Deborah B. Nelson

Symptoms associated with menopausal transition and reproductive hormones in midlife women.

OBJECTIVE: To test the hypothesis that prevalence of women with menopausal symptoms of hot flushes; aches, joint pain, and stiffness; depressed mood; poor sleep; decreased libido; or vaginal dryness increases with progression through the menopausal transition. METHODS: Women in the Penn Ovarian Aging Study were assessed longitudinally for 9 years. Data were obtained from structured interviews, a validated symptom questionnaire, menstrual bleeding dates and early follicular hormone measures (estradiol [E2], follicle-stimulating hormone [FSH], and inhibin b). Menopausal stages were based on menstrual bleeding patterns. Other risk factors included age, race, history of depression, current smoking, body mass index, and perceived stress. Generalized linear regression models for repeated measures were used to estimate associations among the variables with each symptom. RESULTS: The prevalence of hot flushes; aches, joint pain, and stiffness; and depressed mood increased in the menopausal transition. Menopausal stage was associated with hot flushes (P<.001); aches joint pain, and stiffness (P<.001); and depressed mood (P=.002). Within-woman fluctuations of E2 were associated with hot flushes and aches. Poor sleep, decreased libido, and vaginal dryness were not associated with menopausal stages. There was 80% power to detect an absolute difference of 11% for libido and vaginal dryness and 17% for poor sleep in the prevalence of these symptoms in the late menopausal transition compared with premenopausal status. CONCLUSION: The study highlights the role of menopausal stages for some symptoms of midlife women and indicates that stages in the transition to menopause are associated with hot flushes; aches, joint pain, and stiffness; and depressed mood. Fluctuations of E2, decreased levels of inhibin b, and increased FSH levels were associated with these symptoms. LEVEL OF EVIDENCE: II

Botulinum toxin A for the treatment of delayed gastric emptying.

BACKGROUNDObservational data suggest that intrapyloric injection of botulinum toxin A (BoTN/A) reduces symptoms and accelerates gastric emptying in idiopathic and diabetic gastroparesis. Our purpose was to determine whether botulinum toxin improves symptoms to a significantly greater extent than placebo. An additional objective was to determine whether there is an acceleration of gastric emptying after injection.METHODSA single-institution, randomized, double-blind, placebo-controlled trial* was done. Eligible patients had a Gastroparesis Cardinal Symptom Index score >27 with randomization to intrapyloric botulinum toxin, 200 U (units), or saline placebo. Reassessment of symptoms and repeat gastric emptying scan at 1-month follow-up were done.RESULTSThirty-two patients were randomized to botulinum toxin (N = 16) and placebo (N = 16). At 1-month follow-up, 37.5% randomized to botulinum toxin and 56.3% randomized to placebo achieved improvement as defined by this study. There were no identifiable clinical predictors of response. The botulinum toxin group demonstrated improvement in gastric emptying; however, this was not superior to placebo. No serious adverse events were attributable to botulinum toxin.CONCLUSIONSIntrapyloric injection of botulinum toxin improves gastric emptying in patients with gastroparesis, although this benefit was not superior to placebo at 1 month. Also, in comparison to placebo, symptoms do not improve significantly by 1 month after injection. Overall, we are unable to recommend botulinum toxin therapy for widespread use in the treatment of delayed gastric emptying until more data are available.

DEFINING MENOPAUSE STATUS: CREATION OF A NEW DEFINITION TO IDENTIFY THE EARLY CHANGES OF THE MENOPAUSAL TRANSITION

Objective: Several menopausal staging definitions are currently being used in ongoing studies designed to identify changes occurring during menopause. The objective of this study was to determine which definition captures the earliest hormonal changes in the menopausal transition. Design: In this prospective cohort study, women aged 35 to 47 years were followed for 5 years. Women were classified as premenopausal, early transition, late transition, and postmenopausal by 2 different menopausal staging systems defined by bleeding patterns. Definitions from the Study of Women Health Across the Nation (SWAN) and Stages of Reproductive Aging Workshop (STRAW) were compared. A new menopausal staging system (PENN-5) was also developed with five groups rather than four to distinguish among women with more subtle changes in cycle length. For each staging system, a linear regression model was created comparing mean hormone values (inhibin B, FSH, LH, E2) and menopausal stages at each assessment. Race, body mass index, cycle day, smoking, and follow-up time were included in the model. Results: Statistically significant differences in mean inhibin B and FSH levels, but not estradiol levels, were detected between the earliest menopausal stages of each definition. Significant differences in LH values were detected among the earliest stages of the SWAN and STRAW definitions, but not the PENN-5 definition. Conclusions: Subtle changes in menstrual cycle length reflect significant changes in inhibin B and FSH levels during the menopausal transition. Therefore, it appears that subtle changes in bleeding pattern may be helpful in identifying the earliest hormonal changes during menopausal transition.

