Long-term health in women of age more than 40years with polycystic ovary syndrome





Introduction


Polycystic ovary syndrome (PCOS) is the most common endocrinopathy, affecting women in reproductive age. The manifestations of this condition consist of ovulatory, metabolic, aesthetic, psychological, and possibly an elevated risk of cancer as well. Authorities have published guidelines on the management and consequences of PCOS in younger women .


A growing body of evidence focused on identifying the prevalence and describing the manifestations of PCOS in reproductive-aged or postmenopausal women. However, the investigation of PCOS in older women remains challenging due to the lack of available diagnostic criteria to describe the syndrome in aging women. The overall prevalence seems to differ according to the diagnostic criteria implemented, and has been estimated as 6% based on the National Institute of Health criteria, as high as 10% based on Rotterdam criteria, and 10% based on androgen excess-PCOS criteria .


The aim of this review is to present a guide on the manifestations of PCOS in women over 40 years and to summarize the most indicated management pathways.


The aging PCOS phenotypes


The manifestations of PCOS in reproductively active women have been clustered into four distinct phenotypes, namely, Type A (hyperandrogenism, ovulatory dysfunction, and presence of ovaries with polycystic morphology), Type B (hyperandrogenism and ovulatory dysfunction), Type C (hyperandrogenism and presence of ovaries with polycystic morphology), and Type D (ovulatory dysfunction and presence of ovaries with polycystic morphology) .


The age-related changes in ovarian morphology and ovarian function result into amelioration of the PCOS phenotypes defined during reproductive age . Women with PCOS are found to undergo menopause up to 2 years later as opposed to normo-ovulatory women . This finding might either be related with greater ovarian reserve during the reproductive years, with either increased number of germ cells at birth or reduced loss of germ cells . In clinical terms, women of older reproductive age with PCOS have a lower number of follicles compared to younger women with PCOS, and consequently lower levels of inhibin B, which in turn prevents the suppression of follicle stimulating hormone (FSH) levels. Normalization of serum levels of FSH is now inducing follicular growth and ovulation with a normalized frequency, so that older women with PCOS are more likely to experience regular ovulatory cycles ( Fig. 1 ).




Fig. 1


Pathophysiological changes in ovarian function of reproductively older vs younger women with polycystic ovary syndrome.


Aging per se is associated with a progressive decrease in androgen production and a relative decline in ovarian volume and follicle count . The PCOS-related hyperandrogenemia (HA) tends to improve with aging; however, few biochemical and clinical features are likely to persist up to the menopause . The declining androgen levels will theoretically result into some improvement of insulin resistance; however, the possible beneficial implications of decreased androgens on cardiometabolic risk factors seem to be counterregulated by the hormonal changes triggered secondarily to ovarian senescence. Results from a 20-year longitudinal analysis have shown that levels of insulin seem to remain stable throughout the years, irrespective of altered levels of androgens in women with PCOS . The alterations in biochemical parameters of women with PCOS in parallel with aging are presented in Fig. 2 .




Fig. 2


Hormonal profile of women with PCOS in parallel with reproductive aging.


Diagnosis of PCOS in menopause


The diagnosis of PCOS after the menopausal transition remains challenging. The latest guidelines advise that the diagnosis could be considered provided:



  • •

    A previous diagnosis of PCOS documented during the reproductive years or report of a long-term history of menstrual irregularity accompanied by clinical and/or biochemical hyperandrogenism and/or presence of ovaries with polycystic morphology during the reproductive life.



Clinical manifestations of PCOS




  • (1)

    Insulin resistance and diabetes mellitus


    Glycemic dysregulation is highly prevalent in women of late reproductive age. Α growing number of cross-sectional, retrospective, longitudinal studies including population-based samples showed higher prevalence rates of impaired glucose tolerance (IGT) and higher prevalence of diabetes as well as raised fasting glucose levels and indicators of insulin resistance, like the homeostasis model assessment of insulin resistance, in women of age more than 40 years and a previous diagnosis of PCOS vs control group . Prevalence rates of IGT seem to differ according to the severity of PCOS features. A cross-sectional analysis of the Study of Women’s Health Across the Nation (SWAN) cohort including 2543 women of age approximately 45.8 years showed that IGT was more frequent in women with accumulation of PCOS features. More specifically, IGT prevalence rates decreased in parallel with decreasing severity of PCOS manifestations, as follows: HA and oligoamenorrhea (OA) vs HA and normal menstruation vs OA and normal androgens vs normal androgens and normal menstruation, 25% vs 12.7% vs 11.5% vs 9.2%, respectively.


