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Added health benefits of the levonorgestrel contraceptive intrauterine system and other hormonal contraceptive delivery systems

  • Ian S. Fraser
    Correspondence
    Tel.: +61 2 9351 2478; fax: +61 2 9351 4560.
    Affiliations
    Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Camperdown, NSW 2006, Australia
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      Abstract

      Background

      It has been recognized for well over half a century that hormonal preparations designed as contraceptives are also capable of offering health benefits through the treatment and prevention of benign gynecological disease and even some systemic conditions. Increasing attention is now being paid to the extent and detail of such added health benefits, and it is becoming clear that the long-acting, low-dose, hormonal contraceptive delivery systems may offer particular advantages in this regard.

      Methods

      Conventional databases were thoroughly searched, especially for publications from 2006 to 2012, which addressed non-contraceptive-related indications for therapy and prevention.

      Results

      A considerable literature now exists to demonstrate the multiple and substantial noncontraceptive health benefits of long-acting progestogen-releasing systems, especially the levonorgestrel-releasing intrauterine system. These benefits mainly relate to disturbances of menstruation and related symptoms, such as heavy menstrual bleeding (due to many causes); iron deficiency; pelvic pain, especially around endometriosis; and endometrial hyperplasia. The long-acting estrogen–progestogen systems may carry similar added health benefits to those of the combined oral contraceptives, but data are still lacking.

      Conclusion

      Added health benefits are now becoming an important part of the contraceptive choice equation, and the long-acting delivery systems are recognized as suitable primary therapies for a range of gynecological disorders.