Treatment of localized periodontal disease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS)

OBJECTIVE The purpose of this study was to test whether treating periodontal disease (PD) in pregnancy will reduce the incidence of spontaneous preterm delivery (SPTD) at < or = 35 weeks of gestation. STUDY DESIGN A multicenter, randomized clinical trial was performed. Subjects with PD were randomized to scaling and root planing (active) or tooth polishing (control). The primary outcome was the occurrence of SPTD at <35 weeks of gestation. RESULTS We screened 3563 subjects for PD; the prevalence of PD was 50%. Seven hundred fifty-seven subjects were assigned randomly; 378 subjects were assigned to the active group, and 379 subjects were assigned to the placebo group. Active treatment did not reduce the risk of SPTD at <35 weeks of gestation (relative risk, 1.19; 95% confidence interval [CI], 0.62-2.28) or composite neonatal morbidity (relative risk, 1.30; 95% CI, 0.83-2.04). There was a suggestion of an increase in the risk of indicated SPTD at <35 weeks of gestation in those subjects who received active treatment (relative risk, 3.01; 95% CI, 0.95-4.24). CONCLUSION Treating periodontal disease does not reduce the incidence of SPTD.

Effectiveness of treatment strategies of some women with pelvic inflammatory disease: a randomized trial.

Objective: Among all women with pelvic inflammatory disease (PID), prevention of adverse reproductive consequences appears to be similarly achieved by outpatient treatment and inpatient treatment. We assessed whether outpatient is as effective as inpatient treatment in relevant age, race, and clinical subgroups of women with PID. Methods: Women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease (n = 831) were randomized into a multicenter trial of inpatient treatment, initially employing intravenous cefoxitin and doxycycline compared with outpatient treatment consisting of a single intramuscular injection of cefoxitin and oral doxycycline. Comparisons between treatment groups during a mean of 84 months of follow-up were made for pregnancies, live births, time to pregnancy, infertility, PID recurrence, chronic pelvic pain, and ectopic pregnancy. Results: Outpatient treatment assignment did not adversely impact the proportion of women having one or more pregnancies, live births, or ectopic pregnancies during follow-up; time to pregnancy; infertility; PID recurrence; or chronic pelvic pain among women of various races; with or without previous PID; with or without baseline Neisseria gonorrhoeae and/or Chlamydia trachomatis infection; and with or without high temperature/white blood cell count/pelvic tenderness score. This was true even in teenagers and women without a previous live birth. Ectopic pregnancies were more common in the outpatient than the inpatient treatment group, but because these were so rare, the difference did not reach statistical significance (5 versus 1, odds ratio 4.91, 95% confidence interval 0.57–42.25). Conclusion: Among all women and subgroups of women with mild-to-moderate PID, there were no differences in reproductive outcomes after randomization to inpatient or outpatient treatment. Level of Evidence: I

Chlamydia antibodies, chlamydia heat shock protein, and adverse sequelae after pelvic inflammatory disease: the PID Evaluation and Clinical Health (PEACH) Study.

Background: Among women with pelvic inflammatory disease (PID), we assessed the associations among antibodies to Chlamydia trachomatis elementary bodies (EB), antibodies to chlamydia heat shock protein (Chsp60), rates of pregnancy, and PID recurrence. Methods: Four hundred forty-three women with clinical signs and symptoms of mild to moderate PID enrolled in the PID Evaluation and Clinical Health Study were followed for a mean of 84 months for outcomes of time-to-pregnancy and time-to-PID recurrence. Antibodies to EB and Chsp60 were assessed in relation to these long-term sequelae of PID. Results: Rates of pregnancy were significantly lower (adj. hazard ratio 0.47, 95% confidence interval 0.28–0.79) and PID recurrence higher (adj. hazard ratio 2.48, 95% confidence interval 1.00–6.27) after adjusting for confounding factors among women whose antibody titers to chlamydia EB measured in the final year of follow-up were in the highest tertile. Conclusion: Among women with mild to moderate PID, antibodies to C. trachomatis were independently associated with reduced rates of pregnancy and elevated rates of recurrent PID.

