Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids.

To facilitate in vitro mechanistic studies in pelvic inflammatory disease and subsequent tubal factor infertility, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae. The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae. Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in Fannyhessea vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. In summary, we have shown that patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful in vitro model system to study the host-pathogen interaction during bacterial infection.

Functional interferon-epsilon gene polymorphisms and sexually transmitted infections of the endometrium.

PROBLEM: Interferon-epsilon (IFNε) is the only type I IFN constitutively expressed in the female reproductive tract and fluctuates across the menstrual cycle in humans. Mouse models show that IFNε protects against Chlamydia trachomatis, Herpes Simplex Virus, HIV, and Zika in mice, but human studies are limited. Bacterial sexually transmitted infections (STI) can ascend to the upper genital tract and cause pelvic inflammatory disease (PID) and subsequent infertility. However, the host immunological mechanisms that play a role in the ascension and infection of the endometrium in individuals with clinically suspected PID are not elucidated. METHOD OF STUDY: This pilot investigation determined if IFNε gene variants are associated with bacterial vaginosis (BV) and endometrial infection with C. trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium using biospecimens from 154 self-report Black individuals who participated in the PID Evaluation and Clinical Health (PEACH) study. RESULTS: The T allele for rs2039381 was associated with endometrial STI infection (OR 2.7, 95% CI: 1.0-7.1) and the C allele for rs1125488 was inversely associated with BV (OR: .2, 95% CI: .05-.8). CONCLUSIONS: Few studies have examined IFNε gene variants, our study raises the possibility that IFNε gene variants may be a potential host contributor to STI pathogenesis.

Syndemics of Sexually Transmitted Infections in a Sample of Racially Diverse Pregnant Young Women.

INTRODUCTION: Syndemic theory posits that poor health outcomes co-occur and amplify each other in the context of harmful conditions that must be addressed simultaneously to improve health equity. This analysis identifies perinatal syndemic factors and examine how factors are related to STI in a sample of racially diverse young pregnant women. METHODS: Pregnant participants (n = 61) ages 14-21 from racially diverse backgrounds were recruited from a prenatal clinic for an ongoing longitudinal study between October 2019-February 2020. Participants completed a tablet survey assessing pregnancy intention, psychosocial factors (e.g., depression, stress, partner violence, pregnancy history) and consented to provide access to their medical records for STI and clinical urine samples screened for tobacco and cannabis use. Latent class analysis (LCA) was used to examine probabilities of co-occurring Syndemic indicators. RESULTS: Half of the women were Black (52%) and primigravida (54%). Three classes were identified in the LCA, two of them reflecting syndemics related to STI from the medical record. The largest class was half Black (51%), with a high rate of STI (65%), and was characterized by factors including depressive symptoms (93%), stress (64%), and substance use (65% cannabis, 82% tobacco). Additionally, the class with the highest rates of STI (74%) also had higher rates of partner violence (48%), morning sickness (100%), and prenatal cannabis use (63%). CONCLUSION: Findings indicate evidence of a syndemic related to increased STI. A longitudinal evaluation of syndemics in this cohort may inform appropriately tailored intervention strategies to promote perinatal health in racially diverse young pregnant populations.

Genital Chlamydia infection in hyperlipidemic mouse models exacerbates atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory disease, and recent studies have shown that infection at remote sites can contribute to the progression of atherosclerosis in hyperlipidemic mouse models. In this report, we tested the hypothesis that genital Chlamydia infection could accelerate the onset and progression of atherosclerosis. METHODS: Apolipoprotein E (Apoe-/-) and LDL receptor knockout (Ldlr-/-) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses were assessed and quantified. RESULTS: Compared to the uninfected groups, infected Apoe-/- and Ldlr-/- mice developed significantly more atherosclerotic lesions in the aortic sinus and in the descending aorta. Increased lesions were associated with higher circulating levels of serum amyloid A-1, IL-1ß, TNF-α, and increased VCAM-1 expression in the aortic sinus, suggesting an association with inflammatory responses observed during C. muridarum infection. Genital infection courses were similar in Apoe-/-, Ldlr-/-, and wild type mice. Further, Apoe-/- mice developed severe uterine pathology with increased dilatations. Apoe-deficiency also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could have contributed to the genital pathology in Apoe-/- mice. CONCLUSIONS: Overall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.

