PCOS: POLYCYSTIC OVARY SYNDROME

By Dr. Nicole Sundene

Naturopathic Doctor

Polycystic ovary syndrome (PCOS) is a common medical condition of women affecting the reproductive organ and sexual health. It causes hormonal imbalance such as the disruption of estrogen, androgens, and progesterone levels. As a result, various clinical symptoms develop, including abnormal menstruation, infertility, and high cancer risk. ^{[1, 4, 7]}

PCOS is highly common among women of childbearing years, such as between 15 to 44 yrs. of age. According to the Centre for disease control and prevention (CDC), PCOS is affecting 6% to 12% of US women aged between 15–49 years. Also, a research study estimated the worldwide prevalence between 6% and 26%. Women with a family history of PCOS or who have obesity are at high risk of developing PCOS. ^{[1, 2]}

Symptoms of PCOS

PCOS symptoms vary from mild to severe and mostly appear in the late teens or early 20s. It involves a few or many of the below symptoms. ^{[1, 3, 7, 8]}

• Abnormal Menstruation: Irregular, Light Prolonged, or sometimes totally absent periods. It may be accompanied by heavy uterine bleeding.
• Infertility: Women with PCOS show difficulty in conceiving, failure to ovulate, or completely infertile.
• Polycystic Ovaries: Numbers of cysts develop in the ovaries, ovaries get enlarged, and fail to function properly. Also, in some cases, it is accompanied by pelvic pain or pain in the lower abdomen.
• Hirsutism: Excessive hair growth, mainly on the patient's chest, face, back, or buttocks, due to increased level of circulating Androgen hormone. Also, the thinning of hair, hair damage, or hair loss from the head can occur.
• Weight gain: Mainly due to accumulation of fats around the belly and too much insulin production resulting in obesity.
• Skin conditions: PCOS disrupts skin integrity by causing acne, overactive sebaceous gland, and skin discoloration; usually become darkened in the area of the neck, armpits, and under the breast.

Types of PCOS

Research studies categorized PCOS into many types based on the clinical symptoms and causes responsible for the development and progression. The main PCOS types include: ^{[8, 9]}

• Insulin-resistant PCOS: This is the most common PCOS type caused by pollution, smoking, high sugar, overweight, and excess fat content resulting in high insulin level in the body or insulin resistance. Moreover, the high amount of insulin secretion prevents ovulation and favors the production of testosterone.
• Inflammatory PCOS: The inflammation-induced PCOS is characterized by ovulation suppression, hormonal imbalance, and Hyperandrogenemia (HA). Stress, environmental toxins, and inflammatory dietary like gluten are responsible for inflammation-induced PCOS.
• Hidden-cause PCOS: This is considered the simpler PCOS type caused by multiple factors, including thyroid disease, iodine or zinc deficiency (ovaries need iodine and zinc), poor diet, and artificial sweeteners consumption.
• Pill-induced PCOS: The second most common type of PCOS is caused by birth control pills administration that suppresses ovulation. The ovulation may resume after months  or even years after stopping the use of birth control pills.
• Other types include the adrenal PCOS and Lean type of PCOS.

New research on PCOS presented the following subgroups of PCOS patients based on genetic markers. ^{[8, 9]}

• Reproductive group: Patients with high Luteinizing Hormone & Sex hormone-binding globulin level, plus low Body Mass Index and Insulin level.
• Metabolic group: Patients with high Body Mass Index, glucose level & insulin level, plus low Luteinizing Hormone & Sex hormone-binding globulin level.  
• Indeterminate group: Patients who did not fit into the above two groups.

PCOS Diagnosis and its Criteria

Diagnosis of PCOS should begin with the patient's questioning, family history, physical examination, and checking the other endocrine parameters. As PCOS is a complex disease, so research studies devised criteria for its diagnosis; based on the presence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The presences of any two clinical symptoms in the patient among the hyperandrogenism, ovulatory dysfunction, and polycystic ovaries are necessary for PCOS diagnosis. ^{[2, 3]}

The clinician should consider the menstrual history, weight gain or loss, and cutaneous findings such as excessive hair, acne, alopecia, and dark patches for hyperandrogenism confirmation. Plus, ask and evaluate the presence of ovulatory dysfunction via oligomenorrhea and amenorrhea. Also, check for the other medical complications associated with PCOS. ^[3]

Other lab approaches to assist the diagnostic criteria to include; ^{[2, 3]}

• A pelvic examination to check any overgrowth in ovaries or uterus.
• Blood test evaluation is performed to evaluate abnormal endocrine function or hormone levels. Also, to analyze the level of cholesterol, insulin, and triglyceride for comorbidities of PCOS.
• Ultrasonography or other imaging techniques is used for confirming the presence of abnormal follicles in the ovary (12-25 or more, the 25 follicles of 2 to 9 mm in diameter) or any other uterine or ovary damage.

