Levonorgestrel-Releasing Intrauterine System for Women With Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is related to clinical and metabolic comorbidities that may limit the prescription of combined hormonal contraceptives, with consequent need to use progestogen-only contraceptives (POCs). Thus, the objective of the present study was to evaluate the clinical and metabolic effects of a POC, the levonorgestrel-releasing intrauterine system (LNG-IUS), in women with PCOS followed up over a period of 6 months compared to baseline and to women without PCOS. Thus, an observational, prospective, controlled study was conducted on 30 women with a diagnosis of PCOS who presented adverse effect secondary to the use of combined oral contraceptives (nausea, headache, mastalgia or vomiting; PCOS group) paired with 30 ovulatory women without PCOS (control group), both groups being free of comorbidities and having chosen the LNG-IUS as contraceptive. Clinical, laboratory, and ultrasonographic variables were evaluated immediately before LNG-IUS insertion and 6 months after the use of this method. Before LNG-IUS insertion, the PCOS group had higher total testosterone levels (P = .04), lower HDL levels (P = .04), and greater ovarian volume (P < .01) than the control group. Six months after LNG-IUS insertion, there was a 2.3% increase in abdominal circumference (P = .04) and a 3.4% increase in fasting glycemia (P = .02). On the other hand, mean ovarian volume was 10% smaller compared to the volume found before LNG-IUS insertion (P = .04), LDL levels were reduced by 5.2% (P = .03), and total cholesterol levels were reduced by 6.7% (P < .01) compared to baseline evaluation in the PCOS group. The remaining variables did not differ significantly during the 6 months of observation. The control group did not show significant changes compared to the period before LNG-IUS insertion. When the groups were compared after the 6-month follow-up, only glycemia showed a statistically significant variation between the groups, with glycemia levels increasing by 3.4% in the PCOS group and decreasing by 2.6% in the control group (P = .008). In conclusion, the use of the LNG-IUS for 6 months was not associated with relevant changes in clinical or metabolic variables of women with no comorbidities regardless of the presence of PCOS.

Keywords

polycystic ovary syndrome levonorgestrel-releasing intrauterine system contraception progestogens

Get full access to this article

View all access options for this article.

References

Deligeoroglou

Vrachnis

Athanasopoulos

. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol. 2012;28(12):974–978.

Shroff

Kerchner

Maifeld

Van Beek

Jagasia

Dokras

. Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab. 2007;92(12):4609–4614.

The Rotterdam ESHRE/ASRM—Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–47.

Melo

Vieira

Barbieri

. High prevalence of polycystic ovary syndrome in women born small for gestational age. Hum Reprod. 2010;25(8):2124–2131.

Elting

Korsen

Bezemer

Schoemaker

. Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Hum Reprod. 2001;16(3):556–560.

Azzi

Woods

Reyna

Key

Knochenhauer

Yildiz

. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metabol. 2004;89(6):2745–2749.

Fauser

Tarlatzis

Rebar

. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril.2012;97(1):28–38. e25.

Grundy

Cleeman

Daniels

. American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–2752.

World Health Organization. Medical eligibility criteria for contraceptive use. 5th ed. Geneva: World Health Organization. 2015. Web site. http://www.who.int/reproductivehealth/publications/family_planning/MEC-5/en/. Accessed 23 December, 2015.

10.

Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2012;98(2):302–307.

11.

Friedewald

Levy

Fredrickson

. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.

12.

Vieira

Martins

Fernandes

. The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome. Contraception. 2012;86(3):268–275.

13.

Celermajer

Sorensen

Gooch

. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111–1115.

14.

Corretti

Anderson

Benjamin

. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39(2):257–265.

15.

Craiem

Chironi

Simon

Levenson

. New assessment of endothelium-dependent flow-mediated vasodilation to characterize endothelium dysfunction. Am J Ther. 2008;15(4):340–344.

16.

Lin

Wang

Zhao

. Evaluation of a levonorgestrel-releasing intrauterine system for treating endometrial hyperplasia in patients with polycystic ovary syndrome. Gynecol Obstet Invest. 2014;78(1):41–44.

17.