    There seems to be a time-related adverse effect of PCOS on glycemic control. The prevalence of diabetes mellitus ranges from 9.4% to 38.2% and seems to be increasing with increasing age. The results of the Chinese study showed that among women with normal glucose tolerance at baseline, IGT and type 2 diabetes mellitus (T2DM) was developed in 17.6% and 11.8% of cases, respectively, at the time of followup. In fact, the prevalence of T2DM seems to increase with age , since women in the age group 45–54 years have been described to have up to 11.1% prevalence of T2DM; women in the age group 55–64 years have been described to have up to 15.7% prevalence of T2DM, and women of age at least 65 years have been linked with 45.5% of T2DM.


    Incidence rates of DM differ between studies, mainly according to the severity of PCOS features as well as according to the age of the participants and their ethnic background. Incidence rates of DM for the age group 40–49 years have been described in a recent Chinese study , according to which incidence of T2DM per 1000 person-years for women with PCOS was 30.5 (95% CI, 7.64–81.79) and for control women was 10.24 (95% CI, 5.70–17.07). The rate ratio between PCOS and control individuals was as high as 2.93 (95% CI, 0.84–10.30) and not statistically significant. A retrospective analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort of 1127 women reported that incident DM in women with a previous PCOS diagnosis vs control individuals is associated with an OR of 2.4 (95% CI, 1.2–4.9), during a follow-up period of 18 years . For women diagnosed with PCOS at the age of 20–32 years, persistence of PCOS diagnosis during the 18 years of the study was associated with OR of 7.2 for incident DM (95% CI: 11.1–46.5) .


    The number of cross-sectional, retrospective and longitudinal studies describing metabolic manifestations of PCOS in purely postmenopausal samples is smaller when compared to women of reproductive age . Accordingly, age-specific prevalence of T2DM has been described as 15.7% for women of age 55–64 years and 45.5% for women of age at least 65 years . The prevalence rates of DM in women with postmenopausal PCOS e seems to vary based on the diagnostic criteria applied at the time of diagnosis, and the age of the women assessed, ranging from 11.1% up to 24%; however the rates were not significantly different from control women . A retrospective study of 149 women with PCOS treated with wedge resection for PCOS were followed up until a mean age of 49.8 years and prevalence rates of DM were compared with an age-matched subset of the Norwegian country health survey . Accordingly, the standardized incidence ratio (SIR) of DM for women with previous PCOS diagnosis vs control women has been reported as 6.1 (95% CI, 2.2–13, P -value < .0001) ( Table 1 ).



    Table 1

    Prevalence estimates of IGT/DM.


























































































































    Study Design PCOS definition Outcomes Results
    Women > 40 years and mixed studies including perimenopausal populations
    Polotsky 2012 Cross-sectional
    SWAN cohort, 2543 women, age 45.8 years     		OA + HA IGT prevalence (FBG ≥ 110 mg/dL or medications) HA ± OA vs HA ± normal menstruation : 25% vs 12.7%
    OA ± normal androgens vs normal androgens and normal menstruation : 11.5% vs 9.2%
    Hudecova 2011 84 PCOS vs 87 control
    Monitoring: 13.9 years (range 11–20)
    Follow-up age, PCOS vs controls: 43 ± 5.8 vs 43.7 ± 6.2 years     		Rotterdam IGT or DM or insulin sensitivity PCOS vs controls :

    • •

      IGT/DM, 21.4% vs 4.5%


    • •

      IGT, 16.3% vs 2.9%

    PCO ± HA ± OA vs control women :

    • •

      Insulin sensitivity, 1.6 ± 4.0 vs 3.4 ± 4.0 ( P -value < .001 adjusted for BMI)

    PCO ± OA vs control women

    • •

      Insulin sensitivity, 2.4 ± 3.5 vs 3.4 ± 40 ( P -value > .05)

    Hart 2015 Population-based retrospective cohort study based in West Australia
    2897 PCOS hospitalized 1997–2011 and 25,660 randomly selected age-matched women
    Follow up, median age 35.8 years (IQR 31–39.9)     		Variable Late onset DM prevalence PCOS vs controls:
    HR 2.84 (95% CI: 2.49–3.23) adjusted for current/prior admission with diagnosis of obesity
    Elting 2001 Retrospective study
    Total sample, 345 PCOS women
    Controls, total Dutch population 8950 women
    Assessment by age range     		Oligo- or amenorrhea and/or hirsutism and/or infertility DM prevalence Age range 45–54 years
    PCOS vs controls
    9.4% (95% CI: 2–25.0) vs 2.3% (95% CI: 1.7–2.9)
    P -value < .05
    Ng 2019 Longitudinal study
    199 Chinese women with PCOS (age 41.2 ± 6.4 years) vs 225 controls (age 54.1 ± 6.7 years)
    Follow up after 10.6 ± 1.3 years     		Rotterdam Prevalence DM for age range 40–49 years Incidence rate of T2DM per 1000 person-years between Chinese women with PCOS and controls, according to age category:

    • •

      PCOS IR = 30.05 (95% CI: 7.64–81.79)


    • •

      Controls IR = 10.24 (95% CI: 5.70–17.07)


    • •

      PCOS vs controls: 2.93, (95% CI: 0.84–10.30), P -value > .05

    From women with normal glucose tolerance at baseline, glucose status at follow up: IFG 2.2%; IGT 17.6%; IFG/IGT 2.2%; T2DM 11.8%
    Chang 2011 Cross-sectional
    130 postmenopausal women and 697 late premenopausal women
    PCOS, age 40 years (37–42)
    Controls, age 42 years (39–45)     		Rotterdam Glucose levels and HOMA-IR PCOS vs controls,
    Glucose levels , 92 mg/dL (85–102) vs 91.5 mg/dL (85–99), P -value = .56
    HOMA-IR , 3.7 (1.9–5.5) vs 2.7 (1.6–4.5), P -value < .01
    Livadas 2020 Case controls study
    763 lean PCOS women and 376 controls     		Rotterdam HOMA-IR Subgroup age 36–47 years:
    PCOS vs controls, 1.87 ± 1.11 vs 1.78 ± 0.72, P -value < 0.05 significantly higher than age group 17–25 years
    Mani 2013 Prospective study
    Follow-up 20 years
    2391 PCOS women with baseline age 29.6 years and final age 36.3 ± 10 years     		AE-PCOS T2DM Age-specific prevalence of T2DM


    • •

      45–54 years, 11.1% (7.8–14.4)


    • •

      55–64 years, 15.7% (7.8–23.5)


    • •

      ≥ 65 years, 45.5% (16–74.9)

    Incidence of T2DM , 3.6 per 1000 person-years
    Ollila 2017 Prospective general population-based follow-up study of cohort born 1966 ( n = 5889); assessment at age 14, 31 and 46 with blood tests and OGTT Questionnaires on OA and hirsutism Levels of insulin resistance, HbA1c
    Prevalence of T2DM     		PCOS vs controls

    • •

      HOMA-IR, 2.06 (25%–75%, 1.37–3.11) vs 1.67 (25%–75%, 1.15–2.59), P -value < .001 and adjusted for BMI P -value = .185


    • •

      HbA1c, 37.09 ± 6.8 mmol/mol vs 35.78 ± 4.6 mmol/mol, P -value = .08, adjusted for BMI P -value = .029


    • •

      Age 46 years, T2DM:



      • –

        PCOS + BMI ≥ 25 kg/m 2 vs Control + BMI ≥ 25 kg/m 2 , OR 2.45 (95% CI, 1.28–4.67)


    Wang 2011 Retrospective study
    1127 white and black women from cardia cohort
    Baseline, 20–32 years
    Follow-up 18 years
    Second assessment 34–46 years     		NIH Prevalence of DM Follow-up vs baseline

    • •

      Incident DM, 23.1% vs 13.1%, adjusted OR 2.4 (95% CI 1.2–4.9)


    • •

      Persistent PCOS vs no PCOS, adjusted odds ratio 7.2 (95% CI, 11.1–46.5)


    • •

      Normal weight PCOS vs no PCOS, adjusted odds ratio 3.1 (95% CI, 1.2–8.0)

    Cibula 2000 Cross-sectional
    28 PCOS aged 51.9 ± 4.64 years (10 postmenopausal and 18 premenopausal) vs 752 controls aged 51.0 ± 4.21 years     		NIH NIDDM PCOS vs controls, 32% vs 8%, P -value < .001
    Wild 2000 Retrospective cohort
    240 PCOS vs 720 control
    Mean follow-up of PCOS group, 31 years (range: 15–47)
    Mean age at follow up, 56.7 years (range 38–98)     		NIH DM, prevalence, OR and standardized mortality ratio PCOS vs controls:

    • •

      DM, 6.9% vs 3%, P -value = .002


    • •

      OR. 2.2 (95% CI: 0.9–5.2), P -value = .08


      After adjustment for BMI, OR 1.4 (95% CI: 0.9–2.0)


    • •

      SMR, 460 (95% CI: 125–1177)

