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

de Medeiros Reproductive Biology and Endocrinology (2017) 15:93 DOI 10.1186/s12958-017-0313-y REVIEW Open Access Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome Sebastião Freitas de Medeiros1,2 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. Keywords: Polycystic ovary syndrome, Contraception, Oral contraceptive, Progestin, Venous thromboembolism, Dyslipidemia, Dysglicemia Correspondence: 1 Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, MT 78055-728, Brazil 2 Tropical Institute of Reproductive Medicine, Cuiabá, MT, Brazil © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. de Medeiros Reproductive Biology and Endocrinology (2017) 15:93 Background The prevalence of polycystic ovary syndrome (PCOS) ranges from 5% to 22% in women of reproductive age worldwide. It is associated with menstrual disturbances, hyperandrogenism, infertility, obesity and insulin resistance [1, 2]. Dyslipidemia, dysglycemia and metabolic syndrome (MetS) are also common [2, 3]. Adding evidences suggest that non-alcoholic fatty liver disease (NAFLD) exacerbates insulin resistance and predisposes patients with PCOS to an atherogenic status and the release of many proinflammatory, procoagulant and profibrogenic moderators [4]. Collectively, these data demonstrate that PCOS patients exhibit many conditions that could be tightly linked to future development of cardiovascular disease (CVD) and venous thromboembolism (VTE) (Table 1). Despite the complex pathophysiological mechanisms and multiple phenotypes of PCOS, combined oral contraceptives (COCs) are the first-line option for the treatment of all women with PCOS not seeking to become pregnant, and they exert many beneficial effects in these women [5, 6]. However, some deleterious metabolic effects have been demonstrated [7]. Concerns regarding the safety and the potential metabolic and cardiovascular risks of COCs in these patients persist [7–11]. This review has several purposes: (a) to consider the potential risks of isolated PCOS; (b) to estimate the potential additional risks of COC in patients with PCOS; (c) to examine why the use of COCs would be either beneficial or harmful for PCOS patients; (d) to focus on the noncontraceptive advantages/disadvantages of COC use in this syndrome; and (e), when possible, to suggest a specific formulation according to the patients’ phenotype. Methods A comprehensive search and review of published studies on this topic and written in the English-language between Page 2 of 17 1982 and 2017 was performed using PubMed and the Cochrane database. When available, online searches of specialized journals were also used by adding adequate keywords. In addition, these databases were expanded by a manual search of references from the obtained articles. Older articles were also included as they provided basic and essential information. Keywords, alone or in combination, for the search included oral contraceptive, progestin, polycystic ovary syndrome, venous thromboembolism, cardiovascular disease and contraception. On the basis of the literature search, eligible studies that met the inclusion criteria of comparing head-to-head before and after data were identified. Ranges of collected data are given and 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. Impact of combined oral contraceptives in the risk of VTE and CVD in PCOS patients An isolated diagnosis of PCOS increases the risk for VTE and CVD when compared with the general population [12–14]. VTE is considered the third most common cardiovascular disease with an overall annual incidence estimated at 1–2 events for every 1000 adults per year [15], has multiple risk factors and (...truncated)