Polycystic Ovarian Syndrome Awareness Month
Polycystic Ovarian Syndrome, a Summarized Overview
By: Doug Herrett, MD
Editor’s Note: To kick off Polycystic Ovary Syndrome (PCOS) Awareness Month, we are featuring an overview of this common condition that impacts millions of women. PCOS can present with varying symptoms and severity as women can be predisposed to different distinct risk factors. Because of this, management and treatment approaches — which might include the use of fertility awareness-based methods (FABMs) — will vary as well. Doug Herrett, a former FACTS elective participant, summarized a 2016 overview of PCOS published in Frontiers Physiology.
Polycystic ovary syndrome (PCOS) is a common diagnosis among female adolescents and adults, prevalent in approximately 4 to 10% of women of reproductive age. PCOS impacts upwards of 3 to 26% of adolescents, and recent evidence suggests that PCOS might actually be a lifelong syndrome originating in utero. PCOS can present with variable symptomology and severity, but classically includes signs of anovulation and hyperandrogenism with either polycystic or normal ovaries.  Different phenotypes predispose women to distinct risk factors for common complications of PCOS, and management of PCOS may utilize a variety of treatment approaches.
Complications of PCOS
Diagnosis of PCOS is often difficult, as there is considerable diversity in presentation among women of different ages and ethnic groups. In addition to the classic manifestations of PCOS involved in the diagnosis (anovulation, hyperandrogenism, and polycystic ovaries), there are several other common sequelae to consider, including obesity, metabolic syndrome, insulin resistance and hyperinsulinemia.  For example, as a result of increased rates of obesity and metabolic syndrome, individuals with PCOS are at an increased risk for sleep apnea and future cardiovascular events, respectively. Menstrual irregularity, infertility, and hirsutism may also result from anovulation and hyperandrogenism. Psychiatric concerns, such as anxiety, depression, and eating disorders, are also linked with PCOS.  Diagnosis of PCOS is often difficult, as there is marked variability in disease features and severity.
“Diagnosis of PCOS is often difficult, as there is considerable diversity in presentation among women of different ages and ethnic groups.”
Pathophysiology of PCOS
PCOS is a heterogeneous condition with seemingly vast variation in genetic etiology —or perhaps an etiology that is yet undiscovered. However, it is largely accepted that the etiology involves uncontrolled ovarian steroidogenesis, aberrant insulin signaling and/or sensitivity, oxidative stress, and various genetic and environmental factors.  Excessive ovarian steroidogenesis, a primary factor in PCOS, appears to be related to intrinsic dysregulation in theca cell signaling. Among women with PCOS, theca cells release excess androgens due to the activation of steroidogenesis, even without trophic factors present.  Abnormal cell signaling, in conjunction with the decreased FSH:LH ratio typically observed, results in excess androgens that cannot be adequately converted into estrogens. This leads to a relative decrease in estrogen and subsequent anovulation.  Insulin resistance, another aspect of PCOS, may have multiple etiologies involving both signaling and post-receptor binding. Hyperandrogenism and insulin resistance may be further exacerbated by increases in glyco-oxidative stress related to mitochondrial dysfunction observed in certain studies.  The causes of PCOS remain multifactorial with variable patterns of inheritance. 
Diagnosis of PCOS
Given the various presentations of PCOS, it is widely considered a diagnosis of exclusion; however, there are three main sets of criteria used to make the diagnosis: NIH Criteria, PCOS Society Criteria, and Rotterdam Criteria.  They are as follows:
PCOS Society Criteria
(A) + (B) or (C)
(Any 2 of the following)
● Menstrual irregularity
● (A) Hyperandrogenism
● (B) Menstrual irregularity
● (C) Polycystic ovaries on ultrasound
● Menstrual irregularity
● Polycystic ovaries on ultrasound
“It is worth noting that, despite the name, approximately one-third of cases of polycystic ovarian syndrome do not involve polycystic ovaries.”
Workup of suspected PCOS serves to both rule in PCOS and rule out other potential causes of presenting symptoms, including menstrual irregularity and manifestations of hyperandrogenism (e.g. hirsutism, acne, androgenic alopecia). This generally involves detailed medical and family history, thorough physical examination with vital signs (notably blood pressure), and various labs germane to both efforts. Since the differential diagnosis for patients presenting with PCOS symptoms includes thyroid dysfunction, hyperprolactinemia, Cushing syndrome, CAH, acromegaly, and adrenal/ovarian tumors, common rule-out labs may include thyroid function tests, serum prolactin levels, free or 24-hour cortisol, total and free testosterone levels, 17-OH progesterone and free androgen index.  It is not advisable to order all of these labs reflexively; rather, presenting signs and symptoms should dictate testing. Important rule-in labs to confirm a PCOS diagnosis include androgen levels (including DHEA-S), FSH:LH ratio, serum glucose or HbA1C, lipid profile, and serum hormone levels including estrogen and progesterone.  In terms of imaging, the ovaries can be assessed for cysts via ultrasound; a transvaginal approach is preferred if feasible.  If imaging for malignancy is indicated, this generally involves CT or MRI.