    Hossain 2011 Cross-sectional study
    34 PCOS women vs 32 controls matched for age and BMI     		Rotterdam DM prevalence PCOS vs controls
    38.2% vs 22.6%, P -value = .17
    Menopausal women
    Meun 2020 Cross-sectional study
    200 PCOS women and 200 age matched control (mean age, PCOS vs controls, 51 ± 5.2 vs 50.5 ± 5.5 years)
    Menopause, PCOS vs controls 16% vs 40.5%, P -value < .001     		Rotterdam HOMA-IR levels
    Prevalence of DM     		PCOS vs controls
    HOMA-IR, median 2.68 (IQR, 1.54–4.33) vs median 2.43 (IQR, 1.71–3.69), P -value = .65
    DM, 11.1% vs 6.5%, P -value = .11
    Meun 2018 Prospective population-based study
    2578 PCOS aged more than 55 years
    Median follow up 11.36 years
    Final age 70.19 ± 8.71 years and menopausal age 19.85 ± 9.94 years     		Rotterdam FBG and DM prevalence FBG , PCOS vs controls, 6.25 ± 1.83 mmol/L vs 5.79 ± 1.41 mmol/L, P -value = .03
    DM prevalence , PCOS vs controls, 18.9% vs 7%, P -value < .01
    Lunde 2007 Retrospective study
    Baseline, 149 PCOS women aged 15–25 years had wedge resection
    Follow up, mean age 49.8 years (range: 42.2–57.4)
    Control: subset of Norwegian country health survey matched for age     		PCO + two or more symptoms: menstrual irregularity, hirsutism, infertility or obesity Prevalence rates of DM PCOS vs controls:
    DM, SIR = 6.1 (95% CI: 2.2–13), P -value < .0001
    Forslund 2020 Longitudinal and cross-sectional
    27 PCOS women and 94 controls
    Followed up after 24 years
    Mean age at follow up 52 years     		NIH T2DM Follow up, PCOS vs controls,

    • •

      T2DM prevalence: 19% vs 1%;


    • •

      T2DM, unadjusted OR 21.14 (95% CI, 2.35–190.14), P -value > .05; adjusted for BMI, OR 1.45 (95% CI, 1.17–1.80), P -value > .05

    Merz 2016 295 Postmenopausal women enrolled in the WISE study

    • –

      CV outcome according to PCOS ( n = 25) vs controls ( n = 270)

    		Postmenopausal PCOS defined as premenopausal history of menstrual irregularity, current biochemical hyperandrogenemia (top quartile of testosterone, androstendione, free testosterone) Prevalence of DM, FBG > 110 mg/dL and levels of HOMA-IR PCOS vs controls:

    • •

      Prevalence of DM, 24% vs 32.2%, P -value = .66


    • •

      FBG > 110 mg/dL, 12.5% vs 34.6%, P -value = .10


    • •

      HOMA-IR, 3.07 ± 5.02 vs 5.35 ± 8.24, P -value = .12


    BMI , body mass index; CI , confidence interval; FBG , fasting blood glucose; HA , hyperandrogenemia; HbA1c , glycated hemoglobin; HOMA-IR , homeostasis model assessment of insulin resistance; HR , hazard ratio; IGT/DM , impaired glucose tolerance/diabetes mellitus; IQR , interquartile range; IR , incidence rates; OA , oligoammenorhea; PCO , polycystic ovaries; SIR , standardized incidence ratio; SMR , standardized mortality ratio; SWAN , Study of Women’s Health Across the Nation; T2DM , type 2 diabetes mellitus.


  • (2)

    Dyslipidemia


    A number of studies have investigated the prevalence rates of dyslipidemia in women of age more than 40 years, assessing either only women of late reproductive age or study samples including perimenopausal participants . The prevalence of hypertrigliceridemia associated with the presence of PCOS features in a sample of the SWAN cohort of age on average 45.8 years: HA and oligomenorrhea vs HA and normal menstruation vs oligomenorrhea and normal androgens vs normal androgens and normal menstruation, 31.3% vs 20.1% vs 18.4% vs 16.2%, respectively . A comparable prevalence of hypertriglyceridemia was reported in women with HA-PCOS compared to control women, of age > 39 years, has been estimated as 32.6% vs 13.2% . The prevalence of hypercholesterolemia has been estimated as more than threefold higher than control group (adjusting for BMI, OR 3.2, 95% CI: 1.7–6.0, P -value < .001), in women of age 56.7 years (range 38–98) at followup .


    The risk of developing incident dyslipidemia in women with previous diagnosis of PCOS is difficult to be established. A recent national register-based study of 18,112 women with PCOS retrieved from the Danish National Patient Register and 1165 women with PCOS retrieved from Odense University Hospital (OUH) were compared with aged-matched control women ( N = 52,769), over a follow-up period of 11.1 years. The study reported that the rates of incident dyslipidemia have been estimated as 2.5% in OUH, 2.1% in Denmark database, and 1.1% in the control samples. Significant difference was found between the Denmark database and control samples but not between OUH data and control samples . The risk of incident dyslipidemia over a follow-up period of 18 years, in women with PCOS vs control group of age 34–46 years, has been reported as almost twofold higher (41.9% vs 27.7%, adjusted OR 1.9, 95% CI: 1.0–3.6) . The population-based analysis of the Tehran Lipid and Glucose study could not find any difference with regard to incident rates of dyslipidemia per 1000 person-years, comparing PCOS-diagnosed women vs control women, estimated as 20% vs 27.8% (multiple adjusted HR 0.87, 95% CI: 0.3–2) .


