Mestranol

Mestranol

Mestranol is a synthetic steroidal estrogen, recognized as the 3-methyl ether derivative of ethinylestradiol. Historically significant, mestranol was a key component in many of the inaugural oral contraceptive formulations.

Overview

Mestranol functions as a prodrug, which means it undergoes metabolic conversion in the body to produce the active form of estrogen, ethinylestradiol. This conversion occurs primarily in the liver and has an efficiency of approximately 70%. Pharmacokinetically, 50 µg of mestranol is roughly equivalent to 35 µg of ethinylestradiol in terms of biological activity.

Synthesis

Preparation of Mestranol

The synthesis of mestranol exemplifies the unique stereospecificity inherent in certain steroid reactions. The 17-keto steroids, when subjected to nucleophilic reactions, predominantly undergo reactions on the alpha face. This is because the beta face is largely shielded by the 18-methyl group, making it almost inaccessible to reactants. The result of this bias is the predominant formation of isomers resulting from alpha face attacks.

Historical Context

The inclusion of mestranol in the first generation of oral contraceptives marked a significant advancement in reproductive health. Its efficacy as an estrogen component helped establish the viability of hormonal contraceptives as a method for pregnancy prevention.

Pharmacology

Upon administration, mestranol undergoes demethylation in the liver to produce ethinylestradiol, the active estrogenic component. This metabolic pathway accounts for mestranol's role as a prodrug.

Clinical Implications

Given its bioequivalence to ethinylestradiol, mestranol's dosage in oral contraceptives was adjusted to ensure the desired therapeutic effects while minimizing potential side effects. Over time, as advancements in pharmaceuticals were made, newer forms of oral contraceptives replaced those containing mestranol, though its historical significance remains.

See Also

• Oral contraceptive pill
• Ethinylestradiol
• Prodrug
• Steroid synthesis
• Ethynylestradiol
• Estrofurate