Levonorgestrel Intrauterine System: A First-Line Medical Treatment for Heavy Menstrual Bleeding

Chronic heavy menstrual bleeding is a common gynecologic condition that causes significant health problems and negatively impacts a woman's quality of life. Surgical treatments should be reserved for women who have pelvic pathology and for those who fail medical therapy. The recent US FDA approval of the levonorgestrel-releasing intrauterine system as an indicated treatment for heavy menstrual bleeding in women who want to use intrauterine devices for birth control highlights the potential that this top tier contraceptive method offers as a first-line therapy for treatment of this problem in women of any reproductive age, without sacrificing their future fertility.

[1]  J. Guillebaud,et al.  Medical eligibility criteria for contraceptive use , 2018, Advanced Health Assessment of Women.

[2]  A. Lethaby,et al.  Surgery versus medical therapy for heavy menstrual bleeding. , 2016, The Cochrane database of systematic reviews.

[3]  P. Inki,et al.  Bleeding pattern and safety of consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS)--a multicentre prospective study. , 2010, Human reproduction.

[4]  M. Pillai,et al.  The levonorgestrel intrauterine system (Mirena) for the treatment of menstrual problems in adolescents with medical disorders, or physical or learning disabilities , 2010, BJOG : an international journal of obstetrics and gynaecology.

[5]  B. Yawn,et al.  Von Willebrand disease: key points from the 2008 National Heart, Lung, and Blood Institute guidelines. , 2009, Obstetrics and gynecology.

[6]  D. Mishell,et al.  Effects of the levonorgestrel intrauterine system (LNG-IUS) on cervical mucus quality and sperm penetration , 2009 .

[7]  L. Bahamondes,et al.  Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system. , 2009, Contraception.

[8]  P. Kamphuisen,et al.  Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. , 2009, American journal of obstetrics and gynecology.

[9]  P. Inki,et al.  Levonorgestrel-Releasing Intrauterine System and Endometrial Ablation in Heavy Menstrual Bleeding: A Systematic Review and Meta-Analysis , 2009, Obstetrics and gynecology.

[10]  J. Endrikat,et al.  A Canadian, multicentre study comparing the efficacy of a levonorgestrel-releasing intrauterine system to an oral contraceptive in women with idiopathic menorrhagia. , 2009, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[11]  P. T. Onundarson,et al.  Quantification of menstrual flow by weighing protective pads in women with normal, decreased or increased menstruation , 2009, Acta obstetricia et gynecologica Scandinavica.

[12]  L. Alfredsson,et al.  The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a case–control study using the General Practice Research Database , 2009, BJOG : an international journal of obstetrics and gynaecology.

[13]  J. Endrikat,et al.  Ovulation inhibition with four variations of a four-phasic estradiol valerate/dienogest combined oral contraceptive: results of two prospective, randomized, open-label studies. , 2008, Contraception.

[14]  Kihyun Park,et al.  Clinical effects of the levonorgestrel-releasing intrauterine device in patients with adenomyosis. , 2008, American journal of obstetrics and gynecology.

[15]  I. Cameron,et al.  Cyclical progestogens for heavy menstrual bleeding. , 2008, The Cochrane database of systematic reviews.

[16]  D. Mansour Modern management of abnormal uterine bleeding: the levonorgestrel intra-uterine system. , 2007, Best practice & research. Clinical obstetrics & gynaecology.

[17]  P. Darney,et al.  The levonorgestrel intrauterine system in nulliparous women. , 2007, Contraception.

[18]  S. Grénman,et al.  The effect of hysterectomy or levonorgestrel‐releasing intrauterine system on sexual functioning among women with menorrhagia: a 5‐year randomised controlled trial , 2007, BJOG : an international journal of obstetrics and gynaecology.

[19]  J. Aldrighi,et al.  Uterine volume and menstrual patterns in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas. , 2007, Contraception.

[20]  D. Archer Menstrual-cycle-related symptoms: a review of the rationale for continuous use of oral contraceptives. , 2006, Contraception.

[21]  J. Lo,et al.  Pregnancy after endometrial ablation: English literature review and case report. , 2006, Journal of minimally invasive gynecology.

[22]  R. Varma,et al.  Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS)--a systematic enquiry and overview. , 2006, European journal of obstetrics, gynecology, and reproductive biology.

[23]  S. Wyke,et al.  A Scottish postal survey suggested that the prevailing clinical preoccupation with heavy periods does not reflect the epidemiology of reported symptoms and problems. , 2005, Journal of clinical epidemiology.

[24]  P. Reid,et al.  Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts. , 2005, BJOG : an international journal of obstetrics and gynaecology.

