Mestranol

Mestranol is a synthetic estrogen that has been used in some combined oral contraceptives. It is a prodrug of ethinylestradiol, meaning that after oral administration it is metabolically demethylated in the liver to form ethinylestradiol, which provides the primary estrogenic activity.

Because mestranol must be converted to ethinylestradiol, the resulting estrogen exposure can be more variable, and in many formulations the nominal dosage was higher than that of ethinylestradiol-containing pills to achieve comparable activity. This contributed to a shift in clinical practice toward ethinylestradiol–based preparations, which offer more predictable pharmacokinetics. As a result, mestranol-containing products have become less common and are largely seen in older or regional formulations.

In clinical use, mestranol functions by the same general mechanism as other estrogens used in contraception: it binds to estrogen receptors, suppressing the hypothalamic-pituitary-ovarian axis and stabilizing the endometrium to prevent ovulation and implantation. Its effectiveness is similar to other estrogens when properly dosed, but individual conversion to ethinylestradiol can vary, leading to differences in response among users.

Safety considerations for mestranol are consistent with those for other estrogens used in contraception. Potential risks include thromboembolic events, hypertension, migraine, and gallbladder disease, with contraindications including a personal or familial history of thromboembolism, estrogen-dependent tumors, liver disease, and pregnancy. Interactions with hepatic enzyme inducers can reduce contraceptive effectiveness.