Post-use ring weight, residual drug content and drug depletion zone thickness as objective measures of user adherence to a contraceptive progesterone vaginal ring

Objectives:
A major challenge in the development of drug-releasing vaginal rings is the accurate and reliable measurement of adherence in clinical trials. In efforts to move away from reliance on self-reported measures of adherence, there is considerable interest in the development and testing of more objective quantitative measures. Here, we assessed post-use ring weight, residual drug content and drug depletion zone thickness as potential cumulative measures of adherence to a progesterone-releasing ring.

Study design:
Progesterone-releasing rings (n=115) used by women across three sites in Africa were assessed for ring weight, residual progesterone content (via solvent extraction and HPLC-UV analysis), and drug depletion zone thickness (using digital microscopy) as potential measures of user adherence.

Results:
Unused control rings (n=6) had mean progesterone content of 2058 ± 21 mg (99.2 ± 1.0 %; relative to 2074 mg nominal loading) and ring weight of 9.372 ± 0.016 g. Mean residual progesterone content and post-use ring weight for clinical rings were 1245 ± 245 mg and 8.6 ± 0.2 g, respectively. Wide variations in residual progesterone content (range 45.0–100% of controls) and ring weight (range 87.9–100.3%) of used rings were attributed to differences in extent of ring use. Linear correlations were observed between residual progesterone content and post-use ring weight (r2=0.8244), and thickness of the drug depletion zone with post-use ring weight (r2=0.9757) and residual drug content (r2=0.9743).

Conclusions:
Post-use ring weight, residual progesterone content and depletion zone thickness are potentially useful as objective cumulative measures of adherence to a progesterone-releasing vaginal ring.