TY - JOUR
T1 - Increased thrombin generation in women with polycystic ovary syndrome
T2 - A pilot study on the effect of metformin and oral contraceptives
AU - Glintborg, Dorte
AU - Sidelmann, Johannes Jakobsen
AU - Lambaa Altinok, Magda
AU - Mumm, Hanne
AU - Andersen, Marianne
PY - 2015
Y1 - 2015
N2 - Objective. Polycystic ovary syndrome (PCOS) is associated with risk factors for cardiovascular disease (CVD) which may be modified by the use of metformin and oral contraceptives (OC). Thrombin generation (TG) measures are risk markers of CVD and address the composite of multiple factors that influence blood coagulation. This prospective, randomized, intervention study evaluated the potential influence of PCOS on TG measures and the effect of OC and/or metformin on TG measures in women with PCOS.
Material and methods. Ninety patients with PCOS and 35 controls were included. Patients were randomized to 12 months treatment with metformin, metformin + OC or OC alone. C-reactive protein (CRP), fibrinogen, total cholesterol, trunk fat mass, body mass index, estradiol, testosterone, sex hormone binding globulin (SHBG) as well as TG measures, i.e. the lag time for formation of thrombin, the endogenous thrombin potential (ETP), peak thrombin concentration (peak) and time to peak were determined at baseline and after 12 months of treatment.
Results. CRP and total testosterone were significantly higher and SHBG significantly lower in PCOS women than in controls (P=0.012, P<0.001 and P=0.008, respectively). The TG measures ETP, peak and lag time were increased in women with PCOS compared to controls (P<0.01). Significant correlations were observed between TG measures and fibrinogen, CRP, SHBG and fat trunk mass (P>0.01). ETP (P=0.006), peak (P=0.003) and lag time (P=0.023) remained increased after adjustment for these potential confounders. Treatment with OC and metformin +OC further increased ETP (P<0.001) and peak (P<0.005) and reduced time to peak (P<0.04). The increase in ETP was significantly lower in the metformin+OC group than in the OC group (P<0.05). Metformin alone did not affect TG significantly.
Conclusions. PCOS is associated with increase in TG measures independent of other risk factors of CVD. OC increases TG measures further and may thus add to the increased risk of CVD already present in women with PCOS.
AB - Objective. Polycystic ovary syndrome (PCOS) is associated with risk factors for cardiovascular disease (CVD) which may be modified by the use of metformin and oral contraceptives (OC). Thrombin generation (TG) measures are risk markers of CVD and address the composite of multiple factors that influence blood coagulation. This prospective, randomized, intervention study evaluated the potential influence of PCOS on TG measures and the effect of OC and/or metformin on TG measures in women with PCOS.
Material and methods. Ninety patients with PCOS and 35 controls were included. Patients were randomized to 12 months treatment with metformin, metformin + OC or OC alone. C-reactive protein (CRP), fibrinogen, total cholesterol, trunk fat mass, body mass index, estradiol, testosterone, sex hormone binding globulin (SHBG) as well as TG measures, i.e. the lag time for formation of thrombin, the endogenous thrombin potential (ETP), peak thrombin concentration (peak) and time to peak were determined at baseline and after 12 months of treatment.
Results. CRP and total testosterone were significantly higher and SHBG significantly lower in PCOS women than in controls (P=0.012, P<0.001 and P=0.008, respectively). The TG measures ETP, peak and lag time were increased in women with PCOS compared to controls (P<0.01). Significant correlations were observed between TG measures and fibrinogen, CRP, SHBG and fat trunk mass (P>0.01). ETP (P=0.006), peak (P=0.003) and lag time (P=0.023) remained increased after adjustment for these potential confounders. Treatment with OC and metformin +OC further increased ETP (P<0.001) and peak (P<0.005) and reduced time to peak (P<0.04). The increase in ETP was significantly lower in the metformin+OC group than in the OC group (P<0.05). Metformin alone did not affect TG significantly.
Conclusions. PCOS is associated with increase in TG measures independent of other risk factors of CVD. OC increases TG measures further and may thus add to the increased risk of CVD already present in women with PCOS.
KW - Polycystic ovary syndrome, thrombin generation, metformin, oral contraceptives, blood coagulation, drug effects
KW - Blood coagulation
KW - Polycystic ovary syndrome
KW - Thrombin generation
KW - Metformin
KW - Oral contraceptives
U2 - 10.1016/j.metabol.2015.06.011
DO - 10.1016/j.metabol.2015.06.011
M3 - Journal article
SN - 0026-0495
VL - 64
SP - 1272
EP - 1278
JO - Metabolism
JF - Metabolism
IS - 10
ER -