Clinicopathological features of polycystic ovarian syndrome in adolescence

Objectives: To evaluate the clinicopathological features of adolescence diagnosed with polycystic ovarian syndrome. Methods: This is a descriptive study conducted at the Gynecology Clinics of University Obstetric Unit, Teaching HospitalJaffna to evaluate the clinicopathological features of adolescence diagnosed with polycystic ovarian syndrome (PCOS) over a period of 3 years. A total of 56 adolescent girls were diagnosed with PCOS during this period with the currently accepted diagnostic criteria recommended by the Pediatric Endocrine Society and all of them were included in the study. Clinicopathological features at the time of diagnosis of PCOS obtained from medical records were analyzed and descriptive statistics were calculated. Discussion: Emphasizing the importance of early detection of PCOS in women especially during the adolescent periods, its diagnosis should be based on the presence of clinical and/or biochemical hyperandrogenism and irregular menses for at least 1 year as recommended. Our results suggest that the commonest feature of clinical hyperandrogenism being moderate hirsuitism (89.3%) and the commonest type of abnormal uterine bleeding being oligomenorrhea (54%). An obvious rising trend in the number of diagnosed patients with age was also observed. Though the prevalence anovulatory pattern of bleeding among adolescence diagnosed with PCOS consistent with larger studies in Caucasian population, commonest manifestation of clinical hyperandrogenism was moderate hirsutism which was significantly higher compared to other studies. This could be explained by its variation across ethnicities especially with a higher prevalence of hirsuitism among South Asian population. In the absence of any published data on clinicopathological features of adolescence diagnosed with PCOS in Sri Lanka, our series highlights its pattern at the time of diagnosis.


Introduction
Polycystic ovary syndrome (PCOS) affects 6-15% of women of reproductive age and accounts for almost 75% of hyperandrogenism in adults 1 .
Though the cause of PCOS is unknown, considerable evidence suggests that it is a complex trait arising from heritable influences, nonheritable intra-and extrauterine environmental factors, variations in insulin resistance, alterations in steroidogenesis/steroid metabolism, and alternative adaptations to energy excess 2,3 .
Its complex interactions generally mimic an autosomal dominant trait with variable penetrance and metabolic syndrome prevalence is high in parents, siblings and correlates in identical twins 4,5 .
Adult women present with classic features that includes chronic anovulation associated with relative infertility, polycystic ovarian morphology, and hirsutism 6 .
Diagnostic criteria for adult women have been developed by three international conferences namely National Institutes of Health (NIH) conference criteria (1990), the Rotterdam consensus criteria (2003) and the Androgen Excess-PCOS Society consensus criteria (2006) 7,8 .
Though they are somewhat different many criterions overlap. While the first signs of PCOS can be perceptible even during childhood, the unique features of the syndrome in adolescence are not very clear 9 .
Hyperandrogenemia, anovulatory cycles, oligomenorrhea, insulin resistance and hyperinsulinemia are intrinsic reproductive and metabolic manifestations in adolescents and applying the same diagnostic criteria of adult PCOS to this group is controversial and questions still exist regarding the features of PCOS in adolescence 10 .
Despite these difficulties, an early diagnosis of PCOS is of great importance since its presence is related to a greater risk of future infertility, type II diabetes mellitus, metabolic syndrome / abnormalities and cardiovascular disease 11,12 .
With long-term complications due to adolescent PCOS, the temptation to make this diagnosis and consider medical therapy during adolescence should be tempered against the real benefits of such therapy, and the possible risks of the drugs employed to treat this condition 13 .
With growing experience and evidence there are clear indications to treat adolescence PCOS with lifestyle intervention, local therapies/cosmetic, additive pharmaceuticals and consider future reproductive aspects and the psychological impact of PCOS also constitutes a major concern in adolescent PCOS 14 .
The presence of Polycystic Ovarian Morphology (PCOM) in an adolescent who does not have hyperandrogenism/oligo-anovulation does not indicate a diagnosis of PCOS. Anyway, the measurement of ovarian volume, follicle number and size, and uterine dimensions may be useful in the evaluation of amenorrhea, but is not needed for PCOS diagnosis in adolescents 15 .
To overcome these uncertainties the Pediatric Endocrine Society invited an expert group of representatives from the Androgen Excess-PCOS Society and stakeholder international pediatric and adolescent specialty societies with the goal of defining which criteria have sufficient evidence to be used for the diagnosis of PCOS in adolescents. Consensus has recently been reached by international pediatric subspecialty societies that otherwise unexplained persistent hyperandrogenic anovulation using age-and stage-appropriate standards are appropriate diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescents 16 .
The World Health Organization (WHO) defines adolescents as those people between 10 and 19 years of age and it is currently accepted that the diagnosis of PCOS in adolescents should be based on the presence of clinical and/or biochemical hyperandrogenism and irregular menses for at least 1 year. Polycystic ovarian morphology (PCOM) on ultrasound is not a diagnostic criterion in adolescents 17 .
Though prevalence of leading clinical manifestations and laboratory findings of PCOS in adolescence have been studied, information on prevalence of the clinicopathological features as per above recommendation to make a diagnosis is lacking in these studies 18 .
In the absence of any published data on clinicopathological features of adolescence diagnosed with PCOS, our study was designed to investigate the features based on the recommendations and criteria of international pediatric and adolescent specialty societies amongst adolescences diagnosed with PCOS.
Our study was conducted among 56 adolescence girls who were diagnosed with PCOS over a period of three years in a single center at University Unit Gynaecology Clinic, Teaching Hospital Jaffna.

