Expert Commentary

Objective

To compare the effect of hysterectomy versus expanded medical treatment on health-related quality of life in premenopausal women with abnormal uterine bleeding (AUB).

Results

In this multicenter, randomized, controlled trial involving 63 women 30 to 50 years of age in whom medical therapy with medroxyprogesterone acetate had failed, those randomized to hysterectomy had greater improvement at 6 months in Mental Component Survey scores (8 vs 2; P = .04). They also had greater improvement in symptom resolution (75 vs 29; P .001 symptom satisfaction vs>P .001 interference with sex vs>P = .003), sexual desire (21 vs 3; P = .01), health distress (33 vs 13; P = .009), sleep problems (13 vs 1; P =. 03), overall health (12 vs 2; P = .006), and satisfaction with health (31 vs 14; P = .01).

Expert commentary

This study is one of the first randomized studies to compare the effects of surgery versus medical management on quality of life. Unfortunately, participants were included only after 1 course of medical therapy had failed. Thus, although investigators avoided potential skewing of the results by excluding patients who responded easily to treatment, they also caused selection bias.

It also is likely that some of the patients randomized to medical therapy were frustrated after failing 1 course of therapy, which caused a large crossover group: 17 of 32 women in the medical-therapy group eventually underwent hysterectomy. A more accurate outcome may have resulted if all women initially presenting with AUB had been included.

Shortcomings

Sample size was small, and did not reach the projected numbers even after the target sample size was officially decreased. Again, if investigators had randomized any patient initially presenting with AUB, more women might have been willing to participate. If the reason for the low numbers is that more women wanted to undergo surgical treatment after failing therapy with medroxy-progesterone acetate, researchers could have implemented a 2:1 randomization scheme to encourage higher enrollment in the study.

Although performing surgery without attempting medical therapy does not reflect typical management, it might have provided insight into whether medical management is worthwhile and yielded information on which option truly does lead to better quality of life.

Further, researchers compared each patient’s quality-of-life scores to her baseline, which, in the medicine group, was after a mean of 4 years of treatment. Therefore, one would expect less of a difference between scores in the medicine group, since all women were already refractory to medroxyprogesterone acetate at the beginning of the study.

The large crossover from the medical management group makes it difficult to decipher what the outcome of the study really is, despite the intragroup analysis. This leads me to conclude that, at some point, most patients get tired of trying medications and want a guaranteed fast cure.

No data on effects of hysterectomy route

One area that should have been addressed and subanalyzed: whether the type of hysterectomy (36% abdominal versus 64% vaginal) had any effect on short- or longterm outcomes.

Ablation option not included

There is also another treatment option that was not addressed: endometrial ablation. This surgery typically has a quicker recovery than hysterectomy and should correct the bleeding faster than medical management. It would be interesting to see the differences in quality-of-life and sexual-function outcomes with this option, compared with the others.

Bottom line

Until these issues have been thoroughly evaluated, women with AUB should initially be treated with medical therapy. Based on the preliminary screening study for this trial, medroxyprogesterone acetate appears to effectively control most patients’ symptoms. However, when medical therapy fails, the physician should explain to the patient that the improved short-term outcome seen with hysterectomy does not necessarily translate into significant long-term quality-of-life outcomes, as this study points out. The final decision between medical management and hysterectomy thus should fall to the individual patient.

Objective

To compare the effect of hysterectomy versus expanded medical treatment on health-related quality of life in premenopausal women with abnormal uterine bleeding (AUB).

Results

In this multicenter, randomized, controlled trial involving 63 women 30 to 50 years of age in whom medical therapy with medroxyprogesterone acetate had failed, those randomized to hysterectomy had greater improvement at 6 months in Mental Component Survey scores (8 vs 2; P = .04). They also had greater improvement in symptom resolution (75 vs 29; P .001 symptom satisfaction vs>P .001 interference with sex vs>P = .003), sexual desire (21 vs 3; P = .01), health distress (33 vs 13; P = .009), sleep problems (13 vs 1; P =. 03), overall health (12 vs 2; P = .006), and satisfaction with health (31 vs 14; P = .01).

Expert commentary

This study is one of the first randomized studies to compare the effects of surgery versus medical management on quality of life. Unfortunately, participants were included only after 1 course of medical therapy had failed. Thus, although investigators avoided potential skewing of the results by excluding patients who responded easily to treatment, they also caused selection bias.

It also is likely that some of the patients randomized to medical therapy were frustrated after failing 1 course of therapy, which caused a large crossover group: 17 of 32 women in the medical-therapy group eventually underwent hysterectomy. A more accurate outcome may have resulted if all women initially presenting with AUB had been included.

Shortcomings

Sample size was small, and did not reach the projected numbers even after the target sample size was officially decreased. Again, if investigators had randomized any patient initially presenting with AUB, more women might have been willing to participate. If the reason for the low numbers is that more women wanted to undergo surgical treatment after failing therapy with medroxy-progesterone acetate, researchers could have implemented a 2:1 randomization scheme to encourage higher enrollment in the study.

Although performing surgery without attempting medical therapy does not reflect typical management, it might have provided insight into whether medical management is worthwhile and yielded information on which option truly does lead to better quality of life.

Further, researchers compared each patient’s quality-of-life scores to her baseline, which, in the medicine group, was after a mean of 4 years of treatment. Therefore, one would expect less of a difference between scores in the medicine group, since all women were already refractory to medroxyprogesterone acetate at the beginning of the study.

The large crossover from the medical management group makes it difficult to decipher what the outcome of the study really is, despite the intragroup analysis. This leads me to conclude that, at some point, most patients get tired of trying medications and want a guaranteed fast cure.

No data on effects of hysterectomy route

One area that should have been addressed and subanalyzed: whether the type of hysterectomy (36% abdominal versus 64% vaginal) had any effect on short- or longterm outcomes.

Ablation option not included

There is also another treatment option that was not addressed: endometrial ablation. This surgery typically has a quicker recovery than hysterectomy and should correct the bleeding faster than medical management. It would be interesting to see the differences in quality-of-life and sexual-function outcomes with this option, compared with the others.

Bottom line

Until these issues have been thoroughly evaluated, women with AUB should initially be treated with medical therapy. Based on the preliminary screening study for this trial, medroxyprogesterone acetate appears to effectively control most patients’ symptoms. However, when medical therapy fails, the physician should explain to the patient that the improved short-term outcome seen with hysterectomy does not necessarily translate into significant long-term quality-of-life outcomes, as this study points out. The final decision between medical management and hysterectomy thus should fall to the individual patient.

Objective

To compare the effect of hysterectomy versus expanded medical treatment on health-related quality of life in premenopausal women with abnormal uterine bleeding (AUB).

Results

In this multicenter, randomized, controlled trial involving 63 women 30 to 50 years of age in whom medical therapy with medroxyprogesterone acetate had failed, those randomized to hysterectomy had greater improvement at 6 months in Mental Component Survey scores (8 vs 2; P = .04). They also had greater improvement in symptom resolution (75 vs 29; P .001 symptom satisfaction vs>P .001 interference with sex vs>P = .003), sexual desire (21 vs 3; P = .01), health distress (33 vs 13; P = .009), sleep problems (13 vs 1; P =. 03), overall health (12 vs 2; P = .006), and satisfaction with health (31 vs 14; P = .01).

Expert commentary

This study is one of the first randomized studies to compare the effects of surgery versus medical management on quality of life. Unfortunately, participants were included only after 1 course of medical therapy had failed. Thus, although investigators avoided potential skewing of the results by excluding patients who responded easily to treatment, they also caused selection bias.

It also is likely that some of the patients randomized to medical therapy were frustrated after failing 1 course of therapy, which caused a large crossover group: 17 of 32 women in the medical-therapy group eventually underwent hysterectomy. A more accurate outcome may have resulted if all women initially presenting with AUB had been included.

Shortcomings

Sample size was small, and did not reach the projected numbers even after the target sample size was officially decreased. Again, if investigators had randomized any patient initially presenting with AUB, more women might have been willing to participate. If the reason for the low numbers is that more women wanted to undergo surgical treatment after failing therapy with medroxy-progesterone acetate, researchers could have implemented a 2:1 randomization scheme to encourage higher enrollment in the study.

Although performing surgery without attempting medical therapy does not reflect typical management, it might have provided insight into whether medical management is worthwhile and yielded information on which option truly does lead to better quality of life.

Further, researchers compared each patient’s quality-of-life scores to her baseline, which, in the medicine group, was after a mean of 4 years of treatment. Therefore, one would expect less of a difference between scores in the medicine group, since all women were already refractory to medroxyprogesterone acetate at the beginning of the study.

The large crossover from the medical management group makes it difficult to decipher what the outcome of the study really is, despite the intragroup analysis. This leads me to conclude that, at some point, most patients get tired of trying medications and want a guaranteed fast cure.

No data on effects of hysterectomy route

One area that should have been addressed and subanalyzed: whether the type of hysterectomy (36% abdominal versus 64% vaginal) had any effect on short- or longterm outcomes.

Ablation option not included

There is also another treatment option that was not addressed: endometrial ablation. This surgery typically has a quicker recovery than hysterectomy and should correct the bleeding faster than medical management. It would be interesting to see the differences in quality-of-life and sexual-function outcomes with this option, compared with the others.

Bottom line

Until these issues have been thoroughly evaluated, women with AUB should initially be treated with medical therapy. Based on the preliminary screening study for this trial, medroxyprogesterone acetate appears to effectively control most patients’ symptoms. However, when medical therapy fails, the physician should explain to the patient that the improved short-term outcome seen with hysterectomy does not necessarily translate into significant long-term quality-of-life outcomes, as this study points out. The final decision between medical management and hysterectomy thus should fall to the individual patient.

Objective

To assess the efficacy of nightly 5% lidocaine ointment for vulvar vestibulitis.

Results

After 7 weeks of treatment, 76% of 61 women were able to have intercourse, compared with 36% before therapy (P = .002). The intercourse-related pain score—based on a 100-mm visual analog scale—was 39.11 points lower after treatment (95% confidence interval [CI] 30.39–47.83; P.001 with a decrease of points in the daily pain score ci>P = .004). Although few patient characteristics predicted treatment response, women with interstitial cystitis and other vulvar conditions were least likely to benefit.

Expert commentary

Vulvar vestibulitis, a perplexing syndrome of chronic burning/pain with few overt physical findings, has repsonded poorly to medical therapies. When these fail, the only treatment demonstrated to give any improvement is surgical excision of the vestibule, a rather extreme treatment with side effects that can be severe.

Recently, less invasive vestibulitis treatments have been described, with rates of improvement that approach those of surgical excision. For example, Murina and colleagues¹ showed that repeated submucous vestibular injection of lidocaine and methylprednisolone yields substantial improvement in 68% of subjects, a rate similar to that of vestibulectomy—without the side effects.

