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1. Decreased role of neuropeptides in the microvascular function in migraine patients with polycystic ovary syndrome

Author

Al-Hassany, Linda, Linstra, Katie M., Meun, Cindy, van den Berg, Jeffrey, Boersma, Eric, Danser, A. H.Jan, Fauser, Bart C.J.M., Laven, Joop S.E., Wermer, Marieke J.H., Terwindt, Gisela M., MaassenVanDenBrink, Antoinette, Al-Hassany, Linda, Linstra, Katie M., Meun, Cindy, van den Berg, Jeffrey, Boersma, Eric, Danser, A. H.Jan, Fauser, Bart C.J.M., Laven, Joop S.E., Wermer, Marieke J.H., Terwindt, Gisela M., and MaassenVanDenBrink, Antoinette

Abstract

Background and aims: To understand pathophysiological mechanisms underlying migraine as a cardiovascular risk factor, we studied neuropeptide action and endothelial function as measures of peripheral microvascular function in middle-aged women with or without migraine. Methods: We included women with the endocrine disorder polycystic ovary syndrome (PCOS), a population with supposed elevated cardiovascular risk, with and without comorbid migraine. In 26 women without and 23 women with migraine in the interictal phase (mean age 50.8 ± 2.9 years) local thermal hyperemia (LTH) of the skin of the volar forearm was measured cross-sectionally under control conditions, after inhibition of neuropeptide release by 5% lidocaine/prilocaine (EMLA) cream application, and after inhibition of nitric oxide formation by iontophoresis of NG-monomethyl-L-arginine (L-NMMA). Hereafter, changes in the natural logarithm of the reactive hyperemia index (lnRHI) and augmentation index (AI) during reperfusion after occlusion-derived ischemia were measured. Results: While mean values under control conditions and L-NMMA conditions were similar, migraine patients had a significantly higher mean area of the curve (AUC) of the total LTH response after EMLA application than those without (86.7 ± 26.5% versus 67.9 ± 24.2%; p = 0.014). This was also reflected by a higher median AUC of the plateau phase under similar conditions in women with migraine compared to those without (83.2% (IQR[73.2–109.5]) versus 73.2% (IQR[54.3–92.0]); p = 0.039). Mean changes in lnRHI and AI scores were similar in both groups. Conclusions: In PCOS patients with migraine, neuropeptide action was lower compared with those without migraine. While larger studies are warranted, these findings provide a potential mechanism supporting previous findings that migraine may be independent from traditional risk factors, including atherosclerosis.

Published
2023

3. The influence of ethnicity on outcomes of ovulation induction with clomifene citrate in women with PCOS

Author

Meun, Cindy, Oostingh, Eline, Louwers, Yvonne, Laven, Joop, Meun, Cindy, Oostingh, Eline, Louwers, Yvonne, and Laven, Joop

Abstract

Research question: What is the influence of ethnicity on the outcome of ovulation induction with clomifene citrate in women with polycystic ovary syndrome (PCOS)? Design: This was a retrospective cohort study. In total, 420 women diagnosed with PCOS who were of Northern European, Mediterranean, African, South-East Asian or South American descent, and who started ovulation induction treatment with clomifene citrate, were included. All women were treated with clomifene citrate according to a standardized treatment regimen. The minimal effective dose of clomifene citrate and prevalence of clomifene resistance (CRA) were assessed, and the chance of becoming ovulatory was predicted. Results: Differences were observed in body mass index (P = 0.008), waist circumference (P = 0.036) and serum LH, insulin and androgen concentrations (all P < 0.001) in women of different ethnicities with PCOS. Compared with women of Northern European descent, the minimal effective dose of clomifene citrate in women of other ethnic groups was not significantly different. The prevalence of CRA (P = 0.574) was similar in all ethnic groups A similar chance of ovulation (P = 0.504) was predicted for the different ethnic groups. Conclusions: This is the first study aiming to link ethnicity to ovulation induction outcome in PCOS. Although women of different ethnicities who have PCOS exhibit a variation in phenotypic expression, there do not appear to be differences in the prevalence of clomifene-resistant anovulation or the minimal effective dose of clomifene citrate. Furthermore, a prediction model revealed no significant differences in the predicted chance of ovulation. A larger cohort is needed to validate these findings.

