Differences Between Norgestrel and Norgestimate in Androgenic Activity and Contraceptive Use
Norgestimate is a third-generation progestin with significantly lower androgenic activity compared to norgestrel (a second-generation progestin), making it superior for both contraception and acne treatment while maintaining similar contraceptive efficacy. 1
Androgenic Activity Differences
Norgestrel
- Second-generation progestin with higher androgenic activity 2, 1
- Can decrease high-density lipoprotein (HDL) cholesterol levels 3, 4
- May worsen lipid profiles by increasing low-density lipoprotein (LDL)/HDL ratio 3, 4
- More likely to cause androgenic side effects such as acne, hirsutism, and weight gain 1
Norgestimate
- Third-generation progestin with minimal androgenic activity 2, 1, 5
- Increases HDL cholesterol levels when combined with ethinyl estradiol 3, 4
- Improves LDL/HDL ratio, offering potential cardiovascular benefits 1, 4
- Has peripheral anti-androgenic properties through multiple mechanisms 5:
- Inhibition of androgen receptor nuclear translocation
- Higher 5α-reductase inhibition activity compared to other progestins
- Increases sex hormone-binding globulin (SHBG) levels when combined with estrogen
Contraceptive Use Comparison
Efficacy
- Both norgestrel and norgestimate are highly effective for contraception with typical use effectiveness around 91% 1
- Norgestimate is a prodrug that acts mainly through levonorgestrel 6
Formulations and Indications
- Norgestimate/ethinyl estradiol is FDA-approved for both contraception and acne treatment 2
- Norgestimate is available in combined oral contraceptives (COCs) with ethinyl estradiol 2, 1
- Norgestimate is also available in transdermal patch formulations (as norelgestromin, its active metabolite) 7
Clinical Benefits of Norgestimate
- Reduces both inflammatory and comedonal acne lesions 1
- Shows improvement in acne after approximately 3 months of treatment 1
- Has the lowest risk of venous thromboembolism among different COCs 5
- Better metabolic profile with minimal effects on carbohydrate metabolism 6, 4
Patient Selection Considerations
Preferred Use of Norgestimate
- Women requiring contraception who also have:
Preferred Use of Norgestrel
- No specific advantages over norgestimate identified in the literature
- May be considered when other options are unavailable or contraindicated
Contraindications (Apply to Both)
- Age ≥35 years with smoking history
- Hypertension
- History of deep vein thrombosis or pulmonary embolism
- Ischemic heart disease
- History of cerebrovascular accident
- Migraines with aura or focal neurologic symptoms
- Active viral hepatitis or severe liver disease 1
Monitoring Recommendations
- Blood pressure measurement before initiation
- Follow-up visits 1-3 months after starting to assess side effects and adherence 1
- Monitor for improvement in acne when used for this indication
In summary, while both progestins provide effective contraception, norgestimate offers significant advantages due to its lower androgenic profile, beneficial effects on lipid metabolism, and additional indication for acne treatment.