[25]  P. Inki,et al.  The Levonorgestrel Intrauterine System: Long-Term Contraception and Therapeutic Effects , 2005, Women's health.

[26]  F. Lockhat,et al.  The efficacy, side-effects and continuation rates in women with symptomatic endometriosis undergoing treatment with an intra-uterine administered progestogen (levonorgestrel): a 3 year follow-up. , 2005, Human reproduction.

[27]  F. Mukri,et al.  Trends in number of hysterectomies performed in England for menorrhagia: examination of health episode statistics, 1989 to 2002-3 , 2005, BMJ : British Medical Journal.

[28]  A. Hare,et al.  Pregnancy following endometrial ablation: a review article , 2005, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.

[29]  D. Economides,et al.  The use of levonorgestrel‐releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding disorders , 2004, BJOG : an international journal of obstetrics and gynaecology.

[30]  I. Rauramo,et al.  Clinical performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women: a comparative study. , 2004, Contraception.

[31]  A. Stewart,et al.  Effect of hysterectomy vs medical treatment on health-related quality of life and sexual functioning: the medicine or surgery (Ms) randomized trial. , 2004, JAMA.

[32]  S. Grénman,et al.  Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up. , 2004, JAMA.

[33]  H. Maia,et al.  Insertion of mirena after endometrial resection in patients with adenomyosis. , 2003, The Journal of the American Association of Gynecologic Laparoscopists.

[34]  M. Blombäck,et al.  On the correlation between local fibrinolytic activity in menstrual fluid and total blood loss during menstruation and effects of desmopressin , 2003, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[35]  J. Cook,et al.  Pregnancy Following Endometrial Ablation: Case History and Literature Review , 2003, Obstetrical and Gynecological Survey.

[36]  M. Chen-Mok,et al.  Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas. , 2003, Fertility and sterility.

[37]  S. Manek,et al.  The effects of the levonorgestrel intrauterine system (Mirena coil) on endometrial morphology , 2003, Journal of clinical pathology.

[38]  B. Xiao,et al.  Therapeutic effects of the levonorgestrel-releasing intrauterine system in the treatment of idiopathic menorrhagia. , 2003, Fertility and sterility.

[39]  A. Di Spiezio Sardo,et al.  The effect of a levonorgestrel-releasing intrauterine device in the treatment of myoma-related menorrhagia. , 2003, Contraception.

[40]  E. Baldaszti,et al.  Acceptability of the long-term contraceptive levonorgestrel-releasing intrauterine system (Mirena): a 3-year follow-up study. , 2003, Contraception.

[41]  P. Jacobs,et al.  Work Loss Associated With Increased Menstrual Loss in the United States , 2002, Obstetrics and gynecology.

[42]  S. Bryan,et al.  Quality of life instruments in studies of menorrhagia: a systematic review. , 2002, European journal of obstetrics, gynecology, and reproductive biology.

[43]  L. Bahamondes,et al.  Therapeutic use of levonorgestrel-releasing intrauterine system in women with menorrhagia: a pilot study(1). , 2002, Contraception.

[44]  C. Steiner,et al.  Hysterectomy Rates in the United States 1990–1997 , 2002, Obstetrics and gynecology.

[45]  L. Bahamondes,et al.  Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years. , 2002, Contraception.

[46]  I. Fraser,et al.  Estimating Menstrual Blood Loss in Women With Normal and Excessive Menstrual Fluid Volume , 2001, Obstetrics and gynecology.

[47]  S. Lethagen,et al.  No Increased Risk of Venous Thrombosis in Women Taking Tranexamic Acid , 2001, Thrombosis and Haemostasis.

[48]  N. Day,et al.  Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study , 1999, BMJ.

[49]  J. Puolakka,et al.  Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy. , 1998, BMJ.

[50]  J. Suvisaari,et al.  Detailed analysis of menstrual bleeding patterns after postmenstrual and postabortal insertion of a copper IUD or a levonorgestrel-releasing intrauterine system. , 1996, Contraception.

[51]  J. Trussell,et al.  "The Risk of Pregnancy after Tubal Sterilization: Findings from the U.S. Collaborative Review of Sterilization." , 1996 .

[52]  J. Trussell,et al.  The risk of pregnancy after tubal sterilization: findings from the U.S. Collaborative Review of Sterilization. , 1996, American journal of obstetrics and gynecology.

[53]  C. Lindoff,et al.  Reduction of menstrual blood loss in women suffering from idiopathic menorrhagia with a novel antifibrinolytic drug (Kabi 2161) , 1995, British journal of obstetrics and gynaecology.

[54]  N. Black,et al.  Indications for and outcome of total abdominal hysterectomy for benign disease: a prospective cohort study , 1995, British journal of obstetrics and gynaecology.

