My 40-Year-Old-Patient Has Polycystic Ovary Syndrome and New Onset Hypertension. What Is the Optimal Treatment Approach?

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href="/web/20131110154732/http://www.healio.com/"> Healio</a> <span>›</span> <a href="/web/20131110154732/http://www.healio.com/cardiology"> Cardiology</a> <span>›</span> <a href="/web/20131110154732/http://www.healio.com/cardiology/curbside-consultation"> Curbside Consultation</a> </p>  <div class="content"> <h2> My 40-Year-Old-Patient Has Polycystic Ovary Syndrome and New Onset Hypertension. What Is the Optimal Treatment Approach?</h2> <p class="curbside-author"> Farheen A. Shirazi, MD</p> <p class="curbside-author"> Nanette K. Wenger, MD</p> <p>Polycystic ovary syndrome (PCOS) is a complex of irregular menses, hyperandrogenemia, and obesity that approximates the cardiovascular risk of the metabolic syndrome. It composes a largely forgotten segment of women at risk of cardiovascular disease (CVD). Thus, a major focus of treatment should be early recognition and control of their cardiovascular risk factors. </p> <p><strong>Hypertension and Polycystic Ovary Syndrome<br/> </strong></p> <p>The prevalence of PCOS in women of reproductive age ranges from 6% to 10%. PCOS has been shown to be an independent risk factor for the development of diabetes, dyslipidemia, obesity, hypertension (HTN), and elevated C-reactive protein (CRP). A recent study confirmed a greater than 4-fold increased prevalence of elevated CRP levels (>5 mg/L) in patients with PCOS.<sup>1</sup></p> <p>Although no robust longitudinal cohort study shows the long-term cardiovascular effects of PCOS, there is direct evidence of risk in small trials of CVD risk via coronary artery calcification, carotid intima-media thickness (CIMT), and endothelial dysfunction rivaling that of the metabolic syndrome. In a subset of menopausal women from the Women’s Ischemia Syndrome Evaluation (WISE) study who displayed clinical features consistent with PCOS, Shaw and colleagues confirmed increased cardiovascular events and deaths.<sup>2</sup></p> <p>The most effective prevention of CVD is risk factor modification. The prevalence of hypertension in the PCOS population is approximately 33%. The underlying mechanism of HTN is unknown but appears to be multifactorial, mostly related to the associated systemic inflammatory cascade that may be independent of, or as a result of, the coexistent metabolic syndrome. The metabolic syndrome (Syndrome X) shares many characteristics of PCOS, including hyperinsulinemia (insulin resistance [IR]), dyslipidemia (including hypertriglyceridemia and low HDL), central obesity, and hypertension. Inflammatory biomarkers such as endothelin-1 (a potent vasoconstrictor) have also been implicated in the pathogenesis of HTN in women with PCOS.<sup>3</sup> Androgen excess may also play a role. The ovary in the menopausal woman can produce androgens, and unopposed androgens likely contribute to the higher blood pressure in postmenopausal women. There is sparse evidence of long-term CVD outcomes in PCOS women, save for retrospective data. Wild et al found that women with a history of PCOS 30 years previously had a higher prevalence of hypertension and other cardiovascular diseases later in life than control subjects without PCOS.<sup>4</sup></p> <p>Although there are no consensus guidelines regarding treatment for cardiovascular disease in women with PCOS, targeted therapy for HTN in the PCOS population is similar to that for non-PCOS patients. Blood pressure should be treated to a goal level below 140/90 mm Hg in patients with simple hypertension and below 130/80 mm Hg in complex hypertensive patients. Complex hypertensive patients are those with end-organ manifestations, including left ventricular remodeling (such as left-ventricular hypertrophy), atherosclerosis, diabetes, stroke, or chronic kidney disease. The recommendation is to start with aggressive diet/lifestyle modifications that lead to weight loss, indirectly lowering systolic blood pressure (SBP). If weight loss proves inadequate in lowering blood pressure, medical therapy should be initiated on top of diet and lifestyle recommendations. The drugs of choice are angiotensin-converting enzyme inhibitors (ACE-inhibitor) and diuretics. As PCOS women are often insulin resistant and require medication [eg, metformin, thiazolidinediones (TZDs)], it is wise to avoid drugs that further impair insulin sensitivity (eg, metoprolol, atenolol) or may predispose to weight gain (eg, select oral contraceptives). Women with PCOS treated with an ACE-inhibitor had a significant improvement in SBP and in serum testosterone, suggesting that renin-angiotensin system (RAS) blockade protects against androgen synthesis. Thus, ACE-inhibitors are a great treatment option for HTN in these women. They provide the dual benefit of renal and cardiovascular disease prevention via RAS blockade (proposed pathogenesis of PCOS-associated HTN).