Estrogen dose-response relationship [letter]

This letter criticizes a report on the increased relative risk of developing gall bladder disease with increasing dose exposure to the estrogens in oral contraceptives. The chief objection is the assumption that the risk is said to apply to mere dose of estrogen without acknowledging that 2 different estrogens of different potency on various target organs were ingested since 1980. From 1980 to 1980 pills with over 50 mg estrogen contained mestranol while later pills of lower dose contained ethinyl estradiol (EE). Furthermore the effect of estrogens is modified by the type and dose of the progestin used in the combination. Five different progestins were used during the period: norethindrone (with mestranol or EE) northynodrel (with mestranol) ethynodiol diacetate (with either estrogen) and norethindrone acetate and norgestrel (with EE). Norethindrone and norgestrel as such while the others are metabolized to various degrees to norethindrone. Thus the dose-response relationship between estrogen and gall bladder disease cannot be supported by the data presented.