Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies

Fertil Steril. 2014 Jun;101(6):1656-62.e1-4. doi: 10.1016/j.fertnstert.2014.03.004. Epub 2014 Apr 14.

Abstract

Objective: To assess the pharmacokinetics and pharmacodynamics of levonorgestrel intrauterine system (LNG-IUS) 13.5 mg and LNG-IUS 19.5 mg (total content).

Design: Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III studies.

Setting: Randomized, open-label, multicenter studies.

Patient(s): Nulliparous and parous women.

Intervention(s): Levonorgestrel intrauterine system 13.5 mg, LNG-IUS 19.5 mg, or LNG-IUS 20 μg/24 h (total content 52 mg).

Main outcome measure(s): Pharmacokinetics of LNG, ovulation rate, cervical function, and endometrium effects.

Result(s): The in vivo LNG release rate of LNG-IUS 13.5 mg was approximately 14 μg/24 h after 24 days, declining progressively to 5 μg/24 h after 3 years. The average LNG serum concentration over 3 years of use was 74.3 ng/L, 114 ng/L, and 218 ng/L for LNG-IUS 13.5 mg, LNG-IUS 19.5 mg, and LNG-IUS 20 μg/24 h, respectively. All treatments showed very similar progestogenic effects on cervical mucus, with low and similar cervical scores throughout treatment. Ovulation was observed in the majority of women in all groups where assessment was possible, although there was a lower incidence of anovulation with LNG-IUS 13.5 mg and LNG-IUS 19.5 mg compared with LNG-IUS 20 μg/24 h. The progestogenic effect on the endometrium was marked in all three LNG-IUS groups.

Conclusion(s): Levonorgestrel intrauterine system 13.5 mg and LNG-IUS 19.5 mg result in alower systemic exposure to LNG, lower incidence of anovulation, and similar progestin impact on the endometrium and cervical function compared with LNG-IUS 20 μg/24 h.

Trial registration: ClinicalTrials.gov NCT00185380 NCT00528112.

Keywords: Low-dose levonorgestrel intrauterine system; pharmacodynamics; pharmacokinetics.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anovulation / chemically induced
  • Cervix Mucus / metabolism
  • Cervix Uteri / drug effects*
  • Cervix Uteri / metabolism
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / adverse effects
  • Contraceptive Agents, Female / blood
  • Contraceptive Agents, Female / pharmacokinetics*
  • Estradiol / blood
  • Female
  • Humans
  • Intrauterine Devices, Medicated
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / adverse effects
  • Levonorgestrel / blood
  • Levonorgestrel / pharmacokinetics*
  • Ovulation / drug effects*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Contraceptive Agents, Female
  • Estradiol
  • Levonorgestrel

Associated data

  • ClinicalTrials.gov/NCT00185380
  • ClinicalTrials.gov/NCT00528112