    A smaller number of studies evaluated rates of dyslipidemia in pure postmenopausal populations, either as primary or secondary outcome . The cross-sectional studies, which were also characterized by small sample sizes of women with PCOS, described nonsignificant association with regard to levels of total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol , or with regard to the prevalence of dyslipidemia and isolated hypertriglyceridemia . One available longitudinal study described nonsignificant differences was found for women with PCOS and control group during a follow-up period of 21 years, but significant impact of time on levels of triglycerides for both women with PCOS and control women ( Table 2 ).



    Table 2

    Prevalence estimates of dyslipidemia.








































































































    Study Design PCOS definition Outcomes Results
    Women > 40 years and mixed samples including perimenopausal populations
    Polotsky 2012 Cross-sectional
    SWAN cohort, 2543 women, age 45.8 years     		OA + HA Hypertrigliceridemia prevalence, defined as triglycerides ≥ 150 mg/dL HA ± OA vs HA ± normal menstruation : 31.3% vs 20.1%
    OA ± normal androgens vs normal androgens and normal menstruation : 18.4% vs 16.2%
    Wang 2011 Retrospective study
    1127 white and black women from Cardia Cohort
    Baseline, 20–32 years
    Follow up 18 years
    Second assessment 34–46 years     		NIH Rates of Incident Dyslipidemia Follow-up vs baseline, PCOS vs controls
    41.9% vs 27.7%, Adjusted odds ratio 1.9 (95% CI: 1.0–3.6)
    Pinola 2017 Cross-sectional study

    • •

      Normoandrogenic women, PCOS ( n = 686)


    • •

      Hyperandrogenic women, PCOS ( n = 842)


    • •

      Control ( n = 447)

    		Rotterdam criteria Prevalence of triglycerides Age ≥ 39 years, HA-PCOS vs controls :
    Hypertriglyceridemia, 32.6% vs 13.2%, P -value < .05
    Legro 2001 Cross-sectional study
    nonhispanic white women ( n = 195) and ethnic matched controls ( n = 62)
    age 18–45 years     		NIH Blood lipids according to the presence of obesity PCOS vs control, after adjustment for age, BMI, WHR, FBG, fasting insulin
    Effect on LDL-C b-coefficient = 25 (95% CI, 14 to 37), P -value < .001
    Effect on HDL-C b-coefficient = 2 (95% CI, − 2 to 6), P -value = .36
    Effect on triglycerides, b-coefficient = 35 (95% CI, − 5 to 75), P -value = .09
    Glintborg 2018 National register-based study
    PCOS women retrieved from Danish National Patient Register ( N = 18,112) and Odense University Hospital ( N = 1165)
    Control women matched (1:3 matching) for age ( N = 52,769)

    • •

      Age baseline, 29 years (range 23–35)

    Duration of follow up 11.1 years (6.9–16)     		Variable Incidence and prevalence rates of CVD and HTN as well as dyslipidemia PCOS Denmark Database:
    Incidence rates, Dyslipidemia,
    PCOS, OUH , IR = 2.5%; PCOS, Denmark IR = 2.1%; Controls , IR = 1.1%
    P -value (Denmark vs control) < .001
    P -value (OUH vs Control) = .30
    Wild 2000 Retrospective cohort
    240 women PCOS vs 720 control women.
    Mean follow up of PCOS group, 31 years (range: 15–47)
    Mean age at follow up, 56.7 years (range 38–98)     		NIH Hypercholesterolemia prevalence PCOS vs controls
    OR 2.9 (95% CI: 1.6–5.2), P -value < .001
    Adjusted for BMI 3.2 (95% CI: 1.7–6.0), P -value < .001
    Hossain 2011 Cross-sectional study
    34 women PCOS vs 32 control women matched for age and BMI     		Rotterdam Dyslipidemia prevalence PCOS vs controls
    32.4% vs 38.7%, P -value = .59
    Livadas 2020 Case controls study
    763 lean PCOS women and 376 control women     		Rotterdam Levels of TC and TG Subgroup age 36–47 years:
    PCOS vs controls,

    • •

      TC, 4.81 ± 0.83 mg/dL vs 4.69 ± 0.99 mg/dL, P -value > .05

    NS difference from younger age groups

    • •

      TG, 0.79 ± 0.29 mg/dL vs 0.72 ± 0.40 mg/dL, P -value > .05

    NS difference from younger age groups
    Behboudi-Gandevani 2018 Population-based analysis of Tehran Lipid and Glucose study
    1702 reproductive-aged women (178 women PCOS women vs 1524 control women)     		NIH Dyslipidemia prevalence rates Age > 40, PCOS vs controls

