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3. Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia

Author

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 Roeters van Lennep, Jeanine E.

Published
2020
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6. Prevalence of Subclinical Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography in 45- to 55-Year-Old Women With a History of Preeclampsia

Author

Zoet, Gerbrand A., Benschop, Laura, Boersma, Eric, Budde, Ricardo P.J., Fauser, Bart C.J.M., van der Graaf, Yolanda, de Groot, Christianne J.M., Maas, Angela H.E.M., Roeters van Lennep, Jeanine E., Steegers, Eric A.P., Visseren, Frank L., van Rijn, Bas B., Velthuis, Birgitta K., Franx, Arie, Appelman, Yolande E., Baart, Sara J., Brouwers, Laura, Cannegieter, Suzanne C., Dam, Veerle, Eijkemans, M.C.J., Ferrari, Michel D., Gunning, Marlise N., Hoek, Annemieke, Koffijberg, Erik, Koster, M.P.H., Kruit, Mark, Lagerwij, Giske R., Lambalk, C.B., Laven, Joop S., Linstra, Katie, van der Lugt, Aad, Maassen van den Brink, Antoinette, Meun, Cindy, Middeldorp, Saskia, Moons, Karel G.M., Roos-Hesselink, Jolien W., Scheres, Luuk J.J., Steegers-Theunissen, Regine P.M., Terwindt, Gisela M., and Wermer, Marieke J.H.

Published
2018
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7. 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

9. 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

10. 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

11. 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

12. 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

13. 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

16. 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

20. 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

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

Author

Gunning, Marlise N., Meun, Cindy, van Rijn, Bas B., Daan, Nadine M. P., Roeters van Lennep, Jeanine E., Appelman, Yolande, Boersma, Eric, Hofstra, Leonard, Fauser, Clemens G. K. M., Rueda-Ochoa, Oscar L., Ikram, Mohammad A., Kavousi, Maryam, Lambalk, Cornelis B., Eijkemans, Marinus J. C., Laven, Joop S. E., and Fauser, Bart C. J. M.

Subjects
*PREMATURE ovarian failure, *WAIST-hip ratio, *MIDDLE age, *WAIST circumference, *CARDIOVASCULAR diseases risk factors, *SYSTOLIC blood pressure, *AGE groups, *MATERNAL age
Abstract

Background: Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. Methods and findings: We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8–9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0–98.0) versus 80.7 (IQR: 75.1–86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85–0.93) versus 0.79 (IQR: 0.75–0.83), p < 0.01), systolic blood pressure (124 (IQR 112–135) versus 120 (IQR109-131), p < 0.04) and diastolic blood pressure (81 (IQR: 76–89) versus 78 (IQR: 71–86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1–9.4) versus 7.9 (IQR: 7.1–8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 μm (500–615) versus 684 μm (618–737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7–10.6) versus 6.0% (IQR: 3.9–9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. Conclusions: Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life. Trial registration: ClinicalTrials.gov Identifier: NCT02616510. [ABSTRACT FROM AUTHOR]

Published
2020
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23. 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

24. 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

25. 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

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

Author

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

Published
2017
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27. Cardiovascular risk in women with premature ovarian insufficiency compared to premenopausal women at middle age

Author

Daan, Nadine, primary, Muka, Taulant, additional, Koster, Maria, additional, van Lennep, Jaenine Roeters, additional, Lambalk, Cornelis, additional, Laven, Joop, additional, Fauser, Clemens, additional, Meun, Cindy, additional, de Rijke, Yolanda, additional, Boersma, Eric, additional, Franco, Oscar, additional, Kavousi, Maryam, additional, and Fauser, Bart, additional

Published
2017
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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 [0000-0003-3789-7651], Styrkarsdottir, Unnur [0000-0001-8146-8278], Dunger, David B [0000-0002-2566-9304], Sulem, Patrick [0000-0001-7123-6123], Apollo - University of Cambridge Repository, Internal Medicine, and Obstetrics & Gynecology