Now Zolnoun et al report that a topical lidocaine application, even less invasive than submucosal injections, leads to a similar rate of improvement. Patients applied lidocaine 5% ointment to the vestibule via a saturated cotton ball every night and removed it about 8 hours later. Side effects were limited to transient burning at the application site in some patients.

Findings confirm anecdotal evidence. Local lidocaine application is one of several vestibulitis therapies that heretofore was supported only by anecdotal evidence. Zolnoun and colleagues are to be complimented for summarizing patient outcomes, which make it possible for us to quote benefits and risks for topical lidocaine ointment to our patients.

Weaknesses. Investigators failed to include a control group, but many reports of vestibulitis therapies suffer from this shortcoming. However, the history of severe, persistent vestibular pain in the patients in this study makes it unlikely that their pain abated from the emollient effects of the petrolatum base. It will be interesting to see how this treatment fares in a randomized controlled trial.

Bottom line

In light of the safety, simplicity, and low expense of topical lidocaine, it seems reasonable to consider its use in patients with pain isolated to the vestibule who have achieved a normal pattern of vaginal flora free of fungal organisms.

A 2-month trial certainly should be considered before resorting to more drastic treatments such as vestibulectomy.

Objective

To assess the efficacy of nightly 5% lidocaine ointment for vulvar vestibulitis.

Results

After 7 weeks of treatment, 76% of 61 women were able to have intercourse, compared with 36% before therapy (P = .002). The intercourse-related pain score—based on a 100-mm visual analog scale—was 39.11 points lower after treatment (95% confidence interval [CI] 30.39–47.83; P.001 with a decrease of points in the daily pain score ci>P = .004). Although few patient characteristics predicted treatment response, women with interstitial cystitis and other vulvar conditions were least likely to benefit.

Expert commentary

Vulvar vestibulitis, a perplexing syndrome of chronic burning/pain with few overt physical findings, has repsonded poorly to medical therapies. When these fail, the only treatment demonstrated to give any improvement is surgical excision of the vestibule, a rather extreme treatment with side effects that can be severe.

Recently, less invasive vestibulitis treatments have been described, with rates of improvement that approach those of surgical excision. For example, Murina and colleagues¹ showed that repeated submucous vestibular injection of lidocaine and methylprednisolone yields substantial improvement in 68% of subjects, a rate similar to that of vestibulectomy—without the side effects.

Now Zolnoun et al report that a topical lidocaine application, even less invasive than submucosal injections, leads to a similar rate of improvement. Patients applied lidocaine 5% ointment to the vestibule via a saturated cotton ball every night and removed it about 8 hours later. Side effects were limited to transient burning at the application site in some patients.

Findings confirm anecdotal evidence. Local lidocaine application is one of several vestibulitis therapies that heretofore was supported only by anecdotal evidence. Zolnoun and colleagues are to be complimented for summarizing patient outcomes, which make it possible for us to quote benefits and risks for topical lidocaine ointment to our patients.

Weaknesses. Investigators failed to include a control group, but many reports of vestibulitis therapies suffer from this shortcoming. However, the history of severe, persistent vestibular pain in the patients in this study makes it unlikely that their pain abated from the emollient effects of the petrolatum base. It will be interesting to see how this treatment fares in a randomized controlled trial.

Bottom line

In light of the safety, simplicity, and low expense of topical lidocaine, it seems reasonable to consider its use in patients with pain isolated to the vestibule who have achieved a normal pattern of vaginal flora free of fungal organisms.

A 2-month trial certainly should be considered before resorting to more drastic treatments such as vestibulectomy.

Objective

To assess the efficacy of nightly 5% lidocaine ointment for vulvar vestibulitis.

Results

After 7 weeks of treatment, 76% of 61 women were able to have intercourse, compared with 36% before therapy (P = .002). The intercourse-related pain score—based on a 100-mm visual analog scale—was 39.11 points lower after treatment (95% confidence interval [CI] 30.39–47.83; P.001 with a decrease of points in the daily pain score ci>P = .004). Although few patient characteristics predicted treatment response, women with interstitial cystitis and other vulvar conditions were least likely to benefit.

Expert commentary

Vulvar vestibulitis, a perplexing syndrome of chronic burning/pain with few overt physical findings, has repsonded poorly to medical therapies. When these fail, the only treatment demonstrated to give any improvement is surgical excision of the vestibule, a rather extreme treatment with side effects that can be severe.

Recently, less invasive vestibulitis treatments have been described, with rates of improvement that approach those of surgical excision. For example, Murina and colleagues¹ showed that repeated submucous vestibular injection of lidocaine and methylprednisolone yields substantial improvement in 68% of subjects, a rate similar to that of vestibulectomy—without the side effects.

Now Zolnoun et al report that a topical lidocaine application, even less invasive than submucosal injections, leads to a similar rate of improvement. Patients applied lidocaine 5% ointment to the vestibule via a saturated cotton ball every night and removed it about 8 hours later. Side effects were limited to transient burning at the application site in some patients.

Findings confirm anecdotal evidence. Local lidocaine application is one of several vestibulitis therapies that heretofore was supported only by anecdotal evidence. Zolnoun and colleagues are to be complimented for summarizing patient outcomes, which make it possible for us to quote benefits and risks for topical lidocaine ointment to our patients.

Weaknesses. Investigators failed to include a control group, but many reports of vestibulitis therapies suffer from this shortcoming. However, the history of severe, persistent vestibular pain in the patients in this study makes it unlikely that their pain abated from the emollient effects of the petrolatum base. It will be interesting to see how this treatment fares in a randomized controlled trial.

Bottom line

In light of the safety, simplicity, and low expense of topical lidocaine, it seems reasonable to consider its use in patients with pain isolated to the vestibule who have achieved a normal pattern of vaginal flora free of fungal organisms.

A 2-month trial certainly should be considered before resorting to more drastic treatments such as vestibulectomy.

Objective

To explore the role of angiogenic factors in preeclampsia—specifically, whether circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PIGF) and vascular endothelial growth factor (VEGF), plays a pathogenic role.

Results

Increased levels of sFlt-1 and reduced levels of PIGF predicted the subsequent development of preeclampsia.

Expert commentary

In this nested case-control study involving 120 pairs of women, researchers determined serum levels of 3 peptides known to be involved in modulating angiogenesis: sFlt-1, PIGF, and VEGF. They found that levels of sFLT-1 increased and PIGF decreased with advancing gestation in normotensive control pregnancies. These changes occurred earlier in gestation and to a more exaggerated extent among the cases that went on to develop preeclampsia. VEGF levels remained low throughout pregnancy, but did differ between cases and controls.

Levels of sFlt-1 increased 5 weeks prior to the development of clinical preeclampsia, while the decrease in PIGF could be noted in the middle trimester.

Strengths and weaknesses. The analytic, statistical, and methodological aspects of this study are sound. However, because of the nested, case-control design, it is impossible to calculate sensitivity, specificity, and positive and negative predictive values for any of these analytes. As an accompanying editorial notes, not all women with abnormal changes in sFlt-1 and PIGF went on to develop preeclampsia.¹ A larger, prospective trial is needed to establish the clinical utility of these markers in predicting preeclampsia.

Endothelial dysfunction has long been a hallmark of preeclampsia, and various associations or explanations have been proposed (Savvidou²). Levine et al provide a framework that fits the symptoms of edema, hypertension, proteinuria, and resultant end-organ dysfunction into a paradigm that is useful in its organization, ability to generate testable hypotheses, and suggestion of potential therapy other than delivery.

Unanswered questions. This research adds to our understanding of how the pathology of preeclampsia propagates and becomes clinically recognizable. It offers less insight into the equally interesting question of what causes the initial perturbation that goes on to cause preeclampsia. Another important question is whether we should be developing a screening test for a condition that can as yet be cured only by delivery.

One might argue that knowing who is at increased risk would allow closer fetal testing, maternal observation, and an opportunity for earlier intervention in the form of antenatal steroid administration or delivery. However, these may be relatively small advantages over conventional prenatal screening, given the risks of increased maternal anxiety and the additional burden on a system of care that is already financially stressed and legally embattled.

Bottom line

This study is the latest of several publications^3-5 that suggest we may finally be moving toward a more complete understanding of preeclampsia. It should be of interest to all obstetricians because it adds to general, specialty-specific background knowledge and holds promise as a source of therapy. These observations also raise the possibility of a predictive test for preeclampsia that might be applied before clinical symptomatology appears.

Objective

To explore the role of angiogenic factors in preeclampsia—specifically, whether circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PIGF) and vascular endothelial growth factor (VEGF), plays a pathogenic role.

Results

Increased levels of sFlt-1 and reduced levels of PIGF predicted the subsequent development of preeclampsia.

Expert commentary

In this nested case-control study involving 120 pairs of women, researchers determined serum levels of 3 peptides known to be involved in modulating angiogenesis: sFlt-1, PIGF, and VEGF. They found that levels of sFLT-1 increased and PIGF decreased with advancing gestation in normotensive control pregnancies. These changes occurred earlier in gestation and to a more exaggerated extent among the cases that went on to develop preeclampsia. VEGF levels remained low throughout pregnancy, but did differ between cases and controls.

Levels of sFlt-1 increased 5 weeks prior to the development of clinical preeclampsia, while the decrease in PIGF could be noted in the middle trimester.

Strengths and weaknesses. The analytic, statistical, and methodological aspects of this study are sound. However, because of the nested, case-control design, it is impossible to calculate sensitivity, specificity, and positive and negative predictive values for any of these analytes. As an accompanying editorial notes, not all women with abnormal changes in sFlt-1 and PIGF went on to develop preeclampsia.¹ A larger, prospective trial is needed to establish the clinical utility of these markers in predicting preeclampsia.

Endothelial dysfunction has long been a hallmark of preeclampsia, and various associations or explanations have been proposed (Savvidou²). Levine et al provide a framework that fits the symptoms of edema, hypertension, proteinuria, and resultant end-organ dysfunction into a paradigm that is useful in its organization, ability to generate testable hypotheses, and suggestion of potential therapy other than delivery.

Unanswered questions. This research adds to our understanding of how the pathology of preeclampsia propagates and becomes clinically recognizable. It offers less insight into the equally interesting question of what causes the initial perturbation that goes on to cause preeclampsia. Another important question is whether we should be developing a screening test for a condition that can as yet be cured only by delivery.

One might argue that knowing who is at increased risk would allow closer fetal testing, maternal observation, and an opportunity for earlier intervention in the form of antenatal steroid administration or delivery. However, these may be relatively small advantages over conventional prenatal screening, given the risks of increased maternal anxiety and the additional burden on a system of care that is already financially stressed and legally embattled.

