User login
Q Does uterine artery embolization offer long-term relief?
Expert commentary
In the United States, more than 100,000 uterine artery embolizations have been performed over the past decade, but gynecologists have been appropriately cautious about embracing the procedure as an alternative to myomectomy and hysterectomy. The reasons for this caution are varied, but include a lack of data on long-term efficacy, though many shortterm studies have shown favorable outcomes.
That brings us to the study by Spies and colleagues, who convincingly and effectively demonstrated that 73% of 200 patients were satisfied with uterine artery embolization after 5 years. This compares favorably with myomectomy and other therapeutic options as an alternative to hysterectomy. However, the likelihood of symptom recurrence was 25%, with 25 hysterectomies (13.7%), 8 myomectomies (4.4%), and 3 repeat embolizations (1.6%) performed in women with recurrent symptoms.
Why do symptoms recur?
Large fibroids, collateral vessels. Women whose symptoms returned were likely to have baseline leiomyoma volume larger than the median (152 mL) and/or only modest leiomyoma volume reduction (
The specific agents and particle sizes used are among other factors that may contribute to symptom recurrence.
Skewed data? The high rate of postprocedure amenorrhea (23%) in the women undergoing embolization may skew the comparison with myomectomy, which is generally performed on younger women.
Limitations and unanswered questions
The Spies study did not sufficiently differentiate predominant symptoms. Perhaps future studies will elucidate success rates based on presenting symptoms, eg, menorrhagia versus bulk-related symptoms, as menorrhagia appears to respond better.
Long-term relief for most women
Clinicians can rest assured, meanwhile, that uterine artery embolization provides long-term symptom relief in most women with fibroids.
The author reports no financial relationships relevant to this article.
Expert commentary
In the United States, more than 100,000 uterine artery embolizations have been performed over the past decade, but gynecologists have been appropriately cautious about embracing the procedure as an alternative to myomectomy and hysterectomy. The reasons for this caution are varied, but include a lack of data on long-term efficacy, though many shortterm studies have shown favorable outcomes.
That brings us to the study by Spies and colleagues, who convincingly and effectively demonstrated that 73% of 200 patients were satisfied with uterine artery embolization after 5 years. This compares favorably with myomectomy and other therapeutic options as an alternative to hysterectomy. However, the likelihood of symptom recurrence was 25%, with 25 hysterectomies (13.7%), 8 myomectomies (4.4%), and 3 repeat embolizations (1.6%) performed in women with recurrent symptoms.
Why do symptoms recur?
Large fibroids, collateral vessels. Women whose symptoms returned were likely to have baseline leiomyoma volume larger than the median (152 mL) and/or only modest leiomyoma volume reduction (
The specific agents and particle sizes used are among other factors that may contribute to symptom recurrence.
Skewed data? The high rate of postprocedure amenorrhea (23%) in the women undergoing embolization may skew the comparison with myomectomy, which is generally performed on younger women.
Limitations and unanswered questions
The Spies study did not sufficiently differentiate predominant symptoms. Perhaps future studies will elucidate success rates based on presenting symptoms, eg, menorrhagia versus bulk-related symptoms, as menorrhagia appears to respond better.
Long-term relief for most women
Clinicians can rest assured, meanwhile, that uterine artery embolization provides long-term symptom relief in most women with fibroids.
The author reports no financial relationships relevant to this article.
Expert commentary
In the United States, more than 100,000 uterine artery embolizations have been performed over the past decade, but gynecologists have been appropriately cautious about embracing the procedure as an alternative to myomectomy and hysterectomy. The reasons for this caution are varied, but include a lack of data on long-term efficacy, though many shortterm studies have shown favorable outcomes.
That brings us to the study by Spies and colleagues, who convincingly and effectively demonstrated that 73% of 200 patients were satisfied with uterine artery embolization after 5 years. This compares favorably with myomectomy and other therapeutic options as an alternative to hysterectomy. However, the likelihood of symptom recurrence was 25%, with 25 hysterectomies (13.7%), 8 myomectomies (4.4%), and 3 repeat embolizations (1.6%) performed in women with recurrent symptoms.
Why do symptoms recur?
Large fibroids, collateral vessels. Women whose symptoms returned were likely to have baseline leiomyoma volume larger than the median (152 mL) and/or only modest leiomyoma volume reduction (
The specific agents and particle sizes used are among other factors that may contribute to symptom recurrence.
Skewed data? The high rate of postprocedure amenorrhea (23%) in the women undergoing embolization may skew the comparison with myomectomy, which is generally performed on younger women.
Limitations and unanswered questions
The Spies study did not sufficiently differentiate predominant symptoms. Perhaps future studies will elucidate success rates based on presenting symptoms, eg, menorrhagia versus bulk-related symptoms, as menorrhagia appears to respond better.
Long-term relief for most women
Clinicians can rest assured, meanwhile, that uterine artery embolization provides long-term symptom relief in most women with fibroids.
The author reports no financial relationships relevant to this article.
Q How likely is uterine rupture in VBAC attempts?
Expert commentary
The popularity of VBAC is waning in the United States, due mainly to concerns about complications after uterine rupture. The most recent national data show that the VBAC rate, which was 28.3% in 1996, declined to a mere 9.2% in 2004.1 In this context, Macones and colleagues undertook their multicenter case-control trial to determine the incidence of and risk factors for uterine rupture in a variety of hospital settings.
Study involved both community and tertiary-care hospitals
This is the largest trial to date to analyze VBAC success rates in university/tertiary care centers and community hospitals (with or without residency programs) to verify whether the typically quoted uterine rupture rate of less than 1% can be generalized to most settings.2 Macones et al used International Classification of Diseases, 9th revision (ICD-9) codes to perform this retrospective cohort review, identifying 13,706 patients who attempted VBAC in a 5-year period. Within this cohort, after reviewing all the charts, they performed a nested case-control comparison of uterine ruptures and nonruptures in a 5 to 1 ratio.
Women most likely to succeed had prior vaginal delivery
Recent studies have also sought to identify women less likely to experience uterine rupture with VBAC.3-5 In the Macones study, among historical risk factors for uterine rupture, only prior vaginal delivery affected rupture rates, decreasing the incidence by 60% (odds ratio [OR] 0.40; 95% confidence interval [CI] 0.20–0.81).
Hendler and Bujold6 also found that a history of vaginal delivery lowered the VBAC uterine rupture rate—to 0.5%, versus 1.4% in women without that history (P=.02). But they cautioned that this finding may be incidental. Other studies that explored effects of previous vaginal delivery focused on VBAC success rather than uterine rupture. The finding that a previous vaginal delivery increases the likelihood of VBAC success has remained consistent.6-10
How this study differs from others
Macones et al found that neither labor induction with prostaglandins, induction with oxytocin, nor augmentation with oxytocin affected rupture rates. However, sequential use of prostaglandins and oxytocin did increase these rates (OR 4.54; 95% CI 1.66–12.42; P=.003). These findings contrast those of a cohort study by Lydon-Rochelle et al,11 who used ICD-9 codes without chart review to estimate the incidence of uterine rupture in the Washington State Birth Events Database. Using elective repeat cesarean as their reference group, Lydon-Rochelle et al found a 15-fold increase in rupture rates when labor was induced with prostaglandins (relative risk 15.6; 95% CI 8.1–30.0).
Don’t switch to prostaglandins just yet. In response primarily to the Lydon-Rochelle study, the American College of Obstetricians and Gynecologists published a Committee Opinion12 in April 2002, discouraging the use of prostaglandins to induce labor in women attempting VBAC. In the current study by Macones and colleagues, the authors pointed out that prostaglandin E2 (and not misoprostol or prostaglandin E1) was the only type of prostaglandin used in all centers evaluated. Thus, although the study by Macones et al is well designed, it is retrospective and should not encourage the use of prostaglandins for VBAC until the question has been answered prospectively.