Fetal sexual dimorphism in systemic soluble fms-like tyrosine kinase 1 among normotensive and preeclamptic women.

PROBLEM: A handful of studies report sexual dimorphism in the maternal angiogenic profile possibly influencing placental development and preeclampsia risk. This secondary analysis explored associations between fetal sex and soluble fms-like tyrosine kinase-1 (sFLT) and endoglin (9-35 weeks gestation) using data from a nested case-control study within the Danish National Birth Cohort. METHOD OF STUDY: A total of 448 preeclamptic women and 328 normotensive women had data on sFLT and endoglin. Preeclampsia was defined by blood pressure ≥140/90 mm Hg and proteinuria (≥0.3g or 300 mg/24 h.). Generalized linear models adjusting for gestational age of blood draw, body mass index, maternal age, and smoking determined associations between fetal sex and log-transformed biomarkers. RESULTS: Male fetal sex is associated with 11% lower sFLT levels (ß = -0.11, P = 0.03) in preeclamptic women. There were no differences observed in normotensive women. We found no statistically significant differences in endoglin by fetal sex among groups. CONCLUSION: Our results are similar with other studies suggesting that women with female fetuses have increased sFLT levels. However, significant difference was only among women with preeclampsia. This study was exploratory and longitudinal investigations across pregnancy are required to understand the relationship between fetal sex and systemic maternal angiogenic biomarkers.

The impact of female fetal sex on preeclampsia and the maternal immune milieu.

OBJECTIVE: Small studies suggest that fetal sex alters maternal inflammation. We examined the association between fetal sex, preeclampsia and circulating maternal immune markers. METHODS: This was a secondary data analysis within a nested case-control study of 216 preeclamptic women and 432 randomly selected normotensive controls from the Collaborative Perinatal Project. All women had singleton, primiparous pregnancies without chronic health conditions. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between female fetal sex and preeclampsia. Outcomes included preeclampsia, preterm preeclampsia (<37 and <34 weeks), and normotensive preterm birth <37 weeks. Associations between female fetal sex and immune markers [interleukin (IL)-6, IL4, IL5, IL12, IL10, IL8, IL1-beta, interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, and transforming growth factor-beta] were examined using a statistical method developed for large proportions of censored biomarker data. Models were adjusted for maternal age, race, body mass index, and smoking. RESULTS: Women with early preterm preeclampsia (<34 weeks) had higher odds of having a female fetus (ORadj. 3.2, 95% CI 1.1-9.6) and women with normotensive preterm birth had lower odds (ORadj. 0.5, 95% CI 0.3-0.9). Female fetal sex was associated with lower first trimester pro-inflammatory IFNγ and IL-12 but higher second trimester pro-inflammatory IL1ß and TNFß, anti-inflammatory IL4r, and regulatory cytokines IL5 and IL10. Female fetal sex was associated with higher postpartum IL10 in preeclamptic women only. CONCLUSIONS: We identified sexual dimorphism in maternal inflammation. Longitudinal studies are needed to determine if fetal sex impacts the maternal immune milieu across pregnancy.

Toll-like receptor variants and cervical Atopobium vaginae infection in women with pelvic inflammatory disease.

PROBLEM: Toll-like (TLR) receptor genetic variants have been implicated in bacterial vaginosis (BV). We determined whether TLR variants are associated with fastidious BV-associated microbes that are linked with infertility following pelvic inflammatory disease (PID). METHOD OF STUDY: Sneathia spp., Atopobium vaginae, BVAB1, and Ureaplasma urealyticum were measured in 250 women from the PID Evaluation and Clinical Health (PEACH) study. Relative risk (RR) and 95% confidence intervals (CI) were calculated adjusting for chlamydia and gonorrhea. Principal component analysis was used to adjust for population stratification. A false discovery rate q-value of 0.05 was significant. RESULTS: TLR2-1733C>A (P = .003) and TLR2-616A>G (P = .004) were associated with cervical A. vaginae. TLR2-1733C>A and TLR6-438C>T were associated with A. vaginae detection in the endometrium, but this was not significant after adjustment for multiple comparisons (FDR q-value = 0.06). CONCLUSION: Host gene variants in TLR2 signaling pathways were modestly associated with cervical A. vaginae in women with clinical PID.

First and second trimester immune biomarkers in preeclamptic and normotensive women.