Bottom line

This study is the latest of several publications^3-5 that suggest we may finally be moving toward a more complete understanding of preeclampsia. It should be of interest to all obstetricians because it adds to general, specialty-specific background knowledge and holds promise as a source of therapy. These observations also raise the possibility of a predictive test for preeclampsia that might be applied before clinical symptomatology appears.

Objective

To explore the role of angiogenic factors in preeclampsia—specifically, whether circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PIGF) and vascular endothelial growth factor (VEGF), plays a pathogenic role.

Results

Increased levels of sFlt-1 and reduced levels of PIGF predicted the subsequent development of preeclampsia.

Expert commentary

In this nested case-control study involving 120 pairs of women, researchers determined serum levels of 3 peptides known to be involved in modulating angiogenesis: sFlt-1, PIGF, and VEGF. They found that levels of sFLT-1 increased and PIGF decreased with advancing gestation in normotensive control pregnancies. These changes occurred earlier in gestation and to a more exaggerated extent among the cases that went on to develop preeclampsia. VEGF levels remained low throughout pregnancy, but did differ between cases and controls.

Levels of sFlt-1 increased 5 weeks prior to the development of clinical preeclampsia, while the decrease in PIGF could be noted in the middle trimester.

Strengths and weaknesses. The analytic, statistical, and methodological aspects of this study are sound. However, because of the nested, case-control design, it is impossible to calculate sensitivity, specificity, and positive and negative predictive values for any of these analytes. As an accompanying editorial notes, not all women with abnormal changes in sFlt-1 and PIGF went on to develop preeclampsia.¹ A larger, prospective trial is needed to establish the clinical utility of these markers in predicting preeclampsia.

Endothelial dysfunction has long been a hallmark of preeclampsia, and various associations or explanations have been proposed (Savvidou²). Levine et al provide a framework that fits the symptoms of edema, hypertension, proteinuria, and resultant end-organ dysfunction into a paradigm that is useful in its organization, ability to generate testable hypotheses, and suggestion of potential therapy other than delivery.

Unanswered questions. This research adds to our understanding of how the pathology of preeclampsia propagates and becomes clinically recognizable. It offers less insight into the equally interesting question of what causes the initial perturbation that goes on to cause preeclampsia. Another important question is whether we should be developing a screening test for a condition that can as yet be cured only by delivery.

One might argue that knowing who is at increased risk would allow closer fetal testing, maternal observation, and an opportunity for earlier intervention in the form of antenatal steroid administration or delivery. However, these may be relatively small advantages over conventional prenatal screening, given the risks of increased maternal anxiety and the additional burden on a system of care that is already financially stressed and legally embattled.

Bottom line

This study is the latest of several publications^3-5 that suggest we may finally be moving toward a more complete understanding of preeclampsia. It should be of interest to all obstetricians because it adds to general, specialty-specific background knowledge and holds promise as a source of therapy. These observations also raise the possibility of a predictive test for preeclampsia that might be applied before clinical symptomatology appears.

Objective

To compare 2 interventions for growth-restricted fetuses remote from term: early delivery to preempt intrauterine hypoxia, and delayed delivery for as long as possible to gain maturity.

Results

At 2 years, the overall rate of death or severe disability was 55 (19%) of 290 immediate births and 44 (16%) of 283 delayed births. After adjustment for gestational age and umbilical-artery Doppler category, the odds ratio was 1.1, indicating a trend toward more disability with immediate delivery, and the 95% credibility interval was 0.7 to 1.8.

Expert commentary

Optimal timing of delivery in high-risk pregnancies continues to confound obstetricians and perinatologists. This randomized, controlled trial attempts to address the issue in the setting of fetal growth restriction. It involved 548 pregnant women in 13 European countries who had fetal compromise between 24 and 36 weeks of gestation. In all cases, it was uncertain whether immediate delivery was indicated. These women were randomized to immediate delivery (within 48 hours to permit steroid administration) or deferred delivery (until safe delivery could be delayed no longer because of worsening test results or the passage of time). The median interval between randomization and delivery was 0.9 days with immediate delivery and 4.9 days with delayed delivery.

Strengths lie in the trial design, 2-year follow-up of infants, blinded outcomes assessment, and statistical analysis.

Weaknesses include the trial’s multicenter nature, lack of standardization for management interventions, and probable practitioner variability in disability assessment among the 69 hospitals involved.

Unanswered questions. We are not told the degree of growth restriction of the cases enrolled, or whether any misclassification errors occurred.

Decisions regarding route of delivery and intrapartum management were left to the provider’s discretion and were not standardized; this is important because a number of intrapartum events can lead to perinatal morbidity and mortality. Unexplained antepartum fetal death occurred more frequently in the expectantly managed group; the only cases of intrapartum trauma or asphyxia occurred in that group as well.

That said, at 2 years the overall results are similar between the groups. Investigators concluded that, while obstetricians seem to be intervening at the appropriate time, early intervention may not translate into improved outcomes overall.

Absent from the dialogue is the medicolegal risk associated with what some would consider inordinate delay in delivery versus premature intervention. The former generally would have the less favorable medicolegal outcome.

Bottom line

This study fails to definitively identify the optimal intervention in high-risk pregnancies remote from term. Antenatal testing remains imprecise, and fetal demise from delayed intervention must be weighed against the risk of long-term disabilities from intervening too early.

For now, the obstetrician must rely on close fetal surveillance and gestational age as the prime drivers of delivery decisions. It is also crucial that we adequately communicate to patients the potential risks associated with the 2 strategies.

Objective

To compare 2 interventions for growth-restricted fetuses remote from term: early delivery to preempt intrauterine hypoxia, and delayed delivery for as long as possible to gain maturity.

Results

At 2 years, the overall rate of death or severe disability was 55 (19%) of 290 immediate births and 44 (16%) of 283 delayed births. After adjustment for gestational age and umbilical-artery Doppler category, the odds ratio was 1.1, indicating a trend toward more disability with immediate delivery, and the 95% credibility interval was 0.7 to 1.8.

Expert commentary

Optimal timing of delivery in high-risk pregnancies continues to confound obstetricians and perinatologists. This randomized, controlled trial attempts to address the issue in the setting of fetal growth restriction. It involved 548 pregnant women in 13 European countries who had fetal compromise between 24 and 36 weeks of gestation. In all cases, it was uncertain whether immediate delivery was indicated. These women were randomized to immediate delivery (within 48 hours to permit steroid administration) or deferred delivery (until safe delivery could be delayed no longer because of worsening test results or the passage of time). The median interval between randomization and delivery was 0.9 days with immediate delivery and 4.9 days with delayed delivery.

Strengths lie in the trial design, 2-year follow-up of infants, blinded outcomes assessment, and statistical analysis.

Weaknesses include the trial’s multicenter nature, lack of standardization for management interventions, and probable practitioner variability in disability assessment among the 69 hospitals involved.

Unanswered questions. We are not told the degree of growth restriction of the cases enrolled, or whether any misclassification errors occurred.

Decisions regarding route of delivery and intrapartum management were left to the provider’s discretion and were not standardized; this is important because a number of intrapartum events can lead to perinatal morbidity and mortality. Unexplained antepartum fetal death occurred more frequently in the expectantly managed group; the only cases of intrapartum trauma or asphyxia occurred in that group as well.

That said, at 2 years the overall results are similar between the groups. Investigators concluded that, while obstetricians seem to be intervening at the appropriate time, early intervention may not translate into improved outcomes overall.

Absent from the dialogue is the medicolegal risk associated with what some would consider inordinate delay in delivery versus premature intervention. The former generally would have the less favorable medicolegal outcome.

Bottom line

This study fails to definitively identify the optimal intervention in high-risk pregnancies remote from term. Antenatal testing remains imprecise, and fetal demise from delayed intervention must be weighed against the risk of long-term disabilities from intervening too early.

For now, the obstetrician must rely on close fetal surveillance and gestational age as the prime drivers of delivery decisions. It is also crucial that we adequately communicate to patients the potential risks associated with the 2 strategies.

Objective

To compare 2 interventions for growth-restricted fetuses remote from term: early delivery to preempt intrauterine hypoxia, and delayed delivery for as long as possible to gain maturity.

Results

At 2 years, the overall rate of death or severe disability was 55 (19%) of 290 immediate births and 44 (16%) of 283 delayed births. After adjustment for gestational age and umbilical-artery Doppler category, the odds ratio was 1.1, indicating a trend toward more disability with immediate delivery, and the 95% credibility interval was 0.7 to 1.8.

Expert commentary

Optimal timing of delivery in high-risk pregnancies continues to confound obstetricians and perinatologists. This randomized, controlled trial attempts to address the issue in the setting of fetal growth restriction. It involved 548 pregnant women in 13 European countries who had fetal compromise between 24 and 36 weeks of gestation. In all cases, it was uncertain whether immediate delivery was indicated. These women were randomized to immediate delivery (within 48 hours to permit steroid administration) or deferred delivery (until safe delivery could be delayed no longer because of worsening test results or the passage of time). The median interval between randomization and delivery was 0.9 days with immediate delivery and 4.9 days with delayed delivery.

Strengths lie in the trial design, 2-year follow-up of infants, blinded outcomes assessment, and statistical analysis.

Weaknesses include the trial’s multicenter nature, lack of standardization for management interventions, and probable practitioner variability in disability assessment among the 69 hospitals involved.

Unanswered questions. We are not told the degree of growth restriction of the cases enrolled, or whether any misclassification errors occurred.

Decisions regarding route of delivery and intrapartum management were left to the provider’s discretion and were not standardized; this is important because a number of intrapartum events can lead to perinatal morbidity and mortality. Unexplained antepartum fetal death occurred more frequently in the expectantly managed group; the only cases of intrapartum trauma or asphyxia occurred in that group as well.

That said, at 2 years the overall results are similar between the groups. Investigators concluded that, while obstetricians seem to be intervening at the appropriate time, early intervention may not translate into improved outcomes overall.

Absent from the dialogue is the medicolegal risk associated with what some would consider inordinate delay in delivery versus premature intervention. The former generally would have the less favorable medicolegal outcome.

Bottom line

This study fails to definitively identify the optimal intervention in high-risk pregnancies remote from term. Antenatal testing remains imprecise, and fetal demise from delayed intervention must be weighed against the risk of long-term disabilities from intervening too early.

For now, the obstetrician must rely on close fetal surveillance and gestational age as the prime drivers of delivery decisions. It is also crucial that we adequately communicate to patients the potential risks associated with the 2 strategies.

Objective

To assess the effectiveness of paroxetine controlled release (CR), a selective serotonin reuptake inhibitor (SSRI), in relieving hot flashes among a general cross section of menopausal women.

