title: 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.
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).
  
  
  METHODS
  Pooled pharmacokinetic and pharmacodynamic analyses of phase II and III studies.
  
  
  METHODS
  Randomized, open-label, multicenter studies.
  
  
  METHODS
  Nulliparous and parous women.
  
  
  METHODS
  Levonorgestrel intrauterine system 13.5 mg, LNG-IUS 19.5 mg, or LNG-IUS 20 μg/24 h (total content 52 mg).
  
  
  METHODS
  Pharmacokinetics of LNG, ovulation rate, cervical function, and endometrium effects.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sexual Health Clinic, Väestöliitto (Family Federation of Finland), Helsinki, Finland. Electronic address: dan.apter@vaestoliitto.fi.
authors.forename: Dan
authors.initials: D
authors.lastname: Apter
authors.affiliation: Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Gemzell-Danielsson
authors.affiliation: Department of Obstetrics and Gynecology, Foothills Hospital, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hauck
authors.affiliation: Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Rosen
authors.affiliation: Clinical Pharmacology Oncology, Bayer Pharma AG, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zurth
mesh_terms: D000858:Anovulation / Q000139:chemically induced; D002582:Cervix Mucus / Q000378:metabolism; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010060:Ovulation / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D003271:Contraceptive Agents, Female; D004958:Estradiol; D016912:Levonorgestrel
keywords: Low-dose levonorgestrel intrauterine system; pharmacodynamics; pharmacokinetics