Subjects
Aging, Ovary, YAP-Signaling Proteins, Phosphoproteins, Article, White People, Acid Anhydride Hydrolases, Neoplasm Proteins, DNA-Binding Proteins, ErbB Receptors, DNA Repair Enzymes, Case-Control Studies, Follicle Stimulating Hormone, beta Subunit, Humans, Female, Selection, Genetic, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study, Polycystic Ovary Syndrome, Transcription Factors
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, This paper describes the largest genome-wide association study to date on polycystic ovary syndrome (PCOS), a common reproductive disorder in women. Six genetic loci—including known targets of cancer chemotherapy—were identified, and the authors infer causal and balancing selection mechanisms involved in PCOS risk and susceptibility.

Published
2015

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

Author

Joo, Yoonjung Yoonie, Actkins, Ky’Era, Pacheco, Jennifer A, Basile, Anna O, Carroll, Robert, Crosslin, David R, Day, Felix, Denny, Joshua C, Velez Edwards, Digna R, Hakonarson, Hakon, Harley, John B, Hebbring, Scott J, Ho, Kevin, Jarvik, Gail P, Jones, Michelle, Karaderi, Tugce, Mentch, Frank D, Meun, Cindy, Namjou, Bahram, Pendergrass, Sarah, Ritchie, Marylyn D, Stanaway, Ian B, Urbanek, Margrit, Walunas, Theresa L, Smith, Maureen, Chisholm, Rex L, Kho, Abel N, Davis, Lea, and Hayes, M Geoffrey

Published
2020
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30. Coronary artery calcification in middle‐aged women with premature ovarian insufficiency.

Author

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, Marinus J. C., Velthuis, Birgitta K., Laven, Joop S. E., Fauser, Bart C. J. M., Baart, Sara, Brouwers, Laura, Cannegieter, Suzanne, Dam, Veerle, Daan, Nadine, and Eijkemans, Rene

Subjects
*CORONARY arteries, *MIDDLE-aged women, *PREMATURE menopause, *CORONARY artery calcification, *HYPERTENSION, CARDIOVASCULAR disease related mortality
Abstract

Objective: Women with premature ovarian insufficiency (POI) enter menopause before age 40. Early menopause was associated with increased risk for coronary artery disease (CAD), death from cardiovascular disease and all‐cause mortality. We compared the prevalence of CAD between middle‐aged women on average 10 years following the initial POI diagnosis, with a population‐based cohort. Design: Cross‐sectional case‐control study. Participants: Women from two Dutch University Medical Centers above 45 years of age previously diagnosed with POI (n = 98) were selected and compared with age‐ and race‐matched controls from the Multi‐Ethnic Study of Atherosclerosis (MESA). Measurements: The primary outcome was detectable coronary artery calcium (CAC) determined by coronary computed tomography (CCT). Results: Women with POI had significantly higher blood pressure, cholesterol and glucose, despite lower BMI compared to controls. Similar proportions of detectable CAC (CAC score >0 Agatston Units) were observed in women with POI and controls (POI n = 16 (16%), controls n = 52 (18%), P = 0.40 and Padj = 0.93). In women with POI separately, we were not able to identify associations between CVD risk factors and CAC. The following CVD risk factors in controls were positively associated with CAC: age, diabetes mellitus, hypertension and LDL cholesterol. HRT use was negatively associated with CAC in controls. Conclusions: The presence of CAC did not differ significantly in women with POI around 50 years of age, compared to an age‐ and race‐matched control group. We observe no increased calcified coronary disease in POI patients, despite the presence of unfavourable cardiovascular risk factors in these women. [ABSTRACT FROM AUTHOR]

Published
2019
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31. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

Author

Day, Felix, Karaderi, Tugce, Jones, Michelle R., Meun, Cindy, He, Chunyan, Drong, Alex, Kraft, Peter, Lin, Nan, Huang, Hongyan, Broer, Linda, Magi, Reedik, Saxena, Richa, Laisk, Triin, Urbanek, Margrit, Hayes, M. Geoffrey, Thorleifsson, Gudmar, Fernandez-Tajes, Juan, Mahajan, Anubha, Mullin, Benjamin H., and Stuckey, Bronwyn G. A.