Results

After 6 weeks, mean daily hot flash frequency decreased from 7.1 to 3.8 for women receiving 12.5 mg/day paroxetine CR, from 6.4 to 3.2 for those taking 25 mg/day, and from 6.6 to 4.8 for women taking placebo.

Expert Commentary

The vasomotor flush is the hallmark of the female climacteric, experienced to some degree by up to 85% of postmenopausal women.^{Managing menopause-related depression and low libido”).}

It is worth trying to titrate the dose to its lowest effective level because of a small but bothersome incidence of decreased libido. Added advantages with SSRIs are improvements in depression, anxiety, and sleep.

Objective

To assess the effectiveness of paroxetine controlled release (CR), a selective serotonin reuptake inhibitor (SSRI), in relieving hot flashes among a general cross section of menopausal women.

Results

After 6 weeks, mean daily hot flash frequency decreased from 7.1 to 3.8 for women receiving 12.5 mg/day paroxetine CR, from 6.4 to 3.2 for those taking 25 mg/day, and from 6.6 to 4.8 for women taking placebo.

Expert Commentary

The vasomotor flush is the hallmark of the female climacteric, experienced to some degree by up to 85% of postmenopausal women.^{Managing menopause-related depression and low libido”).}

It is worth trying to titrate the dose to its lowest effective level because of a small but bothersome incidence of decreased libido. Added advantages with SSRIs are improvements in depression, anxiety, and sleep.

Objective

To assess the effectiveness of paroxetine controlled release (CR), a selective serotonin reuptake inhibitor (SSRI), in relieving hot flashes among a general cross section of menopausal women.

Results

After 6 weeks, mean daily hot flash frequency decreased from 7.1 to 3.8 for women receiving 12.5 mg/day paroxetine CR, from 6.4 to 3.2 for those taking 25 mg/day, and from 6.6 to 4.8 for women taking placebo.

Expert Commentary

The vasomotor flush is the hallmark of the female climacteric, experienced to some degree by up to 85% of postmenopausal women.^{Managing menopause-related depression and low libido”).}

It is worth trying to titrate the dose to its lowest effective level because of a small but bothersome incidence of decreased libido. Added advantages with SSRIs are improvements in depression, anxiety, and sleep.

Objective

To compare laparoscopic, abdominal, and vaginal hysterectomy, with major and minor complications as the primary endpoints.

Results

The laparoscopic group had less pain, quicker recovery, and better short-term quality of life than the abdominal group, but a significantly greater rate of major complications and operating time. Complication rates were similar for laparoscopic and vaginal hysterectomy, though that arm was underpowered.

Expert Commentary

This is one of only a few randomized, controlled trials comparing the 3 hysterectomy techniques. Women were randomized to laparoscopic (n = 391) versus abdominal (n = 172) hysterectomy (abdominal arm) or to laparoscopic (n = 198) versus vaginal (n = 105) hysterectomy (vaginal arm).

Study strengths and findings. Design was excellent, and investigators reported results of both trial arms, though insufficient numbers were recruited in the vaginal arm. Thus, we can draw reasonable conclusions from the large number of women involved:

• Operating time. Longer with laparoscopic than with abdominal or vaginal hysterectomy.
  
• Quality of life. Significantly improved with laparoscopic hysterectomy up to 1 year.
  
• Minor complications. Similar in all groups.
  
• Detection of additional pathology. Greater with laparoscopy. Surprisingly, in the abdominal arm, additional pathology was reported in 12.7% of patients versus 22.6% for the laparoscopic approach. In the vaginal arm, additional pathology was detected in 4.8% of cases versus 16.4% for the laparoscopic approach.
  
• Pain. Less with laparoscopy in the abdominal arm, but comparable in the vaginal arm.
  

Weaknesses. Some shortcomings in study design were largely unavoidable. For example, by excluding patients with prolapse or with a uterus larger than 12 weeks’ gestation, researchers limited generalizability, as these conditions are common indications for hysterectomy in a typical clinical practice, and frequently are determinants of the approach.

The incidence of major hemorrhage (abdominal arm: 2.4%, versus 4.6% for laparoscopy; vaginal arm: 2.9%, versus 5.1% for laparoscopy) may have been related to the method of utero-ovarian vessel ligation and sealing, but no description or standardization was offered. Thus, it is unclear whether a simple alteration in technique could have eliminated this as a factor in morbidity.

Unintended laparotomy was considered a major complication in this study, but only in the laparoscopy groups. Excluding this, major complications would have been lower in the laparoscopy group compared with the abdominal group. It seems inappropriate to consider a procedure that is standard for 1 group as a major complication in another.

Bottom line

Taken with existing literature, this study supports the premise that laparoscopy is desirable for most women undergoing hysterectomy. It also confirms the superiority of laparoscopic hysterectomy in recognizing and treating other pathology while ensuring a shorter recovery and hospital stay and improved quality of life.

Objective

To compare laparoscopic, abdominal, and vaginal hysterectomy, with major and minor complications as the primary endpoints.

Results

The laparoscopic group had less pain, quicker recovery, and better short-term quality of life than the abdominal group, but a significantly greater rate of major complications and operating time. Complication rates were similar for laparoscopic and vaginal hysterectomy, though that arm was underpowered.

Expert Commentary

This is one of only a few randomized, controlled trials comparing the 3 hysterectomy techniques. Women were randomized to laparoscopic (n = 391) versus abdominal (n = 172) hysterectomy (abdominal arm) or to laparoscopic (n = 198) versus vaginal (n = 105) hysterectomy (vaginal arm).

Study strengths and findings. Design was excellent, and investigators reported results of both trial arms, though insufficient numbers were recruited in the vaginal arm. Thus, we can draw reasonable conclusions from the large number of women involved:

• Operating time. Longer with laparoscopic than with abdominal or vaginal hysterectomy.
  
• Quality of life. Significantly improved with laparoscopic hysterectomy up to 1 year.
  
• Minor complications. Similar in all groups.
  
• Detection of additional pathology. Greater with laparoscopy. Surprisingly, in the abdominal arm, additional pathology was reported in 12.7% of patients versus 22.6% for the laparoscopic approach. In the vaginal arm, additional pathology was detected in 4.8% of cases versus 16.4% for the laparoscopic approach.
  
• Pain. Less with laparoscopy in the abdominal arm, but comparable in the vaginal arm.
  

Weaknesses. Some shortcomings in study design were largely unavoidable. For example, by excluding patients with prolapse or with a uterus larger than 12 weeks’ gestation, researchers limited generalizability, as these conditions are common indications for hysterectomy in a typical clinical practice, and frequently are determinants of the approach.

The incidence of major hemorrhage (abdominal arm: 2.4%, versus 4.6% for laparoscopy; vaginal arm: 2.9%, versus 5.1% for laparoscopy) may have been related to the method of utero-ovarian vessel ligation and sealing, but no description or standardization was offered. Thus, it is unclear whether a simple alteration in technique could have eliminated this as a factor in morbidity.

Unintended laparotomy was considered a major complication in this study, but only in the laparoscopy groups. Excluding this, major complications would have been lower in the laparoscopy group compared with the abdominal group. It seems inappropriate to consider a procedure that is standard for 1 group as a major complication in another.

Bottom line

Taken with existing literature, this study supports the premise that laparoscopy is desirable for most women undergoing hysterectomy. It also confirms the superiority of laparoscopic hysterectomy in recognizing and treating other pathology while ensuring a shorter recovery and hospital stay and improved quality of life.

Objective

To compare laparoscopic, abdominal, and vaginal hysterectomy, with major and minor complications as the primary endpoints.

Results

The laparoscopic group had less pain, quicker recovery, and better short-term quality of life than the abdominal group, but a significantly greater rate of major complications and operating time. Complication rates were similar for laparoscopic and vaginal hysterectomy, though that arm was underpowered.

Expert Commentary

This is one of only a few randomized, controlled trials comparing the 3 hysterectomy techniques. Women were randomized to laparoscopic (n = 391) versus abdominal (n = 172) hysterectomy (abdominal arm) or to laparoscopic (n = 198) versus vaginal (n = 105) hysterectomy (vaginal arm).

Study strengths and findings. Design was excellent, and investigators reported results of both trial arms, though insufficient numbers were recruited in the vaginal arm. Thus, we can draw reasonable conclusions from the large number of women involved:

• Operating time. Longer with laparoscopic than with abdominal or vaginal hysterectomy.
  
• Quality of life. Significantly improved with laparoscopic hysterectomy up to 1 year.
  
• Minor complications. Similar in all groups.
  
• Detection of additional pathology. Greater with laparoscopy. Surprisingly, in the abdominal arm, additional pathology was reported in 12.7% of patients versus 22.6% for the laparoscopic approach. In the vaginal arm, additional pathology was detected in 4.8% of cases versus 16.4% for the laparoscopic approach.
  
• Pain. Less with laparoscopy in the abdominal arm, but comparable in the vaginal arm.
  

Weaknesses. Some shortcomings in study design were largely unavoidable. For example, by excluding patients with prolapse or with a uterus larger than 12 weeks’ gestation, researchers limited generalizability, as these conditions are common indications for hysterectomy in a typical clinical practice, and frequently are determinants of the approach.

The incidence of major hemorrhage (abdominal arm: 2.4%, versus 4.6% for laparoscopy; vaginal arm: 2.9%, versus 5.1% for laparoscopy) may have been related to the method of utero-ovarian vessel ligation and sealing, but no description or standardization was offered. Thus, it is unclear whether a simple alteration in technique could have eliminated this as a factor in morbidity.

Unintended laparotomy was considered a major complication in this study, but only in the laparoscopy groups. Excluding this, major complications would have been lower in the laparoscopy group compared with the abdominal group. It seems inappropriate to consider a procedure that is standard for 1 group as a major complication in another.

Bottom line

Taken with existing literature, this study supports the premise that laparoscopy is desirable for most women undergoing hysterectomy. It also confirms the superiority of laparoscopic hysterectomy in recognizing and treating other pathology while ensuring a shorter recovery and hospital stay and improved quality of life.

Zegura B, Keber I, Sebestjen M, Borko E. Orally and transdermally replaced estradiol improves endothelial function equally in middleaged women after surgical menopause. Am J Obstet Gynecol. 2003; 188:1291–1296.

Objective

To explore whether estradiol’s vascular effects depend on route of administration.

Results

Both oral and transdermal estradiol led to improved endothelial function over 28 weeks in surgically menopausal women.

Methods

Six weeks after surgically induced menopause, 43 healthy women were randomized to 28 weeks of oral or transdermal estradiol. Endothelium-dependent and endothelium-independent dilation were calculated by measuring the diameter of the brachial artery at rest using high-resolution ultrasound after reactive hyperemia, and again after sublingual glyceryl trinitrate.

