Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2017

Open Access 01-12-2017 | Review

Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome

Author: Sebastião Freitas de Medeiros

Published in: Reproductive Biology and Endocrinology | Issue 1/2017

Login to get access

Abstract

Background

Polycystic ovary syndrome (PCOS) is a complex condition with high risk for dyslipidemia, dysglycemia, venous thromboembolism, cardiovascular disease and metabolic syndrome. Because the combined oral contraceptive (COC) use has also been associated with impaired fasting glucose, insulin resistance and increased risk of thromboembolism disease, it is rationale to think that the combination of oral contraceptive and PCOS could make it worse or increase the risks.

Objective

To examine the current data regarding potential additional risks and benefits of contraceptive use, highlights the major gap in knowledge for designing future studies and, when possible, suggests an adequate COC formulation for a determined PCOS phenotype.

Methods

English-language publications reporting on the influence of COCS in the development of venous thromboembolism in PCOS patients published until 2017 were searched using PubMed, Cochrane database, and hand search of references found in consulted articles. Ranges of collected data are given; the pooled data are presented as median and first and third quartiles. Wilcoxon signed-ranks test for paired samples was used to compare before-after original data. P value was set at 0.05.

Results

Most of COCs preparations significantly decrease androgens, and increase sex-hormone binding globulin. Therefore, the benefits of COCs are clear in patients with proved hyperandrogenemia. Regarding the impact of COCs on carbohydrate metabolism of PCOS subjects, the data were inconsistent but they tended to show no additional risk. Regarding lipids, most COCs consistently increased high-density lipoprotein cholesterol, triglycerides and total cholesterol concentrations but the clinical implications of these changes need additional studies.

