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Objective Conjugated estrogens/bazedoxifene (CE/BZA) is indicated to treat moderate/severe menopausal vasomotor symptoms and prevent postmenopausal osteoporosis. This analysis examines the impact of the most bothersome vaginal symptom at baseline on effects of CE/BZA. Methods This post hoc analysis used data from a 12-week clinical trial of nonhysterectomized postmenopausal women (n = 664) randomly assigned to double-blind treatment with CE/BZA (0.45/20 mg and 0.625/20 mg), BZA 20 mg, or placebo. At baseline, women indicated which moderate/severe vaginal symptom (dryness, itching/irritation, or pain with intercourse) bothered them most. Repeated measures models were used to explore treatment effects in relationship to the most bothersome symptom. We calculated effect sizes for treatment differences versus placebo (effect sizes: trivial, 0.1; small, 0.2; medium, 0.5; large, 0.8). Results At baseline, 52% of women selected pain with intercourse, 35% selected vaginal dryness, and 13% selected vaginal itching/irritation as most bothersome. For these three symptom groups respectively, CE/BZA was associated with statistically significant improvements in Menopause-Specific Quality of Life sexual functioning (effect size: 0.45/20 mg, -0.36, -0.30, -0.67; 0.625/20 mg, -0.37, -0.40, -0.26) and/or overall score (effect size: 0.45/20 mg, -0.29, -0.41, -0.78; 0.625/20 mg, -0.41, -0.48, -0.68). Both those doses significantly improved the ease of lubrication item on the Arizona Sexual Experiences Scale in those with pain with intercourse (effect size: 0.45/20 mg, -0.43; 0.625/20 mg, -0.50) and produced some statistically significant improvements in vaginal cell counts in women with dryness or pain with intercourse as the most bothersome symptom. The higher dose was associated with greater treatment satisfaction on the Menopause Symptoms Treatment Satisfaction Questionnaire versus placebo in women who selected pain with intercourse (effect size: 0.40) or dryness (effect size: 0.43) as most bothersome. Conclusions The approved dose of CE/BZA had clear benefits, particularly in women with pain with intercourse (the most common bothersome symptom), in whom it improved lubrication, superficial cell counts, and sexual functioning.

OBJECTIVE The objective of this study was to evaluate the frequency of genitourinary symptoms and their relationships with several factors in a large cohort of postmenopausal women in Turkey. METHODS We performed a cross-sectional study to review genitourinary complaints among 1,328 postmenopausal women; 1,071 of these women were enrolled in the study. They were questioned about their vaginal and urinary symptoms, and the relationships between these symptoms and their demographic characteristics were evaluated. RESULTS The most common vaginal and urinary symptoms were dryness (n = 358; 33.4%) and nocturia (n = 421; 39.3%), respectively. Cigarette smoking and regular exercise were not associated with any vaginal symptoms (P > 0.05), with the exception of an association between regular exercise and vaginal dryness (P = 0.026). Nocturia was more common in women older than 60 years (P = 0.001) and in obese women (P = 0.013). Based on multiple binary logistic regression analysis, lower educational status (primary school vs secondary school or higher) and higher parity were the factors most significantly associated with the appearance of at least three vaginal symptoms. Lower educational status was associated with vaginal pain (P = 0.002; odds ratio [OR], 1.75), itching (P < 0.001; OR, 1.23), and discharge (P = 0.011; OR, 1.46). Higher parity was associated with vaginal itching (P < 0.001; OR, 1.23), discharge (P = 0.07; OR, 1.18), and burning (P = 0.012; OR, 1.16). Body mass index (BMI) was the only factor that was significantly associated with the appearance of at least three urinary symptoms, with each one-unit increase in BMI increasing the risk of urgency (P < 0.001; OR, 1.06), nocturia (P < 0.001; OR, 1.06), and frequency (P = 0.009; OR, 1.04). CONCLUSIONS We identify associations between the frequency of genitourinary complaints and educational status, parity, and BMI. There is no association between regular exercise and urogenital symptoms. However, prospective studies are needed to evaluate the effects of regular exercise on urogenital symptoms. When examining postmenopausal women with risk factors for urinary and vaginal symptoms, clinicians should evaluate these symptoms more thoroughly to facilitate earlier treatment.

Dyspareunia is a common sexual dysfunction. There is a lack of studies that address female sexual dysfunction in Puerto Rico. The present cross-sectional study characterized dyspareunia in a sample of Puerto Rican women aged 40 to 59 years and evaluated the relationship between reported dyspareunia with demographic, lifestyle, and health factors.Nine hundred twenty Puerto Rican women participated in health fairs conducted in 22 municipalities between May 2000 and November 2001 where they filled out a questionnaire. Contingency table and chi statistics were used to evaluate the bivariate associations of dyspareunia with demographic, lifestyle, and health factors. Crude and multivariate logistic regression models were used to estimate the magnitude of the association between dyspareunia and demographic, lifestyle, and health factors.The overall prevalence of dyspareunia in this population was 18%. Dyspareunia was somewhat lower among women aged 40 to 49 years (17%) than among those aged 50 to 59 years (21%), not reaching statistical significance. Dyspareunia was associated with educational attainment, employment status, menopause status, current hormone therapy use, genitourinary symptoms, and loss of libido (P0.05). Current cigarette smoking, body mass index, physical activity, alcohol use, parity, and ever use of oral contraceptives were not associated with dyspareunia in bivariate analysis (P0.05). In the multivariate analysis, incontinence (prevalence odds ratio [POR], 1.67; 95% CI, 1.02-2.73), vaginal dryness (POR, 3.97; 95% CI, 2.49-6.31), vaginal itching (POR, 2.44; 95% CI, 1.55-3.83), loss of libido (POR, 3.08; 95% CI, 1.92-4.94), and partnership (POR, 2.22; 95% CI, 1.29-3.82) remained associated with dyspareunia.Our results agree with previous studies regarding the potential association between health and lifestyle factors and dyspareunia. Additional studies of female sexual dysfunction in Puerto Rican women are highly warranted.