INTRODUCTION: Circulating immune markers may be associated with preeclampsia but further investigations in early pregnancy and among preeclampsia subtypes are warranted. We examined immune markers in 208 preeclamptic women and 411 normotensive controls. METHODS: Our study was nested within the Collaborative Perinatal Project. A total of 242 women had first trimester serum samples and 392 had second trimester serum samples. Preeclampsia was defined as hypertension >20weeks of gestation with proteinuria or pulmonary edema, oliguria, or convulsions. Preterm preeclampsia was defined as preeclampsia with delivery less than 37weeks of gestation. Associations between immune markers RANTES, interleukin (IL)-6, IL4, IL5, IL12, IL10, IL8, IL1-beta, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and beta, transforming growth factor (TGF)-beta and preeclampsia were explored using a modified version of cox regression developed to address data with non-detectable levels. Models were adjusted for body mass index, gestational age of blood sampling, fetal sex, smoking, socioeconomic status and maternal age. RESULTS: In first trimester samples, IL-12 was associated with preeclampsia (p=0.0255). IFN-gamma (p=0.0063), IL1-beta (p=0.0006), IL5 (p=0.0422) and TNFr (p=0.0460) were associated with preterm preeclampsia only. In second trimester samples, IL1-beta was associated with preeclampsia (p=0.0180) and term preeclampsia (p=0.0454). After correction for multiple comparisons, only IL1-beta remained associated with preterm preeclampsia in the first trimester (p=0.0288). DISCUSSION: Elevated first trimester IL1-beta appears to be associated with preterm preeclampsia. However, few associations were observed in the second trimester. Systemic immune markers alone may not be useful for preeclampsia prediction.

Mid-pregnancy circulating immune biomarkers in women with preeclampsia and normotensive controls.

OBJECTIVES: To determine if mid-pregnancy circulating immune biomarkers are associated with preeclampsia. STUDY DESIGN: Nested case-control study of 410 preeclamptic women and 297 normotensive controls with primiparous singleton pregnancies enrolled in the Danish National Birth Cohort. The mean gestational age in our cohort is 16 weeks (range 9-26). MAIN OUTCOME MEASURES: Preeclampsia was defined by blood pressure ⩾140/90 mmHg and proteinuria ⩾3 g/24 h. Serum immune biomarkers included interleukin (IL)-6, IL-6 receptor, IL-4, IL-4 receptor, IL-5, IL-12, IL-2, TNF-α, TNF-ß, TNF-receptor, IL-1ß, IL-1α, IL-8, IL-10, IFN-γ, IL-18, macrophage migration inhibitory factor, macrophage inflammatory protein, transforming growth factor-beta (TGF-ß), and RANTES. Associations with preeclampsia, term preeclampsia and preterm preeclampsia were determined using two logistic regression models; (1) biomarkers were dichotomized by the limit of detection (LOD); (2) on the continuous scale, non-detectable values were imputed by LOD/2 and transformed (base 2). All models were adjusted for body mass index and smoking. RESULTS: IL1ß was significantly associated with a decrease in the log odds of preeclampsia (p=0.0065), term preeclampsia (p=0.0230) and preterm preeclampsia (p=0.0068). Results were similar for IL4r and preeclampsia (p=0.0383). In the dichotomized models, detectable TNF-ß was significantly associated with preeclampsia (ORadj 1.6, 95% CI 1.1-2.3) and term preeclampsia (OR 1.7, 95% CI 1.1-2.5) but not preterm preeclampsia. Detectable IL6 was significantly with term preeclampsia only (OR 1.5, 95% CI 1.1-2.2). CONCLUSION: Mid-pregnancy circulating IL1ß, IL4r, IL6, and TNFß were associated with preeclampsia. However, results were not consistent across statistical models. As the relationship is complex, future studies should explore cytokine clusters in preeclampsia risk.

Serum leptin measured in early pregnancy is higher in women with preeclampsia compared with normotensive pregnant women.