Outcome

Endothelium-dependent dilation increased after both oral (from 6%±3.9% to 13.2%±4.4%, P.0001 and transdermal estradiol to>P.0001 improvements were independent of changes in blood lipids and lipoproteins. endothelium-independent dilation did not change significantly either group.>

Expert Commentary

Both the estrogen-progestin and estrogen-only arms of the Women’s Health Initiative found no reduction in heart-disease risk among participants.^1,2 This differed from findings of many observational studies, such as the Nurses’ Health Study, which reported a 40% to 50% reduction in heart-disease risk in menopausal women taking estrogen for vasomotor symptoms.³ Age and progestin use have been suggested as possible explanations for the differing results.

No clear cause of reduced risk of heart disease. Some experts argue that the cardioprotective effect of menopausal hormone therapy is mediated by alterations in the lipid profile, with an elevation in high-density lipoprotein (HDL) cholesterol and a decline in lowdensity lipoprotein (LDL) cholesterol.⁴ This presumably results from the “first-pass effect” of oral estrogen on the liver, an activity that could be antagonized by progestin or not observed if estrogen is given by another route. Others claim the cardiac benefit stems from a direct effect of estrogen on the endothelium of blood vessels.⁵ Zegura et al provide interesting data supporting both theories.

Both oral and transdermal estrogen caused a rise in HDL cholesterol, but the increase in women taking the oral hormone (15.8%) was double that of women given estrogen transdermally (8.9%). LDL cholesterol and lipoprotein (a) levels declined significantly (13.4% and 18.1%, respectively), but only with oral estrogen. Blood-flow–mediated dilation rose significantly in both groups, jumping from 6% to 13.2% in women given oral estrogen, versus 7% to 14.9% with transdermal use.

Study limitations. The authors were unable to ensure equivalency of the estradiol concentrations within subjects’ systemic circulations. Even if they had measured estradiol concentrations, the expected variation following oral administration would have made interpretation nearly impossible. Thus, it remains unclear whether comparable changes in lipid parameters would be observed by lowering the oral estrogen dose or raising the transdermal dose. It is also unclear whether lower estrogen doses given orally or transdermally would result in improved blood-flow changes.

Since study subjects became menopausal due to surgery, they were relatively young (mean age: 49.2 years, oral group; 47.8 years, transdermal group). Thus, this study does not reveal whether older women who undergo menopause “naturally” and who might have subclinical atherosclerotic heart disease would respond similarly. Finally, the impact of progestin exposure was not addressed.

While Zegura et al provide important data, their finding of equivalency in improved endothelial function for both oral and transdermal estrogen pertains only to younger menopausal women using estrogen for a relatively short time. It remains unknown whether, after years of therapy, the more beneficial lipid alterations induced by oral estrogen would lead to greater improvement in endothelial function than that observed after transdermal estrogen for a similar time.

Bottom Line

Given orally or transdermally, hormone therapy is FDA-approved for the treatment of menopausal symptoms, but not prevention or treatment of cardiovascular disease. The decision to give estrogen orally or transdermally should be based on patient preference or the desire to diminish side effects such as skin irritation or headaches.

Zegura B, Keber I, Sebestjen M, Borko E. Orally and transdermally replaced estradiol improves endothelial function equally in middleaged women after surgical menopause. Am J Obstet Gynecol. 2003; 188:1291–1296.

Objective

To explore whether estradiol’s vascular effects depend on route of administration.

Results

Both oral and transdermal estradiol led to improved endothelial function over 28 weeks in surgically menopausal women.

Methods

Six weeks after surgically induced menopause, 43 healthy women were randomized to 28 weeks of oral or transdermal estradiol. Endothelium-dependent and endothelium-independent dilation were calculated by measuring the diameter of the brachial artery at rest using high-resolution ultrasound after reactive hyperemia, and again after sublingual glyceryl trinitrate.

Outcome

Endothelium-dependent dilation increased after both oral (from 6%±3.9% to 13.2%±4.4%, P.0001 and transdermal estradiol to>P.0001 improvements were independent of changes in blood lipids and lipoproteins. endothelium-independent dilation did not change significantly either group.>

Expert Commentary

Both the estrogen-progestin and estrogen-only arms of the Women’s Health Initiative found no reduction in heart-disease risk among participants.^1,2 This differed from findings of many observational studies, such as the Nurses’ Health Study, which reported a 40% to 50% reduction in heart-disease risk in menopausal women taking estrogen for vasomotor symptoms.³ Age and progestin use have been suggested as possible explanations for the differing results.

No clear cause of reduced risk of heart disease. Some experts argue that the cardioprotective effect of menopausal hormone therapy is mediated by alterations in the lipid profile, with an elevation in high-density lipoprotein (HDL) cholesterol and a decline in lowdensity lipoprotein (LDL) cholesterol.⁴ This presumably results from the “first-pass effect” of oral estrogen on the liver, an activity that could be antagonized by progestin or not observed if estrogen is given by another route. Others claim the cardiac benefit stems from a direct effect of estrogen on the endothelium of blood vessels.⁵ Zegura et al provide interesting data supporting both theories.

Both oral and transdermal estrogen caused a rise in HDL cholesterol, but the increase in women taking the oral hormone (15.8%) was double that of women given estrogen transdermally (8.9%). LDL cholesterol and lipoprotein (a) levels declined significantly (13.4% and 18.1%, respectively), but only with oral estrogen. Blood-flow–mediated dilation rose significantly in both groups, jumping from 6% to 13.2% in women given oral estrogen, versus 7% to 14.9% with transdermal use.

Study limitations. The authors were unable to ensure equivalency of the estradiol concentrations within subjects’ systemic circulations. Even if they had measured estradiol concentrations, the expected variation following oral administration would have made interpretation nearly impossible. Thus, it remains unclear whether comparable changes in lipid parameters would be observed by lowering the oral estrogen dose or raising the transdermal dose. It is also unclear whether lower estrogen doses given orally or transdermally would result in improved blood-flow changes.

Since study subjects became menopausal due to surgery, they were relatively young (mean age: 49.2 years, oral group; 47.8 years, transdermal group). Thus, this study does not reveal whether older women who undergo menopause “naturally” and who might have subclinical atherosclerotic heart disease would respond similarly. Finally, the impact of progestin exposure was not addressed.

While Zegura et al provide important data, their finding of equivalency in improved endothelial function for both oral and transdermal estrogen pertains only to younger menopausal women using estrogen for a relatively short time. It remains unknown whether, after years of therapy, the more beneficial lipid alterations induced by oral estrogen would lead to greater improvement in endothelial function than that observed after transdermal estrogen for a similar time.

Bottom Line

Given orally or transdermally, hormone therapy is FDA-approved for the treatment of menopausal symptoms, but not prevention or treatment of cardiovascular disease. The decision to give estrogen orally or transdermally should be based on patient preference or the desire to diminish side effects such as skin irritation or headaches.

Zegura B, Keber I, Sebestjen M, Borko E. Orally and transdermally replaced estradiol improves endothelial function equally in middleaged women after surgical menopause. Am J Obstet Gynecol. 2003; 188:1291–1296.

Objective

To explore whether estradiol’s vascular effects depend on route of administration.

Results

Both oral and transdermal estradiol led to improved endothelial function over 28 weeks in surgically menopausal women.

Methods

Six weeks after surgically induced menopause, 43 healthy women were randomized to 28 weeks of oral or transdermal estradiol. Endothelium-dependent and endothelium-independent dilation were calculated by measuring the diameter of the brachial artery at rest using high-resolution ultrasound after reactive hyperemia, and again after sublingual glyceryl trinitrate.

Outcome

Endothelium-dependent dilation increased after both oral (from 6%±3.9% to 13.2%±4.4%, P.0001 and transdermal estradiol to>P.0001 improvements were independent of changes in blood lipids and lipoproteins. endothelium-independent dilation did not change significantly either group.>

Expert Commentary

Both the estrogen-progestin and estrogen-only arms of the Women’s Health Initiative found no reduction in heart-disease risk among participants.^1,2 This differed from findings of many observational studies, such as the Nurses’ Health Study, which reported a 40% to 50% reduction in heart-disease risk in menopausal women taking estrogen for vasomotor symptoms.³ Age and progestin use have been suggested as possible explanations for the differing results.

No clear cause of reduced risk of heart disease. Some experts argue that the cardioprotective effect of menopausal hormone therapy is mediated by alterations in the lipid profile, with an elevation in high-density lipoprotein (HDL) cholesterol and a decline in lowdensity lipoprotein (LDL) cholesterol.⁴ This presumably results from the “first-pass effect” of oral estrogen on the liver, an activity that could be antagonized by progestin or not observed if estrogen is given by another route. Others claim the cardiac benefit stems from a direct effect of estrogen on the endothelium of blood vessels.⁵ Zegura et al provide interesting data supporting both theories.

Both oral and transdermal estrogen caused a rise in HDL cholesterol, but the increase in women taking the oral hormone (15.8%) was double that of women given estrogen transdermally (8.9%). LDL cholesterol and lipoprotein (a) levels declined significantly (13.4% and 18.1%, respectively), but only with oral estrogen. Blood-flow–mediated dilation rose significantly in both groups, jumping from 6% to 13.2% in women given oral estrogen, versus 7% to 14.9% with transdermal use.

Study limitations. The authors were unable to ensure equivalency of the estradiol concentrations within subjects’ systemic circulations. Even if they had measured estradiol concentrations, the expected variation following oral administration would have made interpretation nearly impossible. Thus, it remains unclear whether comparable changes in lipid parameters would be observed by lowering the oral estrogen dose or raising the transdermal dose. It is also unclear whether lower estrogen doses given orally or transdermally would result in improved blood-flow changes.

Since study subjects became menopausal due to surgery, they were relatively young (mean age: 49.2 years, oral group; 47.8 years, transdermal group). Thus, this study does not reveal whether older women who undergo menopause “naturally” and who might have subclinical atherosclerotic heart disease would respond similarly. Finally, the impact of progestin exposure was not addressed.

While Zegura et al provide important data, their finding of equivalency in improved endothelial function for both oral and transdermal estrogen pertains only to younger menopausal women using estrogen for a relatively short time. It remains unknown whether, after years of therapy, the more beneficial lipid alterations induced by oral estrogen would lead to greater improvement in endothelial function than that observed after transdermal estrogen for a similar time.

Bottom Line

Given orally or transdermally, hormone therapy is FDA-approved for the treatment of menopausal symptoms, but not prevention or treatment of cardiovascular disease. The decision to give estrogen orally or transdermally should be based on patient preference or the desire to diminish side effects such as skin irritation or headaches.

Objective

To evaluate bacterial vaginosis (BV) as a risk factor for preterm delivery.