      Keywords

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      References

        • Sitruk-Ware R.
        Contraceptive technology: past, present and future.
        Contraception. 2012; (this volume ***)
        • Drill V.A.
        History of the first oral contraceptive.
        J Toxicol Environ Health. 1977; 3: 133-138
        • Bishop P.M.F.
        Treatment of functional menstrual disorders with norethisterone.
        Br Med J. 1960; 9: 1103-1105
        • Kistner R.W.
        Treatment of hyperplasia and carcinoma of the endometrium.
        Clin Obstet Gynecol. 1982; 25: 63-74
        • Mishell Jr., D.R.
        Noncontraceptive health benefits of oral steroidal contraceptives.
        Am J Obstet Gynecol. 1982; 142: 809-816
        • Burkman R.
        • Schlesselman J.J.
        • Zieman M.
        Safety concerns and health benefits associated with oral contraception.
        Am J Obstet Gynecol. 2004; 190: S5-S22
        • Shulman L.P.
        The state of hormonal contraception today: benefits and risks of hormonal contraceptives: combined estrogen and progestin contraceptives.
        AJOG. 2011; 205: S9-S13
        • The ESHRE Capri Workshop Group
        Non-contraceptive health benefits of combined oral contraception.
        Hum Reprod Update. 2005; 11: 513-525
        • Vessey M.
        • Yeates D.
        • Flynn S.
        Factors affecting mortality in a large cohort study with special reference to oral contraceptive use.
        Contraception. 2010; 82: 221-229
        • Fraser I.S.
        The promise and reality of the intrauterine route for hormone delivery for prevention and therapy of gynecological disease.
        Contraception. 2007; 75: S112-S117
        • Fraser I.S.
        Non-contraceptive health benefits of intrauterine health systems.
        Contraception. 2010; 82: 396-403
        • Bahamondes L.
        • Bahamondes M.V.
        • Monteiro I.
        Levonorgestrel-releasing intrauterine system: uses and controversies.
        Expert Rev Med Dev. 2008; 5: 437-445
        • Burke A.E.
        The state of hormonal contraception today: benefits and risks of hormonal contraceptives: progestin-only contraceptives.
        Am J Obstet Gynecol. 2011; 205: S14-S17
        • Heikinheimo O.
        • Gemzell-Danielsson K.
        Emerging indications for the levonorgestrel-releasing intrauterine system (LNG-IUS).
        Acta Obstet Gynecol Scand. 2012; 91: 3-9
        • Luukkainen T.
        The levonorgestrel-releasing IUD.
        Br J Fam Plan. 1993; 19: 221-224
        • Wildemeersch D.
        • Rowe P.J.
        Assessment of menstrual blood loss in women with ideopathic menorrhagia using the frameless levonorgestrel-releasing intrauterine system.
        Contraception. 2004; 70: 165-168
        • Wildemeersch D.
        • Rowe P.J.
        Assessment of menstrual blood loss in Belgian users of a new T-shaped levonorgestrel-releasing intrauterine system.
        Contraception. 2005; 71: 470-473
        • Eaton S.
        • Pike M.C.
        • Short R.V.
        • et al.
        Women's reproductive cancers in evolutionary context.
        Quart Rev Biol. 1994; 69: 353-367
        • Andersson K.
        • Rybo G.
        Levonorgestrel-releasing intrauterine device in the treatment of menorrhagia.
        Br J Obstet Gynaecol. 1990; 97: 690-694
        • Dueholm M.
        Levonorgestrel-IUD should be offered before hysterectomy for abnormal uterine bleeding without uterine structural abnormalities: there are no more excuses!.
        Acta Obstet Gynecol Scand. 2009; 88: 1302-1304
        • Kaunitz A.
        • Inki P.
        The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a risk–benefit review.
        Drugs. 2012; 72: 193-215
        • Shabaan M.M.
        • Zakherah M.S.
        • El-Nashar S.A.
        • Sayed G.H.
        Levonorgestrel-releasing intrauterine system compared to low dose combined oral contraceptive pills for idiopathic menorrhagia: a randomized clinical trial.
        Contraception. 2011; 83: 48-54
        • Endrikat J.
        • Shapiro H.
        • Lukkari-Lax E.
        • et al.
        A Canadian, multicentre study comparing the efficacy of a levonorgestrel-releasing intrauterine system to an oral contraceptive in women with idiopathic menorrhagia.
        JOGC. 2009; 31: 340-347
        • Chelmow D.
        Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: a randomized controlled trial.
        Obstet Gynecol. 2010; 116: 1455-1456
        • Marjoribanks J.
        • Lethaby A.
        • Farquhar C.
        Surgery versus medical therapy for heavy menstrual bleeding.
        Cochrane Database Syst Rev. 2006;
        • National Institute for Health Clinical Excellence