Encourage VBAC in women who have delivered vaginally
Overall, the study by Macones et al adds important information to the literature. The uterine rupture rate (2
In women who have delivered vaginally, VBAC should be encouraged. However, the use of prostaglandins to induce labor in these cases warrants further investigation.
The author reports no financial relationships relevant to this article.
1. National Center for Health Statistics. Preliminary births for 2004: infant and maternal health. Available at: http://www.cdc.gov/nchs/data/hestat/prelimbirths04health_tables.pdf. Accessed December 13, 2005.
2. American College of Obstetricians and Gynecologists. Vaginal Birth After Previous Cesarean Delivery. ACOG Practice Bulletin No. 54. Washington, DC: ACOG; 2004.
3. Chapman SJ, Owen J, Hauth JC. One- versus two-layer closure of a low transverse cesarean: the next pregnancy. Obstet Gynecol. 1997;89:16-18.
4. Durnwald C, Mercer B. Uterine rupture, perioperative and perinatal morbidity after single-layer and double-layer closure at cesarean delivery. Am J Obstet Gynecol. 2003;189:925-929.
5. Bujold E, Bujold C, Hamilton EF, et al. The impact of a single-layer or double-layer closure on uterine rupture. Am J Obstet Gynecol. 2002;186:1326-1330.
6. Hendler I, Bujold E. Effect of prior vaginal delivery or prior vaginal birth after cesarean delivery on obstetric outcomes in women undergoing trial of labor. Obstet Gynecol. 2004;104:273-277.
7. Gyamfi C, Juhasz G, Gyamfi P, Stone JL. Increased success of trial of labor after previous vaginal birth after cesarean. Obstet Gynecol. 2004;104:715-719.
8. Gonen R, Tamir A, Degani S, Ohel G. Variables associated with successful vaginal birth after one cesarean section: a proposed vaginal birth after cesarean section score. Am J Perinatol. 2004;21:447-453.
9. Bedoya C, Bartha JL, Rodriguez I, Fontan I, Bedoya JM, Sanchez-Ramos J. A trial of labor after cesarean section in patients with or without a prior vaginal delivery. Int J Obstet Gynaecol. 1992;39:285-289.
10. McMahon MJ, Luther ER, Bowes WA, Olshan AF. Comparison of a trial of labor with an elective second cesarean section. N Engl J Med. 1996;335:689-695.
11. Lydon-Rochelle M, Holt VL, Easterling TR, et al. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med. 2001;345:3-8.
12. ACOG Committee on Obstetric Practice. Induction of labor for vaginal birth after cesarean delivery. Committee Opinion No. 271. Obstet Gynecol. 2002;99:679-680.
Expert commentary
The popularity of VBAC is waning in the United States, due mainly to concerns about complications after uterine rupture. The most recent national data show that the VBAC rate, which was 28.3% in 1996, declined to a mere 9.2% in 2004.1 In this context, Macones and colleagues undertook their multicenter case-control trial to determine the incidence of and risk factors for uterine rupture in a variety of hospital settings.
Study involved both community and tertiary-care hospitals
This is the largest trial to date to analyze VBAC success rates in university/tertiary care centers and community hospitals (with or without residency programs) to verify whether the typically quoted uterine rupture rate of less than 1% can be generalized to most settings.2 Macones et al used International Classification of Diseases, 9th revision (ICD-9) codes to perform this retrospective cohort review, identifying 13,706 patients who attempted VBAC in a 5-year period. Within this cohort, after reviewing all the charts, they performed a nested case-control comparison of uterine ruptures and nonruptures in a 5 to 1 ratio.
Women most likely to succeed had prior vaginal delivery
Recent studies have also sought to identify women less likely to experience uterine rupture with VBAC.3-5 In the Macones study, among historical risk factors for uterine rupture, only prior vaginal delivery affected rupture rates, decreasing the incidence by 60% (odds ratio [OR] 0.40; 95% confidence interval [CI] 0.20–0.81).
Hendler and Bujold6 also found that a history of vaginal delivery lowered the VBAC uterine rupture rate—to 0.5%, versus 1.4% in women without that history (P=.02). But they cautioned that this finding may be incidental. Other studies that explored effects of previous vaginal delivery focused on VBAC success rather than uterine rupture. The finding that a previous vaginal delivery increases the likelihood of VBAC success has remained consistent.6-10
How this study differs from others
Macones et al found that neither labor induction with prostaglandins, induction with oxytocin, nor augmentation with oxytocin affected rupture rates. However, sequential use of prostaglandins and oxytocin did increase these rates (OR 4.54; 95% CI 1.66–12.42; P=.003). These findings contrast those of a cohort study by Lydon-Rochelle et al,11 who used ICD-9 codes without chart review to estimate the incidence of uterine rupture in the Washington State Birth Events Database. Using elective repeat cesarean as their reference group, Lydon-Rochelle et al found a 15-fold increase in rupture rates when labor was induced with prostaglandins (relative risk 15.6; 95% CI 8.1–30.0).
Don’t switch to prostaglandins just yet. In response primarily to the Lydon-Rochelle study, the American College of Obstetricians and Gynecologists published a Committee Opinion12 in April 2002, discouraging the use of prostaglandins to induce labor in women attempting VBAC. In the current study by Macones and colleagues, the authors pointed out that prostaglandin E2 (and not misoprostol or prostaglandin E1) was the only type of prostaglandin used in all centers evaluated. Thus, although the study by Macones et al is well designed, it is retrospective and should not encourage the use of prostaglandins for VBAC until the question has been answered prospectively.
Encourage VBAC in women who have delivered vaginally
Overall, the study by Macones et al adds important information to the literature. The uterine rupture rate (2
In women who have delivered vaginally, VBAC should be encouraged. However, the use of prostaglandins to induce labor in these cases warrants further investigation.
The author reports no financial relationships relevant to this article.
Expert commentary
The popularity of VBAC is waning in the United States, due mainly to concerns about complications after uterine rupture. The most recent national data show that the VBAC rate, which was 28.3% in 1996, declined to a mere 9.2% in 2004.1 In this context, Macones and colleagues undertook their multicenter case-control trial to determine the incidence of and risk factors for uterine rupture in a variety of hospital settings.
Study involved both community and tertiary-care hospitals
This is the largest trial to date to analyze VBAC success rates in university/tertiary care centers and community hospitals (with or without residency programs) to verify whether the typically quoted uterine rupture rate of less than 1% can be generalized to most settings.2 Macones et al used International Classification of Diseases, 9th revision (ICD-9) codes to perform this retrospective cohort review, identifying 13,706 patients who attempted VBAC in a 5-year period. Within this cohort, after reviewing all the charts, they performed a nested case-control comparison of uterine ruptures and nonruptures in a 5 to 1 ratio.
Women most likely to succeed had prior vaginal delivery
Recent studies have also sought to identify women less likely to experience uterine rupture with VBAC.3-5 In the Macones study, among historical risk factors for uterine rupture, only prior vaginal delivery affected rupture rates, decreasing the incidence by 60% (odds ratio [OR] 0.40; 95% confidence interval [CI] 0.20–0.81).
Hendler and Bujold6 also found that a history of vaginal delivery lowered the VBAC uterine rupture rate—to 0.5%, versus 1.4% in women without that history (P=.02). But they cautioned that this finding may be incidental. Other studies that explored effects of previous vaginal delivery focused on VBAC success rather than uterine rupture. The finding that a previous vaginal delivery increases the likelihood of VBAC success has remained consistent.6-10
How this study differs from others
Macones et al found that neither labor induction with prostaglandins, induction with oxytocin, nor augmentation with oxytocin affected rupture rates. However, sequential use of prostaglandins and oxytocin did increase these rates (OR 4.54; 95% CI 1.66–12.42; P=.003). These findings contrast those of a cohort study by Lydon-Rochelle et al,11 who used ICD-9 codes without chart review to estimate the incidence of uterine rupture in the Washington State Birth Events Database. Using elective repeat cesarean as their reference group, Lydon-Rochelle et al found a 15-fold increase in rupture rates when labor was induced with prostaglandins (relative risk 15.6; 95% CI 8.1–30.0).
