Conclusions
The increased risk of HDP in srPCOS can mostly be attributed to overweight/obesity and weight gain through life. Importantly, normal weight women with srPCOS were not at increased risk for developing HDP. The present results emphasize the importance of weight management prior pregnancy to reduce the incidence of HDP, an important factor cause of postnatal morbidity. The role of hyperandrogenaemia in the pathophysiological process of HDP could not be confirmed, remaining under debate with further research being needed to clarify its role.
Disclosure of interests
None
Contribution to authorship
L.C.M.-P., S.I.W., J.N and J.S.S.R conceived and designed the study. A.H.B. and J.S.S.R. analysed the data and L.M.C.-P., J.N. and M.S.V contributed to its interpretation. J.S.S.R. and J.N drafted the manuscript. M.-M.E.O, K.P, M.-R.J, J.S.T, S.F and T.T.P participated in the revision process and have approved this submission for publication.
Details of ethics approval
The study followed the principles of the Declaration of Helsinki. The Ethics Committee of the Northern Ostrobothnia Hospital District (EETTMK decision number 94/2011) has approved the research on Sebtember 17th, 2012. All participants took part on a voluntary basis and signed an informed consent to use all data.
Grants and funding: This work was supported by grants from the Finnish Medical Foundation, the North Ostrobothnia Regional Fund, Academy of Finland (project grants 315921, 104781, 120315, 129269, 1114194, 24300796, 295760), Center of Excellence in Complex Disease Genetics and SALVE, the Sigrid Juselius Foundation, University Hospital Oulu and University of Oulu (75617), Medical Research Center Oulu, National Institute for Health Research (UK), Genesis Research Trust (UK), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement HEALTH-F4-2007-201413, EU FP7 EurHEALTHAgeing -277849 the European Commission and the Medical Research Council, UK (G0500539, G0600705, G1002319, G0802782, PrevMetSyn/SALVE) and the MRC, Centenary Early Career Award.
The study is not supported or sponsored by any commercial organisation, grant, or fund.
Supporting Information
Additional Supporting Information may be found in the online version of this article:
Figure S1. Flowchart of the HDP diagnosis.
Figure S2. Prevalence of hypertensive disorders of pregnancy (HDP) in different total level of testosterone (A) and free androgen (B) quartiles at ages 31 and 46
References
(1) Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Practice & Research in Clinical Obstetrics & Gynaecology 2004 Oct;18(5):737-754.
(2) Franks S. Polycystic ovary syndrome. N Engl J Med 1995 Sep 28;333(13):853-861.
(3) Kjerulff LE, Sanchez-Ramos L, Duffy D. Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis. Am J Obstet Gynecol 2011 Jun;204(6):558.e1-558.e6.
(4) Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004 Jan;81(1):19-25.
(5) Teede H, Missio M, Costello M, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction 2019;34(2):388.
(6) Sam S. Obesity and Polycystic Ovary Syndrome. Obes Manag 2007 Apr;3(2):69-73.
(7) Lim SS, Kakoly NS, Tan JWJ, Fitzgerald G, Bahri Khomami M, Joham AE, et al. Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. Obes Rev 2019 Feb;20(2):339-352.
(8) Diamanti-Kandarakis E. Role of obesity and adiposity in polycystic ovary syndrome. Int J Obes (Lond) 2007 discussion S31-2; Nov;31(Suppl 2):S8-13.
(9) Hashemi S, Ramezani Tehrani F, Mehrabi Y, Azizi F. Hypertensive pregnancy disorders as a risk factor for future cardiovascular and metabolic disorders (Tehran Lipid and Glucose Study). Journal of Obstetrics & Gynaecology Research 2013 May;39(5):891-897.
(10) American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013 Nov;122(5):1122-1131.
(11) Davison JM, Homuth V, Jeyabalan A, Conrad KP, Karumanchi SA, Quaggin S, et al. New aspects in the pathophysiology of preeclampsia. Journal of the American Society of Nephrology 2004 Sep;15(9):2440-2448.
(12) Wang Y, Zhao X, Zhao H, Ding H, Tan J, Chen J, et al. Risks for gestational diabetes mellitus and pregnancy-induced hypertension are increased in polycystic ovary syndrome. BioMed Research International 2013;2013:182582.
(13) Mannisto T, Mendola P, Vaarasmaki M, Jarvelin M, Hartikainen A, Pouta A, et al. Elevated blood pressure in pregnancy and subsequent chronic disease risk. Circulation 2013 Feb 12;127(6):681-690.
(14) Herrera-Garcia G, Contag S. Maternal preeclampsia and risk for cardiovascular disease in offspring. Curr Hypertens Rep 2014 Sep;16(9):475.
(15) Bahri Khomami M, Joham AE, Boyle JA, Piltonen T, Silagy M, Arora C, et al. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-A systematic review, meta-analysis, and meta-regression. Obes Rev 2019 May;20(5):659-674.
(16) Boomsma CM, Eijkemans MJC, Hughes EG, Visser GHA, Fauser BCJM, Macklon NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006 Nov-Dec;12(6):673-683.
(17) Qin JZ, Pang LH, Li MJ, Fan XJ, Huang RD, Chen HY. Obstetric complications in women with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 2013 Jun 26;11:56.
(18) Altieri P, Gambineri A, Prontera O, Cionci G, Franchina M, Pasquali R. Maternal polycystic ovary syndrome may be associated with adverse pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol 2010 Mar;149(1):31-36.
