Hyperandrogenism

PCOS is a common disorder with systemic metabolic manifestations. Its etiology is complex, heterogeneous, and poorly understood. There are three definitions for PCOS currently in use that variably rely on androgen excess, chronic anovulation, and PCO to make the diagnosis (Table 1). However, all criteria are consistent in that PCOS is considered a diagnosis of exclusion. All three sets of diagnostic criteria include hyperandrogenism, either clinical or biochemical, and anovulation (6 – (link)9 (link)). The Rotterdam criteria were the first to incorporate ovarian morphology on ultrasound as part of the diagnostic criteria (8 (link), 9 (link)).
The panel from a recent National Institutes of Health (NIH)-sponsored Evidence-Based Methodology workshop on PCOS endorsed the Rotterdam criteria, although they identified the strengths and weaknesses of each of the three cardinal features (Table 2). These criteria allow the diagnosis to be made clinically (based upon a history of hyperandrogenic chronic anovulation) as well as biochemically with androgen assays or with ultrasound examination of the ovaries. We do not endorse the need for universal screening with androgen assays or ultrasound if patients already meet two of the three criteria clinically. It is recommended that the features leading to the diagnosis are documented. We recommend using the current definition of the Rotterdam criteria to document PCO morphology (at least one ovary with 12 follicles of 2–9 mm or a volume >10 mL in the absence of a dominant follicle >10 mm), in the absence of age-based criteria.
Disorders that mimic PCOS are comparatively easy to exclude; therefore, all women should be screened with a TSH, prolactin, and 17-OHP level (Table 3) (10 (link)– (link)12 (link)). Hyperprolactinemia can present with amenorrhea or hirsutism (13 (link), 14 (link)). Thyroid disease may present with irregular menstrual cycles. In women with hyperandrogenism, nonclassic congenital adrenal hyperplasia should be excluded because it can be found in 1.5–6.8% of patients presenting with androgen excess (15 (link), 16 ). In select women who present with amenorrhea, virilization, or physical findings not associated with PCOS, such as proximal muscle weakness (Cushing's syndrome) or frontal bossing (acromegaly), other diagnoses should be considered and excluded (Table 4).

The treatment of PCOS in adolescents is controversial. Many support the symptom-driven approach, whereas others support an approach targeting the underlying reproductive/hormonal and metabolic abnormalities associated with PCOS (30 (link)). There are no adequately powered, randomized, double-blind, placebo-controlled trials in adolescents with PCOS. The dual goal of treating hyperandrogenism and providing contraception prompts the use of HCs as the mainstay of therapy for adolescents with PCOS (29 (link), 283 (link), 284 (link)). Additionally, benefits such as normal menses and decreased acne and hirsutism are typically of the greatest importance to an adolescent (285 (link)). Some of these can also be improved by lifestyle therapy and weight loss.
Nonetheless, the initiation of HCs in early adolescence is controversial, and few data exist to guide recommendations. After excluding other causes of primary amenorrhea, HCs could be considered in a patient with proven hyperandrogenism if the patient has achieved a sexual maturity of Tanner stage 4–5 when menarche should have occurred (286 ). The best HC for adolescents and the appropriate duration of therapy are uncertain (287 (link)). A longer duration of treatment with a combined HC may lead to a lower chance of developing signs of hyperandrogenism as an adult (23 (link)). Some authors suggest continuing with HC until the patient is gynecologically mature (defined by these authors as 5 years postmenarcheal) or has lost a substantial amount of weight (288 (link)).
Small, short-term studies demonstrate that metformin restores menstrual regularity and improves hyperandrogenemia, IR, and glucose intolerance in obese and nonobese adolescents with PCOS (289 (link)– (link)291 (link)). Two sequential, randomized, placebo-controlled trials of metformin in adolescents with PCOS demonstrated improvements in hyperandrogenemia, ovulation, and dyslipidemia (223 (link)). These promising but limited data lead to the impression that metformin may be more beneficial for adolescents with PCOS than it is for adults with this condition (292 (link), 293 (link)). The necessary duration of treatment is yet to be established, and the limited available data are conflicting. In one study, the beneficial effects of metformin on menstrual cycles persisted for 6 months after discontinuation of metformin (294 (link)), but in another study the effects were lost 3 months after discontinuing the medication (290 (link)). There is no literature regarding long-term use in adolescents.
Given the limited data, it is necessary to extrapolate from adult data in making adolescent treatment recommendations. Thus, lifestyle therapy should be recommended in overweight/obese adolescents. Metformin therapy may also be considered for treatment of PCOS based on the limited studies cited above. Because lifestyle change and/or metformin may increase ovulatory frequency and because cutaneous manifestations are common, appropriate contraception must be recommended to a sexually active teenager.