Results

In early pregnancy, BV more than doubled the risk for preterm delivery.

Methods

This meta-analysis included 18 English-language reports of prospective or controlled trials involving 20,232 women. Gestational ages were less than 37 weeks; all women had intact amniotic membranes and had been screened for BV.

The outcomes were preterm delivery, spontaneous abortion, maternal or neonatal infection, and perinatal death.

Outcome

BV greatly increased risk of preterm delivery (odds ratio [OR] 2.19; 95% confidence interval [CI], 1.54-3.12). Higher risks were calculated for women at less than 16 weeks’ gestation (OR 7.55; 95% CI, 1.8-31.65) or less than 20 weeks (OR 4.2; 95% CI, 2.11-8.39).

BV also significantly increased the risk of spontaneous abortion (OR 9.91; 95% CI, 1.99-49.34) and maternal infection (OR 2.53; 95% CI, 1.26-5.08). No significant results were found for neonatal infection or perinatal death.

Expert commentary

Preterm birth remains one of the most important problems in obstetrics. It occurs in 7% to 10% of all pregnancies in the United States and accounts for the majority of neonatal deaths and morbidity. The economic burden also is impressive: approximately $6 billion annually in additional costs for low birth weight.

Spontaneous preterm birth occurs between 24 and 37 weeks’ gestation after spontaneous labor or spontaneous rupture of membranes. It is likely multifactorial, with infection implicated as a major factor. Since the late 1970s, accumulating evidence has implicated intrauterine infection as a cause of preterm labor and preterm rupture of membranes.¹

The link between BV and preterm birth. Numerous studies have demonstrated a strong and consistent association between BV and preterm birth. While some evidence indicates that BV treatment may reduce the preterm birth rate in women at high risk,^2,3 BV-specific antibiotic therapy has not reduced the preterm birth rate in women with BV in the general population (see “Does metronidazole eliminate BV in asymptomatic gravidas?” page 44).⁴

This suggests that a subgroup of women with BV are at risk for adverse outcomes. Critical research goals are to identify the optimal treatment strategy and the subgroup in which to apply that strategy. Whether optimal treatment will consist of antimicrobial agents, immunomodulatory agents, or both, remains to be seen.

Strengths of the study. This comprehensive survey of research published from 1966 to 2003 summarized clinical trial data from an impressive total of 20,232 women. The investigators used rigorous criteria for including published data in their analyses and appropriately assessed the heterogeneity of various study designs and populations.

This study not only identifies an association between BV and preterm birth overall, but also estimates the association based on the gestational age at which BV is diagnosed, and highlights the strong association between BV and adverse pregnancy outcomes at early gestational ages—specifically, at less than 16 weeks and less than 20 weeks.

Another great strength is documentation of the relationship between BV and other adverse pregnancy outcomes, such as spontaneous abortion and maternal infection.

Weaknesses. The fact that unpublished data were not included may introduce publication bias into the design and slant findings in favor of an association with BV. The heterogeneity among included trials did not obscure the statistically significant association between BV and preterm birth, as the investigators noted; however, that heterogeneity makes any estimate of the magnitude of the association between BV and preterm birth quite crude.

Bottom line

This important meta-analysis summarizes a 20-year accumulation of literature supporting an association between BV and preterm birth. These data—along with a plethora of evidence supporting infection as an important cause of preterm delivery—underscore the importance of future studies exploring whether identifying high-risk women with BV and treating them early in pregnancy with a long course of oral therapy will play a role in preventing prematurity. Most important, however, are future trials designed to explore the mechanism by which women with BV are at risk of upper genital tract infection.

Objective

To evaluate bacterial vaginosis (BV) as a risk factor for preterm delivery.

Results

In early pregnancy, BV more than doubled the risk for preterm delivery.

Methods

This meta-analysis included 18 English-language reports of prospective or controlled trials involving 20,232 women. Gestational ages were less than 37 weeks; all women had intact amniotic membranes and had been screened for BV.

The outcomes were preterm delivery, spontaneous abortion, maternal or neonatal infection, and perinatal death.

Outcome

BV greatly increased risk of preterm delivery (odds ratio [OR] 2.19; 95% confidence interval [CI], 1.54-3.12). Higher risks were calculated for women at less than 16 weeks’ gestation (OR 7.55; 95% CI, 1.8-31.65) or less than 20 weeks (OR 4.2; 95% CI, 2.11-8.39).

BV also significantly increased the risk of spontaneous abortion (OR 9.91; 95% CI, 1.99-49.34) and maternal infection (OR 2.53; 95% CI, 1.26-5.08). No significant results were found for neonatal infection or perinatal death.

Expert commentary

Preterm birth remains one of the most important problems in obstetrics. It occurs in 7% to 10% of all pregnancies in the United States and accounts for the majority of neonatal deaths and morbidity. The economic burden also is impressive: approximately $6 billion annually in additional costs for low birth weight.

Spontaneous preterm birth occurs between 24 and 37 weeks’ gestation after spontaneous labor or spontaneous rupture of membranes. It is likely multifactorial, with infection implicated as a major factor. Since the late 1970s, accumulating evidence has implicated intrauterine infection as a cause of preterm labor and preterm rupture of membranes.¹

The link between BV and preterm birth. Numerous studies have demonstrated a strong and consistent association between BV and preterm birth. While some evidence indicates that BV treatment may reduce the preterm birth rate in women at high risk,^2,3 BV-specific antibiotic therapy has not reduced the preterm birth rate in women with BV in the general population (see “Does metronidazole eliminate BV in asymptomatic gravidas?” page 44).⁴

This suggests that a subgroup of women with BV are at risk for adverse outcomes. Critical research goals are to identify the optimal treatment strategy and the subgroup in which to apply that strategy. Whether optimal treatment will consist of antimicrobial agents, immunomodulatory agents, or both, remains to be seen.

Strengths of the study. This comprehensive survey of research published from 1966 to 2003 summarized clinical trial data from an impressive total of 20,232 women. The investigators used rigorous criteria for including published data in their analyses and appropriately assessed the heterogeneity of various study designs and populations.

This study not only identifies an association between BV and preterm birth overall, but also estimates the association based on the gestational age at which BV is diagnosed, and highlights the strong association between BV and adverse pregnancy outcomes at early gestational ages—specifically, at less than 16 weeks and less than 20 weeks.

Another great strength is documentation of the relationship between BV and other adverse pregnancy outcomes, such as spontaneous abortion and maternal infection.

Weaknesses. The fact that unpublished data were not included may introduce publication bias into the design and slant findings in favor of an association with BV. The heterogeneity among included trials did not obscure the statistically significant association between BV and preterm birth, as the investigators noted; however, that heterogeneity makes any estimate of the magnitude of the association between BV and preterm birth quite crude.

Bottom line

This important meta-analysis summarizes a 20-year accumulation of literature supporting an association between BV and preterm birth. These data—along with a plethora of evidence supporting infection as an important cause of preterm delivery—underscore the importance of future studies exploring whether identifying high-risk women with BV and treating them early in pregnancy with a long course of oral therapy will play a role in preventing prematurity. Most important, however, are future trials designed to explore the mechanism by which women with BV are at risk of upper genital tract infection.

Objective

To evaluate bacterial vaginosis (BV) as a risk factor for preterm delivery.

Results

In early pregnancy, BV more than doubled the risk for preterm delivery.

Methods

This meta-analysis included 18 English-language reports of prospective or controlled trials involving 20,232 women. Gestational ages were less than 37 weeks; all women had intact amniotic membranes and had been screened for BV.

The outcomes were preterm delivery, spontaneous abortion, maternal or neonatal infection, and perinatal death.

Outcome

BV greatly increased risk of preterm delivery (odds ratio [OR] 2.19; 95% confidence interval [CI], 1.54-3.12). Higher risks were calculated for women at less than 16 weeks’ gestation (OR 7.55; 95% CI, 1.8-31.65) or less than 20 weeks (OR 4.2; 95% CI, 2.11-8.39).

BV also significantly increased the risk of spontaneous abortion (OR 9.91; 95% CI, 1.99-49.34) and maternal infection (OR 2.53; 95% CI, 1.26-5.08). No significant results were found for neonatal infection or perinatal death.

Expert commentary

Preterm birth remains one of the most important problems in obstetrics. It occurs in 7% to 10% of all pregnancies in the United States and accounts for the majority of neonatal deaths and morbidity. The economic burden also is impressive: approximately $6 billion annually in additional costs for low birth weight.

Spontaneous preterm birth occurs between 24 and 37 weeks’ gestation after spontaneous labor or spontaneous rupture of membranes. It is likely multifactorial, with infection implicated as a major factor. Since the late 1970s, accumulating evidence has implicated intrauterine infection as a cause of preterm labor and preterm rupture of membranes.¹

The link between BV and preterm birth. Numerous studies have demonstrated a strong and consistent association between BV and preterm birth. While some evidence indicates that BV treatment may reduce the preterm birth rate in women at high risk,^2,3 BV-specific antibiotic therapy has not reduced the preterm birth rate in women with BV in the general population (see “Does metronidazole eliminate BV in asymptomatic gravidas?” page 44).⁴

This suggests that a subgroup of women with BV are at risk for adverse outcomes. Critical research goals are to identify the optimal treatment strategy and the subgroup in which to apply that strategy. Whether optimal treatment will consist of antimicrobial agents, immunomodulatory agents, or both, remains to be seen.

Strengths of the study. This comprehensive survey of research published from 1966 to 2003 summarized clinical trial data from an impressive total of 20,232 women. The investigators used rigorous criteria for including published data in their analyses and appropriately assessed the heterogeneity of various study designs and populations.

This study not only identifies an association between BV and preterm birth overall, but also estimates the association based on the gestational age at which BV is diagnosed, and highlights the strong association between BV and adverse pregnancy outcomes at early gestational ages—specifically, at less than 16 weeks and less than 20 weeks.

Another great strength is documentation of the relationship between BV and other adverse pregnancy outcomes, such as spontaneous abortion and maternal infection.

Weaknesses. The fact that unpublished data were not included may introduce publication bias into the design and slant findings in favor of an association with BV. The heterogeneity among included trials did not obscure the statistically significant association between BV and preterm birth, as the investigators noted; however, that heterogeneity makes any estimate of the magnitude of the association between BV and preterm birth quite crude.

Bottom line

This important meta-analysis summarizes a 20-year accumulation of literature supporting an association between BV and preterm birth. These data—along with a plethora of evidence supporting infection as an important cause of preterm delivery—underscore the importance of future studies exploring whether identifying high-risk women with BV and treating them early in pregnancy with a long course of oral therapy will play a role in preventing prematurity. Most important, however, are future trials designed to explore the mechanism by which women with BV are at risk of upper genital tract infection.