Medical Complications of PCOS

Women with PCOS are at high risk of developing certain medical complications. These include type 2 diabetes, gestational diabetes, heart disease, hypertension, depression, sleep disorders, eating disorders, anxiety, plaque formation, and stroke. ^[6]

PCOS Treatment Guidelines

Although there is no definite cure for PCOS; however certain kinds of treatment interventions are recommended for resolving PCOS symptoms and complications. These interventions include both pharmacological and non-pharmacological approaches that treat symptoms and regulate normal physiological function. ^{[1, 2, 5]}

PCOS Medication Treatment

Different classes of medicines are used for the treatment of PCOS complaints. These include;

Clomiphene: It is an oral anti-estrogen agent that helps ovulation and infertility. Studies recommend the administration of clomiphene during the first part of the menstrual cycle for better outcomes. Sometimes, clomiphene is given in combination with dexamethasone or metformin to increase the pregnancy rate. The side effects associated with the use of clomiphene include hot flashes, mood changes and can rarely cause vision changes that need immediate attention. It is important to note that some studies reported a high rate of multiple pregnancies, up to 7.8%, with clomiphene use. ^{[1-3, 5]}

Letrozole: It is an anti-estrogen and aromatase inhibitor that helps ovulation induction during PCOS therapy. It stimulates the ovaries and helps the regulation of ovulation, and treats infertility. Studies suggested that the use of letrozole shows higher live-birth and ovulation rates in PCOS patients. Safety studies reported certain side effects, including more fatigue and dizziness with the use of letrozole. Also, it rarely causes hot flashes and possesses a serious concern about teratogenicity compared to clomiphene. In some countries, it is not recommended for women's infertility treatment due to black box warnings. ^{[1-3, 5]}

Metformin: It is an oral anti-diabetic medication that improves insulin resistance and decreases insulin concentration. Mostly, it is recommended as a second-line drug of choice after clomiphene that induces ovulation, lowers serum androgen, and helps menstrual frequency. Moreover, it showed the best results in combination with clomiphene in obese women with PCOS. Side effects associated with the use of metformin include lactic acidosis and gastrointestinal symptoms such as diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia. ^{[1-3, 5]}

Gonadotropins: These are hormones intended for parenteral administration that help a higher rate of ovulation, monofollicular development and increase the chances of conception. ^{[1, 3]}

GLP-1 agonists: GLP-1 (Glucagon-Like Peptide) agonists increase insulin production from pancreatic beta cells and improve insulin sensitivity. Studies reported that they significantly help the treatment of obesity and diabetes. However, it can cause side effects, including appetite suppression, pancreatitis, and increase risk of thyroid cancer and psychiatric conditions. ^{[1, 3]}

Oral contraceptives: Oral contraceptives such as estrogen and progestin therapy help treat PCOS symptoms via inhibition of Luteinizing and androgen hormone secretion, increasing the Sex hormone-binding globulin level, and also act as steroids receptors blocker. The side effects of oral contraceptives include a high risk of thromboembolic events, developing type 2 diabetes, elevated cholesterol and triglyceride level, and may impair insulin sensitivity. Therefore a low dose of oral contraceptives is recommended as the above adverse events are high dose-dependent in high-risk women with PCOS. ^{[1-3, 5]}

Progestin therapy: Progestins such as Cyproterone acetate and drospirenone provide anti-androgenic properties. In some countries, it is highly recommended in combination with an oral contraceptive to treat PCOS. The side effects of progestin therapy include mood elevation, weight gain, and breakthrough bleeding. ^{[1-3, 5]}

Spironolactone: It helps the treatment of excessive hair and acne. However, there are limited studies about its effectiveness. It is advised to use it with caution in women with renal impairment as it aggravates hyperkalemia as a side effect. Also, it is not recommended during pregnancy due to teratogenicity (congenital disabilities). ^{[1-3, 5]}

Flutamide: It is an androgen-receptor antagonist effective for the treatment of excessive hair growth. However, extensive research is needed to establish its proper recommendation. The side effects of Flutamide use include dry skin and teratogenic effects. ^{[1-3, 5]}

5a-reductase inhibitors: 5a-reductase inhibitors such as Finasteride helps the treatment of hirsutism and male alopecia. It shows similar efficacy to spironolactone and flutamide. However, the use of Finasteride is associated with teratogenicity (birth defects) and minimal renal and hepatic toxicity. ^{[1-3, 5]}

Thiazolidinediones: Certain studies reported the benefits of thiazolidinediones such as troglitazone in the management of PCOS. However, these drugs are not recommended in women due to the high concern of severe hepatotoxicity, reproductive toxicity, cardiovascular risk, and weight gain. ^{[1-3, 5]}

Topical agents

A topical formulation such as Eflornithine (Vaniqa) slows down excessive facial hair growth in PCOS women. ^[3]

Non-Pharmacological approach

Non-pharmacological approaches involve applying electrolysis that passes electric current into the hair follicles, damage them, and arrest hirsutism. ^[3]

Weight loss

Weight loss is considered a gold standard for managing PCOS symptoms as weight loss improves insulin sensitivity, particularly in obese PCOS women. Also, obesity increases the risk of metabolic and reproductive abnormalities associated with PCOS. Weight loss is recommended as the first line of treatment for infertility in obese women with PCOS. Unfortunately, there is no approach for permanent weight loss, and weight decrease relapsed in around 90-95% of patients. However, bariatric surgery significantly sustains and reduces weight in obese individuals. Moreover, a hypocaloric diet also helps weight reduction in women with PCOS. But there is no clear evidence of the positive impact of weight reduction On PCOS symptoms. ^{[2, 3]}

Natural management approaches 

The lifestyle modification for the management of PCOS symptoms include the following interventions. 