Conclusion

The review showed consistent beneficial effect of COCs, particularly for hyperandrogenemic PCOS patients. The benefit size of COC’s use by normoandrogenemic PCOS patients is uncertain and need more investigation. The effects of COC use on carbohydrate metabolism of women with PCOS are still unresolved since most studies are observational but the current results demonstrated that COCs do not make their levels worse and may improve insulin sensitivity. The impact of COCs on lipids of PCOS patients seems to be clearer and most preparations increase total cholesterol, high-density lipoprotein cholesterol and triglycerides. In summary, it is important to balance the potential benefits and risks of the COCs individually before prescribing them for PCOS women.
Literature
1.
de Medeiros SF, Barbosa JS, Yamamoto MMW. Comparison of steroidogenic pathways among normoandrogenic and hyperandrogenic polycystic ovary syndrome patients and normal cycling women. J Obstet Gynaecol Res. 2015;41:254–63.CrossRef
2.
3.
Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012; 97:28–38.e25.
4.
Targher G, Zoppini G, Bonora E, Moghetti P. Hemostatic and fibrinolytic abnormalities in polycystic ovary syndrome. Semin Thromb Hemost. 2014;40:600–18.PubMedCrossRef
5.
Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565–92.PubMedPubMedCentralCrossRef
6.
Mendoza N, Simoncini T, Genazzani AD. Hormonal contraceptive choice for women with PCOS: a systematic review of randomized trials and observational studies. Gynecol Endocrinol. 2014;30:850–60.PubMedCrossRef
7.
Korytkowski MT, Mokan M, Horwitz MJ, Berga SL. Metabolic effects of oral contraceptives in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1995;80:3327–34.PubMed
8.
Yildiz BO. Oral contraceptives in polycystic ovary syndrome: risk-benefit assessment. Semin Reprod Med. 2008;26:111–20.PubMedCrossRef
9.
Yildiz BO. Approach to the patient: contraception in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015;100:794–802.PubMedCrossRef
10.
Dokras A. Noncontraceptive use of oral combined hormonal contraceptives in polycystic ovary syndrome-risks versus benefits. Fertil Steril. 2016;106:1572–9.PubMedCrossRef
11.
De Melo AS, Reis RM, Ferriani RA, Vieira CS. Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits. J Contracept. 2017;8:13–23.
12.
de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FMPCOS. Coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reprod Update. 2011;17:495–500.PubMedCrossRef
13.
Okoroh EM, Hooper WC, Atrash HK, Yusuf HR, Boulet SL. Is polycystic ovary syndrome another risk factor for venous thromboembolism? United States, 2003–2008. Am J Obstet Gynecol. 2012; 207:377.e-1-377.e-8.
14.
de Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama VA, Helmerhorst FM, Stijnen T, Dekkers OM. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. 2014;3(3):CD010813.
15.
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158:585–593.
16.
Atiomo WU, Pearson S, Shaw S, Prentice A, Dubbins P. Ultrasound criteria in the diagnosis of polycystic ovary syndrome (PCOS). Ultrassound Med Biol. 2000;26:977–80.CrossRef
17.
Mak W, Dokras A. Polycystic ovarian syndrome and the risk of cardiovascular disease and thrombosis. Semin Thromb Hemost. 2009;35:613–20.PubMedCrossRef
18.
Bird ST, Hartzema AG, Brophy JM, Etminam M, Delaney JA. Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. CMAJ. 2013;185:E115–20.PubMedPubMedCentralCrossRef
19.
Anderson SA, Varry JA, Hardiman PJ. Risk of coronary heart disease and risk of stroke in women with polycystic ovary syndrome: a systematic review and meta-analysis. Inter. J Cardiol. 2014;176:486–7.
20.
Matthesen T, Rasmussen AMO, Nielsen LH, Lidegaard O. Polycystic ovary syndrome hormonal contraception and thrombotic stroke: a historical cohort study. J Neurol Disord Stroke. 2015;3:1–7.
21.
Cibula D, Cifkova R, Fanta M, Poledne R, Zivny J, Skibova J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in permenopausal women with a history of the polycystic ovarysyndrome. Hum Reprod. 2000;15:785–9.PubMedCrossRef
22.
Wild S, Pierpoint T, McKeique P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol. 2000;52:595–600.CrossRef