Objective

To compare blood loss and procedure time for vaginal hysterectomy using electrosurgical bipolar vessel sealing versus sutures.

Results

Compared with sutures, vessel-sealing technology resulted in a 27% reduction in operative time and a 47% reduction in blood loss.

Methods

Sixty women scheduled to undergo vaginal hysterectomy in a single surgical practice were randomized to electrosurgical bipolar vessel sealing or sutures for hemostasis.

Procedure time was measured from the initial mucosal injection to closure of the vaginal cuff with satisfactory hemostasis.

Blood loss was estimated by the anesthesia service.

The study was sponsored by Valleylab (Boulder, Colo), the manufacturer of the electrosurgical bipolar vessel sealer (LigaSure) used in the trial; both investigators had financial ties to the company.

Outcome

Mean procedure time was 39.1 minutes (range 22–93) for electrosurgical bipolar vessel sealing and 53.6 minutes (range 37–160) for sutures.

Mean estimated blood loss was 68.9 mL (range 20–200) for electrosurgical bipolar vessel sealing and 126.7 mL (range 25–600) for sutures.

Complication rates and length of stay did not differ by technique.

Expert Commentary

It took many years for the concept of bipolar desiccation for large vessel hemostasis to be accepted after I introduced the idea at the 1985 meeting of the American Association of Gynecologic Laparoscopists. The Kleppinger bipolar forceps I used (Richard Wolf, Rosemont, Ill) were developed for laparoscopic tubal sterilization. Bipolar desiccation for oophorectomy was considered too dangerous to be published in 1985-86; only a brief abstract of this presentation is in the medical literature.¹

Since the 1988 introduction of laparoscopic hysterectomy using bipolar vessel sealing, bipolar desiccation has prevailed and has become the standard over later techniques, such as staples and sutures.^2-4

High percentage of outpatient procedures. This study is remarkable not only because electrosurgical bipolar vessel sealing achieved a 27% reduction in operative time and a 47% reduction in blood loss, but also because 78% of the cases were outpatient.

I am pleased to see that bipolar techniques for vaginal hysterectomy are being so rapidly accepted (over 100 cases have been done at the Mayo Clinic, Scottsdale, with minimal problems). This acceptance—coupled with the use of laparoscopic hysterectomy—should make abdominal hysterectomy a rare event in the future.

A safe, easy-to-use technology. The electrosurgical vessel sealer is powered by bipolar energy and compression from its handset. The idea of a “cool” cycle after heated sealing is similar to the concept behind the Wolf or ERBE (Atlanta, Ga) bipolar ammeter, which audibly signals the surgeon when the tissue is desiccated to prevent further passage of energy that would increase char around the treated area.

This new bipolar technology (which is actually old technology for the laparoscopic surgeon) will prove valuable in patients with vaginal access so limited that suture ligation of the uterine-vessel and broad-ligament pedicles is difficult. It is much easier to clamp and desiccate these pedicles. Even so, this technique requires a suture to be placed around the uterosacral-ligament pedicles, so that they may be used for vault support.

Adequate access is crucial. In vaginal hysterectomy, access is of utmost importance, since the surgeon must be able to reach the uterosacral ligaments in order to suture-ligate them and, later, close the pubocervical ring. Vaginal surgery may not be possible if access to the uterosacral ligaments is limited; when this is the case, laparoscopic hysterectomy is usually the preferred route.

Bottom line

Electrosurgical bipolar vessel sealing is an effective alternative to suture in vaginal hysterectomy. I enthusiastically recommend it and look forward to doing my next hysterectomy in the manner described in this paper, provided there is adequate vaginal access.

Objective

To compare blood loss and procedure time for vaginal hysterectomy using electrosurgical bipolar vessel sealing versus sutures.

Results

Compared with sutures, vessel-sealing technology resulted in a 27% reduction in operative time and a 47% reduction in blood loss.

Methods

Sixty women scheduled to undergo vaginal hysterectomy in a single surgical practice were randomized to electrosurgical bipolar vessel sealing or sutures for hemostasis.

Procedure time was measured from the initial mucosal injection to closure of the vaginal cuff with satisfactory hemostasis.

Blood loss was estimated by the anesthesia service.

The study was sponsored by Valleylab (Boulder, Colo), the manufacturer of the electrosurgical bipolar vessel sealer (LigaSure) used in the trial; both investigators had financial ties to the company.

Outcome

Mean procedure time was 39.1 minutes (range 22–93) for electrosurgical bipolar vessel sealing and 53.6 minutes (range 37–160) for sutures.

Mean estimated blood loss was 68.9 mL (range 20–200) for electrosurgical bipolar vessel sealing and 126.7 mL (range 25–600) for sutures.

Complication rates and length of stay did not differ by technique.

Expert Commentary

It took many years for the concept of bipolar desiccation for large vessel hemostasis to be accepted after I introduced the idea at the 1985 meeting of the American Association of Gynecologic Laparoscopists. The Kleppinger bipolar forceps I used (Richard Wolf, Rosemont, Ill) were developed for laparoscopic tubal sterilization. Bipolar desiccation for oophorectomy was considered too dangerous to be published in 1985-86; only a brief abstract of this presentation is in the medical literature.¹

Since the 1988 introduction of laparoscopic hysterectomy using bipolar vessel sealing, bipolar desiccation has prevailed and has become the standard over later techniques, such as staples and sutures.^2-4

High percentage of outpatient procedures. This study is remarkable not only because electrosurgical bipolar vessel sealing achieved a 27% reduction in operative time and a 47% reduction in blood loss, but also because 78% of the cases were outpatient.

I am pleased to see that bipolar techniques for vaginal hysterectomy are being so rapidly accepted (over 100 cases have been done at the Mayo Clinic, Scottsdale, with minimal problems). This acceptance—coupled with the use of laparoscopic hysterectomy—should make abdominal hysterectomy a rare event in the future.

A safe, easy-to-use technology. The electrosurgical vessel sealer is powered by bipolar energy and compression from its handset. The idea of a “cool” cycle after heated sealing is similar to the concept behind the Wolf or ERBE (Atlanta, Ga) bipolar ammeter, which audibly signals the surgeon when the tissue is desiccated to prevent further passage of energy that would increase char around the treated area.

This new bipolar technology (which is actually old technology for the laparoscopic surgeon) will prove valuable in patients with vaginal access so limited that suture ligation of the uterine-vessel and broad-ligament pedicles is difficult. It is much easier to clamp and desiccate these pedicles. Even so, this technique requires a suture to be placed around the uterosacral-ligament pedicles, so that they may be used for vault support.

Adequate access is crucial. In vaginal hysterectomy, access is of utmost importance, since the surgeon must be able to reach the uterosacral ligaments in order to suture-ligate them and, later, close the pubocervical ring. Vaginal surgery may not be possible if access to the uterosacral ligaments is limited; when this is the case, laparoscopic hysterectomy is usually the preferred route.

Bottom line

Electrosurgical bipolar vessel sealing is an effective alternative to suture in vaginal hysterectomy. I enthusiastically recommend it and look forward to doing my next hysterectomy in the manner described in this paper, provided there is adequate vaginal access.

Objective

To compare blood loss and procedure time for vaginal hysterectomy using electrosurgical bipolar vessel sealing versus sutures.

Results

Compared with sutures, vessel-sealing technology resulted in a 27% reduction in operative time and a 47% reduction in blood loss.

Methods

Sixty women scheduled to undergo vaginal hysterectomy in a single surgical practice were randomized to electrosurgical bipolar vessel sealing or sutures for hemostasis.

Procedure time was measured from the initial mucosal injection to closure of the vaginal cuff with satisfactory hemostasis.

Blood loss was estimated by the anesthesia service.

The study was sponsored by Valleylab (Boulder, Colo), the manufacturer of the electrosurgical bipolar vessel sealer (LigaSure) used in the trial; both investigators had financial ties to the company.

Outcome

Mean procedure time was 39.1 minutes (range 22–93) for electrosurgical bipolar vessel sealing and 53.6 minutes (range 37–160) for sutures.

Mean estimated blood loss was 68.9 mL (range 20–200) for electrosurgical bipolar vessel sealing and 126.7 mL (range 25–600) for sutures.

Complication rates and length of stay did not differ by technique.

Expert Commentary

It took many years for the concept of bipolar desiccation for large vessel hemostasis to be accepted after I introduced the idea at the 1985 meeting of the American Association of Gynecologic Laparoscopists. The Kleppinger bipolar forceps I used (Richard Wolf, Rosemont, Ill) were developed for laparoscopic tubal sterilization. Bipolar desiccation for oophorectomy was considered too dangerous to be published in 1985-86; only a brief abstract of this presentation is in the medical literature.¹

Since the 1988 introduction of laparoscopic hysterectomy using bipolar vessel sealing, bipolar desiccation has prevailed and has become the standard over later techniques, such as staples and sutures.^2-4

High percentage of outpatient procedures. This study is remarkable not only because electrosurgical bipolar vessel sealing achieved a 27% reduction in operative time and a 47% reduction in blood loss, but also because 78% of the cases were outpatient.

I am pleased to see that bipolar techniques for vaginal hysterectomy are being so rapidly accepted (over 100 cases have been done at the Mayo Clinic, Scottsdale, with minimal problems). This acceptance—coupled with the use of laparoscopic hysterectomy—should make abdominal hysterectomy a rare event in the future.

A safe, easy-to-use technology. The electrosurgical vessel sealer is powered by bipolar energy and compression from its handset. The idea of a “cool” cycle after heated sealing is similar to the concept behind the Wolf or ERBE (Atlanta, Ga) bipolar ammeter, which audibly signals the surgeon when the tissue is desiccated to prevent further passage of energy that would increase char around the treated area.

This new bipolar technology (which is actually old technology for the laparoscopic surgeon) will prove valuable in patients with vaginal access so limited that suture ligation of the uterine-vessel and broad-ligament pedicles is difficult. It is much easier to clamp and desiccate these pedicles. Even so, this technique requires a suture to be placed around the uterosacral-ligament pedicles, so that they may be used for vault support.

Adequate access is crucial. In vaginal hysterectomy, access is of utmost importance, since the surgeon must be able to reach the uterosacral ligaments in order to suture-ligate them and, later, close the pubocervical ring. Vaginal surgery may not be possible if access to the uterosacral ligaments is limited; when this is the case, laparoscopic hysterectomy is usually the preferred route.

Bottom line

Electrosurgical bipolar vessel sealing is an effective alternative to suture in vaginal hysterectomy. I enthusiastically recommend it and look forward to doing my next hysterectomy in the manner described in this paper, provided there is adequate vaginal access.

Objective

To determine whether extended-spectrum antibiotic prophylaxis that targets Ureaplasma urealyticum reduces postcesarean endometritis.

