An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence

Abstract

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)¹. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents.

Towards a circulating marker of hepato‐visceral fat excess: S100A4 in adolescent girls with polycystic ovary syndrome — Evidence from randomized clinical trials

“…Adolescent girls with PCOS—diagnosed by the latest international criteria allowing for a relatively homogeneous phenotype—were found to have elevated concentrations of circulating S100A4, which are lowered by a central fat reducing intervention with SPIOMET for 1 year. Baseline serum S100A4 levels in the total study population associated positively with central fat; in girls with PCOS, on‐treatment changes in S100A4 associated most closely with those of markers of insulin resistance and central fat.…”

Prevalence of Self-reported Polycystic Ovary Syndrome and Profiles of Health Among Women of Different Generations: A Cross Sectional Study

“…Our findings suggest that there is under diagnosis of PCOS among younger and older women, as the clinical features of PCOS typically emerge around menarche (Ibanez et al, 2017) and many (e.g. elevated testosterone) persist as women age (Winters et al, 2000).…”

Polycystic ovary syndrome in adolescent girls

“…Adolescent PCOS is now defined by the co‐presence of irregular menses and androgen excess (clinical evidence + biochemical confirmation) >2 years after menarche, and by the exclusion of disorders such as an androgen‐secreting tumor, 21‐hydroxylase deficiency, and prolactin excess; ovarian morphology is not a diagnostic criterion .…”

“…Rapidly progressive hirsutism and/or virilization (clitoromegaly, deeper voice) requires prompt exclusion of an androgen‐secreting tumor and adrenal hyperplasia. Most girls develop regular ovulatory/menstrual cycles (21–35 days) within 2 years after menarche; current consensus is therefore that oligo‐amenorrhea in the first years post‐menarche can still be viewed as a variant of maturation, but that a more prolonged oligo‐amenorrhea may warrant a screen for androgen excess; rarely does PCOS present with primary amenorrhea in girls with completed growth and puberty .…”

“…However, a testosterone level > 40 ng/dL or > 1.4 nmol/L (and certainly >50 ng/dL or > 1.7 nmol/L) and/or a FAI >5 are generally viewed as a confirmation of androgen excess. A baseline 17‐OH‐progesterone level < 200 ng/dL excludes a clinically relevant 21‐hydroxylase deficiency .…”