Methods
The study was conducted at the University Gynaecology Clinics, Teaching Hospital. All procedures performed were in accordance with good clinical practice.The information was obtained from the case records of adolescence diagnosed with PCOS during a period of 3 years, from 2017. c. Moderate-severe inflammatory acne vulgaris is an indication to test for hyperandrogenemia.
PCOS during this period with the currently accepted diagnostic criteria and all of them were included in the study.
Though ultrasound is not a criterion to make a diagnosis of PCOS in adolescents, all the subjects underwent a trans abdominal ultrasound scan to exclude unexpected pelvic pathology and to visualize the ovaries.
The detailed diagnostic criteria are summarized in Box 1 and the definitions of types of abnormal uterine bleeding in adolescents are summarized in Box 2 17,18 .

Research article
Moderate-severe hirsutism is considered clinical evidence of hyperandrogenism and it was diagnosed using the Ferriman-Gallwey hirsutism scoring. Figure 1 19 .
Moderate-severe inflammatory acne vulgaris is an indication to test for hyperandrogenemia and the scoring system for acne is summarized in Box 3 20,21 .
Clinicopathological features at the time of diagnosis of PCOS obtained from medical records were analyzed and descriptive statistics were calculated using SPSS Statistics Version 23. Each of the 9 body areas most sensitive to androgen is assigned a score from 0 (no hair) to 4 and these separate scores are summed to provide a hormonal hirsutism score.

Results
The age distribution of adolescence diagnosed with PCOS is reflected in Figure 2 and demographics are summarizedin Box 4.

Box 4. Age of adolescence diagnosed with PCOS and their demographics Varable Values
Age Range (y) 10   Excessive anovulatory bleeding 08 (14%)

Box 5. The types of abnormal uterine bleeding
The types of abnormal uterine bleeding in the 56 adolescence are summarized in Box 5 and Figure 3.

Research article
Of the 56-adolescence diagnosed with PCOS clinical evidence of hyperandrogenism in 50 was due to moderate hirsutism and 6 due to severe hirsutism. Though moderate-severe inflammatory acne vulgaris is not considered as clinical evidence of hyperandrogenism it is an indication to test for hyperandrogenemia. Five subjects underwent serum testosterone assays as they were diagnosed with moderate-severe inflammatory acne vulgaris. Two of them were diagnosed with hyperandrogenemia. Anyway, both were already included in the cohort of 56 as they were diagnosed with abnormal uterine bleeding and moderate hirsuitism. Box 7 summarizes the pattern of hyperandrogenism.
The commonest type of abnormal uterine bleedingobserved in this group was oligomenorrhea (54%, n=30) and the pattern of oligomenorrhea is summarized in Box 6 and Figure 4.

Box 7. Pattern of hyperandrogenism
Though ultrasound is not a criterion to make a diagnosis of PCOS in adolescents, all the subjects underwent a trans abdominal ultrasound scan to exclude unexpected pelvic pathology and to visualize the ovaries. In 14 of the 56 adolescence (25%) who were diagnosed with PCOS, polycystic morphology of the ovaries was observed.

Discussion
Emphasizing the importance of early detection of PCOS in women especially during the adolescent period, its diagnosis should be based on the presence of clinical and/or biochemical hyperandrogenism and irregular menses for at least 1 year as recommended.
Abnormal uterine bleeding pattern being the first definitive criterion to make a diagnosis of PCOS in adolescence, the combination of oligomenorrhea (54%) and excessive anovulatory bleeding (14%) accounted for 68% in our study which could be categorized as anovulatory type of abnormal bleeding. This is comparable with symptomatology studies which quote 65% of anovulatory pattern of bleeding among adolescence diagnosed with PCOS 22 . Prevalence of hirsuitism by race suggest that it varies significantly across ethnicities and the lowest being observed among the Northern, fair-skinned Europeans and the highest among Mediterranean women 24 .
An increased prevalence of hirsutism among South Asian adult women and a lower prevalence in Caucasian adult women with PCOS also has been reported and these findings could explain the observations in our Sri Lankan study population 25 .
Though ultrasound is not a criterion to make a diagnosis of PCOS in adolescents a quarter (25%) of our study population had demonstrable polycystic ovarian morphology.
Polycystic ovarian morphology is an inconstant finding in healthy adolescents and up to 35% has been observed in this age group 26 . As does not appear to be associated with decreased ovulatory rate or metabolic abnormalities in healthy adolescents it reiterates that polycystic ovarian morphology should not influence the diagnosis of PCOS in adolescence.
Though the sample size of our study was modest we were able to analyze the clinicopathological features of polycystic ovarian syndrome in adolescence over a period of three years at a tertiary gynaecology hospital clinic. Further, the currently available literature on clinicopathological features of PCOS have been mainly on adults and lack similar studies on adolescence with the diagnostic criteria by international paediatric subspecialty societies.
In the absence of any published data on clinicopathological features of adolescence diagnosed with PCOS in Sri Lanka, our series highlights its pattern at the time of diagnosis.
We also emphasize to follow diagnostic criteria recommended by international paediatric subspecialty societies to diagnose PCOS among adolescence to improve early detection rate and at the same time avoid the possible risks of over diagnosis.
Similar studies with larger sample size in other centers in the country are recommended to understand the pattern clinicopathological features of adolescence diagnosed with PCOS in Sri Lankan population.

Author Declarations
Competing interests: The authors declare that they have no competing interests.

Financial disclosure:
The study was self-financed.

Ethical consideration:
The study was conducted at the University Gynaecology Clinics, Teaching Hospital, Jaffna, after obtaining ethical approval from Ethics Review Committee of the Teaching Hospital, Jaffna. All procedures performed were in accordance with good clinical practice.