23.
Solomon CG, Hu FB, Dunaif A, Rich-Edwards JE, Stampfer MJ, Willett WC, Speizer FE, Manson JE. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab. 2002;87:2013–7.PubMedCrossRef
24.
Zhao L, Zhu Z, Lou H, Zhu G, Huang W, Zhang S, Liu F. Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis. Oncotarget. 2016;7:33715–21.PubMedPubMedCentralCrossRef
25.
Wild RA, Grubb B, Hartz A, Van Nort JJ, Bachmann W, Bartholomew M. Clinical signs of androgen excess as risk factors for coronary artery disease. Fertil Steril. 1990;54:255–9.PubMedCrossRef
26.
Wiltgen D, Spritzer PM. Variation in metabolic and cardiovascular risk in women with different polycystic ovary syndrome phenotypes. Fertil Steril. 2010;94:2493–6.PubMedCrossRef
27.
Cibula D, Sindelka G, Hill M, Fanta M, Skrha J, Zivny J. Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin. Hum Reprod. 2002;17:76–82.PubMedCrossRef
28.
Practice Committee of American Society for Reproductive Medicine. Combined hormonal contraception and the risk of venous thromboembolism: a guideline. Fertil Steril. 2017;107:43–51.CrossRef
29.
Stampfer MJ, Willett WC, Colditz GA, Speizer FE, Hennekens CHA. Prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases. N Engl J Med. 1988;319:1313–7.PubMedCrossRef
30.
Fallah S, Nourozzi V, Seifi M, Samadikuchaksaraei A, Aghdashi EM. Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease. J Clin Lab Anal. 2012;26:120–3.PubMedCrossRef
31.
Dunn N, Thorogood M, Faragher B, Caestecker L, MacDonald T, McCollum C, Thomas S, Mann K. Oral contraceptives and myocardial infarction: results of the MICA case-control study. BMJ. 1999;318:1579–84.PubMedPubMedCentralCrossRef
32.
Sidney S, Cheetham TC, Connell FA, Ouellet-Hellstrom R, Graham DJ, Davis D, Sorel M, Quesenberry CP Jr, Cooper WO. Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception. 2013;87:93–100.PubMedCrossRef
33.
Tanis BC, van den Bosch MAAJ, Kemmeren JM. Oral contraceptives and the risk of myocardial infarction. New Engl J Med. 2001;345:1787–93.PubMedCrossRef
34.
Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2015; 26:350:h2135.
35.
WHO Collaborative Study. Of cardiovascular disease and steroid hormone contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet. 1997;349:1202–9.CrossRef
36.
Seaman HE, de Vries CS, Farmer RD. The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study. Hum Reprod. 2003;18:522–6.PubMedCrossRef
37.
Vrbíková J, Cibula D. Combined oral contraceptives in the treatment of polycystic ovary syndrome. Hum Reprod Update. 2005;11:277–91.PubMedCrossRef
38.
Sitruk-Ware R, Nath A, Mishell DR Jr. Contraception technology: past, present and future. Contraception. 2013;87:319–30.PubMedCrossRef
39.
Mes-Krowinkel MG, Louwers YV, Mulders AGMGJ, de Jong FH, Fauser BC, Laven JS. Influence of oral contraceptives on anthropomorphometric, endocrine, and metabolic profiles of anovulatory polycystic ovary syndrome patients. Fertil Steril. 2014;101:1757–65.PubMedCrossRef
40.
Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012;27:3067–73.PubMedCrossRef
41.
42.
Halperin IJ, Stroup DF, Laredo SE. The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of observational studies. Hum Reprod. 2011;26:191–201.PubMedCrossRef
43.
Haffner SM, Katz MS, Stern MP, Stern MP, Dunn JF. Association of decreased sex hormone binding globulin and cardiovascular risk factors. Arteriosclerosis. 1989;9:136–43.PubMedCrossRef
44.
Ding EL, Song Y, Manson J, Hunter DJ, Lee CC, Rifai N, Buring JE, Gaziano JM, Liu S. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361:1152–63.PubMedPubMedCentralCrossRef
45.
Lapidus L, Lindstedt G, Lundberg PA, Bengtsson C, Gredmark T. Concentrations of sex-hormone binding globulin and corticosteroid binding globulin in serum in relation to cardiovascular risk factors and to 12-year incidence of cardiovascular disease and overall mortality in postmenopausal women. Clin Chem. 1986;32:146–52.PubMed
46.
Sutton-Tyrrel K, Wildman RP, Matthews KA, Chae C, Lasley BL, Brockwell S, Pasternak RC, Lloyd-Jones D, Sowers MF, Torréns JI. Sex-hormone binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the study of women across the nation (SWAN). Circulation. 2005;111:1242–9.CrossRef
