Sir: The paper by Wilson et al. 1 on the relation between oestradiol levels and bacterial vaginosis (BV) provides further evidence for an hormonal influence in this condition. In 1996, or thereabouts, Phillip Hay and I made the suggestion that sex hormone changes might be involved in the aetiology of BV. 2 This was prompted not only by BV being noted, in observations over the course of a menstrual cycle or longer, to occur often in the first part of the cycle, as mentioned by Wilson et al., 1 but also by the results of experiments in mice. In such female animals, subcutaneous administration of oestradiol produced a BV-like picture in Gram-stained vaginal smears through multiplication of the endogenous vaginal bacteria. 3 In addition, this hormone was the key factor in promoting vaginal colonization by Mycoplasma hominis, ureaplasmas and Neisseria gonorrhoeae after their experimental inoculation. 4 -6 On the other hand, progesterone was the hormone that stimulated Chlamydia trachomatis and M. genitalium to grow in mice, oestradiol having no effect whatsoever in promoting growth of these microbes. 7,8 It is not difficult to see, however, that the patterns of hormonal effects are different in women from those in mice. In women high levels of oestradiol are associated with a normal vaginal flora and low levels with an abnormal flora, whereas mice given this hormone develop a BV-like picture and a susceptibility to some organisms, which otherwise is non-existent. The picture is BV-like in the sense that there is proliferation of endogenous murine vaginal bacteria, many adherent to epithelial cells, which, of course, are quite different from the bacteria found in the human vagina. Also different is the vaginal eco-system in women and mice. In women, the healthy vagina is dominated by acid-producing lacto bacilli causing the pH to be less than 4.5, rising to 7.0 or more in subjects with BV. In mice, lactobacilli are sparse and the pH is normally 7.4 (range 6.6-8.5) and not significantly different in mice given oestradiol, that is 7.36 (range 6.5-8.6), or progesterone, namely 7.2 (range 6.4-7.7). In addition, the nature of the cellular composition is somewhat different in women during the menstrual cycle than in mice during the oestrous cycle. In the former, a rising level of oestrogen is associated with proliferation of the vaginal stratified squamous epithelial cells and the surface cells become large and flattened with small or absent nuclei (cornification); in the second half of the cycle, with increasing progesterone, there is mucification of the squamous epithelium with large clear nucleated cells. Only at the end of the cycle, during menstruation, are erythrocytes and leucocytes seen. In the murine reproductive cycle, the oestrogenic phase is defined by squamous epithelial cells, some nucleated (early oestrous stage) or exclusively non-nucleated (oestrous stage) and a di-oestrous phase, stimulated by progesterone, characterized by an infiltration of polymorphonuclear leucocytes to the exclusion of epithelial cells...

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Sir: In this journal, last June 2005, Doctors Brook and Bell 1 expressed reservations that we in Chester appear to have abandoned swabs for gonorrhoea in asymptomatic patients. They were concerned about the issue of false positive tests for gonorrhoea using the APTIMA COMBO 2 transcription mediated amplification test (TMA) in areas of low prevalence. We have now looked at results for the last 12 months and our findings reassure us that not only is APTIMA COMBO 2 testing as good as culture, it in fact out-performs it. Of the 82 cases of gonorrhoea diagnosed between October 2004 and October 2005, there were eight cases where either urethra in men or cervix in women was negative on culture. In five of these cases, however, either culture was positive on another site, or microscopy was positive (Table 1). There were three cases in female patients where microscopy and culture were negative, but the TMA test was positive, indicating that these patients would have been missed if we had not been using APTIMA COMBO 2 TMA test.Of the three cases diagnosed only on TMA we had data indicating that their partner had gonorrhoea allowing us to say with reasonable certainty that these were true positives.This short review allows us to categorically state that the APTIMA COMBO 2 test never missed a single case that had been diagnosed by culture. Our findings are consistent with a view that extra positives by APTIMA COMBO 2 over culture could be labelled 'false positives' in clinical trials and be fed into erroneous calculation of positive predictive values.The specificity of the APTIMA COMBO 2 test is hardly in doubt, based on these results, and we therefore feel confident in continuing our policy of screening genuinely asymptomatic men or women who attend the clinic for a check up with either a first catch urine or if the woman prefers, a self-taken vaginal swab. This is a novel way of maintaining easy access and filtering easy to screen asymptomatic patients into nurse-led parallel clinics.References 1 Brook G, Bell C. Asymptomatic urethritis; the case for a considered view -reply letter. Int J STD AIDS 2005;16:456-7

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