Leptin, an adipocyte-derived hormone, plays an important role in reproduction and angiogenesis. Studies examining leptin in preeclampsia are inconsistent, possibly because of small sample sizes and variability in sampling and outcome. We conducted a nested case-control study to examine associations between serum leptin (measured: 9-26 weeks gestation) and preeclampsia among 430 primiparous preeclamptic women and 316 primiparous normotensive controls from the Danish National Birth Cohort. Median (interquartile range) leptin concentrations were calculated. Associations between leptin and preeclampsia (blood pressure ≥140/90 mm Hg), term preeclampsia (preeclampsia and delivery ≥37 weeks gestation), or preterm preeclampsia (preeclampsia and delivery <37 weeks gestation) were examined using generalized linear models adjusting for body mass index, gestational age at blood draw, maternal age, smoking, and socio-occupational status. As leptin is increased in obese women and the risk of preeclampsia increases with body mass index, we used the Sobel test to examine whether leptin is a mediator of this relationship. After adjustments, leptin concentrations were significantly higher in women with preeclampsia (30.5 [24.6]; P=0.0117) and term preeclampsia (30.4 [24.9]; P=0.0228) compared with controls (20.9 [28.3]). There was no significant difference between preterm preeclampsia (30.6 [23.4]; P=0.2210) and controls. Leptin is a possible mediator of the association between body mass index and preeclampsia (P=0.0276). Leptin concentrations are higher in women with preeclampsia compared with normotensive controls and may mediate some of the relationship between body mass index and preeclampsia.

Fetal sex and race modify the predictors of fetal growth.

The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1 kg/m(2) increase in pre-pregnancy BMI among term females versus males (P = 0.07, P < 0.01 and P = 0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165 g vs. 68 g reduction in birthweight, P < 0.01, interaction), greater reduction in fetal placental ratio (P < 0.01, interaction), PI (P < 0.01, interaction), and greater increase in HCC (P = 0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes.

Prenatal Chlamydia trachomatis infection increases the risk of preeclampsia.

The relationship between Chlamydia trachomatis (CT) and preeclampsia was examined longitudinally among 205 cases and 423 normotensive controls nested within the Collaborative Perinatal Project. Antibodies were analyzed at a first prenatal visit (mean 14.2 weeks) and at delivery. Prenatal infections were identified as IgG/IgM seroconversion or a four-fold rise in IgG antibody titers. Although serological evidence of incident prenatal CT infection was uncommon (n=9, 1.4%) in this general pregnant population, infected women were more likely to develop preeclampsia, after adjustment for maternal age, body mass index, smoking status, race and time between blood draws (ORadj 7.2, 95% CI 1.3 - 39.7).

Chlamydia trachomatis infection may increase the risk of preeclampsia.

BACKGROUND: Although the etiology of preeclampsia is not well understood, it has been suggested that excessive systemic inflammation may lead to oxidative stress, promoting the endothelial dysfunction characteristic of preeclampsia. Few prospective studies have examined the role of infection, an immune system stimulator, as a risk factor for preeclampsia. METHODS: We conducted a longitudinal study of the relationships between Chlamydia trachomatis (CT), Chlamydophila pneumoniae (CP), cytomegalovirus (CMV), herpes simplex virus (HSV) and preeclampsia among 509 preeclamptic cases and 336 normotensive controls nested within the Danish National Birth Cohort study. Antibodies were analyzed at a first prenatal visit (mean 17.0weeks) and at a late second/third trimester study visit. Prenatal infections were identified as IgG/IgM seroconversion or a fourfold rise in IgG antibody titers. Multiple regression models were adjusted for maternal age, BMI, smoking status, and time between blood draws. RESULTS: CT infection was associated with preeclampsia (ORadj 1.6, 95% CI 0.7, 3.6), severe preeclampsia (ORadj 1.8, 95% CI 0.6, 5.3), and preeclampsia resulting in preterm birth (ORadj 1.7, 95% CI 0.6-4.9) or birth of a small for gestational age infant (ORadj 2.1, 95% CI 0.6, 7.5), although CT infection was uncommon (n=33, 4.0%) and associations were not statistically significant. CP, CMV, and HSV infection were not associated with preeclampsia. CONCLUSIONS: Women with serological evidence of prenatal CT infection were more likely to develop preeclampsia, although infection was infrequent and confidence intervals were wide. Studies in populations at higher risk for STIs are needed to corroborate this association.

Second trimester anti-angiogenic proteins and preeclampsia.