47.
Shin JY, Kim SK, Lee MY, Kim HS, Ye BL, Shin YG, Baik SK, Chung CH. Sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2 diabetes. Diabetes Res Clin Pract. 2011;94:156–62.PubMedCrossRef
48.
Simó R, Sáez-López C. Barbosa-Deongles, Hernandez C, Selva D. Novel insights in SHBG regulation and clinical implications. Trend. Endocrinol Metab. 2015;26:376–83.
49.
Cullberg G, Hamberger L, Mattsson LA, Mobacken H, Samsioe G. Effects of a low-dose desogestrel-ethinylestradiol combination on hirsutism, androgens and sex hormone binding globulin in women with a polycystic ovary syndrome. Acta Obstet Gynecol Scand. 1985;64:195–202.PubMedCrossRef
50.
Wiegratz I, Kutschera E, Lee JH, Moore C, Mellinger U, Winkler U, Kuhl H. Effect of four different oral contraceptives on various sex hormones and serum-binding globulins. Contraception. 2003;67:25–32.PubMedCrossRef
51.
Zimmerman Y, Eijkemans MJC, Coelingh Bennink HJT, Blankenstein MA, Fauser BC. The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis. Hum Reprod Update. 2014;20:76–105.PubMedCrossRef
52.
Bhattacharya SM, Jha A. Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome. Fertil Steril. 2012;98:1053–9.PubMedCrossRef
53.
Elter K, Imir G, Durmusoglu F. Clinical, endocrine and metabolic effects of metformin added to ethinylestradiol-cyproterone acetate in non-obese women with polycystic ovarian syndrome: a randomized controlled study. Hum Reprod. 2002;17:1729–37.PubMedCrossRef
54.
Kahraman K, Sükür YE, Atabekoğlu CS, Ates C, Taskim S, Cetinkaya SE, Tolunay HE, Ozmen B, Sonmezer M, Berker B. Comparison of two oral contraceptive forms containing cyproterone acetate and drospirenone in the treatment of patients with polycystic ovary syndrome: a randomized clinical trial. Arch Gynecol Obstet. 2014;290:321–8.PubMedCrossRef
55.
Cagnacci A, Tirelli A, Renzi A, Volpe A. Effects of two different oral contraceptives on homocysteine metabolism in women with polycystic ovary syndrome. Contraception. 2006;73:348–51.PubMedCrossRef
56.
Falsetti L, Galbignani E. Long-term treatment with the combination ethinylestradiol and cyproterone acetate in polycystic ovary syndrome. Contraception. 1990;42:611–9.PubMedCrossRef
57.
Golland IM, Elstein ME. Results of a one year open study with Diane-35 in women with polycystic ovary syndrome. Ann N Y Acad Sci. 1993;687:263–71.PubMedCrossRef
58.
Armstrong VL, Wiggam MI, Ennis CN, Sheridan B, Atkinson AB, Bell PM. Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyloestradiol/cyproterone acetate. Q J Med. 2001;94:31–7.CrossRef
59.
Naka KK, Kalantaridou SN, Bechlioulis A. Effect of ethinylestradiol/cyproterone acetate on endothelial function in young non-obese women with polycystic ovary syndrome: a pilot study. Gynecol Endocrinol. 2011;27:615–21.PubMedCrossRef
60.
Morin-Papunen L, Rautio K, Ruokonen A, Hedberg P, Puukka M, Tapanainen JS. Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:4649–54.PubMedCrossRef
61.
Mastorakos G, Koliopoulos C, Deligeoroglou E, Diamanti-Kandarakis E, Creatsas G. Effects of two forms of combined oral contraceptives on carbohydrate metabolism in adolescents with polycystic ovary syndrome. Fertil Steril. 2006;85:420–7.PubMedCrossRef
62.
Christakou C, Kollias A, Piperi C, Katsikis I, Panidis D, Diamanti-Kandarsakis E. The benefit-to-risk of common treatments in PCOS: effect of oral contraceptives versus metformin on antherogenic markers. Hormones. 2013;4:488–97.
63.
Chen MJ, Yang WS, Chen HF, Kuo JJ, Ho HN, Yang YS, Chen SU. Increased follistatin levels after oral contraceptive treatment in obese and non-obese women with polycystic ovary syndrome. Hum Reprod. 2010;25:779–85.PubMedCrossRef
64.
Prelevic GM, Würzburger MI, Balint-Peric L, Puzigaca Z. Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenisation, hormone profile and ovarian size in patients with polycystic ovary syndrome. Gynecol Endocrinol. 1989;3:269–80.PubMedCrossRef
65.
Guido M, Romualdi D, Giuliani M, Suriano R, Selvaggi L, Apa R, Lanzone A. Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. J Clin Endocrinol Metab. 2004;89:2817–23.PubMedCrossRef
66.