Don’t switch to prostaglandins just yet. In response primarily to the Lydon-Rochelle study, the American College of Obstetricians and Gynecologists published a Committee Opinion12 in April 2002, discouraging the use of prostaglandins to induce labor in women attempting VBAC. In the current study by Macones and colleagues, the authors pointed out that prostaglandin E2 (and not misoprostol or prostaglandin E1) was the only type of prostaglandin used in all centers evaluated. Thus, although the study by Macones et al is well designed, it is retrospective and should not encourage the use of prostaglandins for VBAC until the question has been answered prospectively.
Encourage VBAC in women who have delivered vaginally
Overall, the study by Macones et al adds important information to the literature. The uterine rupture rate (2
In women who have delivered vaginally, VBAC should be encouraged. However, the use of prostaglandins to induce labor in these cases warrants further investigation.
The author reports no financial relationships relevant to this article.
1. National Center for Health Statistics. Preliminary births for 2004: infant and maternal health. Available at: http://www.cdc.gov/nchs/data/hestat/prelimbirths04health_tables.pdf. Accessed December 13, 2005.
2. American College of Obstetricians and Gynecologists. Vaginal Birth After Previous Cesarean Delivery. ACOG Practice Bulletin No. 54. Washington, DC: ACOG; 2004.
3. Chapman SJ, Owen J, Hauth JC. One- versus two-layer closure of a low transverse cesarean: the next pregnancy. Obstet Gynecol. 1997;89:16-18.
4. Durnwald C, Mercer B. Uterine rupture, perioperative and perinatal morbidity after single-layer and double-layer closure at cesarean delivery. Am J Obstet Gynecol. 2003;189:925-929.
5. Bujold E, Bujold C, Hamilton EF, et al. The impact of a single-layer or double-layer closure on uterine rupture. Am J Obstet Gynecol. 2002;186:1326-1330.
6. Hendler I, Bujold E. Effect of prior vaginal delivery or prior vaginal birth after cesarean delivery on obstetric outcomes in women undergoing trial of labor. Obstet Gynecol. 2004;104:273-277.
7. Gyamfi C, Juhasz G, Gyamfi P, Stone JL. Increased success of trial of labor after previous vaginal birth after cesarean. Obstet Gynecol. 2004;104:715-719.
8. Gonen R, Tamir A, Degani S, Ohel G. Variables associated with successful vaginal birth after one cesarean section: a proposed vaginal birth after cesarean section score. Am J Perinatol. 2004;21:447-453.
9. Bedoya C, Bartha JL, Rodriguez I, Fontan I, Bedoya JM, Sanchez-Ramos J. A trial of labor after cesarean section in patients with or without a prior vaginal delivery. Int J Obstet Gynaecol. 1992;39:285-289.
10. McMahon MJ, Luther ER, Bowes WA, Olshan AF. Comparison of a trial of labor with an elective second cesarean section. N Engl J Med. 1996;335:689-695.
11. Lydon-Rochelle M, Holt VL, Easterling TR, et al. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med. 2001;345:3-8.
12. ACOG Committee on Obstetric Practice. Induction of labor for vaginal birth after cesarean delivery. Committee Opinion No. 271. Obstet Gynecol. 2002;99:679-680.
1. National Center for Health Statistics. Preliminary births for 2004: infant and maternal health. Available at: http://www.cdc.gov/nchs/data/hestat/prelimbirths04health_tables.pdf. Accessed December 13, 2005.
2. American College of Obstetricians and Gynecologists. Vaginal Birth After Previous Cesarean Delivery. ACOG Practice Bulletin No. 54. Washington, DC: ACOG; 2004.
3. Chapman SJ, Owen J, Hauth JC. One- versus two-layer closure of a low transverse cesarean: the next pregnancy. Obstet Gynecol. 1997;89:16-18.
4. Durnwald C, Mercer B. Uterine rupture, perioperative and perinatal morbidity after single-layer and double-layer closure at cesarean delivery. Am J Obstet Gynecol. 2003;189:925-929.
5. Bujold E, Bujold C, Hamilton EF, et al. The impact of a single-layer or double-layer closure on uterine rupture. Am J Obstet Gynecol. 2002;186:1326-1330.
6. Hendler I, Bujold E. Effect of prior vaginal delivery or prior vaginal birth after cesarean delivery on obstetric outcomes in women undergoing trial of labor. Obstet Gynecol. 2004;104:273-277.
7. Gyamfi C, Juhasz G, Gyamfi P, Stone JL. Increased success of trial of labor after previous vaginal birth after cesarean. Obstet Gynecol. 2004;104:715-719.
8. Gonen R, Tamir A, Degani S, Ohel G. Variables associated with successful vaginal birth after one cesarean section: a proposed vaginal birth after cesarean section score. Am J Perinatol. 2004;21:447-453.
9. Bedoya C, Bartha JL, Rodriguez I, Fontan I, Bedoya JM, Sanchez-Ramos J. A trial of labor after cesarean section in patients with or without a prior vaginal delivery. Int J Obstet Gynaecol. 1992;39:285-289.
10. McMahon MJ, Luther ER, Bowes WA, Olshan AF. Comparison of a trial of labor with an elective second cesarean section. N Engl J Med. 1996;335:689-695.
11. Lydon-Rochelle M, Holt VL, Easterling TR, et al. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med. 2001;345:3-8.
12. ACOG Committee on Obstetric Practice. Induction of labor for vaginal birth after cesarean delivery. Committee Opinion No. 271. Obstet Gynecol. 2002;99:679-680.
Q Does vacuum extraction increase the risk of brachial plexus palsy?
<huc>A</huc> No, unless the vacuum extraction involves shoulder dystocia, high fetal birth weight, or application of fundal pressure. Shoulder dystocia is by far the most significant risk factor for brachial plexus palsy in this context.
Expert commentary
This excellent study provides indirect scientific evidence that shoulder dystocia is the prominent risk factor for brachial plexus palsy in the setting of vacuum extraction, with an odds ratio (OR) of 16.0 (95% confidence interval [CI] 8.9–28.7). Other independent factors include fetal birth weight of 3,999 g or more (OR 7.1; 95% CI 4.8–10.5) and application of fundal pressure (OR 1.6; 95% CI 1.1–2.3). However, 81% of the infants with brachial plexus palsy did not experience shoulder dystocia during vacuum extraction. This finding is in accord with recent studies of obstetric brachial plexus palsy.1
Duration of vacuum extraction plays a role. The authors determined that 5 minutes of vacuum extraction carries an estimated risk of brachial plexus palsy of 0.8%, whereas 25 minutes carries a risk close to 4%.
Longstanding enigma
Ever since the 1978 landmark study by Benedetti and Gabbe,2 the association between operative vaginal delivery and shoulder dystocia has aroused interest. Even today, clinical questions persist when an infant experiences brachial plexus palsy in the setting of operative vaginal delivery. Did the application of the vacuum or forceps cause the neonatal injury? Was the shoulder dystocia a direct consequence of the vacuum or forceps? Given the marked decrease in forceps usage and increasing reliance on vacuum extraction, this research article is timely and clinically relevant.
Strength in numbers: 13,716 vacuum deliveries
In Sweden since 1973, all deliveries have been recorded in the Medical Birth Registry of the National Board of Health and Welfare. Using this registry, Mollberg and colleagues were able to study 13,716 deliveries involving vacuum extraction, 153 of which resulted in brachial plexus palsy. The strength of this study lies in its immense power, which yielded insight into the approximate incidence (1.1%) of brachial plexus palsy in the setting of vacuum extraction.
Some medical records were incomplete
This study had a relatively high exclusion rate of 32%, since charts were analyzed only if they possessed a completed instrumental delivery protocol. As a result, Mollberg and colleagues were able to evaluate only a limited number of factors that could potentially be tied to brachial plexus palsy: shoulder dystocia, fetal birth weight, fundal pressure, number of tractions, duration of vacuum application, parity, vacuum silicone cup, epidural anesthesia, and fetal station.