</p> <p>Although it is pivotal to treat HTN in PCOS patients, one must not forget aggressive control of the other CVD risk factors that likely predispose to HTN: insulin resistance (IR), obesity, and dyslipidemia (see Table 1).</p> <p><img width="413" height="213" alt="Table 1" src="/web/20131110154732im_/http://www.healio.com/~/media/Curbside/Cardiology/Prevention/Q7/Table 1.jpg"/></p> <p><strong>Insulin Resistance</strong></p> <p>Metformin or TZDs (insulin sensitizers) may be utilized as per endocrinologist recommendations. Twelve weeks of metformin compared with placebo significantly decreased arterial stiffness and improved endothelial function in women with PCOS.<sup>5</sup></p> <p> <br/> <strong>Obesity</strong></p> <p>Moderate sustainable diet and exercise regimen with the goal of significant weight loss (>5% body weight or BMI<30) is encouraged. Bariatric surgery has been shown to improve associated dyslipidemia, HTN, and insulin sensitivity.<sup>6</sup></p> <p><strong>Dyslipidemia</strong></p> <p>The “pleiotropic effects” of statins are proving beneficial in PCOS by decreasing androgen levels and improving insulin sensitivity, offering yet another medication option for PCOS women with persistent dyslipidemia and IR. In a study of 136 women with PCOS randomized to treatment with simvastatin, metformin, or a combination of the 2 drugs for 3 months, insulin sensitivity improved more with simvastatin than with metformin or the combination. Testosterone levels also decreased significantly and comparably in all groups.<sup>7</sup></p> <p><strong>Summary</strong></p> <p>PCOS may be considered analogous to the metabolic syndrome in its complex presentation and associated cardiovascular risk. Thus it warrants a similar rigor applied to early screening and treatment. The goal of antihypertensive therapy in PCOS is to reduce both the individual and the combined risks of cardiovascular, cerebrovascular, and renal disease.</p> <p><strong>References</strong></p> <strong></strong> <p>1. Boulman N, Levy Y, Leiba R, et al. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. <em>J Clin Endocrinol Metab</em>. 2004;89(5):2160-2165.</p> <p>2. Shaw LJ, Bairey Merz CN, Azziz R, et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health—National Heart, Lung, and Blood Institute sponsored Women’s Ischemia Syndrome Evaluation. <em>J Clin Endocrinol Metab</em>. 2008;93(4):1276-1284.</p> <p> 3. Reckelhoff JF. Polycystic ovary syndrome: androgens and hypertension. <em>Hypertension</em>. 2007;49:1220-1221.</p> <p> 4. Wild S, Pierpoint T, Jacobs H, McKeigue P. Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. <em>Hum Fertil (Camb)</em>. 2000;3(2):101–105.</p> <p> 5. Agarwal N, Rice SP, Bolusani H, et al. Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: a randomized, placebo-controlled, crossover trial. <em>J Clin Endocrinol Metab</em>. 2010;95(2):722-730.</p> <p> 6. Malik SM, Traub ML. Defining the role of bariatric surgery in polycystic ovarian syndrome patients. <em>World J Diabetes</em>. 2012;3(4):71-79. </p> <p> 7. Banaszewska B, Pawelczyk L, Spaczynski RZ,  Duleba AJ. Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. <em>J Clin Endocrinol Metab</em>. 2009;94(12):4938-4945.</p>   <p> <div class="fb-like" data-href="" data-send="true" data-width="450" data-show-faces="true"></div> </p> <ul class="share"> <li><a href="#" id="twitter">Tweet</a></li> <li><a href="#" id="facebook">Share</a></li> <li><a href="#" id="linkedin">Link</a></li> <li><a href="#" id="digg">Digg</a></li> <li><a href="#" id="email">Email</a></li> <li class="last"><a href="#" onclick="javascript:window.print();" id="print">Print</a></li> </ul> </div>   <div id="respond"> <h4> Comments</h4> <script language="javascript" type="text/javascript"> var idcomments_acct = 'aa6ff53f9870e40f92f83e1b5df3cddf'; var idcomments_post_id = '{BBC3168B-7FAB-47E9-9209-A3BA0FCE6DF0}'; var idcomments_post_url; </script> <span id="IDCommentsPostTitle" style="display: none"></span> <script type="text/javascript" src="https://web.archive.org/web/20131110154732js_/http://www.intensedebate.com/js/genericCommentWrapperV2.js"></script> <p class="comment-notes"> Healio is intended for health care provider use and all comments will be posted at the discretion of the editors. 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