Femilis® 60 Levonorgestrel-Releasing Intrauterine System–-A Review of 10 Years of Clinical Experience

Abstract

OBJECTIVEThe aim of this study was to update the clinical experience with the Femilis® 60 levonorgestrel-releasing intrauterine system (LNG-IUS), now up to 10 years in parous and nulliparous women, particularly with regard to ease and safety of insertion, contraceptive performance, retention, acceptability, continuation of use, impact on menstrual blood loss (MBL), and duration of action.STUDY DESIGNUsing the Femilis® 60 LNG-IUS releasing 20 µg of levonorgestrel/day, the following studies were conducted: an open, prospective noncomparative contraceptive study, an MBL study, a perimenopausal study, a study for the treatment of endometrial hyperplasia, and early cancer of the uterus, a residue study.RESULTSA total of 599 Femilis LNG-IUS were inserted in various clinical trials, the majority for contraceptive purposes. The total exposure in the first and second contraceptive studies, covering 558 parous and nulliparous women, was 32,717 woman-months. Femilis has high contraceptive effectiveness as only one pregnancy occurred. Expulsion of the LNG-IUS was rare with only two total and no partial expulsions (stem protruding through the cervical canal) occurred. Femilis was well tolerated, with continuation rates remaining high. Several MBL studies were conducted, totaling 80 heavy and normal menstrual bleeders, using the pictorial bleeding assessment chart method or the quantitative alkaline hematin technique. Virtually all women responded well with strongly reduced menstrual bleeding. Amenorrhea rates were high, up to 80% after three months, and ferritin levels simultaneously increased significantly. The Femilis LNG-IUS was tested in 104 symptomatic perimenopausal women for seamless transition to and through menopause, adding estrogen therapy when required. Patient tolerability appeared high as >80% requested a second and a third LNG-IUS. Twenty women presenting with nonatypical and atypical hyperplasia and one woman presenting with early endometrial carcinoma were treated with Femilis LNG-IUS. All histology specimens showed full regression, and patients remained in remission without signs of hyperplasia or cancer at yearly and ongoing follow-up examinations up to 10 years. Residual content of LNG was measured in 37 women having the Femilis LNG-IUS for up to 10 years. In 10 of the 102 women who had the Femilis 60 in situ for 10 years between 20% and 30% of the original 60 mg was recovered confirming the long duration of action of the Femilis 60 LNG-IUS.CONCLUSIONThese studies suggest that the Femilis 60 LNG-IUS releasing 20 µg of LNG/day is an effective, well-tolerated, and well-retained contraceptive both in parous and in nulliparous women. The design of the LNG-IUS, with flexible transverse arm(s) length of 28 mm, allows for a simplification of the insertion technique and training requirements facilitating the use by nonspecialist providers in either developed or developing countries. For nulliparous women, additional evaluation of devices with a 24 mm transverse arm(s), as it relates to tolerability, retention, and...

Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management

“…A case series of 5 patients treated with medroxyprogesterone acetate (MPA) 500 mg daily concurrently with the 52 mg-IUD/10–20 mcg-LNG-14t showed 80% (4 out of 5 patients) complete remission without recurrence in 10.2 months mean surveillance period [ 7 ]. A single case of early stage EC treated with the 60 mg-IUD/14 mcg-LNG or 60 mcg-HD-frameless-IUD/20 mcg-LNG has been reported with sustained complete remission at an average of 32-months [ 16 ]. In one case series at 1-year post insertion, the discontinued 38 mg progesterone releasing IUD achieved complete regression of Stage IA, Grade 1 EC in six of eight (75%) women [ 7 , 12 ].…”

“…The 52 mg levonorgestrel (LNG) intrauterine device (IUD), which delivers 10 mcg to 20 mcg LNG daily for 5 years (52 mg-IUD/10–20 mcg-LNG-14t), the 60 mg LNG IUD, which delivers 14 mcg LNG daily for 5 years (60 mg-IUD/14 mcg-LNG), the 60 mg low-dose frameless LNG intrauterine system, which delivers 14 mcg daily for 3-years (60 mg-LD-frameless-IUD/14 mcg-LNG), and the 60 mcg high-dose frameless LNG intrauterine system, which delivers 20 mcg LNG daily (60 mg-HD-frameless-IUD/20 mcg-LNG), have the obvious advantage of long term patient adherence and proximity to the needed site of action [ 14 , 15 , 16 ]. In contrast to the 60 mg-IUD/14 mcg-LNG with a diffusion rate controlling ethylene vinyl acetate membrane [ 16 ], the 52 mg-IUD/10–20 mcg LNG-14t uses polydimethysiloxane in the drug reservoir, which may account for the difference in daily delivered dose. Selective progesterone receptor modulators (SPRMs) such as ulipristal acetate produce a distinct set of endometrial changes and have not been specifically trialed for EH treatment.…”

Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause

“…Likewise, use of a progestin-containing intra-uterine device (PIUD) as the progestin component of an HRT regimen in young women with POI is not recommended given that PIUD-induced endometrial suppression has not been studied in this population, but only in older postmenopausal women with intact uteri who require a progestin along with low, postmenopausal doses of estradiol (87). Furthermore, the PIUD would prevent pregnancy and lead to cessation of regular menses, undesirable effects for many young women with POI who wish for their HRT regimen to help ‘normalize’ their reproductive lives (88). …”

Pharmaceutical-technological aspects of therapeutic systems for hormonal contraception

“…Budući da FibroPlant ® IUS nema nosač, za razliku od ostalih IUS, prilagođava se šupljini uterusa nezavisno od njenih dimenzija i oblika. Ipak, postavljanje je kompleksnije i zahteva dodatnu obuku zdravstvenog osoblja [82].…”

“…Dolazi i do povećanja gustine cervikalnog mukusa i smanjenja mobilnosti spermatozoida kroz cervikalni kanal i oplodnju. Mada je koncentracija levonorgestrela u kavumu uterusa 1000 puta veća posle primene IUS u odnosu na levonorgestrelski implant, hormon se samo u manjem procentu resorbuje, tako da je inhibicija ovulacije postignuta samo kod oko 20% žena [82][83][84], a izbegavaju se sistemski neželjeni efekti. Intrauterina primena levonorgestrela obezbeđuje nepromenjenu efikasnost kontracepcije tokom upotrebe lekova koji indukuju enzime jetre.…”