Mestranol

Mestranol is a synthetic estrogen used primarily in combination with a progestin as an oral contraceptive. It is an estrogen pro-drug, meaning it is converted into ethinylestradiol within the body.

Chemical Properties: Mestranol is a 3-methyl ether of ethinylestradiol. Its chemical formula is C₂₁H₂₆O₃ and its molecular weight is 326.43 g/mol. It is a white to off-white crystalline powder, practically insoluble in water, but soluble in ethanol and other organic solvents.

Mechanism of Action: Mestranol itself has little estrogenic activity. After oral administration, it is rapidly demethylated in the liver to ethinylestradiol, which is a potent estrogen. Ethinylestradiol then binds to estrogen receptors in various tissues, including the uterus, breast, and brain. This binding triggers a cascade of events that ultimately lead to the effects of estrogen, such as thickening the uterine lining, promoting breast development, and regulating the menstrual cycle. In combination oral contraceptives, the estrogen component (ethinylestradiol from mestranol conversion) primarily works to suppress follicle-stimulating hormone (FSH) release, preventing ovulation.

Medical Uses: Mestranol's primary use is in combination oral contraceptives. In these formulations, it is combined with a progestin to prevent pregnancy. While it was a common estrogen component in earlier oral contraceptives, it has largely been replaced by lower doses of ethinylestradiol due to concerns about its higher estrogenic potency and potential for adverse effects.

Side Effects and Precautions: The side effects associated with mestranol are similar to those of other estrogens, including ethinylestradiol. Common side effects may include nausea, vomiting, breast tenderness, headache, changes in weight, and mood changes. More serious side effects can include an increased risk of blood clots (thromboembolism), stroke, and heart attack, particularly in women over 35 who smoke. It is contraindicated in women with a history of these conditions, as well as those with certain cancers, liver disease, or unexplained vaginal bleeding.

History: Mestranol was one of the first synthetic estrogens to be used in oral contraceptives. It was introduced in the 1960s and was initially used in relatively high doses. Over time, the dosage of mestranol and subsequently ethinylestradiol in oral contraceptives has been reduced to minimize the risk of side effects.