NR 602 WEEK 6 GRAND ROUNDS - PCOS

What is PCOS? Women with Polycystic Ovarian Syndrome (PCOS) have abnormalities with the metabolism of androgens and estrogen, which lead to an increase in androgen production (Beena & Thomas, 2016). PCOS can result from abnormal functioning within the hypothalamic-pituitary-ovarian axis (Beena & Thomas, 2016; Williams, Mortada, & Porter, 2016). PCOS can be diagnosed when a patient presents with two out of three of the following findings: polycystic ovaries (which is when there are 12 or more follicles in 1 ovary), hyperandrogenism, and ovulatory dysfunction (Williams, Mortada, & Porter, 2016). Pathophysiology The pathophysiology of PCOS is complex and no single reason can be confirmed one hundred percent, however, it is thought that insulin resistance plays a key role (Williams, Mortada, & Porter, 2016). Patient’s with PCOS are two times more likely to have metabolic syndrome when compared with the general population and they are four times more likely to have type 2 diabetes (Williams, Mortada, & Porter, 2016). The pathophysiology is also associated with altered luteinizing hormone (LH) action, a predisposition to hyperandrogenism, and insulin resistance (Williams, Mortada, & Porter, 2016). It is believed that the underlying insulin resistance these patients have exacerbate hyperandrogenism via suppression of the synthesis of the sex hormone-binding globulin and increase ovarian and adrenal synthesis of androgens, leading to an overall increase in androgen levels (Williams, Mortada, & Porter, 2016). The increase in androgens is what causes the menses to be irregular as well as the development of physical appearances of hyperandrogenism (Williams, Mortada, & Porter, 2016). Patients with PCOS have also been found to have an increased risk for developing nonalcoholic fatty liver disease, hyperlipidemia, and sleep apnea (Williams, Mortada, & Porter, 2016). Epidemiology PCOS is the most common cause of infertility due to anovulation (Williams, Mortada, & Porter, 2016). It is believed that between 6 to 25 percent of reproductive age women have PCOS (Williams, Mortada, & NR 602 WEEK 6 GRAND ROUNDS - PCOS Porter, 2016). The symptoms typically begin around the time the woman begins her menses, therefore, the diagnosis is commonly made during adolescence or young adulthood (Williams, Mortada, & Porter, 2016). It has been found that these patients are at a higher risk for developing ovarian and endometrial cancers (Williams, Mortada, & Porter, 2016). Risk Factors for PCOS It is not entirely clear what factors can predispose a person to PCOS, however, it is believed that genetics may play a role in its development along with obesity (Begum, Shariff, Ayman, Mohammed, & Housam, 2017). Obesity contributes to hyperinsulinemia, which is thought to be a predisposing factor for PCOS (Begum, Shariff, Ayman, Mohammed, & Housam, 2017). Clinical Physical Assessment Findings Patients will present with variable symptoms, from asymptomatic to metabolic, gynecologic, and dermatologic manifestations (Williams, Mortada, & Porter, 2016). The physical assessment finding one might discover include amenorrhea or oligomenorrhea, infertility, dysfunctional uterine bleeding, hirsutism, insulin resistance, acne, alopecia, acanthosis nigricans, and hypertension (Palomba et al, 2014; Williams, Mortada, & Porter, 2016). It is important for the provider to remember that many features of PCOS are actually normal in puberty-aged girls thanks to the immaturity of the hypothalamic-pituitary-ovarian axis (Goodman et al, 2015). If oligomenorrhea persists 2 to 3 years past menarche, the likelihood of an underlying adrenal or ovarian dysfunction should be considered (Goodman et al, 2015; Legro et al, 2013). Young to adolescent girls with severe acne or acnes resistant to topical and oral agents, especially Accutane, have a 40 percent risk of developing PCOS (Goodman et al, 2015). Differential Diagnosis (3) Primary Ovarian Insufficiency, also known as premature ovarian failure, is characterized by follicle dysfunction that leads to the impairment of ovary functioning (Klein & Poth, 2013). Evidence suggests that there is a genetic