The use of fertility awareness-based methods (FABMs) may also help guide the workup of PCOS. Menstrual irregularity is one of the most common presentations of PCOS, and FABMs can be leveraged to obtain insight into a woman’s cycle through the use of charting. Trained practitioners can use this information to further guide workup and tailor intervention to the patient. For example, many physicians unfamiliar with FABMs opt for a day 21 progesterone level to confirm ovulation. This approach assumes regular cycles with ovulation on day 14, which rarely occurs in women with PCOS. With charting, however, women can track the production of cervical fluid and the changing patterns that may indicate whether ovulation has likely occurred. FABM-trained clinicians can then time laboratory testing to get a more accurate picture of a woman’s hormonal profile, including whether or not she is truly experiencing anovulatory cycles.
Treatment of PCOS
The initial treatment of PCOS is often aimed at addressing individual symptoms, such as irregular cycles, acne, insulin resistance or infertility. However, a more comprehensive approach, including lifestyle modifications and multiple medications may be necessary to adequately address this syndrome.  Many of the short- and long-term consequences of PCOS can be managed effectively through behavioral and medical intervention. It is also important to treat PCOS as early as possible, though diagnosis is not always easy, particularly among adolescents.
First-line treatment for women with PCOS who are overweight should focus on lifestyle modifications, including exercise and calorie-restricted diets. Weight loss, even a small percentage, has been shown to improve menstrual cycle regularity, insulin sensitivity and fertility.   Although no specific diet nor exercise regimen has been empirically shown to be more effective, these interventions should be offered. If lifestyle intervention alone does not adequately manage symptoms, medical management may be pursued.
“First-line treatment for women with PCOS who are overweight should focus on lifestyle modifications, including exercise and calorie-restricted diets.”
Oral contraceptive pills (OCPs) are also often recommended as first-line treatment, particularly for symptoms of hyperandrogenism and menstrual irregularity. OCPs have been shown to decrease androgen levels via suppressing the hypothalamic-pituitary-ovarian (HPO) axis.  OCP use is not without controversy, however, as several studies have demonstrated associations between OCP use in PCOS and increased insulin resistance and worsened cardiovascular profile.  FABMs present an alternative approach to management of PCOS that assesses each facet of a woman’s menstrual cycle and implements interventions accordingly. For example, if she presents with anovulatory cycles , progesterone may be supplemented during the second half of the cycle to improve menstrual regularity.
Metformin is another common medication used in patients with PCOS with mixed reports of effectiveness. While it has been postulated to enhance glucose effectiveness and lower androgen levels among individuals with PCOS, other studies do not show this.  Despite a lack of scientific consensus on metformin use for all women with PCOS, it is still considered first-line for cutaneous manifestations of PCOS (e.g. acanthosis nigricans).
Newer medication options for PCOS treatment include myo-inositol and D-chiro-inositol, both forms of inositol, which have demonstrated promise in managing insulin resistance, aspects of metabolic syndrome, certain complications of androgen excess (e.g. acne), menstrual irregularity, and subfertility. Inositol treatment typically involves combination therapy . Spironolactone has also been shown in several studies to address insulin insensitivity and androgen excess but without consensus in the literature regarding effectiveness.
Myriad lifestyle and medical interventions, including surgical techniques, are available to treat PCOS. In addition to managing physiological symptoms, it is critical to acknowledge and adequately treat psychological or psychiatric consequences of PCOS. A holistic approach, motivated by targeted hormonal profiles in combination with charting using a FABM, may offer women hope for accurate diagnosis and effective treatment.
 El Hayek S, Bitar L, Hamdar LH, Mirza FG, Daoud G. Polycystic Ovarian Syndrome: An Updated Overview. Front Physiol. 2016;7:124. doi: 10.3389/fphys.2016.00124. PMID: 27092084; PMCID: PMC4820451.
 Lucidi, RS. Polycystic Ovarian Syndrome. Practice Essentials, Background, Etiology. Medscape. June 14, 2021. Accessed September 27, 2021. https://emedicine.medscape.com/article/256806-overview.
 Williams T, Mortada R, Porter S. Diagnosis and Treatment of Polycystic Ovary Syndrome. Am Fam Physician. 2016 Jul 15;94(2):106-13. PMID: 27419327.
ABOUT THE AUTHOR
Doug Herrett, MD
Doug Herrett, MD wrote this review as a fourth-year medical student at University of New England planning to specialize in pediatrics. He completed the FACTS elective course during the fall of 2021 while serving in the military.