A Pharmacist’s Guide to the Management of Polycystic Ovarian Syndrome

Polycystic ovary syndrome (PCOS) occurs when there is an overproduction of androgens from the ovaries. PCOS can form cysts around the ovaries due to the lack of hormones needed for ovulation. PCOS affects around 1 in 10 women of childbearing age, with up to 70% of women being undiagnosed globally.¹ The specific cause of PCOS is not fully understood and remains a subject of ongoing research. PCOS can lead to other complications including cancer, diabetes, infertility, hypertension, and cardiovascular disease.²

PCOS can be managed with nonpharmacological and/or pharmacological interventions, depending on the patient's preference and other patient-specific factors. PCOS is an endocrine disorder associated with increased androgen levels, obesity, insulin resistance, irregular menstrual cycles, and other hormonal imbalances. Elevated levels of gonadotropin releasing hormone and luteinizing hormone also contribute to PCOS.³ Symptoms can include hirsutism, acne, alopecia, weight gain, skin tags, acanthosis nigricans, and pelvic pain.³

PCOS can be diagnosed through a combination of physical exams, such as pelvic exam or pelvic sonogram, and blood tests that evaluate levels of follicular stimulating hormone, androgen, and testosterone.⁴ PCOS is most prevalent among women ages 15 to 44 years, and is the leading cause of anovulation and infertility.³ PCOS not only affects a woman’s physical health, but it can also be mentally and financially burdensome, due to the complexity of the condition. As health care workers on the front lines, pharmacists can play an important role in the diagnosis, management, and disease state education of PCOS, in hopes of improving patient outcomes and overall quality of life.

Epidemiology and Etiology

According to the National Institute of Health, approximately 5 million women (1 in 10 women of childbearing age) in the United States are affected by PCOS, making it one of the most common endocrine disorders among women of reproductive age. With varying estimates due to differences in diagnostic criteria, PCOS affects women of all ethnic backgrounds, with some studies suggesting variations in prevalence and clinical features among different populations. As reported in 2017, it was found that Hispanic women with PCOS presented with a higher degree of hyperandrogenism and metabolic aberrations as compared to non-Hispanic women.⁵ Despite these facts, its origin is still largely misunderstood and underdiagnosed.^5,6

PCOS is characterized by hyperandrogenism, which is partly due to increased ovarian and adrenal androgen production. Insulin resistance and compensatory hyperinsulinemia further exacerbate hyperandrogenism by increasing ovarian androgen production and decreasing sex hormone-binding globulin levels, leading to increased free androgens.⁷ Insulin resistance also progresses patients' onset of diabetes and metabolic complications. Lifestyle factors, such as diet and physical activity, also play a role in the development and severity of PCOS. Obesity, particularly central obesity, is commonly associated with PCOS and exacerbates insulin resistance and hyperandrogenism.⁸

Diagnosis and Clinical Presentation

The diagnostic criteria and classification of PCOS have evolved, as more information is learned about the condition.^5,9,10 In 2003, a workshop in Rotterdam formulated a new diagnostic criterion named Rotterdam criteria, which required the presence of 2 conditions out of the following 3: oligomenorrhea/anovulation, clinical/biochemical hyperandrogenism, and polycystic ovaries (≥12 follicles in each ovary measuring 2-9 mm). In 2006, the revised Androgen Excess Society criteria required the specific presence of clinical/biochemical hyperandrogenism in combination with either oligo anovulation or polycystic ovaries.^5,10 The variation in diagnostic criteria adds to the complexity of this disease state in terms of its identification and management.

PCOS can be diagnosed in adolescents soon after menarche and up to menopause. The criteria for diagnosis in adolescents require hyperandrogenism and irregular cycles.⁸ Hallmark signs and symptoms of PCOS include anovulation, hyperandrogenism, and polycystic ovaries.^5,6,9,10 Other major manifestations of PCOS include luteinizing hormone hypersecretion, metabolic disturbances, hyperinsulinemia, insulin resistance, glucose intolerance, dyslipidemia, alopecia, hirsutism, and acne.^5,6,9,10 Women with PCOS are also at increased risk for several comorbidities, including type 2 diabetes, metabolic syndrome, cardiovascular disease, and endometrial cancer.^5-7,9,10 Additionally, PCOS increases the risk of further complications including infertility, pregnancy complications, depression, and anxiety.⁵