No details on fundal pressure. A surprising percentage (58%) of infants with brachial plexus palsy had fundal pressure applied. Unfortunately, no indication was given as to whether this fundal pressure was used to assist with maternal expulsive efforts, to aid with placement of the vacuum extractor, or as a maneuver to alleviate shoulder dystocia.
Prolonged second stage defined differently from ACOG standard. This study defined a prolonged second stage as longer than 60 minutes in parous women and longer than 120 minutes in nulliparous women, whereas the American College of Obstetricians and Gynecologists defines it in multiparous women as longer than 2 hours with or 1 hour without regional anesthesia, and in nulliparous women as longer than 3 hours with or 2 hours without regional anesthesia.
Another weakness: Some vacuum extractions may have been midpelvic, given that cases with the fetal vertex at the level of the ischial spine were allowed.
Take-home message: Don’t retire the vacuum extractor
There is no reason obstetricians should stop using the vacuum extractor for fear of brachial plexus palsy. However, they should continue to:
- minimize the duration of application,
- monitor the rate of fetal descent and,
- as always, employ sound clinical judgment.3
The author reports no financial relationships relevant to this article.
1. Gherman RB, Chauhan S, Oh C, Goodwin TM. Brachial plexus palsy. Fetal Maternal Med Rev. 2005;16:1-23.
2. Benedetti TJ, Gabbe SG. Shoulder dystocia: a complication of fetal macrosomia and prolonged second stage of labor with midpelvic delivery. Obstet Gynecol. 1978;52:526-529.
3. American College of Obstetricians and Gynecologists. Operative Vaginal Delivery. ACOG Practice Bulletin Number 17. Washington, DC: ACOG; 2000.
<huc>A</huc> No, unless the vacuum extraction involves shoulder dystocia, high fetal birth weight, or application of fundal pressure. Shoulder dystocia is by far the most significant risk factor for brachial plexus palsy in this context.
Expert commentary
This excellent study provides indirect scientific evidence that shoulder dystocia is the prominent risk factor for brachial plexus palsy in the setting of vacuum extraction, with an odds ratio (OR) of 16.0 (95% confidence interval [CI] 8.9–28.7). Other independent factors include fetal birth weight of 3,999 g or more (OR 7.1; 95% CI 4.8–10.5) and application of fundal pressure (OR 1.6; 95% CI 1.1–2.3). However, 81% of the infants with brachial plexus palsy did not experience shoulder dystocia during vacuum extraction. This finding is in accord with recent studies of obstetric brachial plexus palsy.1
Duration of vacuum extraction plays a role. The authors determined that 5 minutes of vacuum extraction carries an estimated risk of brachial plexus palsy of 0.8%, whereas 25 minutes carries a risk close to 4%.
Longstanding enigma
Ever since the 1978 landmark study by Benedetti and Gabbe,2 the association between operative vaginal delivery and shoulder dystocia has aroused interest. Even today, clinical questions persist when an infant experiences brachial plexus palsy in the setting of operative vaginal delivery. Did the application of the vacuum or forceps cause the neonatal injury? Was the shoulder dystocia a direct consequence of the vacuum or forceps? Given the marked decrease in forceps usage and increasing reliance on vacuum extraction, this research article is timely and clinically relevant.
Strength in numbers: 13,716 vacuum deliveries
In Sweden since 1973, all deliveries have been recorded in the Medical Birth Registry of the National Board of Health and Welfare. Using this registry, Mollberg and colleagues were able to study 13,716 deliveries involving vacuum extraction, 153 of which resulted in brachial plexus palsy. The strength of this study lies in its immense power, which yielded insight into the approximate incidence (1.1%) of brachial plexus palsy in the setting of vacuum extraction.
Some medical records were incomplete
This study had a relatively high exclusion rate of 32%, since charts were analyzed only if they possessed a completed instrumental delivery protocol. As a result, Mollberg and colleagues were able to evaluate only a limited number of factors that could potentially be tied to brachial plexus palsy: shoulder dystocia, fetal birth weight, fundal pressure, number of tractions, duration of vacuum application, parity, vacuum silicone cup, epidural anesthesia, and fetal station.
No details on fundal pressure. A surprising percentage (58%) of infants with brachial plexus palsy had fundal pressure applied. Unfortunately, no indication was given as to whether this fundal pressure was used to assist with maternal expulsive efforts, to aid with placement of the vacuum extractor, or as a maneuver to alleviate shoulder dystocia.
Prolonged second stage defined differently from ACOG standard. This study defined a prolonged second stage as longer than 60 minutes in parous women and longer than 120 minutes in nulliparous women, whereas the American College of Obstetricians and Gynecologists defines it in multiparous women as longer than 2 hours with or 1 hour without regional anesthesia, and in nulliparous women as longer than 3 hours with or 2 hours without regional anesthesia.
Another weakness: Some vacuum extractions may have been midpelvic, given that cases with the fetal vertex at the level of the ischial spine were allowed.
Take-home message: Don’t retire the vacuum extractor
There is no reason obstetricians should stop using the vacuum extractor for fear of brachial plexus palsy. However, they should continue to:
- minimize the duration of application,
- monitor the rate of fetal descent and,
- as always, employ sound clinical judgment.3
The author reports no financial relationships relevant to this article.
<huc>A</huc> No, unless the vacuum extraction involves shoulder dystocia, high fetal birth weight, or application of fundal pressure. Shoulder dystocia is by far the most significant risk factor for brachial plexus palsy in this context.
Expert commentary
This excellent study provides indirect scientific evidence that shoulder dystocia is the prominent risk factor for brachial plexus palsy in the setting of vacuum extraction, with an odds ratio (OR) of 16.0 (95% confidence interval [CI] 8.9–28.7). Other independent factors include fetal birth weight of 3,999 g or more (OR 7.1; 95% CI 4.8–10.5) and application of fundal pressure (OR 1.6; 95% CI 1.1–2.3). However, 81% of the infants with brachial plexus palsy did not experience shoulder dystocia during vacuum extraction. This finding is in accord with recent studies of obstetric brachial plexus palsy.1
Duration of vacuum extraction plays a role. The authors determined that 5 minutes of vacuum extraction carries an estimated risk of brachial plexus palsy of 0.8%, whereas 25 minutes carries a risk close to 4%.
Longstanding enigma
Ever since the 1978 landmark study by Benedetti and Gabbe,2 the association between operative vaginal delivery and shoulder dystocia has aroused interest. Even today, clinical questions persist when an infant experiences brachial plexus palsy in the setting of operative vaginal delivery. Did the application of the vacuum or forceps cause the neonatal injury? Was the shoulder dystocia a direct consequence of the vacuum or forceps? Given the marked decrease in forceps usage and increasing reliance on vacuum extraction, this research article is timely and clinically relevant.
Strength in numbers: 13,716 vacuum deliveries
In Sweden since 1973, all deliveries have been recorded in the Medical Birth Registry of the National Board of Health and Welfare. Using this registry, Mollberg and colleagues were able to study 13,716 deliveries involving vacuum extraction, 153 of which resulted in brachial plexus palsy. The strength of this study lies in its immense power, which yielded insight into the approximate incidence (1.1%) of brachial plexus palsy in the setting of vacuum extraction.
Some medical records were incomplete
This study had a relatively high exclusion rate of 32%, since charts were analyzed only if they possessed a completed instrumental delivery protocol. As a result, Mollberg and colleagues were able to evaluate only a limited number of factors that could potentially be tied to brachial plexus palsy: shoulder dystocia, fetal birth weight, fundal pressure, number of tractions, duration of vacuum application, parity, vacuum silicone cup, epidural anesthesia, and fetal station.