(19) Haakova L, Cibula D, Rezabek K, Hill M, Fanta M, Zivny J. Pregnancy outcome in women with PCOS and in controls matched by age and weight. Hum Reprod 2003 Jul;18(7):1438-1441.
(20) Mikola M, Hiilesmaa V, Halttunen M, Suhonen L, Tiitinen A. Obstetric outcome in women with polycystic ovarian syndrome. Human Reproduction 2001 Feb;16(2):226-229.
(21) Mumm H, Jensen DM, Sørensen JA, Andersen LLT, Ravn P, Andersen M, et al. Hyperandrogenism and phenotypes of polycystic ovary syndrome are not associated with differences in obstetric outcomes. Acta Obstet Gynecol Scand 2015 02/01; 2019/01;94(2):204-211.
(22) Ollila ME, Piltonen T, Puukka K, Ruokonen A, Jarvelin M, Tapanainen JS, et al. Weight Gain and Dyslipidemia in Early Adulthood Associate With Polycystic Ovary Syndrome: Prospective Cohort Study. J Clin Endocrinol Metab 2016 Feb;101(2):739-747.
(23) Koivuaho E, Laru J, Ojaniemi M, Puukka K, Kettunen J, Tapanainen JS, et al. Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS. Int J Obes (Lond) 2019 Jul;43(7):1370-1379.
(24) Koivunen R, Pouta A, Franks S, Martikainen H, Sovio U, Hartikainen A, et al. Fecundability and spontaneous abortions in women with self-reported oligo-amenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study. Hum Reprod 2008 Sep;23(9):2134-2139.
(25) Rantakallio P. The longitudinal study of the northern Finland birth cohort of 1966. Paediatr Perinat Epidemiol 1988 Jan;2(1):59-88.
(26) Taponen S, Ahonkallio S, Martikainen H, Koivunen R, Ruokonen A, Sovio U, et al. Prevalence of polycystic ovaries in women with self-reported symptoms of oligomenorrhoea and/or hirsutism: Northern Finland Birth Cohort 1966 Study. Hum Reprod 2004 May;19(5):1083-1088.
(27) ZAWADSKI JK DA. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: DUNAIF AGJ, HASELTINE F, EDS. Polycystic Ovary Syndrome. 1992;377-384.(Boston: Blackwell Scientific).
(28) Taponen S, Martikainen H, Jarvelin M, Laitinen J, Pouta A, Hartikainen A, et al. Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study. Journal of Clinical Endocrinology & Metabolism 2003 Jan;88(1):141-147.
(29) Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 2011 Aug;25(4):391-403.
(30) Umesawa M, Kobashi G. Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. Hypertens Res 2017 Mar;40(3):213-220.
(31) Ye C, Ruan Y, Zou L, Li G, Li C, Chen Y, et al. The 2011 survey on hypertensive disorders of pregnancy (HDP) in China: prevalence, risk factors, complications, pregnancy and perinatal outcomes. PLoS ONE 2014;9(6):e100180.
(32) Fuchs F, Senat M, Rey E, Balayla J, Chaillet N, Bouyer J, et al. Impact of maternal obesity on the incidence of pregnancy complications in France and Canada. Sci rep 2017 Sep 07;7(1):10859.
(33) Lonnebotn M, Natvig GK, Benediktsdottir B, Burgess JA, Holm M, Jogi R, et al. Polycystic ovary syndrome, body mass index and hypertensive disorders in pregnancy. Pregnancy Hypertens 2018 Jan;11:32-37.
(34) Palomba S, Falbo A, Russo T, Tolino A, Orio F, Zullo F. Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertil Steril 2010 Oct;94(5):1805-1811.
(35) Naver KV, Grinsted J, Larsen SO, Hedley PL, Jorgensen FS, Christiansen M, et al. Increased risk of preterm delivery and pre-eclampsia in women with polycystic ovary syndrome and hyperandrogenaemia. BJOG 2014 Apr;121(5):575-581.
(36) Carlsen SM, Romundstad P, Jacobsen G. Early second-trimester maternal hyperandrogenemia and subsequent preeclampsia: a prospective study. Acta Obstet Gynecol Scand 2005 Feb;84(2):117-121.
(37) Perez-Sepulveda A, Monteiro LJ, Dobierzewska A, Espana-Perrot PP, Venegas-Araneda P, Guzman-Rojas AM, et al. Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia. PLoS ONE 2015;10(10):e0139682.
(38) Ghorashi V, Sheikhvatan M. The relationship between serum concentration of free testosterone and pre-eclampsia. Endokrynol Pol 2008 Sep-Oct;59(5):390-392.
(39) Hakim C, Padmanabhan V, - Vyas,Arpita K. - Gestational Hyperandrogenism in Developmental Programming. - Endocrinology February 1, 158(2):199 2017 - 2016.
(40) Karjula S, Morin-Papunen L, Auvinen J, Ruokonen A, Puukka K, Franks S, et al. Psychological Distress Is More Prevalent in Fertile Age and Premenopausal Women With PCOS Symptoms: 15-Year Follow-Up. J Clin Endocrinol Metab 2017 Jun 1;102(6):1861-1869.
Table 1 Clinical characteristics of non-PCOS women and women with srPCOS, sorted according to status of hypertensive disorder of pregnancy.