    • •

      incidence rates per 1000 person-years: 20 (95% CI: 9.7–45.5) vs 27.8 (95% CI: 22.5–34.4)


    • •

      HR unadjusted 0.69 (95% CI: 0.3–1.5)


    • •

      HR multiple adjusted 0.87 (95% CI: 0.3–2)

    Menopausal women
    Meun 2020 Cross-sectional study
    200 women PCOS and 200 age-matched control (mean age, PCOS vs controls, 51 ± 5.2 vs 50.5 ± 5.5 years)
    Menopause, PCOS vs controls 16% vs 40.5%, P -value < .001     		Rotterdam Serum TC, triglycerides, HDL-C, LDL-C PCOS vs controls:

    • •

      TC, median 5.3 mmol/L (IQR, 4.5–6) vs median 5.3 mmol/L (IQR, 4.8–6.1), P -value = .44


    • •

      Triglycerides, median 1 mmol/L (IQR, 0.8–1.6) vs median 1.1 mmol/L (IQR, 0.8–1.5), P -value = .35


    • •

      HDL-C, median 1.5 mmol/L (IQR, 1.2–1.8) vs median 1.5 mmol/L (IQR, 1.2–1.8), P -value = 0.68


    • •

      LDL-C, median 3.3 mmol/L (IQR, 2.7–4) vs median 3.1 mmol/L (IQR, 2.6–3.9), P -value = .42

    Meun 2018 Prospective population-based study
    2578 PCOS aged more than 55 years
    Median follow up 11.36 years
    Final age 70.19 ± 8.71 years and menopausal age 19.85 ± 9.94 years     		Rotterdam Triglyceride levels Follow-up, triglyceride levels:
    PCOS vs controls, 1.62 ± 0.86 mmol/L vs 1.39 ± 0.62 mmol/L P -value = .02
    Cibula 2000 Cross-sectional
    28 PCOS aged 51.9 ± 4.64 years (10 postmenopausal and 18 premenopausal) vs 752 controls aged 51.0 ± 4.21 years     		NIH Lipid levels Prevalence, P -value > .05 all cases
    PCOS vs controls

    • •

      Hypercholesterolemia (TC > 5.2mmo/L) 71% vs 71%


    • •

      Low HDL-C (< 1.0 mmol/L) , 7% vs 7%


    • •

      High LDL-C (> 3.7 mmol/L) , 57% vs 44%


    • •

      Triglycerides (> 1.9 mmol/L) , 25% vs 28%

    Schmidt 2011 Longitudinal study
    Baseline: 35 PCOS (age range, 61–79 years) vs 120 age-matched controls
    Follow up: 21 years after     		Rotterdam Serum levels of triglycerides Follow-up vs baseline
    Between groups, P -value = .577

    • •

      Δ(PCOS) 0.3 ± 1.0


    • •

      Δ(control) 0.3 ± 0.5

    Within groups,

    • •

      Δ(PCOS) P -value = .029


    • •

      Δ(control) p -value < .001

    Merz 2016 Cross-sectional
    295 postmenopausal women enrolled in theWISE study
    CV outcome according to PCOS ( n = 25) vs controls ( n = 270)     		Postmenopausal PCOS defined as premenopausal history of menstrual irregularity, current biochemical hyperandrogenemia (top quartile of testosterone, androstendione, free testosterone) Levels of TC, TG, LDL-C, HDL-C
    Prevalence of dyslipidemia     		PCOS vs controls

    • •

      Dyslipidemia, 64% vs 54.1%, P -value = .52


    • •

      TC, 195.3 ± 36.6 mg/dL vs 197.8 ± 48.5 mg/dL, P -value = .80


    • •

      TG > 150 mg/dL, 52% vs 42.4%, P -value = .40


    • •

      HDL, 47.9 ± 10.3 mg/dL vs 52.5 ± 11.2 mg/dL, P -value = .05


    • •

      LDL-C, 110.1 ± 29.4 mg/dL vs 116.2 ± 42.0 mg/dL, P -value = .57

    Chang 2011 Cross-sectional
    130 postmenopausal women and 697 late premenopausal women
    PCOS, age 40 years (37–42)
    Controls, age 42 years (39–45)     		Rotterdam Prevalence of hypertriglyceridemia, hypercholesterolemia PCOS vs controls
    Hypertriglyceridemia prevalence