No details on fundal pressure. A surprising percentage (58%) of infants with brachial plexus palsy had fundal pressure applied. Unfortunately, no indication was given as to whether this fundal pressure was used to assist with maternal expulsive efforts, to aid with placement of the vacuum extractor, or as a maneuver to alleviate shoulder dystocia.
Prolonged second stage defined differently from ACOG standard. This study defined a prolonged second stage as longer than 60 minutes in parous women and longer than 120 minutes in nulliparous women, whereas the American College of Obstetricians and Gynecologists defines it in multiparous women as longer than 2 hours with or 1 hour without regional anesthesia, and in nulliparous women as longer than 3 hours with or 2 hours without regional anesthesia.
Another weakness: Some vacuum extractions may have been midpelvic, given that cases with the fetal vertex at the level of the ischial spine were allowed.
Take-home message: Don’t retire the vacuum extractor
There is no reason obstetricians should stop using the vacuum extractor for fear of brachial plexus palsy. However, they should continue to:
- minimize the duration of application,
- monitor the rate of fetal descent and,
- as always, employ sound clinical judgment.3
The author reports no financial relationships relevant to this article.
1. Gherman RB, Chauhan S, Oh C, Goodwin TM. Brachial plexus palsy. Fetal Maternal Med Rev. 2005;16:1-23.
2. Benedetti TJ, Gabbe SG. Shoulder dystocia: a complication of fetal macrosomia and prolonged second stage of labor with midpelvic delivery. Obstet Gynecol. 1978;52:526-529.
3. American College of Obstetricians and Gynecologists. Operative Vaginal Delivery. ACOG Practice Bulletin Number 17. Washington, DC: ACOG; 2000.
1. Gherman RB, Chauhan S, Oh C, Goodwin TM. Brachial plexus palsy. Fetal Maternal Med Rev. 2005;16:1-23.
2. Benedetti TJ, Gabbe SG. Shoulder dystocia: a complication of fetal macrosomia and prolonged second stage of labor with midpelvic delivery. Obstet Gynecol. 1978;52:526-529.
3. American College of Obstetricians and Gynecologists. Operative Vaginal Delivery. ACOG Practice Bulletin Number 17. Washington, DC: ACOG; 2000.
Q Is misoprostol as effective as surgery for early pregnancy failure?
Expert commentary
About 1 in 5 women experience “early pregnancy failure,” a term that includes incomplete abortion, inevitable abortion, anembryonic gestation, and embryonic or fetal death. Since misoprostol was first described in 1997 as a single agent for evacuating the uterus in early pregnancy failure,1 many cohort studies have evaluated it for this purpose. Zhang et al provide level I evidence that intravaginal misoprostol is effective for uterine evacuation in early pregnancy failure.
“Noninferior,” technically
This study involved 652 women at 10 weeks’ gestation or less (crown-rump length of ≤40 mm or an average gestational sac diameter of ≤45 mm) who were randomized in a 3:1 ratio to misoprostol 800 μg vaginally (repeated in 2 days if necessary) or vacuum aspiration. Complete expulsion of the products of conception in the misoprostol group occurred in 71% of women by the second day after the initial dose and in 84% of women within 1 week.
Although the 1-week failure rate (16%) was higher than that for vacuum aspiration (3%), this was a “noninferiority trial.” That is, Zhang et al recognized that medical treatment was unlikely to surpass the success rate of surgery, so they calculated an absolute difference of 18% as the maximum difference that would demonstrate noninferiority of misoprostol.
Treatment tips
This treatment is not for every patient. However, for women at gestational ages of less than 10 to 11 weeks who prefer to avoid a trip to the operating room, misoprostol is an attractive option.
Follow this protocol:
- provide oral analgesia (eg, ibuprofen and codeine)
- advise patients when to seek emergency care (heavy bleeding for more than 1 to 2 hours or pain unrelieved by medication)
- order a follow-up ultrasound exam.
More cost-effective than surgery
Although expense was not addressed in this study, misoprostol is more cost-effective than uterine curettage. Because only 1 in 7 women treated with misoprostol ultimately require surgery and at least one third of women choosing expectant management do not have a spontaneous abortion in a reasonable amount of time, misoprostol may be more cost-effective than expectant management.
Side effects had little impact
Of the patients treated with misoprostol, three quarters said they would opt to use it again, and four fifths said they would recommend it to others. These proportions were similar for the subgroup who had undergone surgical management for failure of an earlier pregnancy.
This finding is noteworthy because misoprostol caused more side effects. Women taking it had more bleeding (measured by the change in hemoglobin concentrations), gastrointestinal side effects (nausea, vomiting, and diarrhea), and pain.
The author reports no financial relationships relevant to this article.
REFERENCE
1. Creinin MD, Moyer R, Guido R. Misoprostol for medical evacuation of early pregnancy failure. Obstet Gynecol. 1997;89:768-772.
Expert commentary
About 1 in 5 women experience “early pregnancy failure,” a term that includes incomplete abortion, inevitable abortion, anembryonic gestation, and embryonic or fetal death. Since misoprostol was first described in 1997 as a single agent for evacuating the uterus in early pregnancy failure,1 many cohort studies have evaluated it for this purpose. Zhang et al provide level I evidence that intravaginal misoprostol is effective for uterine evacuation in early pregnancy failure.
“Noninferior,” technically
This study involved 652 women at 10 weeks’ gestation or less (crown-rump length of ≤40 mm or an average gestational sac diameter of ≤45 mm) who were randomized in a 3:1 ratio to misoprostol 800 μg vaginally (repeated in 2 days if necessary) or vacuum aspiration. Complete expulsion of the products of conception in the misoprostol group occurred in 71% of women by the second day after the initial dose and in 84% of women within 1 week.
Although the 1-week failure rate (16%) was higher than that for vacuum aspiration (3%), this was a “noninferiority trial.” That is, Zhang et al recognized that medical treatment was unlikely to surpass the success rate of surgery, so they calculated an absolute difference of 18% as the maximum difference that would demonstrate noninferiority of misoprostol.
Treatment tips
This treatment is not for every patient. However, for women at gestational ages of less than 10 to 11 weeks who prefer to avoid a trip to the operating room, misoprostol is an attractive option.
Follow this protocol:
- provide oral analgesia (eg, ibuprofen and codeine)
- advise patients when to seek emergency care (heavy bleeding for more than 1 to 2 hours or pain unrelieved by medication)
- order a follow-up ultrasound exam.
More cost-effective than surgery
Although expense was not addressed in this study, misoprostol is more cost-effective than uterine curettage. Because only 1 in 7 women treated with misoprostol ultimately require surgery and at least one third of women choosing expectant management do not have a spontaneous abortion in a reasonable amount of time, misoprostol may be more cost-effective than expectant management.
Side effects had little impact
Of the patients treated with misoprostol, three quarters said they would opt to use it again, and four fifths said they would recommend it to others. These proportions were similar for the subgroup who had undergone surgical management for failure of an earlier pregnancy.
This finding is noteworthy because misoprostol caused more side effects. Women taking it had more bleeding (measured by the change in hemoglobin concentrations), gastrointestinal side effects (nausea, vomiting, and diarrhea), and pain.
The author reports no financial relationships relevant to this article.
Expert commentary
About 1 in 5 women experience “early pregnancy failure,” a term that includes incomplete abortion, inevitable abortion, anembryonic gestation, and embryonic or fetal death. Since misoprostol was first described in 1997 as a single agent for evacuating the uterus in early pregnancy failure,1 many cohort studies have evaluated it for this purpose. Zhang et al provide level I evidence that intravaginal misoprostol is effective for uterine evacuation in early pregnancy failure.
“Noninferior,” technically
This study involved 652 women at 10 weeks’ gestation or less (crown-rump length of ≤40 mm or an average gestational sac diameter of ≤45 mm) who were randomized in a 3:1 ratio to misoprostol 800 μg vaginally (repeated in 2 days if necessary) or vacuum aspiration. Complete expulsion of the products of conception in the misoprostol group occurred in 71% of women by the second day after the initial dose and in 84% of women within 1 week.
