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The extent to which intrauterine contraceptives act by altering uterine responsiveness to estrogen was examined in ovariectomized rats bearing unilateral IUDs. IUDs caused large increases in weight and glycogen concentration of the treated horns. Exogenous estradiol-17β (0.2 µg) also elevated these parameters and in addition caused increases in water, histamine concentration, and trypan blue permeability. The combination of IUD and estradiol-17β interacted to lessen both the uterine water imbibition and the trypan blue permeability caused by the estrogen alone. The total amount of glygocen was augmented by interaction of the two effects. The results indicate that the uterine growth effects of IUDs are similar to, but independent of, the exogenous estrogen action. Evidence to support the contention that the contraceptive action of IUDs is by reduced responsiveness of the uterus to estrogen was found for two of the five criteria measured.
Wrenn et al. (1969) studied this question.