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Telomere length and AMH levels in patients with PCOS Helena Meden - Vrtovec , Renata Košir-Pogačnik, Srdjan Novaković 9 th Croatian Congress on Gynaecological Endocrinology, Human Reproduction and Menopause Brijuni, 5. - 8. 9. 2013.
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Telomere length and AMH levels in patients with PCOSHelena Meden-Vrtovec, Renata Košir-Pogačnik, Srdjan Novaković9th Croatian Congress on Gynaecological Endocrinology,Human Reproduction and MenopauseBrijuni, 5. - 8. 9. 2013
PCOSWe knowMost common endocrinopathy in young womenpresented with: hirsutism, acne, androgenic alopecia, signs of virilisation, menstrual changes, increased androgen levels, inhibition of follicular development, anovulation
PCOSWe do not knowMetabolic syndrome (Syndrome X)Insulin resistance, obesity, dyslipidemiaIs PCOS an early manifestation of metabolic syndrome?Cardiovascular mortality – higher or lower than in the normal population?Pierpoint et al: J Clin Epidemiol 1998 ; 51 : 581-6.
QTC- interval-prolonged- powerful predictor of cardiovascular mortality in various settings- QTC interval in patients with increased testosterone levels is short- harmful effect of coronary risk factors may be attenuated by testosterone- induced modulation ofQTC intervalMeden-Vrtovec et al. Int J Gynecol Obstet 2007; 99: 87-90.
PCOMWe do not always considerPolycistic ovarian morphology Jonards criteria:12 or more 2-9 mm follicles ovarian volume more than 10 mlPCOM – 16-25% of women with regular cycles without PCOS changes of aging- follicle No decreasesJonards et al. Hum Reprod 2003; 18: 589-603.
LongevityIs positively correlated with- higher total fecundity- later age at last reproduction- older age at menopause- slower rates of cellular aging Role of telomeres?Perls et al. Nature 1997; 389: 133-6.
TelomeresAre the markers for cellular agingShorten with each cell replicationRepresent a cellular marker of biologic age- mitotic clockEnable stability of chromosomes, prevent enzymatic decompositionHanna et al. Hum Reprod 2009; 24: 1206-11.
Telomere length- genetically defined- men have shorter telomeres than women- older people have shorter telomeres- the older the father, the longer the child’s telomeres- cell division is stopped- apoptosis- in critically short telomeresDe Meyer et al. Front Biosci 2008; 13: 2960-70.
Determination of telomere length telomere specific quantitative polymerase chain reaction telomere to single copy gene (T/S) ratio was calculated fromT/S ratio the length of the telomere was calculated, using specific formula
1,910x+4,157 (x is ratio T/S) Cawthon RM. NucleicAcidsRes 2002;30(10):e47
Preliminary report of our studySTUDY GROUP- 18 with PCOS (Rotterdam criteria)CONTROL GROUP 30 healthy womenAnalysis of: FSH, LH, PRL, AMH, TSHTelomere length- peripheral blood leukocytes
T/S relation and telomere length according to age of individual case of control groupSample Date of birth Relation T/S Length of telomereMix74 1974 1 6.07C42 1980 1.19 6.42Mix84 1984 1.62 7.26K86 1986 1.68 7.36K87 1987 2.06 8.09K92 1992 2.42 8.78
PCOS Average relation T/S adapted to the age of tested groups Control
AMH- produced and secreted by granulosa cells- regulates the development to primary follicle- inhibits FSH secretion- reduces follicle sensitivity to FSH Durlinger ALL, etal. Reproduction 2002; 124: 601 – 9.
AMH valuesElisa, Beckman-Coulter reagent0.7 mg/l – 3.5 mg/l normal>0.3 mg/l low0.3 mg/l – 0.7 mg/l borderline low3.5 mg/l – 5.0 mg/l borderline high>5.0 mg/l high
High AMH- women at risk for OHSS and ART- individualized treatment: low FSH dose, GnRH- antagonist- AMH level - 3.5 ng/ml – cut off value
Results of our preliminary reportAverage AMH values (after logarithm normalization)
Conclusion I- telomere length in PCO group is the same as in controls- PCOS group included also the patients with AMH lower than 3.5 ng/ml
Conclusion IISuggestion: Rotterdam criteria for PCOS should include AMH determinationThe way to avoid inclusion of PCOM in PCOS
Thank you! renata.kosir@inbox.com