OBJECTIVE: To measure the relationships between soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and preeclampsia. STUDY DESIGN: We utilized a nested case-control study comprised of 211 preeclamptic women and 213 normotensive women with primiparous singleton pregnancies enrolled from ≥13 and <27 gestational weeks among the Danish National Birth Cohort of 100,000 women. Relationships between sFlt1, sEng and preeclampsia were estimated using smoothing splines in generalized linear models, adjusting for maternal age, body mass index, pre-existing hypertension, smoking, and gestational age. MAIN OUTCOME MEASURES: Preeclampsia was confirmed by an International Classification of Diseases (ICD) discharge diagnosis of 637.03, 637.04 637.09, 637.19 (ICD-8) or DO14 to DO15 (ICD-10) in the National Hospital Discharge Registry. In this sample, few cases delivered small for gestational age infants (8.1%) and the mean gestational age at delivery was term (38.2 ± 2.3 weeks). RESULTS: Doublings in the expressions of sFlt1 and sEng were associated with 39% (95% CI = 3%, 86%) and 74% (95% CI = 1%, 198%) increased risks of preeclampsia respectively. CONCLUSIONS: We conclude that second trimester high sFlt1 and sEng levels were possibly associated with an increased risk of preeclampsia after adjustment for maternal factors traditionally associated with the syndrome.

Microbial correlates of delayed care for pelvic inflammatory disease.

OBJECTIVE: We studied the microbial correlates of time to care and long-term outcomes among pelvic inflammatory disease (PID) patients, as delayed care may increase the risk for reproductive sequelae. METHODS: Mean days of pain before care were compared by microbial pathogen (Chlamydia trachomatis only, Neisseria gonorrhoeae only, Mycoplasma genitalium only, coinfection with 2 or more pathogens, or no pathogens) among 298 women with histologically confirmed endometritis from the PID Evaluation and Clinical Health study. Times to pregnancy and recurrent PID were assessed over a mean of 84 months and compared between women who delayed care (≥14 days) and women who sought early care, in the entire cohort and in subsets defined by microbial infection. Analyses were adjusted for age and race, additionally time to pregnancy was adjusted for self-reported baseline infertility. RESULTS: Patients waited a mean of 7 days before seeking care for symptoms. Time to care was longest among women infected by C. trachomatis only (12.3 ± 9.4 days) and M. genitalium only (10.9 ± 8.9 days) and the shortest among women infected by N. gonorrhoeae only (4.6 ± 5 days) or coinfection (5.6 ± 5.1 days, P < 0.001). Rates of infertility, recurrent PID, and chronic pelvic pain were frequent overall (17%, 20%, and 36%) and tended to be higher, albeit nonsignificantly, after delayed care. CONCLUSIONS: Among women with clinically suspected PID, time to care was generally high. C. trachomatis and M. genitalium positive women had the longest times to care. Although reproductive morbidity was high in this cohort, associations with delayed care were nonsignificant.

Mycoplasma genitalium among women with nongonococcal, nonchlamydial pelvic inflammatory disease.

Pelvic inflammatory disease (PID) is a frequent condition of young women, often resulting in reproductive morbidity. Although Neisseria gonorrhoeae and/or Chlamydia trachomatis are/is recovered from approximately a third to a half of women with PID, the etiologic agent is often unidentified. We need PCR to test for M genitalium among a pilot sample of 50 women with nongonococcal, nonchlamydial endometritis enrolled in the PID evaluation and clinical health (PEACH) study. All participants had pelvic pain, pelvic organ tenderness, and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. Endometritis was defined as > or =5 surface epithelium neutrophils per x400 field absent of menstrual endometrium and/or > or =2 stromal plasma cells per x120 field. We detected M genitalium in 7 (14%) of the women tested: 6 (12%) in cervical specimens and 4 (8%) in endometrial specimens. We conclude that M genitalium is prevalent in the endometrium of women with nongonococcal, nonchlamydial PID.

Association between allelic variants in cytokine genes and preeclampsia.

OBJECTIVE: The purpose of this study was to examine the relationship between cytokine genotypes and preeclampsia. STUDY DESIGN: We conducted a case-control study that examined cytokine genotypes among 150 primiparous preeclamptic women and 661 primiparous, normotensive women. Analyses were adjusted for age, prepregnancy cigarette smoking, and education. RESULTS: Preeclamptic white women were more likely than normotensive white women to carry the up-regulating tumor necrosis factor-alpha-308 A/A (odds ratio, 4.1; 95% CI, 1.1-15.3) genotype. Both black and white women with preeclampsia were more likely than normotensive control subjects to carry the interleukin-1alpha-producing-4845 G/G genotype (black odds ratio, 11.6; 95% CI, 1.5-89.3; white odds ratio, 1.7; 95% CI, 0.7-3.9), -889 C/C genotype (black odds ratio, 5.1; 95% CI, 0.6-41.6; white odds ratio, 1.9; 95% CI, 0.8-4.7), and the interleukin-1alpha-4845/interleukin-1alpha-889/interleukin-1beta-3957 GCC/GCC haplotype (black odds ratio, 3.4; 95% CI, 1.3-8.7; white odds ratio, 2.1; 95% CI, 1.4-3.2). CONCLUSION: Cytokine genotypes were associated with preeclampsia and may identify women who are at high risk for preeclampsia.