Bian

Shao

Liu

. Efficacy of the Levonorgestrel-Releasing System on IVF-ET Outcomes in PCOS with simple Endometrial Hyperplasia. Reprod Sci. 2015;22(6):758–766.

18.

Guazzelli

Barreiros

Barbosa

Torloni

Barbieri

. Extended regimens of the contraceptive vaginal ring versus hormonal oral contraceptives: effects on lipid metabolism. Contraception. 2012;85(4):389–393.

19.

Morin-Papunen

Martikainen HMcCarthy

Franks

. Comparison of metabolic and inflammatory outcomes in women who used oral contraceptives and the levonorgestrel-releasing intrauterine device in a general population. Am J Obstet Gynecol. 2008;199(5):529.e1–10.

20.

Battaglia

Mancini

Fabbri

. Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study. Fertil Steril. 2010;94(4):1417–1425.

21.

Mastorakos

Koliopoulos

Creatsas

. Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril. 2002;77(5):919–927.

22.

Kayikcioglu

Gunes

Ozdegirmenci

Haberal

. Effects of levonorgestrel-releasing intrauterine system on glucose and lipid metabolism: a 1-year follow-up study. Contraception. 2006;73(5):528–531.

23.

Nilsson

Kostiainen

Ehnholm

. Serum lipids and high-density-lipoprotein cholesterol in women on long-term sustained low-dose IUD treatment with levonorgestrel. Int J Fertil. 1981;26(2):135–137.

24.

Graff-Iversen

Tonstad

. Use of progestogen-only contraceptives/medications and lipid parameters in women age 40 to 42 years: results of a population-based cross-sectional Norwegian survey. Contraception. 2002;66(1):7–13.

25.

Ferreira

Vieira

Rosa-E-Silva

Rosa-e-Silva

Nogueira

Ferriani

. Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue. Contraception. 2010;81(2):117–122.

26.

Berneis

Rizzo

Lazzarini

Fruzzetti

Carmina

. Atherogenic lipoprotein phenotype and low-density lipoproteins size and subclasses in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92(1):186–189.

27.

Gode

Karagoz

Posaci

. Alteration of cardiovascular risk parameters in women with polycystic ovary syndrome who were prescribed to ethinyl estradiol-cyproterone acetate. Arch Gynecol Obstet. 2011;284(4):923–929.

28.

Naka

Kalantaridou

Bechlioulis

. Effect of ethinylestradiol/cyproterone acetate on endothelial function in young non-obese women with polycystic ovary syndrome: a pilot study. Gynecol Endocrinol. 2011;27(9):615–621.

29.

Visser

Snel

Van Vliet

. Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2. Cochrane Database Syst Rev. 2006;18(4):CD003990.

30.

de Paula Martins

Santana

Nastri

Ferriani

de Sa

Dos Reis

. Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women. Eur J Obstet Gynecol Reprod Biol. 2007;133(2):203–207.

31.

Bots

Hoes

Hofman

Witteman

Grobbee

. Cross-sectionally assessed carotid intima-media thickness relates to longterm risk of stroke, coronary heart disease and death as estimated by available risk functions. J Intern Med. 1999;245(3):269–276.

32.

Meyer

McGrath

Teede

. Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome. Diabetes Care. 2007;30(3):471–478.

33.

Selim

Hussein

. Endothelial function in women using levonorgestrel-releasing intrauterine system (LNG-IUS). Contraception. 2013;87(4):396–403.

34.

Sprung

Atkinson

Cuthbertson

. Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies. Clin Endocrinol (Oxf). 2013;78(3):438–446.

35.

Meyer

Malek

Wild

Korytkowski

Talbott

. Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(2):112–126.

36.

Pugeat

Déchaud

Raverot

. Recommendations for investigation of hyperandrogenism. Ann Endocrinol (Paris). 2010;71(1):2–7.

37.

Martin

Chang

Ehrmann

. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(4):1105–1120.

38.

Xiao

Zeng

Sun

Xiao

. Effect of levonorgestrel-releasing intrauterine device on hormonal profile and menstrual pattern after long-term use. Contraception. 1995;51(6):359–365.

39.

Odlind

Milsom

Persson

Victor

. Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills? Acta Obstet Gynecol Scand. 2002;81(6):482–490.