        Long-acting reversible contraception. National Collaborating Centre for Women's and Children's Health, London2005
        • Jensen J.
        • Parke S.
        • Mellinger U.
        • Machlitt A.
        • Fraser I.S.
        Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest.
        Obstet Gynecol. 2011; 117: 777-787
        • Fraser I.S.
        • Romer T.
        • Parke S.
        • et al.
        Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing oestradiol valerate and dienogest: a randomised, double-blind and placebo-controlled phase III trial.
        Hum Reprod. 2011; 26: 2698-2708
        • Kaunitz A.M.
        • Meredith S.
        • Inki P.
        • Kubba A.
        • Sanchez-Ramos L.
        Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis.
        Obstet Gynecol. 2009; 113: 1104-1116
        • Kaunitz A.M.
        Progestin-releasing intrauterine systems and leiomyoma.
        Contraception. 2007; 75: S130-S133
        • Mercorio F.
        • De Simone R.
        • Di Spiezio Sardo A.
        • et al.
        The effect of a levonorgestrel-releasing intrauterine device in the treatment of myoma-related menorrhagia.
        Contraception. 2003; 67: 277-280
        • Grigorieva V.
        • Chen-Mok M.
        • Tarasova M.
        • Mikhailov A.
        Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas.
        Fertil Steril. 2003; 79: 1194-1198
        • Soysal S.
        • Soysal M.E.
        The efficacy of levonorgestrel-releasing intrauterine device in selected cases of myoma-related menorrhagia: a prospective controlled trial.
        Gynecol Obstet Invest. 2005; 59: 29-35
        • Sayed G.H.
        • Zakherah M.S.
        • El-Nashar S.A.
        • Shaaban M.M.
        A randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia.
        Int J Gynecol Obstet. 2011; 112: 126-130
        • Magalhães J.
        • Aldrighi J.M.
        • de Lima G.R.
        Uterine volume and menstrual patterns in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas.
        Contraception. 2007; 75: 193-198
        • Xiao B.
        • Wu S.C.
        • Chong J.
        • et al.
        Therapeutic effects of the levonorgestrel-releasing intrauterine system in the treatment of idiopathic menorrhagia.
        Fertil Steril. 2003; 79: 963-969
        • Kriplani A.
        • Singh B.M.
        • Lal S.
        • Agarwal N.
        Efficacy, acceptability and side effects of the levonorgestrel intrauterine system for menorrhagia.
        Int J Gynecol Obstet. 2007; 97: 190-194
        • Fedele L.
        • Portuese A.
        • Bianchi S.
        • Dorta M.
        • Raffaelli R.
        Treatment of adenomyosis-associated menorrhagia with a levonorgestrel- releasing intrauterine device.
        Fertil Steril. 1997; 68: 426-429
        • Bragheto A.M.
        • Caserta N.
        • Bahamondes L.
        • Petta C.A.
        Effectiveness of the levonorgestrel-releasing intrauterine system in the treatment of adenomyosis diagnosed and monitored by magnetic resonance imaging.
        Contraception. 2007; 76: 195-199
        • Cho S.
        • Nam A.
        • Kim H.
        • et al.
        Clinical effects of the levonorgestrel-releasing intrauterine device in patients with adenomyosis.
        Am J Obstet Gynecol. 2008; 198: 373.e1-373.e7
        • Fong Y.F.
        • Singh K.
        Medical treatment of a grossly enlarged adenomyotic uterus with the levonorgestrel-releasing intrauterine system.
        Contraception. 1999; 60: 173-175
        • Sheng J.
        • Zhang W.Y.
        • Zhang J.P.
        • Lu D.
        The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis.
        Contraception. 2009; 79: 189-193
        • Kadir R.A.
        • Chi C.
        Levonorgestrel intrauterine system: bleeding disorders and anticoagulant therapy.
        Contraception. 2007; 75: S123-S129
        • Kingman C.E.C.
        • Kadir R.A.
        • Lee C.A.
        • Economides D.L.
        The use of levonorgestrel-releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding disorders.
        BJOG. 2004; 111: 1425-1428
        • Schaedel Z.E.
        • Dolan G.
        • Powell M.C.
        The use of the levonorgestrel-releasing intrauterine system in the management of menorrhagia in women with hemostatic disorders.
        Am J Obstet Gynecol. 2005; 193: 1361-1363
        • Lukes A.S.
        • Reardon B.
        • Arepally G.
        Use of the levonorgestrel-releasing intrauterine system in women with hemostatic disorders.
        Fertil Steril. 2008; 90: 673-677
        • Vilos G.A.
        • Tureanu V.
        • Garcia M.
        • Abu-Rafea B.