predisposition to primary ovarian syndrome (Klein & Poth, 2013). These patients are at a higher risk for a thromboembolic event and for developing osteoporosis (Klein & Poth, 2013). The ovaries rely on physiologic stimulation by pituitary gonadotropins for estrogen production and follicular development (Klein & Poth, 2013). Functional hypothalamic amenorrhea will happen when there is suppression of the hypothalamic-pituitary-ovarian axis related to energy deficits arising from stress, disordered eating, and excessive exercise (Klein & Poth, 2013). Once the discriminating factor is uncovered and addressed, menses will typically return (Klein & Poth, 2013). These patients should be prescribed vitamin D and calcium supplementation to stop any further loss of bone density (Klein & Poth, 2013). Patients with Turners Syndrome present with classic symptoms such as a webbed neck, cardiac defects, low hairline, lymphedema, amenorrhea, and a short stature (Klein & Poth, 2013). Although some patients with Turners Syndrome only present with variable ovarian function defects and a short stature (Klein & Poth, 2013). Any patient that presents with Amenorrhea and a short stature should be evaluated for Turners Syndrome; providers who do not have knowledge of the syndrome should refer the patient to an Endocrinologist (Klein & Poth, 2013). Diagnostic Studies Ray Wolf A diagnosis can typically be made based on a thorough history, a thorough physical exam, and basic blood work (Williams, Mortada, & Porter, 2016). The workup to diagnose a patient with PCOS needs to start with a thorough history and physical and should focus on the menstrual history, any dermatological issues, and any fluctuations in weight (Williams, Mortada, & Porter, 2016). According to the Rotterdam Criteria, the patient must meet at least 2 out of 3 criteria to be diagnosed, this criteria is chronic anovulation or ovulatory dysfunction, polycystic ovaries, and hyperandrogenism (Goodman et al, 2015). Baseline lab work should include a thyroid panel, serum prolactin, free and total testosterone, free androgen index, FSH, LH, GnRH-stimulation testing, insulin level, serum glucose, HCG level, IGF-1, and 17-OHPG (Williams, Mortada, & Porter, 2016). A pelvic ultrasound in young adults can help diagnose ovary enlargement and polycystic ovaries but it is not necessary criteria for diagnosis (Goodman et al, 2015; Williams, Mortada, & Porter, 2016). In teenage girls, multi-cystic and enlarged ovaries are common so an ultrasound would not be a good choice in a female younger than 17 years old (Goodman et al, 2015). Prevention The only way to potentially avoid developing PCOS is to recognize the risk factors associated with the disease. Genetics cannot be changed but obesity, diet, and exercising can. It is not proven that those who are not obese will not develop PCOS because there are thin patients who have developed it. However, in order to attempt to prevent the development of PCOS, one can exercise and consume a healthy diet to stay at a healthy weight (Begum, Shariff, Ayman, Mohammed, & Housam, 2017). Treatment - nonpharmacologic management and pharmacologic management Pharm  For adolescent girls, Metformin is commonly used as a first-line monotherapy, then oral contraceptives (OCPs) and anti-androgen medications can be added to the regimen as needed (Goodman et al, 2015). OCPs are effective because they lower androgen levels by suppressing ovarian androgen production and increasing the sex hormone-binding globulin (Goodman et al, 2015). OCPs will also induce regular menses (Williams, Mortada, & Porter, 2016). Anti-androgens, such as spironolactone, work via competitive antagonism of the androgen receptor, or in other words, they block the effects of androgen in the hair follicles (Goodman et al, 2015). Nonpharm  One can try to be as healthy as possible by watching their weight, eating healthy, and exercising. However, if one develops PCOS pharmacologic management is necessary. Education Lifestyle modifications can and should be incorporated into the patient’s daily living. A research study conducted by Beena and Thomas (2016), showed that following certain interventions such as calorie