Semin Reprod Med 2014; 32(03): 222-229
DOI: 10.1055/s-0034-1371094
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Menopausal Implications of Polycystic Ovarian Syndrome

Rashmi Kudesia
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine
,
Genevieve S. Neal-Perry
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine
2   Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York
› Author Affiliations
Further Information

Publication History

Publication Date:
08 April 2014 (online)

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting up to 8 to 10% of reproductive-aged women. Although the medical and metabolic consequences of PCOS are well-described in young reproductive-aged women, its impact on female reproductive senescence and the menopausal transition is poorly understood. This review summarizes current knowledge regarding the effect of PCOS is menopausal and perimenopausal women. We also highlight areas that are ripe for clinical research.

 
  • References

  • 1 Carmina E. Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines. Minerva Ginecol 2004; 56 (1) 1-6
  • 2 Franks S. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: in defense of the Rotterdam criteria. J Clin Endocrinol Metab 2006; 91 (3) 786-789
  • 3 Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome; towards a rational approach. In: Dunaif A, Givens JR, Haseltine F, , eds. Polycystic Ovary Syndrome. Boston: Blackwell Scientific; 1992: 377-384
  • 4 Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab 2006; 91 (3) 781-785
  • 5 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33 (6) 981-1030
  • 6 Taffe JR, Dennerstein L. Menstrual patterns leading to the final menstrual period. Menopause 2002; 9 (1) 32-40
  • 7 Van Voorhis BJ, Santoro N, Harlow S, Crawford SL, Randolph J. The relationship of bleeding patterns to daily reproductive hormones in women approaching menopause. Obstet Gynecol 2008; 112 (1) 101-108
  • 8 Vollman RF. The menstrual cycle. Major Probl Obstet Gynecol 1977; 7: 1-193
  • 9 Dahlgren E, Johansson S, Lindstedt G , et al. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 1992; 57 (3) 505-513
  • 10 Elting MW, Kwee J, Korsen TJ, Rekers-Mombarg LT, Schoemaker J. Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles. Fertil Steril 2003; 79 (5) 1154-1160
  • 11 Harlow SD, Gass M, Hall JE , et al; STRAW + 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 2012; 97 (4) 1159-1168
  • 12 Shah D, Bansal S. Polycystic ovaries - beyond menopause. Climacteric . Epub, October 28, 2013
  • 13 Schmidt J, Brännström M, Landin-Wilhelmsen K, Dahlgren E. Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls. J Clin Endocrinol Metab 2011; 96 (7) 2178-2185
  • 14 Hudecova M, Holte J, Moby L , et al. Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study. Fertil Steril 2011; 95 (3) 1146-1148
  • 15 Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005; 90 (7) 3847-3853
  • 16 McConnell DS, Stanczyk FZ, Sowers MR, Randolph Jr JF, Lasley BL. Menopausal transition stage-specific changes in circulating adrenal androgens. Menopause 2012; 19 (6) 658-663
  • 17 Stanczyk FZ, Lee JS, Santen RJ. Standardization of steroid hormone assays: why, how, and when?. Cancer Epidemiol Biomarkers Prev 2007; 16 (9) 1713-1719
  • 18 Alsamarai S, Adams JM, Murphy MK , et al. Criteria for polycystic ovarian morphology in polycystic ovary syndrome as a function of age. J Clin Endocrinol Metab 2009; 94 (12) 4961-4970
  • 19 Hudecova M, Holte J, Olovsson M, Sundström Poromaa I. Long-term follow-up of patients with polycystic ovary syndrome: reproductive outcome and ovarian reserve. Hum Reprod 2009; 24 (5) 1176-1183
  • 20 Webber LJ, Stubbs S, Stark J , et al. Formation and early development of follicles in the polycystic ovary. Lancet 2003; 362 (9389) 1017-1021
  • 21 van Disseldorp J, Faddy MJ, Themmen AP , et al. Relationship of serum antimüllerian hormone concentration to age at menopause. J Clin Endocrinol Metab 2008; 93 (6) 2129-2134
  • 22 Dólleman M, Faddy MJ, van Disseldorp J , et al. The relationship between anti-Müllerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies. J Clin Endocrinol Metab 2013; 98 (5) 1946-1953
  • 23 Mulders AG, Laven JS, Eijkemans MJ, de Jong FH, Themmen AP, Fauser BC. Changes in anti-Müllerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility. Hum Reprod 2004; 19 (9) 2036-2042
  • 24 Tehrani FR, Solaymani-Dodaran M, Hedayati M, Azizi F. Is polycystic ovary syndrome an exception for reproductive aging?. Hum Reprod 2010; 25 (7) 1775-1781
  • 25 Holte J, Bergh T, Gennarelli G, Wide L. The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women. Clin Endocrinol (Oxf) 1994; 41 (4) 473-481
  • 26 Schmidt J, Landin-Wilhelmsen K, Brännström M, Dahlgren E. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab 2011; 96 (12) 3794-3803