    • •

      15.3% vs 14.1%, P -value > .05

    Dyslipidemia

    • •

      Triglyceride levels, PCOS 83 mg/dL (64–127) vs control 85.5 mg/dL (60–118), P -value > .05


    • •

      LDL-C levels, PCOS 98 mg/dL (80–123) vs control 102 mg/dL (84–119), P -value > .05


    BMI , body mass index; CI , confidence interval; FBG , fasting blood glucose; HA , hyperandrogenemia; HDL-C , high-density lipid cholesterol; HR , hazard ratio; LDL-C , low density cholesterol; NIH , national institute of health; NS , nonsignificant; OA , oligoamenorrhea; OR , odds ratio; OUH , Odense University Hospital; PCOS , polycystic ovarian syndrome; SWAN , Study of Women’s Health Across the Nation; TC , total cholesterol.


  • (3)

    Central and total obesity ( Table 3 )



    Table 3

    Prevalence estimates of obesity.


































































































    Study Design PCOS definition Outcomes Results
    Women > 40 years and mixed samples including perimenopausal populations
    Olilia 2017 Prospective general population-based follow-up study of cohort born 1966 ( n = 5889);
    assessment at age 14, 31 and 46 with blood tests and OGTT     		Questionnaires on OA and hirsutism Values of waist circumference and BMI at age 46 years PCOS vs controls

    • •

      BMI, 28.6 ± 6.3 kg/m 2 vs 26.3 ± 5.3 kg/m 2 , P -value < .001


    • •

      Waist circumference, 88.5 cm (25%–75%: 81–99.05) vs 84 cm (25%–75%: 77–94), P -value < .001

    Hart 2015 Population-based retrospective cohort study based in West Australia
    2897 PCOS hospitalized 1997–2011 and 25,660 randomly selected age-matched women
    Follow-up, median age 35.8 years (IQR 31–39.9)     		Variable Diagnosis of obesity PCOS vs controls:
    HR 4.71 (95% CI: 4.19–5.28)
    Livadas 2020 Case controls study
    763 lean PCOS women and 376 controls     		Rotterdam Waist circumference Subgroup age 36–47 years:
    PCOS vs controls, 77.75 ± 10.01 cm vs 74.85 ± 6.14 cm, P -value > .05
    NS compared with younger age groups
    Polotsky 2012 Cross-sectional
    SWAN cohort, 2543 women, age 45.8 years     		OA + HA BMI values or central obesity rates BMI values :
    HA ± OA vs HA ± normal menstruation : 30.9 kg/m 2 (95% CI: 29.4–32.6) vs 28 kg/m 2 (95% CI: 27.5–28.4);
    OA ± normal androgens vs normal androgens and normal menstruation : 27.6 kg/m 2 (95% CI: 26.6–28.6) vs 26.6 kg/m 2 (95% CI: 26.3–26.9)
    Central obesity :
    HA ± OA vs HA ± normal menstruation : 57.8% vs 45.5%;
    OA ± normal androgens vs normal androgens and normal menstruation : 47.1% vs 35.9%
    Behboudi-Gandevani 2018 Population-based analysis of Tehran Lipid and Glucose study
    1702 reproductive aged women (178 PCOS women vs 1524 controls)     		NIH Obesity and central obesity prevalence rates Age > 40, PCOS vs controls
    Obesity

    • •

      incidence rates per 1000 person-years: 13.2 (95% CI: 5.9–29.5) vs 20 (95% CI: 23.9–32.4)


    • •

      HR unadjusted 0.67 (95% CI: 0.2–1.5)


    • •

      HR multiple adjusted 0.57 (95% CI: 0.2–1.3)

    Central obesity

    • •

      incidence rates per 1000 person-years: 51.5 (95% CI: 30.5–87) vs 48.1 (95% CI: 41.4–55.9)


    • •

      HR unadjusted 1.13 (95% CI: 0.6–1.9)


    • •

      HR multiple adjusted 1.04 (95% CI: 0.6–1.8)

    Hudecova 2011 84 PCOS vs 87 control
    Monitoring: 13.9 years. (range 11–20)
    Follow up Age, PCOS vs controls: 43 ± 5.8 vs 43.7 ± 6.2 years     		Rotterdam BMI values PCO ± HA ± OA vs controls :
    29.2 ± 5.7 kg/m 2 vs 25.6 ± 4.2 kg/m 2
    P -value < .05–.001
    PCO ± HA ± OA vs PCO ± OA :
    29.2 ± 5.7 kg/m 2 vs 26.2 ± 5.2 kg/m 2
    P -value < .05–.001
    Pinola 2017 Cross-sectional study


    • •

      Normoandrogenic women, PCOS ( n = 686)


    • •

      Hyperandrogenic women, PCOS ( n = 842)


    • •

      Control ( n = 447)

