Effects of tampon co-usage on the pharmacokinetics of segesterone acetate and ethinyl estradiol released from Annovera vaginal ring system

Contraception. 2026 Feb:154:111274. doi: 10.1016/j.contraception.2025.111274. Epub 2025 Oct 20.

Abstract

Objectives: To evaluate effects of tampon co-usage on the pharmacokinetics of segesterone acetate (SA) and ethinyl estradiol (EE) released from Annovera Contraceptive Vaginal Ring System with a 21-day in/7-day out regimen.

Study design: We enrolled 24 participants in an open-label crossover study in Canada and the United States. Participants used combined oral contraceptive pills for 28 days before randomization (1:1) to either Annovera alone or Annovera while using four tampons daily on days 2-5 for one 28-day cycle; in the next cycle, participants switched treatments. We evaluated the steady-state interval for SA and EE from days 2-5 for concomitant Annovera and tampon use. We measured serum SA and EE using validated liquid chromatography-tandem mass spectrometry. The primary end point was the area under the curve (AUC) of SA and EE on cycle days 2-3 (AUC(2-3)). Bioequivalence is established if the 90% confidence interval (CI) of the geometric mean ratio (GMR) for AUC(2-3) is wholly contained within (0.80-1.25).

Results: We observed bioequivalence for SA with GMR of 0.98 (90% CI: 0.921, 1.043) and EE with GMR of 0.97 (90% CI: 0.91, 1.026), for AUC(2-3), and also for AUC from days 2-5 with GMRs of 1.02 (90% CI: 0.99, 1.06) for SA and 1.02 (90% CI: 0.97, 1.087) for EE. We observed no safety issues or serious adverse events.

Conclusions: Individuals using Annovera with 4 consecutive days of tampon use experienced no change in SA or EE absorption. Light/regular tampon co-usage for up to 4 consecutive days should not impact contraceptive efficacy or bleeding profile.

Implications: A significant proportion of reproductive-age women use tampons when experiencing vaginal bleeding; they can be reassured that tampon and contraceptive ring co-usage should not affect the contraceptive efficacy of the SA/EE contraceptive vaginal ring.

Keywords: Contraceptive; Ethinyl estradiol; Pharmacokinetics; Segesterone acetate; Tampon; Vaginal ring.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Canada
  • Contraceptive Agents, Female* / administration & dosage
  • Contraceptive Agents, Female* / blood
  • Contraceptive Agents, Female* / pharmacokinetics
  • Contraceptive Devices, Female*
  • Contraceptives, Oral, Combined / pharmacokinetics
  • Cross-Over Studies
  • Ethinyl Estradiol* / administration & dosage
  • Ethinyl Estradiol* / blood
  • Ethinyl Estradiol* / pharmacokinetics
  • Female
  • Humans
  • Menstrual Hygiene Products* / adverse effects
  • Therapeutic Equivalency
  • United States
  • Young Adult

Substances

  • Ethinyl Estradiol
  • Contraceptive Agents, Female
  • Contraceptives, Oral, Combined