[55]  G. Tang,et al.  Levonorgestrel intrauterine device in the treatment of menorrhagia in Chinese women: efficacy versus acceptability. , 1995, Contraception.

[56]  N. Gleeson Cyclic changes in endometrial tissue plasminogen activator and plasminogen activator inhibitor type 1 in women with normal menstruation and essential menorrhagia. , 1994, American journal of obstetrics and gynecology.

[57]  K McPherson,et al.  The epidemiology of hysterectomy: Findings in a large cohort study , 1992, British journal of obstetrics and gynaecology.

[58]  I. Milsom,et al.  A comparison of flurbiprofen, tranexamic acid, and a levonorgestrel-releasing intrauterine contraceptive device in the treatment of idiopathic menorrhagia. , 1991, American journal of obstetrics and gynecology.

[59]  M. Rees Role of menstrual blood loss measurements in management of complaints of excessive menstrual bleeding , 1991, British journal of obstetrics and gynaecology.

[60]  I. Fraser,et al.  Randomized Trial of 2 Hormonal and 2 Prostaglandin‐inhibiting Agents in Women with a Complaint of Menorrhagia , 1991, The Australian & New Zealand journal of obstetrics & gynaecology.

[61]  D. Mishell,et al.  Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T 380Ag intrauterine devices: a five-year randomized study. , 1990, Contraception.

[62]  J. Higham,et al.  Assessment of menstrual blood loss using a pictorial chart , 1990, British journal of obstetrics and gynaecology.

[63]  G. Rybo,et al.  Levonorgestrel‐releasing intrauterine device in the treatment of menorrhagia , 1990, British journal of obstetrics and gynaecology.

[64]  R. Garry,et al.  Management of menorrhagia. , 1990, BMJ.

[65]  I. Cameron,et al.  The effects of danazol mefanamic acid, norethistherone and a progesterone-impragnated coil on endometrial prostaglandin concentrations in women with monorrhagia , 1987 .

[66]  J. Bonnar,et al.  The fibrinolytic enzyme system in normal menstruation and excessive uterine bleeding and the effect of tranexamic acid. , 1987, European journal of obstetrics, gynecology, and reproductive biology.

[67]  O. Ylikorkala,et al.  Primary and myoma‐associated menorrhagia: role of prostaglandins and effects of ibuprofen , 1986, British Journal of Obstetrics and Gynaecology.

[68]  T. Luukkainen,et al.  TISSUE CONCENTRATIONS OF LEVONORGESTREL IN WOMEN USING A LEVONORGESTREL‐RELEASING IUD , 1982, Clinical endocrinology.

[69]  D. Baird,et al.  PROSTAGLANDIN SYNTHESIS IN THE ENDOMETRIUM OF WOMEN WITH OVULAR DYSFUNCTIONAL UTERINE BLEEDING , 1981, British journal of obstetrics and gynaecology.

[70]  A. Turnbull,et al.  RELATION BETWEEN MEASURED MENSTRUAL BLOOD LOSS AND PATIENT'S SUBJECTIVE ASSESSMENT OF LOSS, DURATION OF BLEEDING, NUMBER OF SANITARY TOWELS USED, UTERINE WEIGHT AND ENDOMETRIAL SURFACE AREA , 1980, British journal of obstetrics and gynaecology.

[71]  I. Fraser,et al.  A benefit-risk review of systemic haemostatic agents: part 2: in excessive or heavy menstrual bleeding. , 2008 .

[72]  T. Backman Benefit-Risk Assessment of the Levonorgestrel Intrauterine System in Contraception , 2004, Drug safety.

[73]  I. Sivin Risks and Benefits, Advantages and Disadvantages of Levonorgestrel-Releasing Contraceptive Implants , 2003, Drug safety.

[74]  I. Cameron The levonorgestrel intrauterine system: the benefits of reduced bleeding. , 2001, The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception.

[75]  A. Lethaby,et al.  Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding. , 2000, The Cochrane database of systematic reviews.

[76]  C. Farquhar,et al.  Antifibrinolytics for heavy menstrual bleeding. , 2000, The Cochrane database of systematic reviews.

[77]  V. Odlind,et al.  Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: a randomized comparative trial. , 1994, Contraception.

[78]  J. Toivonen The levonorgestrel-releasing intrauterine device. , 1994, Advances in contraceptive delivery systems : CDS.

[79]  I. Cameron,et al.  The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia. , 1987, Prostaglandins.

[80]  I. Fraser,et al.  Long-term treatment of menorrhagia with mefenamic acid. , 1983, Obstetrics and Gynecology.

[81]  S. G. Clayton,et al.  Studies in the involvement of prostaglandins in uterine symptomatology and pathology. , 1976, British journal of obstetrics and gynaecology.