  • 27 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18 (6) 774-800
  • 28 Solomon CG, Hu FB, Dunaif A , et al. Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus. JAMA 2001; 286 (19) 2421-2426
  • 29 Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010; 16 (4) 347-363
  • 30 Hudecova M, Holte J, Olovsson M, Larsson A, Berne C, Poromaa IS. Diabetes and impaired glucose tolerance in patients with polycystic ovary syndrome—a long term follow-up. Hum Reprod 2011; 26 (6) 1462-1468
  • 31 Fauser BC, Tarlatzis BC, Rebar RW , et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012; 97 (1) 28-38.e25
  • 32 Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003; 163 (4) 427-436
  • 33 Glueck CJ, Dharashivkar S, Wang P , et al. Obesity and extreme obesity, manifest by ages 20-24 years, continuing through 32-41 years in women, should alert physicians to the diagnostic likelihood of polycystic ovary syndrome as a reversible underlying endocrinopathy. Eur J Obstet Gynecol Reprod Biol 2005; 122 (2) 206-212
  • 34 Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab 1987; 65 (3) 499-507
  • 35 Panidis D, Tziomalos K, Chatzis P , et al. Association between menstrual cycle irregularities and endocrine and metabolic characteristics of the polycystic ovary syndrome. Eur J Endocrinol 2013; 168 (2) 145-152
  • 36 Panidis D, Tziomalos K, Macut D , et al. Age- and body mass index-related differences in the prevalence of metabolic syndrome in women with polycystic ovary syndrome. Gynecol Endocrinol 2013; 29 (10) 926-930
  • 37 ESHRE Capri Workshop Group. Hormones and cardiovascular health in women. Hum Reprod Update 2006; 12 (5) 483-497
  • 38 Grundy SM, Cleeman JI, Daniels SR , et al; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112 (17) 2735-2752
  • 39 Bajuk Studen K, Jensterle Sever M, Pfeifer M. Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome. Front Horm Res 2013; 40: 64-82
  • 40 Spanos N, Tziomalos K, Macut D , et al. Adipokines, insulin resistance and hyperandrogenemia in obese patients with polycystic ovary syndrome: cross-sectional correlations and the effects of weight loss. Obes Facts 2012; 5 (4) 495-504
  • 41 Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 2013; 19 (3) 268-288
  • 42 Toulis KA, Goulis DG, Mintziori G , et al. Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum Reprod Update 2011; 17 (6) 741-760
  • 43 Beydoun HA, Beydoun MA, Wiggins N, Stadtmauer L. Relationship of obesity-related disturbances with LH/FSH ratio among post-menopausal women in the United States. Maturitas 2012; 71 (1) 55-61
  • 44 Hudecova M, Holte J, Olovsson M, Larsson A, Berne C, Sundstrom-Poromaa I. Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up. Fertil Steril 2011; 96 (5) 1271-1274
  • 45 Elting MW, Korsen TJ, Schoemaker J. Obesity, rather than menstrual cycle pattern or follicle cohort size, determines hyperinsulinaemia, dyslipidaemia and hypertension in ageing women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2001; 55 (6) 767-776
  • 46 Carmina E. PCOS: metabolic impact and long-term management. Minerva Ginecol 2012; 64 (6) 501-505
  • 47 Carmina E. Obesity, adipokines and metabolic syndrome in polycystic ovary syndrome. Front Horm Res 2013; 40: 40-50
  • 48 Welt CK, Carmina E. Lifecycle of polycystic ovary syndrome (PCOS): from in utero to menopause. J Clin Endocrinol Metab 2013; 98 (12) 4629-4638
  • 49 Shaw LJ, Bairey Merz CN, Azziz R , et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health—National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation. J Clin Endocrinol Metab 2008; 93 (4) 1276-1284
  • 50 Krentz AJ, von Mühlen D, Barrett-Connor E. Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease. Menopause 2007; 14 (2) 284-292
  • 51 Cibula D, Cífková R, Fanta M, Poledne R, Zivny J, Skibová J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod 2000; 15 (4) 785-789
  • 52 Pierpoint T, McKeigue PM, Isaacs AJ, Wild SH, Jacobs HS. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 1998; 51 (7) 581-586
  • 53 Wild S, Pierpoint T, Jacobs H, McKeigue P. Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. Hum Fertil (Camb) 2000; 3 (2) 101-105
  • 54 ESHRE Capri Workshop Group. Health and fertility in World Health Organization group 2 anovulatory women. Hum Reprod Update 2012; 18 (5) 586-599
  • 55 Hosseinpanah F, Barzin M, Tehrani FR, Azizi F. The lack of association between polycystic ovary syndrome and metabolic syndrome: Iranian PCOS prevalence study. Clin Endocrinol (Oxf) 2011; 75 (5) 692-697
  • 56 Da Fonseca AM, Bagnoli VR, Souza MA , et al. Impact of age and body mass on the intensity of menopausal symptoms in 5968 Brazilian women. Gynecol Endocrinol 2013; 29 (2) 116-118
  • 57 Gambacciani M, Ciaponi M, Cappagli B , et al. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab 1997; 82 (2) 414-417