Subjects
POLYCYSTIC ovary syndrome, HYPERANDROGENISM, INSULIN resistance, GLUCOSE, HOMEOSTASIS, HUMAN genetics
Abstract

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
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32. 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

33. 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

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

Author

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

Published
2016
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37. 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

38. 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

39. 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

40. Pre-Conception Characteristics Predict Obstetrical and Neonatal Outcomes in Women With Polycystic Ovary Syndrome.

Author

Christ, Jacob P, Gunning, Marlise N, Meun, Cindy, Eijkemans, Marinus J C, van Rijn, Bas B, Bonsel, Gouke J, Laven, Joop S E, and Fauser, Bart C J M

Abstract

Women with polycystic ovary syndrome (PCOS) are at increased risk for obstetric and perinatal complications. At present, it is unknown how characteristics of PCOS relate to the likelihood of these complications.

Published
2019
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41. Health in middle-aged and elderly women: A conceptual framework for healthy menopause

Author

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

Published
2015
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42. Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women: A Population-Based Cohort Study and Meta-analysis.

Author

Muka, Taulant, Nano, Jana, Jaspers, Loes, Meun, Cindy, Bramer, Wichor M., Hofman, Albert, Dehghan, Abbas, Kavousi, Maryam, Laven, Joop S. E., and Franco, Oscar H.

Subjects
HORMONE therapy for menopause, THERAPEUTIC use of sex hormones, STEROIDS, TYPE 2 diabetes risk factors, TESTOSTERONE
Abstract

It remains unclear whether endogenous sex hormones (ESH) are associated with risk of type 2 diabetes (T2D) in women. Data of 3,117 postmenopausal women participants of the Rotterdam Study were analyzed to examine whether ESH and sex hormone-binding globulin (SHBG) were associated with the risk of incident T2D. Additionally, we performed a systematic review and meta-analysis of studies assessing the prospective association of ESH and SHBG with T2D in women. During a median follow-up of 11.1 years, we identified 384 incident cases of T2D in the Rotterdam Study. No association was observed between total testosterone (TT) or bioavailable testosterone (BT) with T2D. SHBG was inversely associated with the risk of T2D, whereas total estradiol (TE) was associated with increased risk of T2D. Similarly, in the meta-analysis of 13 population-based prospective studies involving more than 1,912 incident T2D cases, low levels of SHBG and high levels of TE were associated with increased risk of T2D, whereas no associations were found for other hormones. The association of SHBG with T2D did not change by menopause status, whereas the associations of ESH and T2D were based only in postmenopausal women. SHBG and TE are independent risk factors for the development of T2D in women. [ABSTRACT FROM AUTHOR]

Published
2017
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43. Correction: Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

Author

Day, Felix, Karaderi, Tugce, Jones, Michelle R., Meun, Cindy, He, Chunyan, Drong, Alex, Kraft, Peter, Lin, Nan, Huang, Hongyan, Broer, Linda, Magi, Reedik, Saxena, Richa, Laisk, Triin, Urbanek, Margrit, Hayes, M. Geoffrey, Thorleifsson, Gudmar, Fernandez-Tajes, Juan, Mahajan, Anubha, Mullin, Benjamin H., and Stuckey, Bronwyn G. A.