Pehlivanov B, Mitkov M. Efficacy of an oral contraceptive containing drospirenone in the treatment of women with polycystic ovary syndrome. Eur J Contracept Reprod Health Care. 2007;12:30–5.PubMedCrossRef
67.
Lello S, Primavera G, Colonna L, Vittori G, Guardianelli F, Sorge R, Raskovic D. Effects of two estroprogestins containing ethynilestradiol 30 microg and drospirenone 3 mg and ethynilestradiol 30 microg and chlormadinone 2 mg on skin and hormonal hyperandrogenic manifestations. Gynecol Endocrinol. 2008;24:718–23.PubMedCrossRef
68.
Oner G, Muderris II. A Prospective randomized trial comparing low-dose ethinylestradiol and drosperionone 24/4 combined oral contraceptive vs ethinyl estradiol and drospirenone 21/7 combined oral contraceptive in the treatment of hirsutism. Contraception. 2011;84:508–11.PubMedCrossRef
69.
Aydin K, Cinar N, Aksoy DY, Bozdag G, Yildiz BO. Body composition in lean womrn with polycystic ovary syndrome: effect of ethinyl estradiol and drosperinone combination. Contraception. 2013;87:358–62.PubMedCrossRef
70.
Harmanci A, Cinar N, Bayraktar M, Yildiz B. Oral contraceptive plus antiandrogen therapy and cardiometabolic risk in polycystic ovary syndrome. Clin Endocrinol. 2013;78:120–5.CrossRef
71.
Batukan C, Muderris II. Efficacy of a new oral contraceptive containing drospirenone and ethinyl estradiol in the long-term treatment of hirsutism. Fertil Steril. 2006;85:436–40.PubMedCrossRef
72.
Battaglia C, Mancini F, Fabbri R, Persico N, Busacchi P, Facchinetti F, Venturoli S. 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;94:1417–25.PubMedCrossRef
73.
De Leo V, Di Sabatino A, Musacchio MC, Morgante G, Scolaro V, Cianci A, Petraglia F. Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome. Contraception. 2010;82:276–80.PubMedCrossRef
74.
Kriplani A, Priyasamy AJ, Agarwal N, Kulshrestha V, Kumar A, Ammini AC. Effect of oral contraceptive containing ethinyl estradiol combined with drosperinone VS desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome. Contraception. 2010;82:139–46.PubMedCrossRef
75.
Yildizhan R, Gokce AI, Yildizhan B, Cim N. Comparison of the effects of chlormadinone acetate versus drospirenone containing oral contraceptives on metabolic and hormonal parameters in women with PCOS for a period of two-year follow-up. Gynecol Endocrinol. 2015;31:396–400.PubMedCrossRef
76.
Romualdi D, De Cicco S, Busacca M, Gagliano D, Lanzone A, Guido M. Clinical efficacy and metabolic impact of two different dosages of ethynil-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: a randomized study. J Endocrinol Investig. 2013;36:636–41.CrossRef
77.
Bhattacharya SM, Jha A, DasMukhopadhyay L. Comparison of two contraceptive pills containing drospirene and 20 μg or 30 μg ethinylestradiol for polycystic ovary syndrome. Int J Gynecol Obstet. 2016;132:210–3.CrossRef
78.
Klipping C, Marr J. Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism. Contraception. 2005;71:409–16.PubMedCrossRef
79.
Uras R, Orrú M, Pani F, Marotto MF, Pilloni M, Guerriero S, Etzi R, Zedda P, Sorge R, Lello S, Melis GB, et al. Endocrinological, metabolic and clinical features of treatment with oral contraceptive formulation containing ethinylestradiol plus chlormadione acetate in nonobese women with polycystic ovary syndrome. Contraception. 2010;82:131–8.PubMedCrossRef
80.
Gomes VA, Vieira CS, Jacob-Ferreira NA, Belo VA, Soares GM, França JB, Ferriani RA, Tanus-Santos JE. Oral contraceptive containing chlormadinone acetate and ethinylestradiol reduces plasma concentrations of matrix metalloproteinase-2 in women with polycystic ovary syndrome. Basic Clin Pharmacol Toxicol. 2012;111:211–6.PubMed
81.
Vieira CS, Martins WP, Fernandes JB, Soares GM, dos Reis RM, de Sá MF, Ferriani RA. The effects of 2 mg chormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome. Contraception. 2012;86:268–75.PubMedCrossRef
82.
Bouchard P. Chlormadinone acetate (CMA) in oral contraception-a new opportunity. Eur J Contracept Reprod Health Care. 2005;10(Suppl 1):7–11.PubMedCrossRef
83.
Matorakos G, Koliopoulos C, Creatsas C. Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril. 2002;77:919–27.CrossRef
84.