  • 58 Espeland MA, Stefanick ML, Kritz-Silverstein D , et al; Postmenopausal Estrogen-Progestin Interventions Study Investigators. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. J Clin Endocrinol Metab 1997; 82 (5) 1549-1556
  • 59 Rachoń D, Teede H. Ovarian function and obesity—interrelationship, impact on women's reproductive lifespan and treatment options. Mol Cell Endocrinol 2010; 316 (2) 172-179
  • 60 Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S. Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online 2009; 19 (3) 398-405
  • 61 Haoula Z, Salman M, Atiomo W. Evaluating the association between endometrial cancer and polycystic ovary syndrome. Hum Reprod 2012; 27 (5) 1327-1331
  • 62 Schildkraut JM, Schwingl PJ, Bastos E, Evanoff A, Hughes C. Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol 1996; 88 (4 Pt 1) 554-559
  • 63 Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids 2013; 78 (8) 782-785
  • 64 Talamini R, Franceschi S, Favero A, Negri E, Parazzini F, La Vecchia C. Selected medical conditions and risk of breast cancer. Br J Cancer 1997; 75 (11) 1699-1703
  • 65 Baron JA, Weiderpass E, Newcomb PA , et al. Metabolic disorders and breast cancer risk (United States). Cancer Causes Control 2001; 12 (10) 875-880
  • 66 Gammon MD, Thompson WD. Polycystic ovaries and the risk of breast cancer. Am J Epidemiol 1991; 134 (8) 818-824
  • 67 Atiomo WU, El-Mahdi E, Hardiman P. Familial associations in women with polycystic ovary syndrome. Fertil Steril 2003; 80 (1) 143-145
  • 68 Adami S, Zamberlan N, Castello R, Tosi F, Gatti D, Moghetti P. Effect of hyperandrogenism and menstrual cycle abnormalities on bone mass and bone turnover in young women. Clin Endocrinol (Oxf) 1998; 48 (2) 169-173
  • 69 Carmina E, Guastella E, Longo RA, Rini GB, Lobo RA. Correlates of increased lean muscle mass in women with polycystic ovary syndrome. Eur J Endocrinol 2009; 161 (4) 583-589
  • 70 Good C, Tulchinsky M, Mauger D, Demers LM, Legro RS. Bone mineral density and body composition in lean women with polycystic ovary syndrome. Fertil Steril 1999; 72 (1) 21-25
  • 71 Kassanos D, Trakakis E, Baltas CS , et al. Augmentation of cortical bone mineral density in women with polycystic ovary syndrome: a peripheral quantitative computed tomography (pQCT) study. Hum Reprod 2010; 25 (8) 2107-2114
  • 72 To WW, Wong MW. A comparison of bone mineral density in normal weight and obese adolescents with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 2012; 25 (4) 248-253
  • 73 Schmidt J, Dahlgren E, Brännström M, Landin-Wilhelmsen K. Body composition, bone mineral density and fractures in late postmenopausal women with polycystic ovary syndrome - a long-term follow-up study. Clin Endocrinol (Oxf) 2012; 77 (2) 207-214
  • 74 de Sousa G, Schlüter B, Buschatz D , et al. A comparison of polysomnographic variables between obese adolescents with polycystic ovarian syndrome and healthy, normal-weight and obese adolescents. Sleep Breath 2010; 14 (1) 33-38
  • 75 Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med 2002; 3 (5) 401-404
  • 76 Nandalike K, Strauss T, Agarwal C , et al. Screening for sleep-disordered breathing and excessive daytime sleepiness in adolescent girls with polycystic ovarian syndrome. J Pediatr 2011; 159 (4) 591-596
  • 77 Shreeve N, Cagampang F, Sadek K , et al. Poor sleep in PCOS; is melatonin the culprit?. Hum Reprod 2013; 28 (5) 1348-1353
  • 78 Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 2001; 86 (2) 517-520
  • 79 Guidozzi F. Sleep and sleep disorders in menopausal women. Climacteric 2013; 16 (2) 214-219
  • 80 Veltman-Verhulst SM, Boivin J, Eijkemans MJ, Fauser BJ. Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Hum Reprod Update 2012; 18 (6) 638-651
  • 81 Ching HL, Burke V, Stuckey BG. Quality of life and psychological morbidity in women with polycystic ovary syndrome: body mass index, age and the provision of patient information are significant modifiers. Clin Endocrinol (Oxf) 2007; 66 (3) 373-379
  • 82 Jedel E, Waern M, Gustafson D , et al. Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index. Hum Reprod 2010; 25 (2) 450-456
  • 83 Cronin L, Guyatt G, Griffith L , et al. Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS). J Clin Endocrinol Metab 1998; 83 (6) 1976-1987
  • 84 Ewens KG, Jones MR, Ankener W , et al. Type 2 diabetes susceptibility single-nucleotide polymorphisms are not associated with polycystic ovary syndrome. Fertil Steril 2011; 95 (8) 2538-2541 , e1–e6
  • 85 Ewens KG, Jones MR, Ankener W , et al. FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. PLoS ONE 2011; 6 (1) e16390
  • 86 Goodarzi MO, Jones MR, Li X , et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J Med Genet 2012; 49 (2) 90-95