Polycystic Ovary Syndrome in Adolescents

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.