Expert Clarifies Guidance on Adolescent Polycystic Ovary Syndrome

Heidi Splete

July 17, 2020

A trio of international expert recommendations mainly agree on essentials for the diagnosis and treatment of polycystic ovary syndrome in adolescents, but some confusion persists, according to Robert L. Rosenfield, MD, of the University of California, San Francisco.

In a commentary published in the Journal of Pediatric & Adolescent Gynecology, Dr. Rosenfield, who convened one of the three conferences at which guidance was developed, noted that the three recommendations — published by the Pediatric Endocrine Society, the International Consortium of Paediatric Endocrinology, and the International PCOS Network in 2015, 2017, and 2018, respectively — "are fairly dense" and reviews have suggested a lack of agreement. His comments offer perspective and practice suggestions that follow the consensus of the recommendations.

"All the documents agree on the core diagnostic criteria for adolescent PCOS: otherwise unexplained evidence of ovulatory dysfunction, as indicated by menstrual abnormalities based on stage-appropriate standards, and evidence of an androgen excess disorder," Dr. Rosenfield said.

The main differences among the recommendations from the three groups reflect tension between the value of an early diagnosis and the liabilities of a mistaken diagnosis in the context of attitudes about adolescent contraception. "These are issues not likely to be resolved easily, yet they are matters for every physician to consider in management of each case," he said.

Dr. Rosenfield emphasized that clinicians must consider PCOS "in the general context of all causes of adolescent menstrual disturbances," when evaluating a girl within 1-2 years of menarche who presents with a menstrual abnormality, hirsutism, and/or acne that has been resistant to topical treatment.

A key point on which the recommendations differ is whether further assessment is needed if the menstrual abnormality has persisted for 1 year (the 2018 recommendations) or 2 years (the 2015 and 2017 recommendations), Dr. Rosenfield explained. "What the conferees struggled with is differentiating how long after menarche a menstrual abnormality should persist to avoid confusing PCOS with normal immaturity of the menstrual cycle," known as physiologic adolescent anovulation (PAA). "The degree of certainty is improved only modestly by waiting 2 years rather than 1 year to make a diagnosis."

However, the three documents agree that girls suspected of having PCOS within the first 1-2 years after menarche should be evaluated at that time, and followed with a diagnosis of "at risk for PCOS" if the early test results are consistent with a PCOS diagnosis, he said.

Another point of difference among the groups is the extent to which hirsutism and acne represent clinical evidence of hyperandrogenism that justifies testing for biochemical hyperandrogenism, Dr. Rosenfield said.

"All three sets of adolescent PCOS recommendations agree that investigation for biochemical hyperandrogenism be initiated by measuring serum total and/or free testosterone by specialty assays with well-defined reference ranges," he said.

However, "documentation of biochemical hyperandrogenism has been problematic because standard platform assays of testosterone give grossly inaccurate results."

As for the management of PCOS in teens, "different perspectives about pharmacologic treatment [reflect] the multicultural views about adolescent contraception," said Dr. Rosenfield. Guidelines in the United States favor estrogen-progestin combined oral contraceptives as first-line therapy, while the international guidelines support contraceptives if contraception also is desired; otherwise the 2017 guidelines recommend metformin as a first-line treatment.

"Agreement is uniform that healthy lifestyle management is first-line therapy for management of the associated obesity and metabolic disturbances, i.e., prior to and/or in conjunction with metformin therapy," he noted.

In general, Dr. Rosenfield acknowledged that front-line clinicians cannot easily evaluate all early postmenarcheal girls for abnormal menstrual cycles. Instead, he advocated a "middle ground" approach between early diagnosis and potentially labeling a girl with a false positive diagnosis.

Postmenarcheal girls who are amenorrheic for 2 months could be assessed for signs of PCOS or pregnancy, and whether she is generally in good health, he said. "However, for example, if she remains amenorrheic for more than 90 days or if two successive periods are more than 2 months apart, laboratory screening would be reasonable."

PCOS is "a diagnosis of exclusion for which referral to a specialist is advisable" to rule out other conditions such as non-classic congenital adrenal hyperplasia, hyperprolactinemia, endogenous Cushing syndrome, thyroid dysfunction, and virilizing tumors, said Dr. Rosenfield.

However, PCOS accounts for most cases of adolescent hyperandrogenism. The symptomatic treatment of early postmenarcheal girls at risk of PCOS is recommended to manage menstrual abnormality, hirsutism, acne, or obesity, and these girls should be reassessed by the time they finish high school after a 3-month treatment withdrawal period, he emphasized.

Dr. Rosenfield had no relevant financial conflicts to disclose.

SOURCE: Rosenfield RL. J Pediatr Adolesc Gynecol. 2020 June 29. doi: 10.1016/j.jpag.2020.06.017.

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