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PCOS: Alternative Management and Long-Term Risks

By Desiree’ M. McCarthy-Keith, MD, MPH

Most practitioners are able to recognize the classic features of PCOS: obesity, androgen excess and irregular menstrual cycles. However, many patients will have few features or a subtler presentation. Despite varying degrees of the condition, all women with PCOS are at risk for metabolic and endocrine sequelae. Women’s health providers should understand that the metabolic complications of PCOS do not resolve after menopause, and for some women they may worsen.

Lifestyle Modications
Women with PCOS may be normal weight or lean, but the majority of women with PCOS in the United States are obese. Obesity may worsen the presentation of PCOS and increase the risk for insulin resistance (IR), impaired glucose tolerance (IGT), type 2 diabetes (T2D) and dyslipidemia. Weight loss, achieved through diet modification and exercise, is first-line management for obese women with PCOS. A 2011 Cochrane review concluded that exercise, with or without dietary modification, reduces total testosterone, hirsutism, weight, waist circumference and fasting insulin levels in women with PCOS.1 Diets high in fiber and low in trans fatty acids were significant predictors of weight loss and metabolic improvement.2 Both high-protein and normal protein diets produce comparable metabolic benefits.3

Adjunctive Treatment in PCOS
While lifestyle modification is first-line therapy for PCOS, insulin sensitizing medications are often prescribed to remedy the metabolic complications. Metformin is the standard medical treatment for IR in PCOS, but it’s effectiveness is limited due to poor tolerance and limited compliance by patients. Acupuncture is a favorable alternative treatment, due to its relative safety and lower incidence of adverse effects compared to conventional medical therapies. In Traditional Chinese Medicine, specific abdominal acupuncture points correspond to metabolic, endocrine and reproductive function and stimulation of these points can improve the effects of PCOS. One randomized study comparing daily acupuncture to standard metformin therapy found reduced BMI, reduced waist-to-hip ratio and improved clinical androgen effects in both groups. Lipid profile, glucose and insulin values were also improved in both groups, with greater improvement in menstrual frequency in the abdominal acupuncture group.4

Dietary supplements may be a useful adjunct or alternative to metformin therapy. Myo-inositol demonstrates effective insulin sensitizing activity, comparable to metformin, with potentially greater tolerability.5 Both inositol isoforms, D- chiro-inositol and myo-inositol, improve ovarian function and metabolic parameters in patients with PCOS.6 There is some evidence that N-acetyl cysteine (NAC), derived from the amino acid L-cysteine, also improves fasting glucose, fasting insulin and lipid parameters in women with PCOS when compared to metformin.7 Limited data also suggest that cinnamon supplements may regulate menstrual cycles and co- enzyme Q10 (CoQ10) supplementation improves glucose metabolism and lipid parameters in women with PCOS.8,9

The Older PCOS patient
In younger women, the management of PCOS is primarily focused on the reproductive aspects of the condition. As women with PCOS enter their late 30s and 40s, the metabolic and cardiovascular risks become more significant. The greatest long-term health risks for women with PCOS are for development of T2D, cardiovascular disease (CVD) and metabolic syndrome. The progression from normal glucose tolerance to IGT or T2D occurs more rapidly in women with PCOS and the deterioration in glucose tolerance is more signficant in obese women and those with first degree relatives with T2D.10

The risk for CVD in women with PCOS is the result of longstanding metabolic dysfunction, and risk is further compounded by aging. Long-term studies identify several cardiovascular risk factors, including diabetes, hypertension, obesity and elevated cholesterol. Women with PCOS also exhibit more severe carotid-intima media thickening and coronary artery calcification compared to women without PCOS.11 In addition, women with a history of premenopausal menstrual irregularity and androgen excess experience more cardiovascular events and atherosclerotic CVD compared to controls.12,13

The menopausal PCOS phenotype is difficult to describe, since the diagnostic criteria for PCOS are generally not applicable after menopause. The menstrual irregularities of PCOS are no longer observable and the natural course of androgen excess is unknown. Women with PCOS demonstrate higher prevalence of obesity, T2D and CVD risk factors and these conditions are expected to worsen as women transition through menopause. All peri- and postmenopausal women should be routinely screened for IGT, T2D and CVD and history of PCOS, prior irregular menses and hirsutism should be considered in their risk assessment.
To avoid missed opportunities for intervention, look beyond the typical PCOS phenotype in your patients. Always consider lifestyle modification, with diet and regular exercise, as the foundation of PCOS management and consider adjunctive therapies, including acupuncture and dietary supplementation as useful alternatives to standard medical therapy. Lastly, remember that the metabolic, endocrine and cardiovascular consequences of PCOS do not subside when reproductive function ends.


References

1. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2011 16;(2).

2. Nybacka A, Hellstrom PM, Hirschberg AL. Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement in overweight polycystic ovary syndrome-Substudy of randomized trial between diet, exercise and diet plus exercise for weight control. Clin Endocrinol 2017;87(6):680-688.

3. Toscani MK, Mario FM, Radavelli-Bagatini S, Wiltgen D, Matos MC, Spritzer PM. Effect of high-protein or normal-protein diet on weight loss, body composition, hormone, and metabolic profile in southern Brazilian women with polycystic ovary syndrome: a randomized study. Gynecol Endocrinol. 2011;27(11):925-30.

4. Zheng YH, Wang XH, Lai MH, Yao H, Liu H, Ma HX. Effectiveness of abdominal acupuncture for patients with obesity-type polycystic ovary syndrome: a randomized controlled trial. J Altern Complement Med. 2013;19(9):740-5.
5. Tagliaferri V, Romualdi D, Immediata V, De Cicco S, Di Florio C, Lanzone A. Metformin vs myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study. Clin Endocrinol 2017;86(5):725-730.

6. Pizzo A, Laganà AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositolon ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol 2014;30(3):205-8.

7. Javanmanesh F, Kashanian M, Rahimi M, Sheikhansari N. A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome. Gynecol Endocrinol 2016;32(4):285-9.

8. Kort DH, Lobo RA. Preliminary evidence that cinnamon improves menstrual cyclicity in women with polycystic ovary syndrome: a randomized controlled trial. Am J Obstet Gynecol 2014;211(5):487.e1-6.

9.Samimi M, Zarezade Mehrizi M, Foroozanfard F, Akbari H, Jamilian M, Ahmadi S. The effects of coenzyme Q10 supplementation on glucose metabolism and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol 2017;86(4):560-6.

10. [Celik C, Tasdemir N, Abali R, Batsu E, Yilmaz M. Progression to Impaired glucose tolerance or type 2 diabetes mellitus in polycystic ovary syndrome: a controlled follow-up study. Fertil Steril 2014;101(4):1123-8.

11. Cibula D, Cifková R, Fanta M, Poledne R, Zivny J, Skibová J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod 2000;15(4):785-9.

12. Shaw LJ, Bairey Merz CN, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD, 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. J Clin Endocrinol Metab 2008;93 (4)K:1276-84.

13. Krentz AJ, von Mühlen D, Barrett-Connor E. Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease. Menopause 2007;14:284-92.

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