To the Editor:
We read with great interest the article of Escobar-Morreale et al., in which the authors report that women with polycystic ovary syndrome (PCOS) exhibit an elevation in circulating C-reactive protein (CRP) that was independent of obesity. We agree with their conclusion that this finding confirms the existing molecular evidence of a chronic low-grade inflammation possibly being involved in the pathogenesis of PCOS (1).
A possible autoimmune etiology of at least some cases of PCOS was mentioned in the early 1990s (2). Gleicher et al. have hypothesized that functional autoantibodies could contribute to its development, which represents hyperfunction of follicular recruitment in the ovaries (3). Moreover, the incidence of autoimmune thyroid diseases such as Hashimoto’s thyroiditis has been reported to be three-fold higher in women with PCOS than in the general female population (4).
We used the publication by Escobar-Morreale et al. as an occasion to re-analyze our data set that was previously published in Fertility and Sterility. We had reported an association between elevated anti-thyroid peroxidase antibodies (antiTPO) levels and poor treatment response in infertile, anovulatory women with PCOS. For 109 of our patients (median age, 26.5 years [range, 17 – 39 years]; median body mass index [BMI] 25.3 kg/m2 [range, 18.8 – 47.8 kg/m2]), a serum CRP level that had been determined together with the antiTPO was available. For these patients, we were able to rule out any other acute or chronic diseases, especially inflammatory diseases, by retrospective chart review. The median CRP and antiTPO levels were 0.26 mg/dL [range 0 – 2.5 mg/dL] and 11.0 IU/mL [range 0 – 595.0 IU/mL], respectively. CRP and antiTPO levels were positively correlated (r= 0.181, p= 0.30 in Spearman’s rank correlation). We subdivided our study population into the following groups according to the classification in our original article (5): (i) PCOS women resistant to clomiphene citrate (CC) stimulation and concomitant metformin treatment (n=58); (ii) PCOS women who had become pregnant after CC stimulation and concomitant metformin treatment (n=22); and (iii) PCOS women who had become pregnant after first-line metformin monotherapy (n=29). No significant difference was found for median CRP between these three groups (0.25 [range 0 – 2.3 mg/dL), 0.37 [range 0 – 2.5 mg/dL], and 0.22 [range 0 – 1.10 mg/dL], respectively), although a trend was found in the Kruskal-Wallis test (p= 0.062).
These results confirm the observation that a chronic low-grade inflammation is present in at least some cases of PCOS. When focusing on the association with Hashimoto’s thyroiditis, this chronic autoimmune disorder might contribute to the elevated CRP levels in women suffering from PCOS.
Birgit Jatzko, M.D.
Johannes Ott, M.D.
Department of Gynecologic Endocrinology and Reproductive Medicine
Medical University of Vienna
1. Escobar-Morreale HF, Luque-Ramírez M, González F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril. 2011;95:1048-58.
2. Van Gelderen CJ, Gomes dos Santos MI. Polycystic ovarian syndrome. Evidence for an autoimmune mechanism in some cases. J Reprod Med 1993;38:381–6.
3. Gleicher N, Barad D, Weghofer A. Functional autoantibodies, a new paradigm in autoimmunity? Autoimmun Rev 2007;7:42-5.
4. Janssen OE, Mehlmauer N, Hahn S, Offner AH, Gärtner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol 2004;150:363-9.
5. Ott J, Aust S, Kurz C, Nouri K, Wirth S, Huber JC, et al. Elevated antithyroid peroxidase antibodies indicating Hashimoto’s thyroiditis are associated with the treatment response in infertile women with polycystic ovary syndrome. Fertil Steril. 2010;94:2895-7.
Published online in Fertility and Sterility