Predictors of chronic pelvic pain in an urban population of women with symptoms and signs of pelvic inflammatory disease.

OBJECTIVE: The objective of this study was to assess the risk profile for chronic pelvic pain (CPP) after pelvic inflammatory disease (PID). STUDY: Multivariate logistic regression was used to assess risk factors for CPP in a longitudinal study of 780 predominately black, urban women with clinically suspected PID: complaints of acute pain (<30 days); a clinical finding of pelvic tenderness; and leukorrhea, mucopurulent cervicitis, or untreated gonococcal or chlamydial cervicitis. CPP was defined as pain reported at >or=2 consecutive interviews conducted every 3 to 4 months for 2 to 5 years. RESULTS: Nonblack race (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.31-3.58), being married (OR, 2.06; 95% CI, 1.02-4.18), a low SF-36 mental health composite score (OR, 2.71; 95% CI, 1.69-4.34), >or=2 prior PID episodes (OR, 2.84; 95% CI, 1.07-7.54), and smoking (OR, 1.65; 95% CI, 1.01-2.71) independently predicted CPP. Histologic endometritis or evidence of endometrial Neisseria gonorrhoeae or Chlamydia trachomatis infection was negatively associated with CPP (OR, 0.69; 95% CI, 0.44-1.10). CONCLUSIONS: A range of demographic, clinical, historical, and behavioral factors predict CPP after PID.

The impact of estrogen and progesterone on asthma.

OBJECTIVE: This paper describes evidence of a positive effect of both endogenous and exogenous estrogen and progesterone on lung function across the life span in women. DATA SOURCES: Articles were identified using the keywords asthma, pulmonary function, menarche, menopause, estrogen, progesterone, hormone replacement therapy, oral contraceptives, and menstrual cycle from years 1966 to 2001 in MEDLINE. Additional studies were identified from article reference lists. STUDY SELECTION: Relevant, peer-reviewed original research articles in the English language were selected. RESULTS: Estrogen and/or progesterone may alter pulmonary function and asthma. Premenopausal women experience decreases in pulmonary function and increases in asthma exacerbations and hospitalizations during the premenstrual and menstrual phases. Oral contraceptives and hormone replacement therapy are associated with improved pulmonary function and decrease in asthma exacerbation. Some asthmatic patients experience improved pulmonary function and reduced asthma medication requirement during pregnancy. CONCLUSIONS: Estrogen and progesterone modify airway responsiveness. Further research is needed to elucidate the clinical relevance of estrogen and progesterone in the pathophysiology and therapy of asthma.

Endometritis does not predict reproductive morbidity after pelvic inflammatory disease.

OBJECTIVE: We investigated the association between endometritis and reproductive morbidity. STUDY DESIGN: Participants were 614 women in the PID Evaluation and Clinical Health (PEACH) Study with pelvic pain, pelvic organ tenderness, and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. We compared women with endometritis (>or=5 neutrophils or >or=2 plasma cells), Neisseria gonorrhoeae or Chlamydia trachomatis upper genital tract infection (UGTI) or both to women without endometritis/UGTI for outcomes of pregnancy, infertility, recurrent pelvic inflammatory disease (PID), and chronic pelvic pain (CPP), adjusting for age, race, education, PID history, and baseline infertility. RESULTS: Endometritis/UGTI was not associated with reduced pregnancy (odds ratio [OR] 0.8, 95% CI 0.6-1.2) or elevated infertility (OR 1.0, 95% CI 0.6-1.6), recurrent PID (OR 0.6, 95% CI 0.4-0.9), or CPP (OR 0.6, 95% CI 0.4-0.9). PEACH participants with and without endometritis/UGTI had higher age- and race-specific pregnancy rates than 1997 national rates. CONCLUSION: Among women with clinically suspected mild-to-moderate PID treated with standard antibiotics, endometritis/UGTI was not associated with reproductive morbidity.