Bleeding patterns for the Liletta^® levonorgestrel 52 mg intrauterine system

Abstract

Purpose: Evaluate bleeding patterns for the Liletta V R levonorgestrel 52 mg intrauterine system (IUS) using the World Health Organization Belsey definitions. Material and methods: This prospective multicenter trial evaluates the efficacy and safety of Liletta V R (Clinicaltrials.gov NCT00995150). We evaluated bleeding patterns for 1700 nulliparous and multiparous women using a daily diary completed by participants for the first 2 years and by questionnaire every 3 months thereafter. We assessed amenorrhea rates over 3 years and the proportion of subjects with infrequent, frequent, prolonged and irregular bleeding per 90-day reference period over 2 years for the entire study population as well as comparing nulliparous and parous women and obese and non-obese women. Results: Amenorrhea rates at 1 and 3 years in levonorgestrel 52 mg IUS users were 19 and 37%, respectively. The infrequent bleeding rate increased from 14% in the first 90 days to 30% at the end of Year 1, and was maintained at the same rate through Year 2. Frequent, prolonged and irregular bleeding declined to low levels by the end of the first year. Discontinuation for bleedingrelated complaints occurred in 35 (2.1%, 95% CI 1.3-2.7%) women during the first 36 months; only one subject discontinued for amenorrhea (in Year 2). Outcomes did not vary for nulliparous versus parous or obese versus non-obese women. Conclusions: Among Liletta users, amenorrhea and infrequent bleeding become more prevalent over time and amenorrhea rates continue to increase after the first year of use. Bleeding patterns do not differ significantly by parity or by obesity-status. Discontinuation for bleeding concerns is uncommon with this product. ARTICLE HISTORY

Bleeding patterns with the 19.5 mg LNG-IUS, with special focus on the first year of use: implications for counselling

“…This retrospective analysis of early bleeding pattern data builds on the knowledge provided by previously published data from the phase II and III trials of the 19.5 mg LNG-IUS [4,5,7] and shows that women generally experience progressively lighter (i.e., more spotting and less bleeding) and shorter bleeding episodes with use of the 19.5 mg LNG-IUS in months 1 and 3. Reported discontinuation rates due to bleeding (4.5% at 3 years and 5.2% at 5 years) reflect those observed in other studies [5,21].…”

Comparing bleeding patterns for the levonorgestrel 52 mg, 19.5 mg, and 13.5 mg intrauterine systems

“…Women in these studies also had different rates of nulliparity and mean BMI; the levonorgestrel 52 mg IUS study included more nulliparous and obese women [12]. Although variations in characteristics of the study populations could account for some bleeding pattern differences, analyses of the levonorgestrel 52 mg IUS data shows no difference in bleeding patterns based on parity or BMI [8]. Thus, the likelihood that these differences are impacting the outcomes is low.…”

“…The levonorgestrel 19.5 mg and 13.5 mg products had available diary data through 3 years [12]. We limited the comparisons of prolonged, frequent, infrequent and irregular bleeding to two years because the levonorgestrel 52 mg IUS studies only used daily diaries for the first two years after which investigators obtained bleeding information by interview [8]. The LNG 52 mg IUS data uses the interview information to provide amenorrhea rates at 3 years which allowed an amenorrhea comparison after two years.…”

“…We assessed bleeding patterns using the WHO Belsey criteria (Table 1) over 90-day intervals (reference periods) [1] through 3 years for amenorrhea and two years for other bleeding descriptors for the three marketed levonorgestrel IUS dose products. We compared the patterns using published or publicly available data for the levonorgestrel 52 mg, [8] 19.5 mg [4,9] and 13.5 mg [7,10] IUS products. Although two levonorgestrel 52 mg IUS products are FDA approved in the United States, published data using the WHO Belsey criteria are available for only one (Liletta®, Medicines360, San Francisco, CA and Allergan, Irvine, CA).…”

Levonorgestrel-Releasing Intrauterine System as a Contraceptive Method in Nulliparous Women: A Systematic Review

“…Nevertheless, bleeding pattern seems to be a crucial aspect of contraception for women, since Marions et al reported that the level of satisfaction was dependent on the frequency and volume of bleeding and dysmenorrhea [39]. Several authors obtained similar amenorrhea rates in nulliparous LNG-IUS users-from 18% to 26% at the end of the first year of use, and even up to 36% at the end of the third year in the study by Schreiber et al [33,[35][36][37]39,40,44,45]. Moreover, the latter found that: infrequent bleeding rate increased from 12% to 30%, frequent bleeding rate decreased from 29% to 4%, prolonged bleeding rate decreased from 50% to 2% and irregular bleeding rate decreased from 39% to 4% during the last 90 days of the second year, in comparison to the first 90 days of usage.…”