Results

Following cesarean, the frequency of endometritis, wound infections, and a combination of the 2 was significantly lower among treated women than women given placebo.

Methods

The 597 women enrolled in this randomized, double-blind trial all were given cefotetan prophylaxis after cord clamping at cesarean delivery. Subjects then were randomized to receive doxycycline plus azithromycin (n = 301) or placebo (n = 296). Both groups were monitored for endometritis, defined as a fever of 100.4° F or higher with 1 or more supporting clinical signs (maternal tachycardia, foul-smelling or purulent lochia, tender uterus, and maternal leukocytosis) or as a physician diagnosis of endometritis and no nonpelvic source of fever. Among study participants, 56% were black, with an age of 25.5±6.2 years, and 43% were nulliparous. Groups were similar for race, parity, maternal age, and most risk factors for postcesarean endometritis.

Outcome

Postcesarean endometritis occurred in 16.9% of treated women versus 24.7% of controls (P = .02), and wound infections affected 0.8% of treated women versus 3.6% of controls (P = .03).

Although the 2 groups were dissimilar for maternal leukocytosis (24.9% of treated women versus 12.5% of controls, P = .042) and classic uterine incision (7.6% versus 12.5%, P = .048), adjusting for these factors did not alter the risk ratio for postcesarean endometritis in the active versus placebotreated groups (relative risk 0.65, 95% confidence interval 0.43-0.98).

Length of stay was longer in the placebo group (104±56 versus 95±32 hours, P = .016) and among women with endometritis (146±52 versus 127±46 hours, P = .047).

Expert Commentary

This study tried to demonstrate that U. urealyticum is a significant pathogen and the etiologic agent for postpartum endometritis. However, the fact that U. urealyticum is found in the genital tract of approximately 70% to 90% of women does not support the thesis that it plays a major role in the microbial pathogenesis of postpartum endometritis.

Just because a microorganism is present in the lower genital tract does not mean that, in a state of infection, it is the etiologic agent. For example, many women harbor Enterococcus feacalis or Staphylococcus epidermidis in the genital tract; these often are isolated along with other bacteria from the site of infection. Yet the infection often is treated with antibiotics that offer no activity against these bacteria.

Lack of bacteriology limits relevance. Upon first analysis, this study appears to be sound, since it is both randomized and blinded. However, a major flaw weakens the conclusions significantly: lack of bacteriology.

The researchers neglected to obtain specimens for culture of bacteria from the uterus of each infected patient. Instead, they relied on statistical analysis, comparing the endpoint of infection versus no infection to extrapolate as to the cause. They failed to realize that the antibiotics used for prophylaxis—specifically doxycycline and azithromycin—also provide activity against Gram-positive and Gram-negative bacteria that make up the endogenous bacteriology of the vagina.

If endometrial specimens had been obtained from each infected patient, they would have provided a database on the frequency of involvement of the bacteria causing endometritis.

The authors do not state why they chose to use both doxycycline and azithromycin. In regard to the activity of these antibiotics against U. urealyticum there is probably not much difference as to efficacy.

Bottom Line

The use of combinations of antibiotics for surgical prophylaxis is not advisable because it can lead to the selection of resistant strains that will remain in the patient’s lower genital tract. Therefore, I would not use a cephalosporin plus doxycycline and/or azithromycin as a regimen for surgical prophylaxis. Before such a combination can be recommended, further study is necessary that includes microbiology to establish which bacteria are responsible for postpartum endometritis. The microbiological studies must be quantitative—not qualitative—before conclusions can be drawn and clinical recommendations made.

Objective

To determine whether extended-spectrum antibiotic prophylaxis that targets Ureaplasma urealyticum reduces postcesarean endometritis.

Results

Following cesarean, the frequency of endometritis, wound infections, and a combination of the 2 was significantly lower among treated women than women given placebo.

Methods

The 597 women enrolled in this randomized, double-blind trial all were given cefotetan prophylaxis after cord clamping at cesarean delivery. Subjects then were randomized to receive doxycycline plus azithromycin (n = 301) or placebo (n = 296). Both groups were monitored for endometritis, defined as a fever of 100.4° F or higher with 1 or more supporting clinical signs (maternal tachycardia, foul-smelling or purulent lochia, tender uterus, and maternal leukocytosis) or as a physician diagnosis of endometritis and no nonpelvic source of fever. Among study participants, 56% were black, with an age of 25.5±6.2 years, and 43% were nulliparous. Groups were similar for race, parity, maternal age, and most risk factors for postcesarean endometritis.

Outcome

Postcesarean endometritis occurred in 16.9% of treated women versus 24.7% of controls (P = .02), and wound infections affected 0.8% of treated women versus 3.6% of controls (P = .03).

Although the 2 groups were dissimilar for maternal leukocytosis (24.9% of treated women versus 12.5% of controls, P = .042) and classic uterine incision (7.6% versus 12.5%, P = .048), adjusting for these factors did not alter the risk ratio for postcesarean endometritis in the active versus placebotreated groups (relative risk 0.65, 95% confidence interval 0.43-0.98).

Length of stay was longer in the placebo group (104±56 versus 95±32 hours, P = .016) and among women with endometritis (146±52 versus 127±46 hours, P = .047).

Expert Commentary

This study tried to demonstrate that U. urealyticum is a significant pathogen and the etiologic agent for postpartum endometritis. However, the fact that U. urealyticum is found in the genital tract of approximately 70% to 90% of women does not support the thesis that it plays a major role in the microbial pathogenesis of postpartum endometritis.

Just because a microorganism is present in the lower genital tract does not mean that, in a state of infection, it is the etiologic agent. For example, many women harbor Enterococcus feacalis or Staphylococcus epidermidis in the genital tract; these often are isolated along with other bacteria from the site of infection. Yet the infection often is treated with antibiotics that offer no activity against these bacteria.

Lack of bacteriology limits relevance. Upon first analysis, this study appears to be sound, since it is both randomized and blinded. However, a major flaw weakens the conclusions significantly: lack of bacteriology.

The researchers neglected to obtain specimens for culture of bacteria from the uterus of each infected patient. Instead, they relied on statistical analysis, comparing the endpoint of infection versus no infection to extrapolate as to the cause. They failed to realize that the antibiotics used for prophylaxis—specifically doxycycline and azithromycin—also provide activity against Gram-positive and Gram-negative bacteria that make up the endogenous bacteriology of the vagina.

If endometrial specimens had been obtained from each infected patient, they would have provided a database on the frequency of involvement of the bacteria causing endometritis.

The authors do not state why they chose to use both doxycycline and azithromycin. In regard to the activity of these antibiotics against U. urealyticum there is probably not much difference as to efficacy.

Bottom Line

The use of combinations of antibiotics for surgical prophylaxis is not advisable because it can lead to the selection of resistant strains that will remain in the patient’s lower genital tract. Therefore, I would not use a cephalosporin plus doxycycline and/or azithromycin as a regimen for surgical prophylaxis. Before such a combination can be recommended, further study is necessary that includes microbiology to establish which bacteria are responsible for postpartum endometritis. The microbiological studies must be quantitative—not qualitative—before conclusions can be drawn and clinical recommendations made.

Objective

To determine whether extended-spectrum antibiotic prophylaxis that targets Ureaplasma urealyticum reduces postcesarean endometritis.

Results

Following cesarean, the frequency of endometritis, wound infections, and a combination of the 2 was significantly lower among treated women than women given placebo.

Methods

The 597 women enrolled in this randomized, double-blind trial all were given cefotetan prophylaxis after cord clamping at cesarean delivery. Subjects then were randomized to receive doxycycline plus azithromycin (n = 301) or placebo (n = 296). Both groups were monitored for endometritis, defined as a fever of 100.4° F or higher with 1 or more supporting clinical signs (maternal tachycardia, foul-smelling or purulent lochia, tender uterus, and maternal leukocytosis) or as a physician diagnosis of endometritis and no nonpelvic source of fever. Among study participants, 56% were black, with an age of 25.5±6.2 years, and 43% were nulliparous. Groups were similar for race, parity, maternal age, and most risk factors for postcesarean endometritis.

Outcome

Postcesarean endometritis occurred in 16.9% of treated women versus 24.7% of controls (P = .02), and wound infections affected 0.8% of treated women versus 3.6% of controls (P = .03).

Although the 2 groups were dissimilar for maternal leukocytosis (24.9% of treated women versus 12.5% of controls, P = .042) and classic uterine incision (7.6% versus 12.5%, P = .048), adjusting for these factors did not alter the risk ratio for postcesarean endometritis in the active versus placebotreated groups (relative risk 0.65, 95% confidence interval 0.43-0.98).

Length of stay was longer in the placebo group (104±56 versus 95±32 hours, P = .016) and among women with endometritis (146±52 versus 127±46 hours, P = .047).

Expert Commentary

This study tried to demonstrate that U. urealyticum is a significant pathogen and the etiologic agent for postpartum endometritis. However, the fact that U. urealyticum is found in the genital tract of approximately 70% to 90% of women does not support the thesis that it plays a major role in the microbial pathogenesis of postpartum endometritis.

Just because a microorganism is present in the lower genital tract does not mean that, in a state of infection, it is the etiologic agent. For example, many women harbor Enterococcus feacalis or Staphylococcus epidermidis in the genital tract; these often are isolated along with other bacteria from the site of infection. Yet the infection often is treated with antibiotics that offer no activity against these bacteria.

Lack of bacteriology limits relevance. Upon first analysis, this study appears to be sound, since it is both randomized and blinded. However, a major flaw weakens the conclusions significantly: lack of bacteriology.

The researchers neglected to obtain specimens for culture of bacteria from the uterus of each infected patient. Instead, they relied on statistical analysis, comparing the endpoint of infection versus no infection to extrapolate as to the cause. They failed to realize that the antibiotics used for prophylaxis—specifically doxycycline and azithromycin—also provide activity against Gram-positive and Gram-negative bacteria that make up the endogenous bacteriology of the vagina.

If endometrial specimens had been obtained from each infected patient, they would have provided a database on the frequency of involvement of the bacteria causing endometritis.

The authors do not state why they chose to use both doxycycline and azithromycin. In regard to the activity of these antibiotics against U. urealyticum there is probably not much difference as to efficacy.

Bottom Line

The use of combinations of antibiotics for surgical prophylaxis is not advisable because it can lead to the selection of resistant strains that will remain in the patient’s lower genital tract. Therefore, I would not use a cephalosporin plus doxycycline and/or azithromycin as a regimen for surgical prophylaxis. Before such a combination can be recommended, further study is necessary that includes microbiology to establish which bacteria are responsible for postpartum endometritis. The microbiological studies must be quantitative—not qualitative—before conclusions can be drawn and clinical recommendations made.