• Improve Carb-Protein uptake as it positively impacts insulin synthesis in the body.
• Add a Mediterranean diet to the meal as it contains olive oil, green vegetables, and fish like tuna and mackerel that provide anti-inflammatory effects.
• Increase the consumption of a fiber-rich diet will help digestion relation symptoms.
• Consume supplements such as Iron as it improves hemoglobin and also helps anemia.
• Avoid caffeine and alcohol as it favors insulin resistance.
• Supplementation of Zinc may help the alopecia symptoms.
• Evening primrose oil, calcium, chromium, inositol, cinnamon, Berberine and Vit D intake improve insulin resistance and may reduce pain associated with menstrual cycle irregularities.
• Regular exercise could be beneficial for weight reduction and may improve diabetic symptoms.  

References

1. Ndefo, U. A., Eaton, A., & Green, M. R. (2013). Polycystic ovary syndrome: a review of treatment options with a focus on pharmacological approaches. P & T : a peer-reviewed journal for formulary management, 38(6), 336–355.
2. Williams, T., Mortada, R., & Porter, S. (2016). Diagnosis and Treatment of Polycystic Ovary Syndrome. American family physician, 94(2), 106–113. https://pubmed.ncbi.nlm.nih.gov/27419327/
3. Legro RS. Evaluation and Treatment of Polycystic Ovary Syndrome. [Updated 2017 Jan 11]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278959/
4. Goodarzi, M., Dumesic, D., Chazenbalk, G. et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7, 219–231 (2011). https://doi.org/10.1038/nrendo.2010.217
5. Ajossa, S., Guerriero, S., Paoletti, A. M., Orrù, M., & Melis, G. B. (2004). The treatment of polycystic ovary syndrome. Minerva ginecologica, 56(1), 15–26.
6. Palomba, S., Santagni, S., Falbo, A., & La Sala, G. B. (2015). Complications and challenges associated with polycystic ovary syndrome: current perspectives. International journal of women's health, 7, 745–763. https://doi.org/10.2147/IJWH.S70314
7. Rasquin Leon LI, Mayrin JV. Polycystic Ovarian Disease. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459251/
8. Matthew Dapas, Frederick T. J. Lin, Girish N. Nadkarni, Ryan Sisk, Richard S. Legro, Margrit Urbanek, M. Geoffrey Hayes , Andrea Dunaif; “Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis” Published: June 23, 2020, https://doi.org/10.1371/journal.pmed.1003132
9. https://thehormonedietitian.com/types-of-pcos/
10. McCartney, C. R., & Marshall, J. C. (2016). CLINICAL PRACTICE. Polycystic Ovary Syndrome. The New England journal of medicine, 375(1), 54–64. https://doi.org/10.1056/NEJMcp1514916
11. Sirmans, S. M., & Pate, K. A. (2014). Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology, 6, 1–13.
12. Witchel, S. F., Oberfield, S. E., & Peña, A. S. (2019). Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls. Journal of the Endocrine Society, 3(8), 1545–1573. https://doi.org/10.1210/js.2019-00078

Dr. Nicole Sundene, NMD

(480) 837-0900

Dr. Sundene is a Naturopathic Doctor in Scottsdale, Arizona, and is considered a Female Hormone Expert  in Women's Health and Bioidentical Hormones. She specializes in Holistic Women's Health for Menopause, Thyroid, Hashimotos, PMS, Perimenopause, Autoimmune, Postpartum, Chronic Fatigue, Depression, Anxiety, Food Allergies, Digestion, Dermatology , Acne, Psoriasis, Eczema and Adrenal Hormonal Conditions. In 1999 she began working for a Hormone Doctor prior to starting Naturopathic Medical School. With over 22 years of experience in both Prescription and Natural women's health and hormones she presents to women the best integrated health solutions for their Chronic Disease. She has been an Herbalist for over 27 years and enjoys teaching women how to use herbs to balance their hormones, nutrition and optimize their health. Dr. Sundene relies on blood testing for her hormone metrics. The hormone testing is covered per the patient's insurance plan and conducted at certain points in the woman's menstrual cycle. To learn more about Hormone Testing for Women Visit: Bioidentical Hormones. Follow Dr. Sundene on Instagram, Twitter and Facebook for more tips on Women's Health, Female Hormones and Naturopathy!