Evidence-Based Strategies for Common Clinical Questions

PCOS in Adolescents: Diagnostic Difficulties and the Opportunity for Interventions

Author: Kaitlin Wittler, MD | Resident of Internal Medicine/Pediatrics

Column Editor: Kathleen Berg, MD | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Clinical Assistant Professor of Pediatrics, UMKC School of Medicine 

Polycystic ovary syndrome (PCOS) can be a difficult diagnosis to make in adolescent females. Over the past five years, three international and multidisciplinary expert conferences have published recommendations clarifying the diagnosis and treatment of the disorder. Recognition of the syndrome is important in primary care medicine because of the opportunity to lessen patients’ symptoms and to recognize potential comorbidities.

Current diagnostic criteria for adolescents involve the combination of the following: abnormal menstrual pattern due to ovulatory dysfunction (beyond 1-2 years after menarche) and clinical and/or laboratory evidence of hyperandrogenism.¹ Adult criteria sometimes include the addition of polycystic ovaries noted on ultrasound. Ultrasonographic evidence of polycystic ovaries should not be used in the adolescent diagnostic algorithm, as multifollicular ovaries can be secondary to normal physiological changes during the adolescent period.^2,6 This is important to explain to patients and families who may read ultrasonography reports describing multifollicular ovaries.

In the first 1-2 years after menarche, menstrual irregularity is common and usually the result of physiological anovulatory cycles. If a female continues to have menstrual intervals shorter than 20 days or longer than 45 days, this is suggestive of oligoovulation or anovulation. Intervals longer than 90 days are especially unusual and warrant further evaluation.^2,6

Clinical evidence of hyperandrogenism can include hirsutism and severe acne.³ Racial variations should be considered when evaluating for hirsutism. Mild hirsutism may not be pathologic, but when combined with menstrual irregularity, the likelihood of hyperandrogenism increases. Moderate to severe hirsutism should increase suspicion for the diangosis.^4,6

Laboratory evidence of hyperandrogenism is made by persistent elevation of serum total and/or free testosterone levels. These levels should be obtained in the morning and must be measured by a reliable reference laboratory with well-determined normal ranges.³ Beyond this, laboratory evaluation for PCOS and other etiologies of menstrual irregularity/hyperandrogenism may include a pregnancy test, luteinizing hormone, follicle stimulating hormone, prolactin, 17-hydroxyprogesterone (to rule-out non-classic congenital adrenal hyperplasia), dehydroepiandrosterone sulfate, thyroid stimulating hormone, free thyroxine and cortisol. Especially when obesity is present at time of diagnosis, evaluation for comorbidities such as insulin resistance, hyperlipidemia and fatty liver disease should include basic metabolic panel, lipid panel and liver function tests. While hemoglobin A1c and fasting plasma glucose are most convenient to evaluate for type 2 diabetes, the current preferred testing is an oral glucose tolerance test to assess for early impaired glucose tolerance.^1,2,6

No imaging studies are recommended for diagnosis of PCOS in adolescents. For reasons stated above, pelvic ultrasound should not be obtained for evaluation of polycystic ovaries. However, this may be considered if the clinician wishes to rule out a less common diagnosis, like a virilizing ovarian tumor.

Treatment is individualized for each patient. Combined oral contraceptives (COCs) have been shown to help with menstrual irregularity and improve both clinical and laboratory markers of hyperandrogenism.³ Clinicians should be aware that if there is suspicion for PCOS as the cause of menstrual irregularity, labs must be obtained prior to starting COCs as COCs will affect testosterone and other hormone levels. If referral to specialty care (adolescent medicine, endocrinology, gynecology) is made for initial evaluation, starting COCs should be delayed, if possible, to assure laboratory accuracy at that visit.

Lifestyle modification should be implemented as treatment for females with PCOS who are overweight or obese. Weight loss and intensified exercise reduced testosterone levels in one well-controlled clinical trial and two small, randomized control trials.⁴ While metformin is not FDA approved for the treatment of PCOS, an increasing number of studies show its safety and efficacy. Metformin improves hyperandrogenism and, when combined with lifestyle modifications, can improve BMI.⁴ In females with abnormal glucose tolerance tests or diagnosis of type 2 diabetes mellitus, metformin can improve insulin sensitivity.^2,6

Diagnosis of PCOS can be challenging due to the normal physiological changes in adolescents. Identification of PCOS should alert clinicians to potential comorbidities such as obesity, type 2 diabetes mellitus, decreased fertility, depression, anxiety, obstructive sleep apnea and eating disorders.⁶ When the diagnosis is not clear, patients might be considered “at-risk for PCOS” or given “presumptive diagnosis of PCOS.” Clinicians should be just as vigilant for comorbidities in these adolescents. Prospective longitudinal research is needed to establish more validated diagnostic criteria and to help these females in the future.^2,6

References:

1. Rosenfield RL. Perspectives on the International Recommendations for the Diagnosis and Treatment of Polycystic Ovary Syndrome in Adolescence. J Pediatr Adolesc Gynecol. 2020. 33(5):445–447. doi: 10.1016/j.jpag.2020.06.017.
2. Witchel SF, Oberfield S, Rosenfield RL, et al. The Diagnosis of Polycystic Ovary Syndrome during Adolescence. Horm Res Paediatr. 2015. 83(6):376–389. doi: 10.1159/000375530.
3. Kamboj MK and Bonny AE. Polycystic Ovary Syndrome in Adolescence: Diagnostic and Therapeutic Strategies. Transl Pediatr. 2017. 6(4):248-255. doi: 10.21037/tp.2017.09.11.
4. Ibáñez L, Oberfield SE, Witchel S, et al. An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence. Horm Res Paediatr. 2017. 88(6):371–395. doi: 10.1159/000479371.
5. Trang N LE, Wickham EP, Nestler JE. Insulin Sensitizers in Adolescents with Polycystic Ovary Syndrome. Minerva Pediatr. 2017. 69(5):434–443. doi: 10.23736/S0026-4946.17.04976-3.
6. Teede HJ, Misso ML, Costello MF, et al. Recommendations from the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Hum Reprod. 2018.  33(9):1602–1618. doi: 10.1093/humrep/dey256.