        The levonorgestrel intrauterine system is an effective treatment in women with abnormal uterine bleeding and anticoagulant therapy.
        J Minim Invasive Gynecol. 2009; 16: 480-484
        • Culwell K.R.
        • Curtis K.M.
        Use of contraceptive methods by women with current venous thrombosis on anticoagulant therapy: a systematic review.
        Contraception. 2009; 80: 337-345
        • Chi C.
        • Huq F.Y.
        • Kadir R.A.
        Levonorgestrel-releasing intrauterine system for the management of heavy menstrual bleeding in women with inherited bleeding disorders: long-term follow-up.
        Contraception. 2011; 83: 242-247
        • Depypere H.T.
        • Hillard T.
        • Erkkola R.
        • et al.
        A 60-month non-comparative study on bleeding profiles with the levonorgestrel intrauterine system from the late transition period to estrogen supplemented menopause.
        Eur J Obstet Gynecol Reprod Biol. 2010; 153: 176-180
        • Vilos G.A.
        • Marks J.
        • Tureanu V.
        • Abu-Rafea B.
        • Vilos A.G.
        The levonorgestrel intrauterine system is an effective treatment in selected obese women with abnormal uterine bleeding.
        J Minim Invasive Gynecol. 2011; 18: 75-80
        • Imperato F.
        • Perniola G.
        • Mossa B.
        • et al.
        The role of copper-releasing intrauterine device or levonorgestrel-releasing intrauterine system on uterine bleeding and iron status (prospective study of 8 years).
        Minerva Ginecol. 2002; 54: 271-278
        • Wang L.
        • Zhao G.
        • Chen L.
        Investigation on the prevalence and influencing factors to anemia in women at reproductive age.
        Chung-Hua Liu Hsing Ping Hsueh Tsa Chih Chin J Epidemiol. 1999; 20: 158-161
        • Varma R.
        • Soneja H.
        • Bhatia K.
        • et al.
        The effectiveness of a levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of endometrial hyperplasia — a long-term follow-up study.
        Eur J Obstet Gynecol Reprod Biol. 2008; 139: 169-175
        • Ørbo A.
        • Arnes M.
        • Hancke C.
        • et al.
        Treatment results of endometrial hyperplasia after prospective D-score classification. A follow-up study comparing effect of LNG-IUD and oral progestins versus observation only.
        Gynecol Oncol. 2008; 111: 68-73
        • Ørbo A.
        • Rise C.E.
        • Mutter G.L.
        Regression of latent endometrial precancers by progestin infiltrated intrauterine device.
        Cancer Res. 2006; 66: 5613-5617
        • Bahamondes L.
        • Ribeiro-Huguet P.
        • De Andrade K.C.
        • Leon-Martins O.
        • Petta C.A.
        Levonorgestrel-releasing intrauterine system (Mirena®) as a therapy for endometrial hyperplasia and carcinoma.
        Acta Obstet Gynecol Scand. 2003; 82: 580-582
        • Buttini M.J.
        • Jordan S.J.
        • Webb P.M.
        The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: an Australian study and systematic review.
        ANZJOG. 2009; 49: 316-322
        • Gallos I.D.
        • Shehmar M.
        • Thangaratinam S.
        • et al.
        Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis.
        AJOG. 2010; 203: 547.e1-547.e10
        • Wan Y.L.
        • Holland C.
        The efficacy of levonorgestrel intrauterine systems for endometrial protection: a systematic review.
        Climacteric. 2011; 14: 622-632
        • Gardner F.J.E.
        • Konje J.C.
        • Bell S.C.
        • et al.
        Prevention of tamoxifen induced endometrial polyps using a levonorgestrel releasing intrauterine system. Long-term follow-up of a randomised control trial.
        Gynecol Oncol. 2009; 114: 452-456
        • Vercellini P.
        • Aimi G.
        • Panazza S.
        • et al.
        A levonorgestrel-releasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study.
        Fertil Steril. 1999; 72: 505-508
        • Bahamondes L.
        • Petta C.A.
        • Fernandes A.
        • Monteiro I.
        Use of the levonorgestrel-releasing intrauterine system in women with endometriosis, chronic pelvic pain and dysmenorrhea.
        Contraception. 2007; 75: S134-S139
        • Petta C.A.
        • Ferriani R.A.
        • Abrao M.S.
        • et al.
        Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis.
        Hum Reprod. 2005; 20: 1993-1998
        • Alhamdan D.
        • Bignardi T.
        • Hardas G.
        • Merkur H.
        • Condous G.
        Mirena intrauterine system: does it improve long-term symptoms in women with chronic pelvic pain and/or endometriosis after laparoscopy? A multicentre randomized controlled trial.
        Rev Recent Clin Trials. 2010; 5: 143-146
