Polycystic ovary syndrome and leukocyte telomere length: cross-sectional and longitudinal changes

Abstract

Objective Telomeres are DNA-protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular ageing. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardio-metabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population. Design Population-based cohort study: women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (PCOS) (age 31:N=190; age 46:N=207) and referent women (age 31:N=1054; age 46:N=1324) with data on LTL. Methods The association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age. Results Women with PCOS had similar mean LTL at ages 31 and 46 (P>0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P=0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P<0.001), but not in women with PCOS (P=0.96). Conclusions This finding may suggest a difference in LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms.

Causal association between telomere length and female reproductive endocrine diseases: a univariable and multivariable Mendelian randomization analysis

“…On the other hand, Li et al [ 71 ] discovered that PCOS patients had shorter LTL compared to the control group that was 6.16 years older, and LTL was negatively correlated with serum dehydroepiandrosterone sulfate levels. Surprisingly, Pölönen et al [ 72 ] did not observe any leukocyte telomere attrition in PCOS patients aged 31 and 46 years. Similarly, Pedroso et al [ 73 ] reported that in cumulus cells of mature and immature oocytes, TL was not significantly different between PCOS and healthy populations, but TA was significantly increased in PCOS individuals.…”

“…Gene variants related to LTL may specifically participate in the pathophysiological processes underlying menorrhagia, which is often linked to abnormal endometrial proliferation, myometrial anomalies and abnormal uterine artery blood flow, among other related factors > [ 89 , 90 ]. These processes may involve systemic factors such as inflammation, oxidative stress and cellular aging, which are reflected in LTL [ 72 , 91 ] PMS is generally thought to be influenced by fluctuations in GABA conductance and neurosteroid levels [ 92 ], which are often more susceptible to external environment and present transient characteristics, inconsistent with the long-term systemic processes predicted by the telomere biology. And beyond that, considering the close interplay between sex hormones and the aforementioned disorders, as well as their impact on TL and TA, further experiments are required in the future to illustrate the biological mechanisms connecting these factors.…”