Published
2022

4. Antimüllerian hormone to determine polycystic ovarian morphology

Author

Dietz de Loos, Alexandra, Hund, Martin, Buck, Katharina, Meun, Cindy, Sillman, Johanna, Laven, Joop S.E., Dietz de Loos, Alexandra, Hund, Martin, Buck, Katharina, Meun, Cindy, Sillman, Johanna, and Laven, Joop S.E.

Abstract

Objective: To determine a cutoff for the Elecsys AMH Plus immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) to identify polycystic ovarian morphology (PCOM), a polycystic ovary syndrome (PCOS) criterion. Design: The AMH Protein in Humans for polycystic ovaRian mOrphology DIagnostic TEsting (APHRODITE) study was a retrospective, multicenter, case-control study. The serum antimüllerian hormone (AMH) level was measured using the Elecsys AMH Plus immunoassay. The antral follicle count was determined using transvaginal ultrasound. An AMH cutoff was derived and validated in separate cohorts with cases of PCOS with full phenotype A (oligo/anovulation, hyperandrogenism, and PCOM) versus that with controls. Exploratory analyses of age and PCOS phenotype were performed. Setting: Not applicable. Patient(s): Polycystic ovary syndrome-positive (PCOS A–D per the Rotterdam criteria) and PCOS-negative women aged 25–45 years. Intervention(s): None. Main Outcome Measure(s): A validated cutoff for AMH using the Elecsys AMH Plus assay for PCOM. Result(s): In the validation cohort (455 cases and 500 controls), an AMH cutoff of 3.2 ng/mL (23 pmol/L) resulted in a sensitivity of 88.6% (95% confidence interval [CI] 85.3–91.3) and specificity of 84.6% (95% CI 81.1–87.7) for PCOM diagnosis as well as an area under the receiver-operator characteristic curve of 93.6% (95% CI 92.2–95.1). In women aged 25–35 years, the sensitivity and specificity for the cutoff were 88.5% and 80.3%, respectively, versus 77.8% and 90.1%, respectively, in women aged 36–45 years. The results were consistent across PCOS phenotypes A–D. Conclusion(s): The Elecsys AMH Plus immunoassay, with a cutoff of 3.2 ng/mL (23 pmol/L), is a robust method for identifying PCOM to aid in PCOS diagnosis.

Published
2021

5. The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Author

Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, Zoet, Gerbrand, Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, and Zoet, Gerbrand

Published
2020

6. A Polygenic and Phenotypic Risk Prediction for Polycystic Ovary Syndrome Evaluated by Phenome-Wide Association Studies

Author

Joo, YY, Actkins, K, Pacheco, JA, Basile, AO, Carroll, R, Crosslin, DR, Day, F, Denny, JC, Edwards, D R V, Hakonarson, H, Harley, JB, Hebbring, S J, Ho, K, Jarvik, GP, Jones, M, Karaderi, T, Mentch, FD, Meun, Cindy, Namjou, B, Pendergrass, S, Ritchie, MD, Stanaway, IB, Urbanek, M, Walunas, TL, Smith, M, Chisholm, RL, Kho, AN, Davis, L, Hayes, MG, Joo, YY, Actkins, K, Pacheco, JA, Basile, AO, Carroll, R, Crosslin, DR, Day, F, Denny, JC, Edwards, D R V, Hakonarson, H, Harley, JB, Hebbring, S J, Ho, K, Jarvik, GP, Jones, M, Karaderi, T, Mentch, FD, Meun, Cindy, Namjou, B, Pendergrass, S, Ritchie, MD, Stanaway, IB, Urbanek, M, Walunas, TL, Smith, M, Chisholm, RL, Kho, AN, Davis, L, and Hayes, MG

Published
2020

7. The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Author

Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, Zoet, Gerbrand, Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, and Zoet, Gerbrand

Published
2020

8. The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Author

Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, Zoet, Gerbrand, Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, and Zoet, Gerbrand