Pharmacological and Nonpharmacological Management

The management of PCOS involves a tailored approach depending on the patient's preferences, such as fertility, menstrual regulation, weight reduction, or relief from hyperandrogenic symptoms like acne, hirsutism, or androgenic alopecia. There is no single ideal treatment or cure for PCOS, so therapy is often based on symptomatic relief. The need to improve the clinical and therapeutic management of PCOS patients has become increasingly evident in the last decade. Many treatment possibilities exist to correct the severity of clinical symptoms of PCOS, but no current gold standard or FDA-approved drugs have been identified for the treatment and management of these patients. Below, we will cover a few of the nonpharmacological and pharmacological treatment options for managing symptoms of PCOS.

Lifestyle modifications including weight loss, exercise, dieting, low carbohydrate and sugar diets, nutritional supplements, and smoking cessation can significantly improve many of the symptoms associated with PCOS.^11-14 By addressing lifestyle factors and incorporating complementary therapies, women with PCOS can manage their symptoms and reduce the risk of associated complications. A tailored diet rich in fiber and low in saturated fats and carbohydrates is recommended. Low glycemic index foods like vegetables and whole grains are preferred over high glycemic index foods like white rice, sugary snacks, and processed foods.^12,14 Weight reduction and calorie intake restriction is crucial, as even a 5% to 10% weight loss can restore regular menstrual cycles, reduce metabolic syndrome risk, decrease free testosterone levels, and improve insulin resistance.^11,14

Various supplements, such as vitamin D, alpha-lipoic acid, and omega-3, folic acid, may be effective in managing PCOS symptoms.^11,12,14 These supplements can improve insulin sensitivity, reduce inflammation, and support reproductive health. Regular physical activity can also improve insulin sensitivity and help resume ovulation. Additionally, for the management of hirsutism, treatments can include waxing, plucking, depilatory creams for hair removal, thermolysis, and laser therapy are also effective.

Pharmacological management of PCOS can include oral contraceptives, metformin, leuprolide, clomiphene, and/or spironolactone. The first-line treatment for insulin resistance is metformin, which is a common symptom associated with PCOS.^11,12 Metformin is also weight-neutral and may assist in weight loss and obesity; evidence also shows it may help improve fertility in this patient population.^12,13

Other diabetic agents used include GLP-1 agonists, which are selected for their weight reduction benefit and improved insulin/glycemic control.^11,12 Insulin-sensitizing agents are indicated for most women with PCOS because they have positive effects on insulin resistance, menstrual irregularities, anovulation, hirsutism, and obesity.

Hormonal contraceptives, either oral tablets, patches, or vaginal rings, are first-line treatments for ovulation irregularities, hirsutism, and acne associated with PCOS. Clomiphene (Serophene; Cosette Pharmaceuticals) is the first-line treatment for inducing ovulation.^11,12 Medications such as desogestrel/ethinyl estradiol and letrozole (Femara; Novartis AG) are also commonly prescribed. Combination oral contraceptives, especially those with progestins like norgestimate, desogestrel, or drospirenone (due to their low androgenic effects), are among the most used medications for hirsutism in women with PCOS. Drospirenone is also particularly helpful in reducing hormonal acne.^11,12 First-line treatments for hirsutism include spironolactone (Aldactone; Pfizer), metformin, finasteride (Propecia; Merck & Co), and eflornithine (Vaniqa; USWM, LLC).^12,13 Spironolactone is one of the most prescribed medications for hirsutism, which works by blocking androgens at the hair follicle/sebaceous gland and reduces the secretion of androgens from the adrenal gland, thereby reducing facial hair growth.^11-13

Pharmacists can work alongside patients and physicians to create a comprehensive treatment plan based on a patient’s symptoms. For example, a patient whose primary goals are to control acne and insulin resistance may benefit from a combination regimen of a drospirenone-based oral contraceptive medication and metformin.

The Pharmacist’s Role

Patients with PCOS are often prescribed medications to help manage various symptoms associated with their condition, making a pharmacist vital to their care. Pharmacists can provide important counseling points when dispensing these medications for proper use. Pharmacists are often the last line of defense to educate patients about PCOS, its implications, and the importance of adherence to medication regimens.