Although the 1-week failure rate (16%) was higher than that for vacuum aspiration (3%), this was a “noninferiority trial.” That is, Zhang et al recognized that medical treatment was unlikely to surpass the success rate of surgery, so they calculated an absolute difference of 18% as the maximum difference that would demonstrate noninferiority of misoprostol.
Treatment tips
This treatment is not for every patient. However, for women at gestational ages of less than 10 to 11 weeks who prefer to avoid a trip to the operating room, misoprostol is an attractive option.
Follow this protocol:
- provide oral analgesia (eg, ibuprofen and codeine)
- advise patients when to seek emergency care (heavy bleeding for more than 1 to 2 hours or pain unrelieved by medication)
- order a follow-up ultrasound exam.
More cost-effective than surgery
Although expense was not addressed in this study, misoprostol is more cost-effective than uterine curettage. Because only 1 in 7 women treated with misoprostol ultimately require surgery and at least one third of women choosing expectant management do not have a spontaneous abortion in a reasonable amount of time, misoprostol may be more cost-effective than expectant management.
Side effects had little impact
Of the patients treated with misoprostol, three quarters said they would opt to use it again, and four fifths said they would recommend it to others. These proportions were similar for the subgroup who had undergone surgical management for failure of an earlier pregnancy.
This finding is noteworthy because misoprostol caused more side effects. Women taking it had more bleeding (measured by the change in hemoglobin concentrations), gastrointestinal side effects (nausea, vomiting, and diarrhea), and pain.
The author reports no financial relationships relevant to this article.
REFERENCE
1. Creinin MD, Moyer R, Guido R. Misoprostol for medical evacuation of early pregnancy failure. Obstet Gynecol. 1997;89:768-772.
REFERENCE
1. Creinin MD, Moyer R, Guido R. Misoprostol for medical evacuation of early pregnancy failure. Obstet Gynecol. 1997;89:768-772.
Q Does testosterone have a role in treating decreased sexual desire in postmenopausal women?
NAMS position statement on exogenous testosterone
The experts charged with formulating the statement noted that, while endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women, exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause, according to randomized controlled trials. The panel agreed on these points:
Existing data do not support using testosterone for any other indication. Nor known whether testosterone treatment raises the risk of breast cancer, cardiovascular disease, or thromboembolic events. The optimal duration of therapy beyond months is also unknown.
No level of testosterone has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency, nor do available assays accurately detect testosterone concentrations at the values typically found in women.
It is important to rule out other causes of decreased desire not related to testosterone levels, such as physical and psychosocial factors, and medications. Also recommended is ensuring a physiologic cause of reduced testosterone levels, such as bilateral oophorectomy.
Laboratory testing of testosterone levels is warranted only to monitor for supraphysiologic levels during therapy, not to diagnose testosterone insufficiency. The panel recommended non-oral testosterone to avoid first-pass hepatic effects.
Few data support the use of testosterone without concomitant estrogen therapy.
Dosing can be inconsistent in custom-compounded products, which should be used with caution.
Dosage of testosterone should be at the lowest level for the shortest time that meets treatment goals.
Expert Commentary
This position statement shows what progress can be made when you put the right people in the right room talking about a topic they know an awful lot about. The clinicians and researchers contributing to the position statement included the best and most practical in the field.
Of critical importance is the section on testosterone testing, in which utilization of testosterone blood levels (for saliva levels, that matter) to diagnose sexual dysfunction is discouraged except to avoid supraphysiologic levels during therapy. The problem here is that a total testosterone level that is supraphysiologic may be coupled with a free testosterone level within the normal range, usually due to elevated levels of sex hormone binding globulin, as is seen with oral estrogen therapy. Hence, one needs to be careful with the term “supraphysiologic” and not depend on the total testosterone level.
An empiric trial of therapy is implied if other causes are ruled out, and a “normal” blood level should not discourage therapy in affected patients.
Some women experience “double whammy”
The ovaries account, directly or indirectly, for approximately 50% of circulating testosterone even after menopause, leading to significantly decreased testosterone levels after bilateral oophorectomy. Thus, the combination of oral estrogen, with its concomitant increase in sex hormone binding globulin, and bilateral oophorectomy, with its 50% reduction in testosterone levels, becomes a “double whammy” that leads to greatly reduced bioavailable testosterone (and estrogen) and its signs of testosterone insufficiency (as well as relapse of vasomotor symptoms).
Post-Oprah counseling
The lack of FDA approval for use of any available testosterone products in women renders their utilization “off-label” in this country, which means we need to add counseling about this issue to any discussion of testosterone therapy for decreased sexual desire.
Another question that has arisen more frequently, especially since Oprah Winfrey advised her TV viewers to ask their doctors for testosterone: Should testosterone be used by a woman who wants to avoid any estrogen therapy? Women with this concern should be told that testosterone can also be aromatized to estradiol endogenously. In contrast, oral methyltestosterone is not aromatized to estradiol and, at least in vitro, has been shown to be a potential aromatase inhibitor.
Science lags behind therapy
This is a fascinating time for this area of study and therapy, but the science needs to catch up to the therapy. That will be difficult until the FDA stops its footdragging and approves a product for female use.
NAMS advisory is excellent
As for the position statement itself, NAMS has put forth an excellent treatise on the role of testosterone therapy, instead of another medicolegal-inspired statement like the one it issued after the Women’s Health Initiative, which led to more confusion and controversy.
This position statement should be read by all clinicians who manage issues of female sexual function and dysfunction. I could not have said it better myself.
NAMS position statement on exogenous testosterone
The experts charged with formulating the statement noted that, while endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women, exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause, according to randomized controlled trials. The panel agreed on these points:
Existing data do not support using testosterone for any other indication. Nor known whether testosterone treatment raises the risk of breast cancer, cardiovascular disease, or thromboembolic events. The optimal duration of therapy beyond months is also unknown.
No level of testosterone has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency, nor do available assays accurately detect testosterone concentrations at the values typically found in women.
It is important to rule out other causes of decreased desire not related to testosterone levels, such as physical and psychosocial factors, and medications. Also recommended is ensuring a physiologic cause of reduced testosterone levels, such as bilateral oophorectomy.
Laboratory testing of testosterone levels is warranted only to monitor for supraphysiologic levels during therapy, not to diagnose testosterone insufficiency. The panel recommended non-oral testosterone to avoid first-pass hepatic effects.
Few data support the use of testosterone without concomitant estrogen therapy.
Dosing can be inconsistent in custom-compounded products, which should be used with caution.
Dosage of testosterone should be at the lowest level for the shortest time that meets treatment goals.
Expert Commentary
This position statement shows what progress can be made when you put the right people in the right room talking about a topic they know an awful lot about. The clinicians and researchers contributing to the position statement included the best and most practical in the field.
Of critical importance is the section on testosterone testing, in which utilization of testosterone blood levels (for saliva levels, that matter) to diagnose sexual dysfunction is discouraged except to avoid supraphysiologic levels during therapy. The problem here is that a total testosterone level that is supraphysiologic may be coupled with a free testosterone level within the normal range, usually due to elevated levels of sex hormone binding globulin, as is seen with oral estrogen therapy. Hence, one needs to be careful with the term “supraphysiologic” and not depend on the total testosterone level.
An empiric trial of therapy is implied if other causes are ruled out, and a “normal” blood level should not discourage therapy in affected patients.
Some women experience “double whammy”
The ovaries account, directly or indirectly, for approximately 50% of circulating testosterone even after menopause, leading to significantly decreased testosterone levels after bilateral oophorectomy. Thus, the combination of oral estrogen, with its concomitant increase in sex hormone binding globulin, and bilateral oophorectomy, with its 50% reduction in testosterone levels, becomes a “double whammy” that leads to greatly reduced bioavailable testosterone (and estrogen) and its signs of testosterone insufficiency (as well as relapse of vasomotor symptoms).