Published
2020

9. The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Author

MS VPG/Gynaecologie, Child Health, Arts-assistenten DV&B, MS Radiologie, Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Biostatistiek Onderzoek, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Methodologie, MS Verloskunde, Brain, HEE Team 1, HEE, ZL Cerebrovasculaire Ziekten Medisch, Epi Methoden, Cancer, Cardiovasculaire Epidemiologie, Researchgr. Hart-brein as., Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, Zoet, Gerbrand, MS VPG/Gynaecologie, Child Health, Arts-assistenten DV&B, MS Radiologie, Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Biostatistiek Onderzoek, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Methodologie, MS Verloskunde, Brain, HEE Team 1, HEE, ZL Cerebrovasculaire Ziekten Medisch, Epi Methoden, Cancer, Cardiovasculaire Epidemiologie, Researchgr. Hart-brein as., Meun, Cindy, Gunning, Marlise N., Louwers, Yvonne, V, Peters, Henrike, Roos-Hesselink, Jolien, van Lennep, Jeanine Roeters, Rueda Ochoa, Oscar-Leonel, Appelman, Yolande, Lambalk, Nils, Boersma, Eric, Kavousi, Maryam, Fauser, Bart C. J. M., Laven, Joop S. E., Baart, Sara, Benschop, Laura, Brouwers, Laura, Budde, Ricardo, Cannegieter, Suzanne, Dam, Veerle, Eijkemans, Rene, Ferrari, Michel, Franx, Arie, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Laven, Joop, Linstra, Katie, van der Lugt, Aad, Maas, Angela, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel G. M., van Rijn, Bas, Scheres, Luuk, van der Schouw, Yvonne T., Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Velthuis, Birgitta, Wermer, Marieke, Zick, Bart, and Zoet, Gerbrand

Published
2020

10. The cardiovascular risk profile of middle age women previously diagnosed with premature ovarian insufficiency: A case-control study

Author

Gunning, MN, Meun, Cindy, van Rijn, Bas, Daan, NMP, Roeters van Lennep, Jeanine, Appelman, Y, Boersma, Eric, Hofstra, L, Fauser, Cgkm, Rueda-Ochoa, OL, Ikram, Arfan, Kavousi, Maryam, Lambalk, CB, Eijkemans, MJC, Laven, Joop, Fauser, BCJM, Gunning, MN, Meun, Cindy, van Rijn, Bas, Daan, NMP, Roeters van Lennep, Jeanine, Appelman, Y, Boersma, Eric, Hofstra, L, Fauser, Cgkm, Rueda-Ochoa, OL, Ikram, Arfan, Kavousi, Maryam, Lambalk, CB, Eijkemans, MJC, Laven, Joop, and Fauser, BCJM

Published
2020

11. The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Author

Meun, Cindy, Gunning, MN, Louwers, Yvonne, Peters, H, Hesselink, Jolien, Roeters van Lennep, Jeanine, Rueda Ochoa, Oscar, Appelman, Y, Lambalk, NB, Boersma, E, Kavousi, Maryam, Fauser, BC, Laven, Joop, Meun, Cindy, Gunning, MN, Louwers, Yvonne, Peters, H, Hesselink, Jolien, Roeters van Lennep, Jeanine, Rueda Ochoa, Oscar, Appelman, Y, Lambalk, NB, Boersma, E, Kavousi, Maryam, Fauser, BC, and Laven, Joop

