Chlamydia antibodies and self-reported symptoms of oligo-amenorrhea and hirsutism: a new etiologic factor in polycystic ovary syndrome?
To investigate whether the systemic inflammation induced by chlamydial infections might be associated with symptoms of polycystic ovary syndrome (PCOS).
Nested case-control study.
A questionnaire including questions about hirsutism and oligo-amenorrhea was distributed to a representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. Those who reported both symptoms were defined as symptomatic (n=81).
A representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort.
None.
To test the presence of serum antibodies to Chlamydia pneumoniae (IgG titers ≥32) and Chlamydia trachomatis (IgG titers ≥8) by microimmunofluorescence in symptomatic and control women.
Antibodies were investigated in 79 symptomatic and 1427 control women (C. pneumoniae) and in 79 symptomatic and 425 control women (C trachomatis). C. trachomatis antibodies (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.6) and C. pneumoniae antibodies (OR, 1.5; 95% CI, 1.0-2.4) were more commonly present in symptomatic women, and the simultaneous presence of elevated highly sensitive C-reactive protein levels strengthened this association.
Chronic inflammation, which is associated with chlamydial infections, could contribute to the pathogenetic processes that lead to the metabolic and hormonal disorders of PCOS.
Morin-Papunen LC
，Duleba AJ
，Bloigu A
，Järvelin MR
，Saikku P
，Pouta A
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Irregular menstruation and hyperandrogenaemia in adolescence are associated with polycystic ovary syndrome and infertility in later life: Northern Finland Birth Cohort 1986 study.
Do teenage girls with a history of menstrual irregularity and/or elevated androgen levels in adolescence exhibit an increased risk of polycystic ovary syndrome (PCOS) and/or infertility later on in adulthood?
Our results suggest that menstrual irregularity and/or elevated androgen levels at 16 years are still associated with symptoms of PCOS at 26 years as well as infertility problems at 26 years but not with decreased pregnancy or delivery rates at 26 years.
Hyperandrogenaemia is associated with menstrual irregularity, hirsutism, acne and potentially higher risk for PCOS, but there are few follow-up studies investigating whether adolescent hyperandrogenaemia and/or menstrual irregularity are an early sign of PCOS.
A prospective population-based cohort study was conducted using two postal questionnaires targeting girls in the Northern Finland Birth Cohort 1986 (NFBC1986, n = 4567). The NFBC1986 comprises all expected births from the year 1986 in the two northernmost provinces of Finland. Collection of the database was performed at the age of 16 and 26. The 16-year and 26-year questionnaires included one question about the regularity and length of the menstrual cycle. The 26-year questionnaire also included questions about symptoms of PCOS, reproduction and infertility problems.
The response rates for the questionnaires were 80% (n = 3669) at 16 years and 50% (n = 2270) at 26 years. At 15-16 years, of 2448 girls, 709 (29%) girls reported menstrual irregularity (symptomatic girls) and 1739 (71%) had regular periods (non-symptomatic girls). After combining data from the two questionnaires a total of 2033 girls were included in the analyses. The χ(2) and Student's t-test was used to compare reproductive outcome and prevalence of clinical hyperandrogenaemia, PCOS and infertility at 26 years between the study groups. Univariate and multivariate logistic regression models were employed to estimate the association of menstrual irregularity at 16 years with clinical hyperandrogenaemia, PCOS and infertility at 26 years.
At follow-up, the proportion of symptomatic girls who had conceived at least once (68.0 versus 67.9%) and had delivered at least one child (25.7 versus 28.1%) was similar to the non-symptomatic women and the groups had similar miscarriage rates (11.6 versus 12.1%). Logistic regression analyses indicated that menstrual irregularity at 16 years was associated with an increased risk of menstrual irregularity [adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.00-1.88, P = 0.050], PCOS (adjusted OR 2.91, 95% CI 1.74-4.84, P < 0.001) and infertility problems (adjusted OR 2.07, 95% CI 1.16-3.76, P = 0.013) at 26 years. At 26 years, women with PCOS (P = 0.013), hirsutism (P = 0.001) and acne (P < 0.001) exhibited significantly higher values of free androgen index (FAI) at 16 years than control women. There was a significant linear trend in the higher FAI quartiles at 16 years towards higher prevalence of PCOS (P = 0.005), hirsutism (P < 0.001) and acne (P < 0.001) at 26 years. Only 10.5% of the girls with menstrual irregularity at 16 years had PCOS at 26 years.
The diagnosis of menstrual irregularity was based on a self-reported questionnaire, thus introducing a risk of information bias in reporting the symptoms. Moreover, ovarian ultrasonography was not available to aid the diagnosis of PCOS and there was no clinical evaluation of hyperandrogenism. The relatively low rate of participation to the questionnaire at 26 years may also have biased the results.
Our findings confirm that menstrual irregularity and/or elevated androgen levels are already present in adolescence in women with PCOS and infertility in later life, which strengthens the importance of early identification of menstrual irregularity.
This work was supported by grants from the Finnish Medical Society Duodecim, the North Ostrobothnia Regional Fund, the Academy of Finland, the Sigrid Juselius Foundation, University Hospital Oulu and University of Oulu, the European Commission and the Medical Research Council, UK, Welcome Trust (089549/Z/09/Z). None of the authors have any conflict of interest.
West S
，Lashen H
，Bloigu A
，Franks S
，Puukka K
，Ruokonen A
，Järvelin MR
，Tapanainen JS
，Morin-Papunen L
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