        • Matorras R.
        • Ballesteros A.
        • Prieto B.
        • et al.
        Efficacy of the levonorgestrel-releasing intrauterine device in the treatment of recurrent pelvic pain in multitreated endometriosis.
        J Reprod Med. 2011; 56: 497-503
        • Bayoglu Tekin Y.
        • Dilbaz B.
        • Altinbas S.K.
        • Dilbaz S.
        Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue.
        Fertil Steril. 2011; 95: 492-496
        • Rönnerdag M.
        • Odlind V.
        Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use.
        Acta Obstet Gynecol Scand. 1999; 78: 716-721
        • Lete I.
        • Del Carme Cuesta M.
        • Marín J.M.
        • et al.
        Acceptability of the levonorgestrel intrauterine system in the long-term treatment of heavy menstrual bleeding: how many women choose to use a second device?.
        Eur J Obstet Gynecol Reprod Biol. 2011; 154: 67-70
        • Hurskainen R.
        • Teperi J.
        • Rissanen P.
        • et al.
        Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial.
        Lancet. 2001; 357: 273-277
        • Reid P.C.
        • Mukri F.
        Trends in number of hysterectomies performed in England for menorrhagia: examination of health episode statistics, 1989 to 2002–3.
        BMJ. 2005; 330: 938-939
        • Heliövaara-Peippo S.
        • Halmesmäki K.
        • Hurskainen R.
        • et al.
        The effect of hysterectomy or levonorgestrel-releasing intrauterine system on lower abdominal pain and back pain among women treated for menorrhagia: a five-year randomized controlled trial.
        Acta Obstet Gynecol Scand. 2009; 88: 1389-1396
        • Ozdegirmenci O.
        • Kayikcioglu F.
        • Akgul M.A.
        • et al.
        Comparison of levonorgestrel intrauterine system versus hysterectomy on efficacy and quality of life in patients with adenomyosis.
        Fertil Steril. 2011; 95: 497-502
        • Goñi A.Z.
        • Lacruz R.L.
        • Paricio J.J.P.
        • Hernández Rivas F.J.
        The levonorgestrel intrauterine system as an alternative to hysterectomy for the treatment of idiopathic menorrhagia.
        Gynecol Endocrinol. 2009; 25: 581-586
        • Von Drygalski A.
        • Adamson J.W.
        Ironing out fatigue.
        Blood. 2011; 118: 3191-3192
        • Vercellini P.
        • Frontino G.
        • De Giorgi O.
        • et al.
        Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study.
        Fertil Steril. 2003; 80: 305-309
        • Tanmahasamut P.
        • Rattanachaiyanont M.
        • Angsuwathana S.
        • et al.
        Postoperative levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: a randomized controlled trial.
        Obstet Gynecol. 2012; 119: 519-526
        • Paterson H.
        • Ashton J.
        • Harrison-Woolrych M.
        A nationwide cohort study of the use of the levonorgestrel intrauterine device in New Zealand adolescents.
        Contraception. 2009; 79: 433-438
        • Pillai M.
        • O'Brien K.
        • Hill E.
        The levonorgestrel intrauterine system (Mirena) for the treatment of menstrual problems in adolescents with medical disorders, or physical or learning disabilities.
        BJOG. 2010; 117: 216-221
        • Al-Jefout M.
        • Palmer J.
        • Fraser I.S.
        Simultaneous use of a levonorgestrel intrauterine system and an etonogestrel subdermal implant for debilitating adolescent endometriosis.
        ANZJOG. 2007; 47: 247-249
        • Nilsson C.G.
        • Haukkamaa M.
        • Vierola H.
        • Luukkainen T.
        Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD.
        Clin Endocrinol. 1982; 17: 529-536
        • Tokushige N.
        • Markham R.
        • Russell P.
        • Fraser I.S.
        Effects of hormonal treatment on nerve fibres in endometrium and myometrium of women with endometriosis.
        Fertil Steril. 2008; 90: 1589-1598
        • Tokushige N.
        • Markham R.
        • Russell P.
        • Fraser I.S.
        Effect of progestogens and combined oral contraceptives on nerve fibers in peritoneal endometriosis.
        Fertil Steril. 2009; 92: 1234-1239
        • Yisa S.B.
        • Okenwa A.A.
        • Husemeyer R.P.
        Treatment of pelvic endometriosis with the etonogestrel subdermal implant (Implanon).
        J Fam Plann Reprod Health Care. 2005; 31: 67-70
        • Fraser I.S.
        • Weisberg E.
        • Minehan E.
        • Johansson E.D.B.
        A detailed analysis of menstrual blood loss in women using Norplant and Nestorone progestogen-only contraceptive implants or vaginal rings.
        Contraception. 2000; 61: 241-251