Endocrine Abstracts

Background and aim: KS has been classically described as characterized by hyperestrogenism and elevated serum E₂ together with increased gonadotropins and low-to-normal serum testosterone (T). In literature, data on increased serum E₂ are not solid. The aim of this study is to meta-analyse data from studies evaluating serum E₂ in both KS and healthy subjects (HS) in order to verify if E₂ is increased in KS.

Methods: An extensive MEDLINE was performed using ‘PubMed’ with the following key words: ‘KS’ and ‘E₂’ or ‘T’ or ‘sex steroids’ from 1946 to January 2015 (current contents-ISI was used for searching oldest studies). All studies (case–control, case–series, case–reports) reporting E₂ measurement were considered. Controlled–studies were used for meta-analysis, the others only for reviews. Only serum E₂ at baseline (no ongoing treatments) was included. Meta-analysis was conducted according to the PRISMA statement using RevMan.

Results: Out of 956 articles, 26 case–control studies, 15 case–series and 21 case–reports had data on serum E₂. A total of 878 KS and 1000 HS were included in the meta-analysis. Serum E₂ was significantly higher in HS than in KS, with a mean difference of 7.93 pg/ml (CI: 2.24, 13.61; P=0.006), with a χ²=688.32 (I-square=97%). Serum T was significantly lower in KS than in HS, with a mean difference of −2.79 ng/ml (CI:−3,46,−2,11; P<0.001), with a χ²=198,29 (I-square=89%). Data from case–series and case–reports confirmed that E₂ is not above the normal range in KS.

Conclusions: Serum E₂ is not increased in KS and is significantly lower than in HS in this meta-analysis. The limits of this study are the heterogeneity of methods for steroids measurement and the lack of studies having the comparison of serum E₂ between KS and HS as primary endpoint. The traditional belief that KS is associated to elevated E₂ should be reconsidered together with some pathophysiological and clinical issues.