Post-Oprah counseling
The lack of FDA approval for use of any available testosterone products in women renders their utilization “off-label” in this country, which means we need to add counseling about this issue to any discussion of testosterone therapy for decreased sexual desire.
Another question that has arisen more frequently, especially since Oprah Winfrey advised her TV viewers to ask their doctors for testosterone: Should testosterone be used by a woman who wants to avoid any estrogen therapy? Women with this concern should be told that testosterone can also be aromatized to estradiol endogenously. In contrast, oral methyltestosterone is not aromatized to estradiol and, at least in vitro, has been shown to be a potential aromatase inhibitor.
Science lags behind therapy
This is a fascinating time for this area of study and therapy, but the science needs to catch up to the therapy. That will be difficult until the FDA stops its footdragging and approves a product for female use.
NAMS advisory is excellent
As for the position statement itself, NAMS has put forth an excellent treatise on the role of testosterone therapy, instead of another medicolegal-inspired statement like the one it issued after the Women’s Health Initiative, which led to more confusion and controversy.
This position statement should be read by all clinicians who manage issues of female sexual function and dysfunction. I could not have said it better myself.
NAMS position statement on exogenous testosterone
The experts charged with formulating the statement noted that, while endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women, exogenous testosterone—regardless of route of administration—positively affects sexual function after spontaneous or surgically induced menopause, according to randomized controlled trials. The panel agreed on these points:
Existing data do not support using testosterone for any other indication. Nor known whether testosterone treatment raises the risk of breast cancer, cardiovascular disease, or thromboembolic events. The optimal duration of therapy beyond months is also unknown.
No level of testosterone has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency, nor do available assays accurately detect testosterone concentrations at the values typically found in women.
It is important to rule out other causes of decreased desire not related to testosterone levels, such as physical and psychosocial factors, and medications. Also recommended is ensuring a physiologic cause of reduced testosterone levels, such as bilateral oophorectomy.
Laboratory testing of testosterone levels is warranted only to monitor for supraphysiologic levels during therapy, not to diagnose testosterone insufficiency. The panel recommended non-oral testosterone to avoid first-pass hepatic effects.
Few data support the use of testosterone without concomitant estrogen therapy.
Dosing can be inconsistent in custom-compounded products, which should be used with caution.
Dosage of testosterone should be at the lowest level for the shortest time that meets treatment goals.
Expert Commentary
This position statement shows what progress can be made when you put the right people in the right room talking about a topic they know an awful lot about. The clinicians and researchers contributing to the position statement included the best and most practical in the field.
Of critical importance is the section on testosterone testing, in which utilization of testosterone blood levels (for saliva levels, that matter) to diagnose sexual dysfunction is discouraged except to avoid supraphysiologic levels during therapy. The problem here is that a total testosterone level that is supraphysiologic may be coupled with a free testosterone level within the normal range, usually due to elevated levels of sex hormone binding globulin, as is seen with oral estrogen therapy. Hence, one needs to be careful with the term “supraphysiologic” and not depend on the total testosterone level.
An empiric trial of therapy is implied if other causes are ruled out, and a “normal” blood level should not discourage therapy in affected patients.
Some women experience “double whammy”
The ovaries account, directly or indirectly, for approximately 50% of circulating testosterone even after menopause, leading to significantly decreased testosterone levels after bilateral oophorectomy. Thus, the combination of oral estrogen, with its concomitant increase in sex hormone binding globulin, and bilateral oophorectomy, with its 50% reduction in testosterone levels, becomes a “double whammy” that leads to greatly reduced bioavailable testosterone (and estrogen) and its signs of testosterone insufficiency (as well as relapse of vasomotor symptoms).
Post-Oprah counseling
The lack of FDA approval for use of any available testosterone products in women renders their utilization “off-label” in this country, which means we need to add counseling about this issue to any discussion of testosterone therapy for decreased sexual desire.
Another question that has arisen more frequently, especially since Oprah Winfrey advised her TV viewers to ask their doctors for testosterone: Should testosterone be used by a woman who wants to avoid any estrogen therapy? Women with this concern should be told that testosterone can also be aromatized to estradiol endogenously. In contrast, oral methyltestosterone is not aromatized to estradiol and, at least in vitro, has been shown to be a potential aromatase inhibitor.
Science lags behind therapy
This is a fascinating time for this area of study and therapy, but the science needs to catch up to the therapy. That will be difficult until the FDA stops its footdragging and approves a product for female use.
NAMS advisory is excellent
As for the position statement itself, NAMS has put forth an excellent treatise on the role of testosterone therapy, instead of another medicolegal-inspired statement like the one it issued after the Women’s Health Initiative, which led to more confusion and controversy.
This position statement should be read by all clinicians who manage issues of female sexual function and dysfunction. I could not have said it better myself.
Q Is it better to remove or spare ovaries at hysterectomy?
It only seems that this controversy is coming to the fore for the first time. In reality, it has been hotly debated for decades. One camp favors oophorectomy to prevent ovarian cancer; the other, preservation of the ovaries to reduce the risk of heart disease and hip fracture.
What is the function of the postovulatory ovary?
GUZICK: Some experts recommend conserving the ovaries to reduce the risk of heart disease. Why? The postovulatory ovary continues to produce androgens, which are converted to circulating estrogens. The androgens themselves are said to improve libido (itself a controversial assertion),1 and their conversion to estrogens may reduce the risk of heart disease2 and hip fracture.3
Parker and colleagues used a Markov decision-analysis model to estimate whether, on balance, the ovaries should be removed or conserved during hysterectomy for benign disease in women at least 40 years old. Using this model, ovarian conservation averted enough heart disease and hip fracture cases to more than offset new cases of ovarian and breast cancers.
About half of all women older than 40 will die of heart disease,4 while fewer than 1% will die of ovarian cancer.5 If women undergoing hysterectomy for benign disease are roughly 50 times more likely to die of heart disease than ovarian cancer, then clearly even a small protective effect of ovarian conservation on heart disease will outweigh the potential for ovarian cancer.
For the moment, let’s take the study by Parker and colleagues at face value. Given the high base rate of cardiovascular disease, it is not surprising that oophorectomy markedly diminishes the overall probability of survival at age 80 among women undergoing hysterectomy at age 50 to 54. The authors estimate that oophorectomy reduces this probability from 62% to 54%. Moreover, the estimated impact of oophorectomy on mortality varies by age. This effect is built into the model because of the age-associated increase in the base rate of ovarian cancer mortality and the estimate that the risk of coronary heart disease declines 6% each year oophorectomy is delayed after menopause.6
Significant differences in survival curves between groups of women undergoing ovarian removal or conservation are found between the ages of 40 and 54, and the curves converge after age 65. Thus, Parker and colleagues conclude that “ovarian conservation until age 65 benefits long-term survival.”
Other factors may influence survival
GUZICK: Ovarian conservation reduces hip fracture3 but increases breast cancer, at least up until age 50.6 Such factors are included in the Parker analysis, but the main drivers of the model are heart disease and ovarian cancer. The conceptual framework for the model, and the pattern of the results, are clear strengths of this study.
MENZIN: Parker et al noted that their study did not address the benefits of oophorectomy among women with known or possible hereditary predisposition to ovarian cancer. Nevertheless, being aware of this major risk factor and its relevance to an informed consent discussion of hysterectomy is important, especially given the recognized benefits of risk-reducing surgery in this setting.
For women whose risk of ovarian cancer is equivalent to that of the general population, the decision is more complex. Hysterectomy, even with ovarian conservation, itself appears to reduce the risk of ovarian cancer by 10% to 40%—probably because abnormal-appearing ovaries are usually removed at hysterectomy.7,8 The prognosis of ovarian cancer in conserved ovaries appears equivalent to that in women without hysterectomy,9 although several studies suggest that 5% to 15% of ovarian cancers might have been prevented by oophorectomy at the time of prior hysterectomy for benign disease.