Rojanasajul A, Sirimongkolkasem R, Piromsawasdi S, Sumavong V. Chailurkit la-or, Chaturachinda K. Effects of combined ethinylestradiol and desogestrel on hormone profiles and sex hormone binding globulin in women polycystic ovarian disease. Contraception. 1987;36:633–40.CrossRef
85.
Minozzi M, Constantino D, Guaraldi C, Unfer V. The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol. 2011;27:920–4.PubMedCrossRef
86.
Sitruk-Ware RL, Menard J, Rad M, Burggraaf J, De Kam ML, Tokay BA, Sivin I, Kluft C. Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen. Contraception. 2007;75:430–7.PubMedCrossRef
87.
White T, Ozel B, Jain JK, Stanczyk FZ. Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic proteins. Contraception. 2006;4:293–6.CrossRef
88.
Sodergard R, Bäckström T, Shanbhag V, Carstensen H. Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem. 1982;16:801–10.PubMedCrossRef
89.
90.
Falsetti L, Pasinetti E. Effects of long-term administration of an oral contraceptive containing ethinylestradiol and cyproterone acetate on lipid metabolism in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 1995;74:56–60.PubMedCrossRef
91.
Ibañez L, de Zegher F. Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity. Hum Reprod. 2004;19:1725–7.PubMedCrossRef
92.
Nader S, Riad-Gabriel MG, Saad MF. The effect of a desogestrel-containing oral contraceptive on glucose tolerance and leptin concentrations in hyperandrogenic women. J Clin Endocrinol Metab. 1997;82:3074–7.PubMed
93.
Glintborg D, Altinok ML, Mumm H, Hermann AP, Ravn P, Andersen M. Body composition is improved during 12 months' treatment with metformin alone or combined with oral contraceptives compared with treatment with oral contraceptives in polycystic ovary syndrome. J Clin Endocrinol Metab. 2014;7:2584–91.CrossRef
94.
Bilgir O, Kebapcilar L, Taner C, Bilgir F, Kebapcilar A, Bozkaya G, Yildiz Y, Yuksel A, Sari I. The effect of ethinylestradiol (EE)/cyproterone acetate (CA) and EE/CA plus metformin treatment on adhesion molecules in cases with polycystic ovary syndrome (PCOS). Intern Med. 2009;48:1193–9.PubMedCrossRef
95.
Kebapcilar L, Taner CE, Kebapcilar AG, Alacacioglu A, Sari I. Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome. Arch Gynecol Obstet. 2010;281:35–42.PubMedCrossRef
96.
Palep-Singh M, Mook K, Barth J, Balen A. An observational study of Yasmin in the management of women with polycystic ovary syndrome. J Fam Plann Reprod Health Care. 2004;30:163–5.PubMedCrossRef
97.
Sänger N, Stahlberg S, Manthey T, Mittmann K, Mellinger U, Lange E, Kuhl H, Wiegratz I. Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use. Contraception. 2008;6:420–5.CrossRef
98.
Di Carlo C, Gargano V, Sparice S, Tommaselli GA, Bifulco G, Schettino D, Nappi C. Short-term effects of an oral contraceptive containing oestradiolvalerate and dienogest on bone metabolism and bone mineral density: an observational, preliminary study. Eur J Contracept Reprod Health Care. 2013;18:388–93.PubMedCrossRef
99.
Adeniji AA, Essah PA, Nestler JE, Cheang KI. Metabolic effects of a commonly used combined hormonal oral contraceptive in women with and without polycystic ovary syndrome. J Women's Health. 2016;25:638–45.CrossRef
100.
Wang QY, Song Y, Huang W. Comparison of drospirenone- with cyproterone acetate-containing oral contraceptives, combined with metformin and lifestyle modifications in women with polycystic ovary syndrome and metabolic disorders: a prospective randomized control trial. Chinese Med J. 2016;129:883–90.CrossRef
101.
Orio F, Muscogiuri G, Giallauria F, Savastano S, Bottiglieri P, Tafuri D, Predotti P, Colarieti G, Colao A, Palomba S. Oral contraceptives versus physical exercise on cardiovascular and metabolic risk factors in women with polycystic ovary syndrome: a randomized controlled trial. Clin Endocrinol. 2016;85:764–71.CrossRef
102.
Wu H, Ruan X, Jin J, Mueck AO. Metabolic profile of Diane-35 versus Diane-35 plus metformin in Chinese PCOS women under standardized life-style changes. Gynecol Endocrinol. 2015;31:548–51.PubMedCrossRef
103.
Shahnazi M, Farshbaf-Khalili A, Pourzeinali-Beilankouh S, Sadrimehr F. Effects of second and third generation oral contraceptives on lipid and carbohydrate metabolism in overweight and obeses women: a randomized triple-blind controlled trial. Iran Red Crescent Med J. 2016;18:e36982.PubMedPubMedCentral
