What is the difference between norgesterel and norgestimate in clinical practice?

Differences Between Norgestrel and Norgestimate in Clinical Practice

Norgestimate is preferred over norgestrel due to its lower androgenic activity, more favorable lipid profile, and better side effect profile, making it a superior choice for contraception and acne treatment.

Classification and Pharmacological Properties

• Generation classification:

  • Norgestrel: Second-generation progestin (more androgenic)
  • Norgestimate: Third-generation progestin (less androgenic) 1

• Androgenic activity:

  • Norgestrel has higher androgenic activity
  • Norgestimate demonstrates minimal androgenic activity 2, 3
  • Norgestimate is a prodrug that undergoes metabolism to levonorgestrel (approximately 22% of dose) and other metabolites 4

Clinical Effects and Benefits

Lipid Profile Effects

• Norgestimate combined with ethinyl estradiol:

  • Significantly increases HDL cholesterol
  • Causes moderate increases in LDL cholesterol
  • Improves LDL/HDL ratio 2, 3

• Norgestrel combined with ethinyl estradiol:

  • Significantly decreases HDL cholesterol
  • Causes pronounced increases in LDL cholesterol
  • Results in potentially adverse changes to LDL/HDL ratio 2, 3

Sex Hormone Binding Globulin (SHBG) Effects

• Norgestimate increases SHBG levels, which:
  • Binds androgens
  • Reduces bioactive (unbound) androgen levels
  • Decreases potential for androgenic side effects 2

FDA Approvals and Clinical Applications

Acne Treatment

• Ethinyl estradiol/norgestimate is FDA-approved for acne treatment in women who desire contraception 1
• Norgestimate-containing COCs reduce both inflammatory and comedonal acne lesions 1
• Improvement typically becomes noticeable after 3 months of treatment 5

Contraception

• Both are effective for contraception with typical use effectiveness around 91% 5
• Norgestimate-containing COCs demonstrate better compliance, particularly in younger women 6

Side Effect Profiles

Cardiovascular Risk

• All COCs increase risk of venous thromboembolism (VTE) compared to non-users
• Baseline VTE risk in non-pregnant, non-COC users: 1-5 per 10,000 woman-years
• COC users: 3-9 per 10,000 woman-years 1
• Less androgenic progestins like norgestimate have less impact on ethinyl estradiol-induced changes in lipid metabolism, potentially offering cardiovascular benefits 7

Androgenic Side Effects

• Norgestimate has significantly fewer androgenic side effects (acne, hirsutism, weight gain) compared to norgestrel 2, 3
• Norgestimate is preferable for patients with hyperandrogenemia 7

Clinical Decision-Making Algorithm

1. For women requiring contraception with history of acne or PCOS:

   • Choose norgestimate-containing COCs (preferred)
   • Avoid norgestrel-containing COCs

2. For women with lipid disorders or cardiovascular risk factors:

   • Choose norgestimate-containing COCs (preferred)
   • Avoid norgestrel-containing COCs

3. For women with androgenic symptoms (acne, hirsutism, etc.):

   • Choose norgestimate-containing COCs (preferred)
   • Consider drospirenone-containing COCs as an alternative (has antiandrogenic properties)
   • Avoid norgestrel-containing COCs

Important Considerations and Contraindications

• Contraindications for both progestins:

  • Age ≥35 years and smoking
  • Hypertension (systolic ≥160 mm Hg; diastolic ≥100 mm Hg)
  • 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
  • Severe liver disease 1

• Monitoring:

  • Blood pressure measurement before initiation
  • Follow-up visits 1-3 months after initiation to assess side effects and adherence 5

In summary, norgestimate offers significant advantages over norgestrel in clinical practice due to its lower androgenic activity, more favorable effects on lipid metabolism, and reduced androgenic side effects, making it a superior choice for most women requiring hormonal contraception, especially those with concerns about acne, lipid disorders, or androgenic symptoms.