Subjects
POLYCYSTIC ovary syndrome, META-analysis, INDUCED ovulation
Abstract

Correction: Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria Table 2 The 14 genome-wide significant variants associated with PCOS in the meta-analysis. All PCOS meta-analysis, PCOS meta-analysis without self-report, NIH, non-NIH Rotterdam and self-report meta-analysis results. [Extracted from the article]

Published
2019
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44. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria

Author

Day, Felix, Karaderi, Tugce, Jones, Michelle R, Meun, Cindy, He, Chunyan, Drong, Alex, Kraft, Peter, Lin, Nan, Huang, Hongyan, Broer, Linda, Magi, Reedik, Saxena, Richa, Laisk, Triin, Urbanek, Margrit, Hayes, M Geoffrey, Thorleifsson, Gudmar, Fernandez-Tajes, Juan, Mahajan, Anubha, Mullin, Benjamin H, Stuckey, Bronwyn GA, Spector, Timothy D, Wilson, Scott G, Goodarzi, Mark O, Davis, Lea, Obermayer-Pietsch, Barbara, Uitterlinden, André G, Anttila, Verneri, Neale, Benjamin M, Jarvelin, Marjo-Riitta, Fauser, Bart, Kowalska, Irina, Visser, Jenny A, Andersen, Marianne, Ong, Ken, Stener-Victorin, Elisabet, Ehrmann, David, Legro, Richard S, Salumets, Andres, McCarthy, Mark I, Morin-Papunen, Laure, Thorsteinsdottir, Unnur, Stefansson, Kari, 23andMe Research Team, Styrkarsdottir, Unnur, Perry, John RB, Dunaif, Andrea, Laven, Joop, Franks, Steve, Lindgren, Cecilia M, and Welt, Corrine K

Subjects
2. Zero hunger, endocrine system diseases, female genital diseases and pregnancy complications, White People, 3. Good health, Cohort Studies, Phenotype, Asian People, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Polycystic Ovary Syndrome
Abstract

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.

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

Author

Meun C, Oostingh E, Louwers Y, and Laven J

Subjects
Citrates therapeutic use, Clomiphene therapeutic use, Ethnicity, Female, Fertility Agents, Female pharmacology, Fertility Agents, Female therapeutic use, Humans, Ovulation Induction, Retrospective Studies, Infertility, Female therapy, Metformin therapeutic use, Polycystic Ovary Syndrome drug therapy
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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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46. The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome.

Author

Meun C, Gunning MN, Louwers YV, Peters H, Roos-Hesselink J, Roeters van Lennep J, Rueda Ochoa OL, Appelman Y, Lambalk N, Boersma E, Kavousi M, Fauser BC, and Laven JS

Subjects
Age Factors, Body Weights and Measures, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Carotid Intima-Media Thickness, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Insulin blood, Lipids blood, Metabolic Syndrome epidemiology, Middle Aged, Netherlands epidemiology, Polycystic Ovary Syndrome blood, Polycystic Ovary Syndrome physiopathology, Prevalence, Risk Factors, Heart Disease Risk Factors, Polycystic Ovary Syndrome complications, Polycystic Ovary Syndrome epidemiology
Abstract

Objectives: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score., Design: A cross-sectional study., Participants: 200 women aged >45 with PCOS, and 200 age-matched controls., Measurements: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured., Results: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls., Conclusions: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD., (© 2019 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Published
2020
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47. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome.

Author

Day FR, Hinds DA, Tung JY, Stolk L, Styrkarsdottir U, Saxena R, Bjonnes A, Broer L, Dunger DB, Halldorsson BV, Lawlor DA, Laval G, Mathieson I, McCardle WL, Louwers Y, Meun C, Ring S, Scott RA, Sulem P, Uitterlinden AG, Wareham NJ, Thorsteinsdottir U, Welt C, Stefansson K, Laven JSE, Ong KK, and Perry JRB

Subjects
Acid Anhydride Hydrolases, Adaptor Proteins, Signal Transducing genetics, Aging physiology, Case-Control Studies, DNA Repair Enzymes genetics, DNA-Binding Proteins genetics, ErbB Receptors genetics, Female, Follicle Stimulating Hormone, beta Subunit genetics, Genome-Wide Association Study, Humans, Neoplasm Proteins genetics, Ovary physiology, Phosphoproteins genetics, Transcription Factors, YAP-Signaling Proteins, Polycystic Ovary Syndrome genetics, Selection, Genetic, White People genetics
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
Full Text
View/download PDF

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