Phenotypic spectrum of polycystic ovary syndrome and their relationship to the circadian biomarkers, melatonin and cortisol

Abstract

Summary Objective Firstly, to investigate whether polycystic ovary syndrome (PCOS) shows a continuum of severity with increasing number of phenotypic features comprising the Rotterdam criteria for PCOS and secondly, to explore relationships of these phenotypes to the circadian biomarkers, cortisol and melatonin. Background Studies characterizing the spectrum of PCOS subphenotypes give little emphasis to the distinction among women who manifest zero, one or two of the three phenotypic features comprising the Rotterdam criteria. The relationship of circadian biomarkers to PCOS phenotypes is unclear. Design Cross‐sectional study of 321 participants from 2011 to 2016 conducted at the National University Hospital (NUH), Singapore. Participants Participants included women who attended a health screen for NUH staff, volunteers from the university community, and women referred for possible PCOS from gynaecological clinics at NUH and KK Women's and Children's Hospital (Singapore). Methods All participants underwent a physical examination, ovarian ultrasound scan and follicular‐phase blood testing, and completed a health and lifestyle questionnaire. Results A significant positive linear trend in all clinical and biochemical characteristics of PCOS with increasing number of phenotypic features comprising the Rotterdam criteria. We observed a similar trend in serum cortisol and melatonin, two biomarkers of the circadian rhythm. Conclusion PCOS may not be an “all‐or‐none” condition, but rather a continuous spectrum. The positive relationship between number of PCOS criteria with melatonin and cortisol merits further investigation on the role of circadian biorhythms in the pathogenesis of PCOS.

Melatonin, Clock Genes, and Mammalian Reproduction: What Is the Link?

“…It has been reported long ago that melatonin rhythms are disrupted in night shift workers [79]. Similar disruption was found in women with PCOS [80][81][82][83].…”

Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome

“…PCOS is a disease with complex etiology affecting 6–7% of adult women ( Franks, 2008 ). Recently, many studies have indicated that biological clock genes are associated with the development of PCOS ( Li et al, 2011 ; Lim et al, 2019 ). A study by Li et al (2011) , identified that a polymorphism in Melatonin receptor 1A ( MTNR1A ) gene, a regulator of circadian rhythm, is associated with PCOS.…”

“…A study by Li et al (2011) , identified that a polymorphism in Melatonin receptor 1A ( MTNR1A ) gene, a regulator of circadian rhythm, is associated with PCOS. Studies have identified a dysregulation in biological clock factors such cortisol ( Lim et al, 2019 ), per2, and clock ( Chen et al, 2016 ) to be highly correlated with an incidence of PCOS. However, till date the molecular mechanism associating biological genes to PCOS is still unclear.…”

The Need to Reassess the Diagnosis of Polycystic Ovary Syndrome (PCOS): A Review of Diagnostic Recommendations from the International Evidence-Based Guideline for the Assessment and Management of PCOS

“…The extensive evidence synthesis and review process required for guideline formulation highlighted that each diagnostic criteria constitutes a continuum. 20,21 Specific cut-offs or thresholds are most often arbitrarily defined and are often based on an arbitrary percentiles assessed in variably defined populations, 10,22,23 limiting the accuracy and validity of the PCOS diagnosis. The guideline process improved diagnostic accuracy by prioritizing defining cut-off for each of the diagnostic features.…”