    		Rotterdam criteria Raised waist circumference and BMI status Obesity prevalence
    HA-PCOS vs controls
    Age > 39 years, 73.8% vs 46.1%, P -value < .05
    HA-PCOS vs NA-PCOS
    Age > 39 years, 73.8% vs 41.9%, P -value < .05
    Chang 2011 Cross-sectional
    130 postmenopausal women and 697 late premenopausal women
    PCOS, age 40 years (37–42)
    Controls, age 42 years (39–45)     		Rotterdam BMI and WHR BMI values , PCOS 31.7 kg/m 2 (26.5–38.1) vs controls 28.7 kg/m 2 (25.5–33.9), P -value < .01
    WHR , PCOS 0.86 (0.81–0.90) vs controls 0.84 (0.79–0.88), P -value < .01
    Menopausal women
    Merz 2016 295 postmenopausal women enrolled in the WISE study, follow-up up to 10 years
    CV outcome according to PCOS ( n = 25) vs controls ( n = 270)     		Postmenopausal PCOS defined as premenopausal history of menstrual irregularity, current biochemical hyperandrogenemia (top quartile of testosterone, androstendione, free testosterone) Prevalence BMI ≥ 30 kg/m 2 and waist > 35 in. PCOS vs controls:


    • •

      BMI ≥ 30 kg/m 2 36% vs 40.6%, P -value = .83


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      waist > 35 in., 68% vs 60.2%, P -value = .52

    Echiburu 2016 Cross-sectional
    190 PCOS and 90 controls, aged 18–55 women (groups: early reproductive, late reproductive ≤ 40 years, perimenopause 41–55 years)     		NIH BMI and WHR BMI, perimenopause
    PCOS ( n = 30) vs controls ( n = 42), median 26.4 kg/m 2 (IQR 24.1–31.5) vs median 26.8 kg/m 2 (IQR, 24.4–29.6), P -value = .964
    WHR, perimenopause
    PCOS ( n = 30) vs controls ( n = 42), median 0.85 (IQR 0.80–0.87) vs 0.84 (IQR 0.80–0.89), P -value = .749
    Meun 2020 Cross-sectional study
    200 PCOS women and 200 age matched control (mean age, PCOS vs controls, 51 ± 5.2 vs 50.5 ± 5.5 years)
    Menopause, PCOS vs controls 16% vs 40.5%, P -value < .001     		Rotterdam BMI and WHR PCOS vs controls:
    BMI, median 28.4 kg/m 2 (IQR, 23.8–32.9) vs median 26.3 kg/m 2 (IQR, 23.7–29.8), P -value = .02
    WHR, median 0.88 cm (IQR, 0.83–0.93) vs median 0.81 cm (IQR, 0.77–0.86), P -value < .001
    Cibula 2000 Cross-sectional
    28 PCOS aged 51.9 ± 4.64 years (10 postmenopausal and 18 premenopausal) vs 752 controls aged 51.0 ± 4.21 years     		NIH Waist circumference, WHR and BMI BMI values , PCOS vs controls 28.0 ± 4.21 kg/m 2 vs 28.2 ± 5.42 kg/m 2
    High BMI > 28.9 kg/m 2 , PCOS vs controls, 36% vs 40%, P -value > .05
    WHR , PCOS vs controls, 0.8 ± 0.05 cm vs 0.83 ± 0.07 cm, P -value > .05
    High WHR > 0.85 cm , PCOS vs controls, 18% vs 36%, P -value > .05
    Schmidt 2011 Prospective study
    Baseline: 35 PCOS (age range, 61–79 years) vs 120 age-matched controls
    Follow up: 21 years after     		Rotterdam Waist circumference Baseline measurements

    • •

      PCOS, 83.7 ± 14.9 cm


    • •

      Controls, 79.8 ± 10.0 cm

    Follow-up measurements

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      PCOS, 90.9 ± 12.8 cm


    • •

      Controls, 88.6 ± 13.9 cm

    Comparison follow up vs baseline

    • •

      Δ(waist) pcos P -value > .05


    • •

      Δ(waist) control P -value > 0.05

    Meun 2018 Prospective population-based study
    106 PCOS aged more than 55 years and 171 controls
    Median follow up 11.36 years
    Final age 70.19 ± 8.71 years and menopausal age 19.85 ± 9.94 years     		Rotterdam WHR and BMI WHR , PCOS vs controls 0.89 ± 0.08 vs 0.86 ± 0.08, P -value = .01
    BMI , PCOS vs controls, 27.92 ± 4.53 kg/m 2 vs 26.84 ± 3.83 kg/m 2 , P -value = .03

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Nov 27, 2021 | Posted by in GYNECOLOGY | Comments Off on Long-term health in women of age more than 40years with polycystic ovary syndrome

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