Polycystic Ovary Syndrome in Adolescents
How should adolescents with PCOS be managed?
The treatment of PCOS is symptom-directed and should be tailored according to the complaints of the individual patient. However, it also must focus on the core dysfunctions: anovulation, hyperandrogenemia, obesity, and insulin resistance. It also requires bridging patient expectations of regulating menses, lessening the troublesome clinical signs of hyperandrogenemia (hirsutism, acne), and obesity management with the health care provider’s goals of preventing endometrial hyperplasia and cancer, diabetes mellitus, and cardiovascular disease.
Regulating menstruation and reducing cutaneous manifestations of hyperandrogenemia is the priority for any adolescent with PCOS. Combined oral contraceptive pills (COCs) are the first line of medical treatment for most adolescents. COCs restore endometrial cycling and suppress androgen levels, and are therefore optimal in treating abnormal uterine bleeding, protecting against endometrial carcinoma, and alleviating cutaneous manifestations of hyperandrogenemia (hirsutism and acne). Progestin monotherapy is considered an alternative therapy in individuals with contraindications to COCs (ie, thromboembolic risk). Although it is not effective in lowering androgen levels thus does not help reduce hair growth and acne, progestin monotherapy protects the endometrium and reduces the risk of endometrial cancer [50].
The majority of patients with PCOS are overweight or obese. Regardless of BMI, patients with PCOS have profound intrinsic insulin resistance that gets worse with overweight or obesity. Weight reduction by restricting caloric intake and increasing physical exercise is vital and has shown to be effective in regulating menstrual cycles, but is difficult to achieve [51–53]. Metformin can regulate menstrual cycles and decrease androgen levels by improving insulin sensitivity [54,55]. The use of metformin in PCOS patients is still controversial and abnormal glucose tolerance is the only approved indication [61]. However, combing metformin with COCs and lifestyle modification in obese PCOS patients has been shown to be used more frequently in pediatric endocrine clinics [56]. COCs are the only agents that can lower testosterone levels and improve ovulation and hirsutism; these effects are seen less frequently with lifestyle modification or metformin, either used alone or in combination.
COC monotherapy is first-line therapy to treat hirsutism. Consider anti-androgen treatment for hirsutism if there is no improvement after 6–9 months of hormonal treatment [57]. Antiandrogens reduce hirsutism by decreasing androgen production and binding the androgen receptors in target tissue. Spironolactone is the most commonly used antiandrogen therapy in adolescent girls with PCOS. Given the risk of teratogenicity with antiandrogens if pregnancy occurs, it is recommended to use it in combination with COCs [57]. Cosmetic measures including direct hair removal and electrolysis should be discussed with patients as other options for treatment of hirsutism.
Obese patients with PCOS are at higher risk for metabolic syndrome, a constellation of features including glucose intolerance, central obesity, hypertension, and dyslipidemia. Hyperandrogenemia and insulin resistance are linked with metabolic syndrome in PCOS. Reducing hyperandrogenemia and insulin resistance could reverse metabolic derangements and further reduce the risk of cardiovascular disease [58].
Worsening insulin resistance with COCs in PCOS has raised the concern of long-term metabolic derangements and cardiovascular adverse effects. COCs tend to increase total cholesterol, triglyceride, and high-sensitivity C-reactive protein levels [59]. However, the long-term implications of these findings are not well understood, attributable to the lack of longitudinal studies, especially in women with PCOS receiving COCs. Newer COCs containing less androgenic progestin may have less deleterious effect on insulin resistance and lipid profile. Due to insufficient use in adolescent patients, a definitive conclusion about their long-term safety cannot be drawn. Thus, there remains a theoretical risk of COCs exacerbating the underlying metabolic derangements in PCOS that can lead to subsequent adverse cardiovascular events.
Adolescent girls with PCOS are also at an increased risk for depression and anxiety disorders. The 2013 Endocrine Society clinical practice guideline suggests that adolescent girls with PCOS should be screened for depression and anxiety by history [51].If symptoms are present, patients should receive appropriate psychological referral and treatment.
Case Continued
As she had no contraindications to COCs, the patient was started on COC therapy to regulate her menstrual periods and alleviate the symptoms of hirsutism. Due to impaired glucose tolerance test results and increased risk for type 2 diabetes, treatment with metformin was also initiated. The patient met with a dietician, who offered recommendations for adopting a healthy lifestyle and introduced her to the “3,2,1,0, blast off” model: 3 consistent meals, 2 hours or less of screen time, 1 hour or more of physical activity, and 0 sweetened beverages a day. The patient was also advised to increase daily consumption of fruits and vegetables. Results of the 2-item Patient Health Questionnaire (PHQ-2) for depression were negative.
At a follow-up visit 6 months later, the patient reported that her menstrual periods were regular. There was some improvement in hirsutism, requiring less shaving, and there was no increase in weight. Repeat laboratory evaluations showed normal free testosterone level, decreased HbA1c (5.2%), and improved random blood glucose (130 mg/dL). The patient was seen regularly and treatment results monitored. No side effects were seen over a 4.5-year period. As PCOS is a lifelong condition, at the age of 21 the patient was referred to an adult endocrine clinic for further management.
Corresponding author: Alvina R. Kansra, MD, Medical College of Wisconsin, 8701 Watertown Plank Rd., Wauwatosa, WI 53226, akansra@mcw.edu.
Financial disclosures: None.