Published
2020

12. Early Onset of Coronary Artery Calcification in Women with Previous Preeclampsia

Author

Arts-assistenten DV&B, Circulatory Health, MS VPG/Gynaecologie, Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Researchgr. Hart-brein as., Brain, ZL Cerebrovasculaire Ziekten Medisch, MS Verloskunde, Benschop, Laura, Brouwers, Laura, Zoet, Gerbrand A., Meun, Cindy, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., De Groot, Christianne M.J., Van Der Schouw, Yvonne T., Maas, Angela H.E.M., Velthuis, Birgitta K., Linstra, Katie M., Kavousi, Maryam, Duvekot, Johannes J., Franx, Arie, Steegers, Eric, Van Rijn, Bas B., Van Lennep, Jeanine E.Roeters, Arts-assistenten DV&B, Circulatory Health, MS VPG/Gynaecologie, Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Researchgr. Hart-brein as., Brain, ZL Cerebrovasculaire Ziekten Medisch, MS Verloskunde, Benschop, Laura, Brouwers, Laura, Zoet, Gerbrand A., Meun, Cindy, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., De Groot, Christianne M.J., Van Der Schouw, Yvonne T., Maas, Angela H.E.M., Velthuis, Birgitta K., Linstra, Katie M., Kavousi, Maryam, Duvekot, Johannes J., Franx, Arie, Steegers, Eric, Van Rijn, Bas B., and Van Lennep, Jeanine E.Roeters

Published
2020

13. Coronary artery calcification in middle-aged women with premature ovarian insufficiency

Author

UMC Utrecht, MS VPG/Gynaecologie, Child Health, MS Verloskunde, Circulatory Health, Brain, MS Radiologie, Biostatistiek Onderzoek, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Methodologie, Researchgr. Hart-brein as., Arts-assistenten DV&B, Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, HEE Team 1, HEE, ZL Cerebrovasculaire Ziekten Medisch, Epi Methoden, Cancer, Julius Centrum, Cardiovasculaire Epidemiologie, Gunning, Marlise N., Meun, Cindy, van Rijn, Bas B., Maas, Angela H.E.M., Benschop, Laura, Franx, Arie, Boersma, Eric, Budde, Ricardo P.J., Appelman, Yolande, Lambalk, Cornelis B., Eijkemans, Rene, Velthuis, Birgitta K., Laven, Joop S.E., Fauser, Bart C.J.M., Baart, Sara, Brouwers, Laura, Cannegieter, Suzanne, Dam, Veerle, Daan, Nadine, Ferrari, Michel, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Lambalk, Nils, Linstra, Katie, van der Lugt, Aad, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel, van Lennep, Jeanine Roeters, Roos-Hesselink, Jolien, Scheres, Luuk, van der Schouw, Yvonne, Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Wermer, Marieke, Zick, Bart, Zoet, Gerbrand, On behalf of the CREW-consortium, UMC Utrecht, MS VPG/Gynaecologie, Child Health, MS Verloskunde, Circulatory Health, Brain, MS Radiologie, Biostatistiek Onderzoek, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Methodologie, Researchgr. Hart-brein as., Arts-assistenten DV&B, Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, HEE Team 1, HEE, ZL Cerebrovasculaire Ziekten Medisch, Epi Methoden, Cancer, Julius Centrum, Cardiovasculaire Epidemiologie, Gunning, Marlise N., Meun, Cindy, van Rijn, Bas B., Maas, Angela H.E.M., Benschop, Laura, Franx, Arie, Boersma, Eric, Budde, Ricardo P.J., Appelman, Yolande, Lambalk, Cornelis B., Eijkemans, Rene, Velthuis, Birgitta K., Laven, Joop S.E., Fauser, Bart C.J.M., Baart, Sara, Brouwers, Laura, Cannegieter, Suzanne, Dam, Veerle, Daan, Nadine, Ferrari, Michel, de Groot, Christianne, Hoek, Annemieke, Koffijberg, Erik, Koster, Wendy, Kruit, Mark, Lagerweij, Giske, Lambalk, Nils, Linstra, Katie, van der Lugt, Aad, van den Brink, Antoinette Maassen, Middeldorp, Saskia, Moons, Karel, van Lennep, Jeanine Roeters, Roos-Hesselink, Jolien, Scheres, Luuk, van der Schouw, Yvonne, Steegers, Eric, Steegers, Regine, Terwindt, Gisela, Wermer, Marieke, Zick, Bart, Zoet, Gerbrand, and On behalf of the CREW-consortium

