Re-evaluation of oral contraceptive classifications

Area of Science:

• Pharmacology
• Endocrinology
• Drug Development

Background:

• Traditional classification of combination oral contraceptives (OCs) by "generation" is based on introduction time.
• This generational approach is problematic due to varying component doses and interactions.
• It also overlooks unique characteristics of individual progestins within a generation.

Purpose of the Study:

• To clarify issues in OC classification by examining dosage changes and progestin pharmacologic profiles.
• To differentiate the unique characteristics of specific progestins like norgestimate, desogestrel, and gestodene.
• To evaluate the utility of generational classification versus individual progestin properties.

Main Methods:

• Analysis of combination OC evolution, focusing on dosage adjustments.
• Differentiation of individual progestin pharmacologic profiles.
• In vitro assays measuring progestin and androgen receptor binding affinity.
• In vivo measurements of progestin interactions with sex hormone-binding globulin (SHBG).

Main Results:

• Minor structural modifications in steroids cause significant biochemical activity changes.
• In vitro assays indicate a more favorable androgen/progestin (A/P) binding ratio for norgestimate compared to levonorgestrel, gestodene, and desogestrel.
• In vivo SHBG interaction data support the inadequacy of generational OC classification.
• Progestins exhibit distinct clinical properties, including differential effects on lipoprotein metabolism.

Conclusions:

• Generational classification of oral contraceptive progestins is misleading.
• Individual progestins possess unique biochemical and clinical properties.
• Understanding these individual profiles is crucial for clarifying OC formulation effects and potential side effects.