Many of the medications prescribed for PCOS have other indications as well, thus emphasizing the pharmacist’s role to educate the patient on proper use. For example, metformin, a medication commonly prescribed for PCOS, is an insulin-sensitizing agent used for type 2 diabetes mellitus as well as first-line treatment for PCOS patients with no ovulation.¹⁵ Patients should be counseled on the indications and adverse effects of their medications to mitigate any confusion and polypharmacy risks. Pharmacists can also directly influence the treatment plan for patients with PCOS and can work closely alongside physicians to make evidence-based pharmacotherapeutic recommendations on the most effective treatments for patients with PCOS, based on their patient-specific factors. The pharmacist’s role in monitoring patients with PCOS also allows for an assessment of the effectiveness of the prescribed treatment plan and the patient’s overall health. In addition to medication recommendations and counseling, pharmacists can offer advice on diet, exercise, and weight management strategies to help mitigate symptoms associated with PCOS and reduce the risk of developing associated conditions such as type 2 diabetes mellitus and cardiovascular disease.¹⁵

Conclusion

Significant health disparities surrounding PCOS persist, encompassing physical, emotional, and financial burdens.¹⁶ To improve the outcomes of the women affected by PCOS, providers should focus on the patients’ needs and involve patients in goals of care and provide more educational resources as necessary. Additionally, utilizing nonpharmacological options to address a patient's PCOS symptoms can lead to a more sustainable resolution, significantly reducing health care costs while promoting overall well-being and quality of life.

REFERENCES

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2. Polycystic ovary syndrome (PCOS). Johns Hopkins Medicine. February 28, 2022. Accessed June 26, 2024. https://www.hopkinsmedicine.org/health/conditions-and-diseases/polycystic-ovary-syndrome-pcos

3. Polycystic ovary syndrome. Office on Women’s Health. Accessed June 26, 2024. https://www.womenshealth.gov/a-z-topics/polycystic-ovary-syndrome

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6. PCOS (polycystic ovary syndrome) and diabetes. Centers for Disease Control and Prevention. December 30, 2022. Accessed June 28, 2024. https://www.cdc.gov/diabetes/risk-factors/pcos-polycystic-ovary-syndrome.html?CDC_AAref_Val=https://www.cdc.gov/diabetes/basics/pcos.html.

7. Armanini D, Boscaro M, Bordin L, Sabbadin C. Controversies in the pathogenesis, diagnosis and treatment of PCOS: focus on insulin resistance, inflammation, and hyperandrogenism. Int J Mol Sci. 2022;23(8):4110. doi:10.3390/ijms23084110

8. Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022;10(9):668-680. doi:10.1016/S2213-8587(22)00163-2

9. Overview Polycystic ovary syndrome. NHS. Accessed April 14, 2024. https://www.nhs.uk/conditions/polycystic-ovary-syndrome-pcos/

10. Williams T, Mortada R, Porter S. Diagnosis and Treatment of Polycystic Ovary Syndrome. Am Fam Physician. 2016;94(2):106-113.

11. Radosh L. Drug treatments for polycystic ovary syndrome. Am Fam Physician. 2009;79(8):671-676.

12. Calcaterra V, Verduci E, Cena H, et al. Polycystic Ovary Syndrome in Insulin-Resistant Adolescents with Obesity: The Role of Nutrition Therapy and Food Supplements as a Strategy to Protect Fertility. Nutrients. 2021;13(6):1848. doi:10.3390/nu13061848

13. Cumming DC, Yang JC, Rebar RW, Yen SSC. Treatment of Hirsutism With Spironolactone. JAMA. 1982;247(9):1295–1298. doi:10.1001/jama.1982.03320340049034

14. Singh S, Pal N, Shubham S, et al. Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. J Clin Med. 2023;12(4):1454. doi:10.3390/jcm12041454

15. Stankiewicz M, Norman R. Diagnosis and management of polycystic ovary syndrome: a practical guide. Drugs. 2006;66(7):903-912. doi:10.2165/00003495-200666070-00002

16. Contemporary OB/GYN. Petronelli M, ed. Study reveals critical gaps in care for PCOS patients. May 17, 2024. Accessed July 9, 2024. https://www.contemporaryobgyn.net/view/study-reveals-critical-gaps-in-care-for-pcos-patients