Published
2019

14. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria

Author

Day, F, Karaderi, T, Jones, MR, Meun, Cindy, He, CY, Drong, A, Kraft, P, Lin, N, Huang, HY, Broer, Linda, Magi, R, Saxena, R, Laisk, T, Urbanek, M, Hayes, MG, Thorleifsson, G, Fernandez-Tajes, J, Mahajan, A, Mullin, BH, Stuckey, BGA, Spector, TD, Wilson, SG, Goodarzi, MO, Davis, L, Obermayer-Pietsch, B, Uitterlinden, André, Anttila, V, Neale, BM, Jarvelin, MR, Fauser, B, Kowalska, I, Visser, Jenny, Andersen, M, Ong, K, Stener-Victorin, E, Ehrmann, D, Legro, RS, Salumets, A, McCarthy, MI, Morin-Papunen, L, Thorsteinsdottir, U, Stefansson, K, Styrkarsdottir, U, Perry, JRB, Dunaif, A, Laven, Joop, Franks, S, Lindgren, CM, Welt, CK, Day, F, Karaderi, T, Jones, MR, Meun, Cindy, He, CY, Drong, A, Kraft, P, Lin, N, Huang, HY, Broer, Linda, Magi, R, Saxena, R, Laisk, T, Urbanek, M, Hayes, MG, Thorleifsson, G, Fernandez-Tajes, J, Mahajan, A, Mullin, BH, Stuckey, BGA, Spector, TD, Wilson, SG, Goodarzi, MO, Davis, L, Obermayer-Pietsch, B, Uitterlinden, André, Anttila, V, Neale, BM, Jarvelin, MR, Fauser, B, Kowalska, I, Visser, Jenny, Andersen, M, Ong, K, Stener-Victorin, E, Ehrmann, D, Legro, RS, Salumets, A, McCarthy, MI, Morin-Papunen, L, Thorsteinsdottir, U, Stefansson, K, Styrkarsdottir, U, Perry, JRB, Dunaif, A, Laven, Joop, Franks, S, Lindgren, CM, and Welt, CK

Published
2018

15. Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO) : Rationale and design of a multicenter cohort study

Author

Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, Velthuis, Birgitta K., Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, and Velthuis, Birgitta K.

Published
2017

16. Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO) : Rationale and design of a multicenter cohort study

Author

Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, Velthuis, Birgitta K., Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, and Velthuis, Birgitta K.

Published
2017

17. Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO) : Rationale and design of a multicenter cohort study

Author

Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, Velthuis, Birgitta K., Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, and Velthuis, Birgitta K.

Published
2017

18. Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): Rationale and design of a multicenter cohort study

Author

UMC Utrecht, MS Verloskunde, Circulatory Health, MS Radiologie, MS VPG/Gynaecologie, Brain, Child Health, Epi Methoden, Cancer, JC onderzoeksprogramma Methodologie, DV&B-MT-Medisch, Researchgr. Hart-brein as., Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, Velthuis, Birgitta K., UMC Utrecht, MS Verloskunde, Circulatory Health, MS Radiologie, MS VPG/Gynaecologie, Brain, Child Health, Epi Methoden, Cancer, JC onderzoeksprogramma Methodologie, DV&B-MT-Medisch, Researchgr. Hart-brein as., Zoet, Gerbrand A., Meun, Cindy, Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., de Groot, Christianne J. M., van der Lugt, Aad, Maas, Angela H E M, Moons, Karl G.M., Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W, Steegers, Eric A. P., van Rijn, Bas B., Laven, Joop S E, Franx, Arie, and Velthuis, Birgitta K.

Published
2017

19. Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study

Author

Zoet, GA, Meun, Cindy, Benschop, L, Boersma, Eric, Budde, Ricardo, Fauser, B, de Groot, CJM, van der Lugt, Aad, Maas, AIR, Moons, KGM, Roeters van Lennep, Jeanine, Roos - Hesselink, Jolien, Steegers, Eric, Rijn, BB, Laven, Joop, Franx, A (Arie), Velthuis, BK, Zoet, GA, Meun, Cindy, Benschop, L, Boersma, Eric, Budde, Ricardo, Fauser, B, de Groot, CJM, van der Lugt, Aad, Maas, AIR, Moons, KGM, Roeters van Lennep, Jeanine, Roos - Hesselink, Jolien, Steegers, Eric, Rijn, BB, Laven, Joop, Franx, A (Arie), and Velthuis, BK