Only recently, we began to understand that our bodies are not our own – rather, we are hosts to and share space with trillions of microbes that perform valuable, beneficial functions1. The dialogue between our human cells and these microbial colonizers in part determines health from disease. The premenopausal human vagina is home to billions of microbes, dominated by species of the Lactobacillus genus that make lactic acid and maintain a low vaginal pH. These lactobacilli are supported by the glycogen content of vaginal epithelial cells, driven in part by local estrogen levels – thus we know that menopausal women not using hormone therapy are less likely to be colonized with healthy Lactobacillus species than those using hormonal therapy, either local or systemic2. It is also known that symptoms of vaginal itching, burning or discomfort affect almost half of postmenopausal women3, 4 and can have a significant impact on sexual function and quality of life. However, it is not known whether postmenopausal vaginal symptoms and the vaginal microbiome are connected. In this issue, Brotman et al describe the composition of the bacterial communities in 30 pre-, 29 peri- and 28 post-menopausal women, and evaluate the relationship between microbes and signs of vulvovaginal atrophy (VVA)5. Participants were randomly chosen from women enrolled in a study of human papillomavirus in perimenopausal women. VVA was diagnosed by a standardized clinical exam. The composition of the vaginal microbiota was described using PCR amplification of a conserved portion of the 16S ribosomal subunit gene with subsequent deep sequencing. This methodology captures microbial species not easily cultured - species often associated with vaginal disorders like bacterial vaginosis 6. Participants were grouped into 5 “community state types” or “CSTs”, defined by the dominant microbe in the community, as previously described by Ravel et al7. Not surprisingly, Brotman et al found that most pre-menopausal women had few signs of VVA, and a largely Lactobacillus-dominant microbiota. Postmenopausal women were more likely to have VVA and to have a more diverse, non-Lactobacillus dominant flora. The molecular tools used by the authors are powerful and offer new insight into the menopausal microbiome by identifying difficult to cultivate microbial species. However, there are several potential limitations to this analysis. First, as noted by the authors, the forward primer used has multiple mismatches with the common vaginal bacterium Gardnerella vaginalis, thus results may not reflect the full complement of vaginal microbes and might misclassify bacterial communities where G. vaginalis is actually dominant. Second, although the authors generated microbial sequences for a novel cohort including peri- and postmenopausal women, they forced their results into the community state type generated by data from premenopausal women, and combined some CSTs for analysis due to low numbers of subjects. Although vaginitis symptoms in menopausal women have long been attributed to vulvovaginal atrophy, subjective report of symptoms correlates poorly with objective markers of atrophy such as the vaginal maturation index (VMI)8. A recent study by Hummelen et al of 32 postmenopausal women showed that vaginal dryness observed by a nurse examiner was associated with decreased abundance of lactobacilli and increased diversity of the vaginal microbiota9. However, participant’s self-reported vaginal symptoms correlated poorly with the nurse’s assessment of atrophy and dryness. Critically, Brotman et al did not report the subjective vaginal complaints of their study participants. Clinically, this is what matters to patients. Few women care what their vaginal microbial “community state type” is as long as their vagina feels normal. Thus, our challenge. Molecular tools for describing the vaginal microbiome are powerful and certainly enhance our view of the microbial community. However, technology for technology’s sake does not further science. Hillier et al demonstrated the lack of lactobacilli and increased diversity in menopausal women using culture-based techniques in 199710. Vaginal atrophy seen on exam is associated with low estrogen, which in turn is associated with low levels of colonization with Lactobacillus - thus it is not surprising that women with more VVA are less likely to have Lactobacillus-dominant flora. The important question is, why do some women have symptoms while others do not? Are symptoms related to atrophy and low estrogen, or to the presence of a microbial colonizer that causes mucosal irritation? Do alterations in the microbiota over time correlate with changes in the vaginal symptom profile? Likely, the answer will not be a simple linear relationship, given the complexity of the vaginal microenvironment and the variety of patient symptoms. We applaud the attention being paid to the menopausal vagina – however, the small studies to date have focused on biologic signs in isolation, with minimal reference to patient symptoms. Understanding the “vagina dialogues” between microbes and a host’s clinical symptoms requires an analysis of all parts to come up with a whole answer to the problem of postmenopausal vaginitis symptoms.