Zinc as a non-hormonal contraceptive: a better alternative to the copper intrauterine device (IUD)

Long-acting and reversible contraceptives (LARC) are the most widely used form of female contraception worldwide, however they have significant side-effects that often result in early removal. Most LARCs are hormonal, but the use of exogenous hormones is not suitable for all women and causes side-effects in many others. The copper IUD (CuIUD) is the only non-hormonal LARC, but a large proportion of users suffer severe side effects. This study proposes the use of zinc as a suitable alternative to the CuIUD. A rat intrauterine device (IUD) model was established to test the efficacy of a zinc IUD (ZnIUD) against a CuIUD, and a control nylon IUD. The IUD was surgically implanted into one uterine horn while the other remained untreated. Both the ZnIUD and CuIUD resulted in significantly fewer implantation sites compared to untreated horns. There was no significant difference between treated and untreated horns in the control nylon IUD group. Histological assessment revealed damage and inflammation in the endometrium of CuIUD treated horns, but only minor epithelial damage in ZnIUD treated horns, closely resembling the normal appearance of the control horns. This suggests ZnIUDs may not share the side-effect profile of the CuIUD. To test the long-term efficacy of the ZnIUD, rats had a ZnIUD surgically implanted into both horns and cohoused with males for 3 months. These rats mated regularly but did not get pregnant, confirming the long-term effectiveness of the ZnIUD. Reversibility of the ZnIUD was also established, as removal of the ZnIUD after 3 months resulted in no significant difference in the number of implantation sites between treated and untreated horns. This study demonstrated the contraceptive efficacy of zinc and its potential as a LARC. The ZnIUD had minimal histological impact on the endometrium compared to the current copper standard, indicating that IUDs containing zinc may offer highly effective contraception while causing fewer side effects. ### Competing Interest Statement The authors have declared no competing interest.