Prevention of Ovulation Achieved by Single Intra-vaginal Administration of Levogel as Compared to Oral LNG
Condition: Female Contraception
Study type: Interventional
Phase: Phase 1

Summary: 
      It has been proposed that levonorgestrel (LNG) in a vaginal gel could be used as an 'on
      demand' contraceptive when used before coitus. Levonorgestrel was selected as it is a
      component of many approved oral contraceptive pills and also it is the active agent in Plan
      B, an FDA-approved regimen for emergency contraception (EC). In previous studies it was
      demonstrated that an LNG vaginal gel was absorbed and was effective in preventing follicular
      rupture. The overall proportion of cycles with lack of follicular rupture within 5 days of
      LNG administration or with ovulatory dysfunction (follicle rupture preceded by an inadequate
      LH surge) was 96% for LNG gel and 39% in the inert gel cycles (control group).
    

Detailed description: 
      A dose of 0.75mg of LNG in a vaginal gel was shown to prevent ovulation in a higher
      percentage than what has been observed with oral LNG at the approved doses for EC of 1.5mg.
      Results from a study with a1.5 mg LNG oral dose or a single 0 ,75mg dose demonstrated that
      the proportion of cycles without follicle rupture or ovulatory dysfunction within 5 days was
      86% and 79% respectively (Croxatto et al, 2004) , whereas lack of follicular rupture or the
      presencr of ovulatory dsyfunction was 96% with administration of a LNG gel formulation. In
      the group of women with follicle size ≥18mm the gel induced 50% ovulation suppression while
      oral LNG in previous studies blocked only 16% of ovulation in the same follicle size group .
      These encouraging results could be explained by higher bioavailability of LNG when
      administered vaginally. This comparison was made using historical data from another study;
      therefore this study will compare vaginal administration of LNG to oral in a direct
      cross-over comparative study.

      LNG is known to affect the cervical mucus by making it hostile to sperm penetration and its
      effect may appear after only a few hours following oral administration (Kesseru, 1984;
      Brache, unpublished observations). Application of LNG gel in the vagina close to the cervical
      os may exert a direct effect on the cervical mucus. The potential local action of LNG on the
      cervical mucus may be another important mechanism by which protection is conferred to women
      who do not experience ovulation suppression.

      An "on demand" precoital contraceptive is an attractive alternative to the post-coital
      emergency contraception currently available, especially due to the higher efficacy of this
      route of administration on ovulation suppression as compared with oral tablets of LNG. Should
      the present study confirm the superiority of vaginal administration of half the dose of the
      oral dose of LNG approved for emergency contraception, further development of that
      formulation and method would be warranted.
    

Intervention name(s): Levonorgestrel (LNG) gel (Levogel) and oral LNG (Plan B)
Intervention type(s): Drug
Intervention description(s): This is a randomized study with a cross-over design comparing two single dose treatment sequences of either Levogel (LNG vaginal gel 0.750 mg/4g) or oral LNG (1.5mg).
All women with a leading follicle diameter of ≥18 mm will be randomized to treatment with a single intra-vaginal application of LNG gel or oral LNG. After a washout cycle, the women will be crossed over to receive the other treatment and the study procedures will be repeated.
Intervention MeSH terms: Levonorgestrel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: LNG gel; oral LNG; follicle rupture; intra-vaginal administration; growth of the leading follicle; preovulatory peak of serum luteinizing hormone; characteristics of the cervical mucus; serum levels of estradiol (E2) and progesterone (P)