Condom Use and the Risk of Recurrent Pelvic Inflammatory Disease, Chronic Pelvic Pain, or Infertility Following an Episode of Pelvic Inflammatory Disease

Among 684 sexually active women with pelvic inflammatory disease (PID) followed up for a mean of 35 months, we related contraceptive use to self-reported PID recurrence, chronic pelvic pain, and infertility. Persistent use of condoms during the study reduced the risk of recurrent PID, chronic pelvic pain, and infertility. Consistent condom use (about 60% of encounters) at baseline also reduced these risks, after adjustment for confounders, by 30% to 60%. Self-reported persistent and consistent condom use was associated with lower rates of PID sequelae.

The relationship between obesity and race on inhibin B during the menopause transition.

Objective: Data are lacking on the effects of obesity and race on inhibin B levels during the menopause transition. The purpose of this study was to determine the relationship among inhibin B levels, body mass index (BMI), and race during the menopause transition. Design: In the Penn Ovarian Aging Study, a prospective cohort study of reproductive aging, 436 women aged 35 to 47 years were followed up with serial hormones, anthropometric measures, and questionnaires for 6 years. Univariate and multivariable analyses were performed comparing mean log transformed inhibin B levels among menopause stages, age groups, BMI categories, races, and smoking groups. Results: In the univariate analyses, mean inhibin B levels were negatively associated with menopause stage, age, and BMI, but not significantly with race or smoking. Interactions of menopause status and BMI were significant (P < 0.001). Premenopausal women with a BMI of 25 or higher had significantly lower inhibin B levels compared with women with a BMI of less than 25 (41.8 pg/mL vs 58.4 pg/mL, P < 0.001), whereas postmenopausal women with a BMI of 30 or higher had significantly higher inhibin B levels compared with the postmenopausal women with a BMI of less than 25 (29.1 pg/mL vs 26.7 pg/mL, P < 0.001). Conclusions: Although BMI is a significant independent predictor of inhibin B levels, the relationship between BMI and inhibin B changes with advancing menopause stage. These data provide additional evidence that obesity influences hormones during the menopause transition.

Does Stress Influence Early Pregnancy Loss

PURPOSE The purpose of this study is to examine the relationship between stress, cortisol level and the risk for spontaneous abortion and determine the influence of stress on health-related behaviors. METHODS Three hundred and twenty-six pregnant women presenting to the emergency department at the Hospital of the University of Pennsylvania from March 1999 through March 2000 were recruited and followed through 22 weeks gestation. Cases were women who experienced a spontaneous abortion and controls were women who maintained their pregnancy. Stress was measured by the Perceived Stress Scale (PSS), the Prenatal Social Environment Inventory (PSEI) and the Index of Spousal Abuse (ISA) prior to confirmation of spontaneous abortion. Blood samples were collected to measure cortisol and sex hormone levels. Urine samples were collected to assess cotinine, cocaine and marijuana use. RESULTS No relationship was found between psychosocial stress, as determined by the three stress scales or cortisol level, and the risk for spontaneous abortion. Women with high stress, as measured by the PSEI, were more likely to use cigarettes and marijuana during pregnancy. High psychosocial stress during early pregnancy was not related to spontaneous abortion but high stress was associated with substance use during pregnancy. CONCLUSION The influence of psychosocial stress on the risk of spontaneous abortion is unclear.

Self-collected versus provider-collected vaginal swabs for the diagnosis of bacterial vaginosis: an assessment of validity and reliability

Bacterial vaginosis (BV) in pregnancy is related to numerous adverse events; however, the validity of different methods of vaginal swab collection to diagnosis BV among pregnant women is unclear. This study examines the validity of self-collected compared with provider-collected vaginal swabs and describes the intra-rater and inter-rater reliability of BV assessment among a sample of pregnant women early in gestation. Gram-stain evaluation of vaginal samples using the Nugent criteria was conducted to determine the overall and morphotype-specific BV scores. We found strong validity for the overall and morphotype-specific scores comparing self-collected swabs to provider-collected swabs. In addition, we found excellent overall and morphotype-specific inter-rater reliability and excellent intra-rater reliability in our sample. These study results support the use of self-collected vaginal swabs for diagnosing BV and document the reliability of BV assessment among pregnant women.