104.
Lindh I, Ellström AA, Milsom I. The long-term influence of combined oral contraceptives on body weight. Hum Reprod. 2011;26:1917–24.PubMedCrossRef
105.
Van der Vange N, Blankenstein MA, Kloosterboer HJ, Haspels AA, Thijssen JH. Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone. Contraception. 1990;41:345–52.PubMedCrossRef
106.
Milsom I, Lete I, Bjertnaes A, Rokstad K, Lindh I, Gruber CJ, Birkhäuser MH, Aubeny E, Knudsen T, Bastianelli C. Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone. Hum Reprod. 2006;21:2304–11.PubMedCrossRef
107.
Pasquali R, Gambineri A, Anconetani B, Vicennati V, Colitta D, Caramelli E, Casimirri F, Morselli-Labate AM. The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment. Clin Endocrinol. 1999;50:517–27.CrossRef
108.
Kilic S, Yilmaz N, Zulfikaroglu E, Erdogan G, Aydin BS. Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome durinf metformin and oral contraceptive treatment. Gynecol Endocrinol. 2011;(9):622–9.
109.
Cibula D, Fanta M, Vrbikova J, Stanicka S, Dvorakova K, Hill M, Skrha J, Zivny J, Skrenkova J. Effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. Hum Reprod. 2005;20:180–4.PubMedCrossRef
110.
Gaspard U, Scheen A, Endrikat J, Buicu C, Lefebvre P, Gerlinger C, Heithecker RA. Randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism. Contraception. 2003;67:423–9.PubMedCrossRef
111.
Essah PA, Arrowood JA, Cheang KI, Adawadkar SS, Stovall DW, Nestler JE. Effect of combined metformin and oral contraceptive therapy on metabolic factors and endothelial function in overweight and obese women with polycystic ovary syndrome. Fertil Steril. 2011;2:501–4.CrossRef
112.
Celik C, Abali R, Bastu E, Tasdemir N, Tasdemir UG, Gul A. Assesment of impaired glucose tolerance with hemoglobin A1c and oral glucose tolerance test in 252 Turkish women with polycystic ovary syndrome: a prospective, controlled study. Hum Reprod. 2013;28:1062–8.PubMedCrossRef
113.
Kim JJ, Choi YM, Cho YM, Jung HS, Chae SJ, Hwang KR, Hwang SS, SY K, Kim SH, Kim JG, et al. Prevalence of elevated glycated hemoglobin in women with polycystic ovary syndrome. Hum Reprod. 2012;27:1439–44.PubMedCrossRef
114.
de Medeiros SF, Yamamoto MMW, Bueno HB, Belizario D, Barbosa J. Prevalence of elevated glycated hemoglobin concentrations in the polycystic ovary syndrome: anthropometrical and metabolic relationship in Amazonian women. J Clin Med Res. 2014;6:278–86.PubMedPubMedCentral
115.
Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia. 2007;50:2239–44.PubMedCrossRef
116.
Sadaria RG, Ravi BV. A study on assessment of testosterone, insulin resistance and HbA1c in women with polycystic ovarian syndrome. Inter J Health Scien Res. 2015;5:180–5.
117.
Mosorin AE, Piltonen T, Tapananainen J, Papunen-Mortin L. Both oral and vaginal combined hormonal contraceptive induce unbeneficial metabolic effects in women with PCOS: a randomized study. Endocr Abstr. 2017;49
Metadata
Title
Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome
Author
Sebastião Freitas de Medeiros
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2017
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-017-0313-y

Other articles of this Issue 1/2017

Reproductive Biology and Endocrinology 1/2017 Go to the issue

Research

Effect of local endometrial injury in proliferative vs. luteal phase on IVF outcomes in unselected subfertile women undergoing in vitro fertilization

Research

Expression of genes associated with BMP signaling pathway in porcine oocytes before and after IVM – a microarray approach

Review

The regulation of ovary and conceptus on the uterine natural killer cells during early pregnancy

Research

Differential gene expression profiling of endometrium during the mid-luteal phase of the estrous cycle between a repeat breeder (RB) and non-RB cows

Research

A single trophectoderm biopsy at blastocyst stage is mathematically unable to determine embryo ploidy accurately enough for clinical use

Research

The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction