Desogestrel is safe for most healthy, non-smoking women of reproductive age when properly screened for contraindications 2, 3, 5. The primary safety concern is the elevated VTE risk compared to second-generation progestins, making levonorgestrel-containing formulations potentially safer first-line choices for women with any VTE risk factors 4, 2. However, desogestrel's low androgenic activity may make it particularly appropriate for women with androgen-sensitive conditions like acne or hirsutism 3, 5.