Published
2017

20. Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age

Author

Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, Fauser, Bart C J M, Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, and Fauser, Bart C J M

Published
2016

21. Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age

Author

Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, Fauser, Bart C J M, Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, and Fauser, Bart C J M

Published
2016

22. Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age

Author

Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, Fauser, Bart C J M, Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, and Fauser, Bart C J M

Published
2016

23. Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age

Author

Child Health, MS VPG/Gynaecologie, Groep Timmers, Cardiologie, Brain, Circulatory Health, Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, Fauser, Bart C J M, Child Health, MS VPG/Gynaecologie, Groep Timmers, Cardiologie, Brain, Circulatory Health, Daan, Nadine M P, Muka, Taulant, Koster, Maria P H, Roeters van Lennep, Jaenine E, Lambalk, Cornelis B, Laven, Joop S E, Fauser, Clemens G K M, Meun, Cindy, de Rijke, Yolanda B, Boersma, Eric, Franco, Oscar H, Kavousi, Maryam, and Fauser, Bart C J M

Published
2016

24. Health in middle-aged and elderly women : A conceptual framework for healthy menopause

Author

Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., Kavousi, Maryam, Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., and Kavousi, Maryam

Published
2015

25. Health in middle-aged and elderly women : A conceptual framework for healthy menopause

Author

Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., Kavousi, Maryam, Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., and Kavousi, Maryam

Published
2015

26. Health in middle-aged and elderly women : A conceptual framework for healthy menopause

Author

Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., Kavousi, Maryam, Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., and Kavousi, Maryam

Published
2015

27. Health in middle-aged and elderly women: A conceptual framework for healthy menopause

Author

UMC Utrecht, Child Health, MS VPG/Gynaecologie, Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., Kavousi, Maryam, UMC Utrecht, Child Health, MS VPG/Gynaecologie, Jaspers, Loes, Daan, Nadine M P, Van Dijk, Gabriella M., Gazibara, Tatjana, Muka, Taulant, Wen, Ke Xin, Meun, Cindy, Zillikens, M. Carola, Roeters Van Lennep, Jeanine E., Roos-Hesselink, Jolien W., Laan, Ellen, Rees, Margaret, Laven, Joop S E, Franco, Oscar H., and Kavousi, Maryam

Published
2015

28. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome

Author

Day, Felix R, Hinds, David A, Tung, Joyce Y, Stolk, Lisette, Styrkarsdottir, Unnur, Saxena, Richa, Bjonnes, Andrew, Broer, Linda, Dunger, David B, Halldorsson, Bjarni V, Lawlor, Debbie A, Laval, Guillaume, Mathieson, Iain, McCardle, Wendy L, Louwers, Yvonne, Meun, Cindy, Ring, Susan, Scott, Robert A, Sulem, Patrick, Uitterlinden, André G, Wareham, Nicholas J, Thorsteinsdottir, Unnur, Welt, Corrine, Stefansson, Kari, Laven, Joop S E, Ong, Ken K, Perry, John R B, Day, Felix R, Hinds, David A, Tung, Joyce Y, Stolk, Lisette, Styrkarsdottir, Unnur, Saxena, Richa, Bjonnes, Andrew, Broer, Linda, Dunger, David B, Halldorsson, Bjarni V, Lawlor, Debbie A, Laval, Guillaume, Mathieson, Iain, McCardle, Wendy L, Louwers, Yvonne, Meun, Cindy, Ring, Susan, Scott, Robert A, Sulem, Patrick, Uitterlinden, André G, Wareham, Nicholas J, Thorsteinsdottir, Unnur, Welt, Corrine, Stefansson, Kari, Laven, Joop S E, Ong, Ken K, and Perry, John R B

Abstract

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10(-8)), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10(-9)), higher insulin resistance (P=6 × 10(-4)) and lower serum sex hormone binding globulin concentrations (P=5 × 10(-4)). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10(-5)). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.

Published
2015

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