Why the Parker findings can’t be taken at face value
GUZICK: The estimated benefit of ovarian conservation in regard to heart disease was based on data acquired between 1976 and 1982 from the Nurses’ Health Study (NHS).2 This is problematic for several reasons. First, the relative risk of 2.2 was estimated in the NHS for coronary heart disease events, not deaths.2 It is not clear how Parker et al converted relative risk of events to relative risk of deaths, but apparently the risk estimate for events was applied to a baseline death rate. If so, then, because not all women with a cardiovascular event from 1976 to 1982 died of cardiovascular disease, the effect of oophorectomy is overstated.
Translating event effects to mortality effects is even more problematic when applied to contemporary medical practice. Women at risk of common cardiovascular problems such as hypertension and coronary artery disease now have the benefit of advances in diagnosis (blood pressure monitoring, biochemical markers, endothelial function tests, and coronary imaging) and treatment (eg, statins, antihypertensives, and coronary artery stents), which can reduce the likelihood of both cardiovascular events and deaths.
Finally, the relative risk for oophorectomy is based not on a randomized trial but on the observational, longitudinal NHS study,2 which may have been subject to selection bias. Were women who went against prevailing wisdom and retained their ovaries at the time of hysterectomy the same ones who had a prevention/wellness view of personal health? Did they follow a regimen of personal fitness and nutrition that reduced their risk of heart disease? In such a scenario, not captured by the statistical controls in the study,4 the dual facts of ovarian conservation and reduced heart disease are true but unrelated.
MENZIN: I agree that the modeling used by Parker and colleagues depends on several reference data sets that have their own potential biases and limitations. For example, the authors recognized that “no published data were found for coronary risk when oophorectomy was performed after menopause,” yet their study purportedly demonstrated that the excess mortality associated with oophorectomy between the ages of 50 and 65 years was primarily a result of coronary disease.
The clinical importance of postmenopausal hormone production has not been fully determined. Furthermore, the duration of effective estrogen production in conserved ovaries also can be hard to predict; almost 33% of women experience menopause within 2 years after hysterectomy with ovarian conservation.10
The Parker study focuses on mortality; however, the likelihood of medical or surgical intervention for benign or equivocal adnexal pathology also should be considered, along with the potential complexity of such treatments.
Women feel uninformed about their options
GUZICK: In my judgment, the fate of the ovaries in a woman undergoing hysterectomy for benign disease should be based on a thorough discussion with the patient that takes into account her individual risk profile and the psychological weight she attaches to the various outcomes. Key factors in the risk profile include age; menopausal status; family history of heart disease and breast and ovarian cancer; and biochemical, genetic, or imaging findings related to cancer, cardiovascular disease, and osteoporosis.
For example, a 45-year-old woman who is lean and normotensive with a favorable lipid profile, and who greatly fears the prospect of ovarian cancer because a friend died of the disease, may choose to have her ovaries removed. Whether this decision is “right” or “wrong” in general is hard to say, but for this patient the decision is acceptable. Her individual risk for cardiovascular disease and osteoporosis can be monitored more carefully and, if necessary, treated effectively early on. She can be given estrogen for vasomotor symptoms.
For postmenopausal women in their early to mid-50s, the situation is murkier, but a blanket recommendation still seems unwarranted. For women in their late 50s and older, although the Parker model shows a “visual” difference between projected survival curves until age 65, it is not clear whether such differences are statistically significant.
MENZIN: A critical point was highlighted in a recent description of interviews with women awaiting hysterectomy. Bhavnani and Clarke11 found that “many women felt inadequately informed about their treatment options and were unaware of important longer-term outcomes of oophorectomy.” Although the work by Parker and colleagues adds another dimension to the counseling of women considering hysterectomy for benign indications, the complexity of that counseling continues to evolve.
Ultimately, the Parker study demonstrates that oophorectomy does not provide a survival benefit over ovarian conservation. This does not mean oophorectomy is always unadvised. Equivalent treatment arms of randomized trials in oncology have demonstrated that quality of life can vary between alternate therapies. Parker and colleagues did not address this critical issue—one I believe to be at the core of every therapeutic decision and informed consent discussion.
In the end, we must individualize the operation to meet the goals and expectations of the patient.
GUZICK: I agree. A one-size-fits-all approach to clinical decision-making is rarely appropriate. The study by Parker et al provides a framework for women to determine which size is best for them.
The authors report no financial relationships relevant to this article.
1. Guzick DS, Hoeger K. Sex, hormones, and hysterectomies. N Engl J Med. 2000;343:730-731.
2. Colditz GA, Willett WC, Stampfer MJ, et al. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105-1110.
3. Melton LJ, 3rd, Khosla S, Malkasian GD, et al. Fracture risk after bilateral oophorectomy in elderly women. J Bone Miner Res. 2003;18:900-905.
4. National Cancer Institute, Statistical Research and Applications Branch. DevCan database: SEER 13 incidence and mortality, 2000–2002, released April 2005, based on the November 2004 submission. For more information see: http://srab.cancer.gov/devcan/. Accessed October 13, 2005.
5. American Heart Association. Heart disease and stroke statistics-2005 update. Available at: www.american-heart.org/presenter.jhtml?identifier=1200026. Accessed October 13, 2005.
6. Shairer C, Persson I, Falkeborn M, Naessen T, Troisi R, Brinton LA. Breast cancer risk associated with gynecologic surgery and indications for such surgery. Int J Cancer. 1997;70:150-154.
7. Parazzini F, Negri E, La Vecchia C, Luchini L, Mezzopane R. Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. Obstet Gynecol. 1993;81:363-366.
8. Chiaffarino F, Parazzini F, Decarli A, et al. Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer. Obstet Gynecol Surv. 2005;60:586-587.
9. Fine BA, Yazigi R, Risser R. Prognosis of ovarian cancer developing in the residual ovary. Gynecol Oncol. 1991;43:164-166.
10. Siddle N, Sarrel P, Whitehead M. The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function. A literature review. Fertil Steril. 1987;47:94-100.
11. Bhavnani V, Clarke A. Women awaiting hysterectomy: a qualitative study of issues involved in decisions about oophorectomy. BJOG. 2003;110:168-174.
It only seems that this controversy is coming to the fore for the first time. In reality, it has been hotly debated for decades. One camp favors oophorectomy to prevent ovarian cancer; the other, preservation of the ovaries to reduce the risk of heart disease and hip fracture.
What is the function of the postovulatory ovary?
GUZICK: Some experts recommend conserving the ovaries to reduce the risk of heart disease. Why? The postovulatory ovary continues to produce androgens, which are converted to circulating estrogens. The androgens themselves are said to improve libido (itself a controversial assertion),1 and their conversion to estrogens may reduce the risk of heart disease2 and hip fracture.3
Parker and colleagues used a Markov decision-analysis model to estimate whether, on balance, the ovaries should be removed or conserved during hysterectomy for benign disease in women at least 40 years old. Using this model, ovarian conservation averted enough heart disease and hip fracture cases to more than offset new cases of ovarian and breast cancers.
About half of all women older than 40 will die of heart disease,4 while fewer than 1% will die of ovarian cancer.5 If women undergoing hysterectomy for benign disease are roughly 50 times more likely to die of heart disease than ovarian cancer, then clearly even a small protective effect of ovarian conservation on heart disease will outweigh the potential for ovarian cancer.
For the moment, let’s take the study by Parker and colleagues at face value. Given the high base rate of cardiovascular disease, it is not surprising that oophorectomy markedly diminishes the overall probability of survival at age 80 among women undergoing hysterectomy at age 50 to 54. The authors estimate that oophorectomy reduces this probability from 62% to 54%. Moreover, the estimated impact of oophorectomy on mortality varies by age. This effect is built into the model because of the age-associated increase in the base rate of ovarian cancer mortality and the estimate that the risk of coronary heart disease declines 6% each year oophorectomy is delayed after menopause.6
Significant differences in survival curves between groups of women undergoing ovarian removal or conservation are found between the ages of 40 and 54, and the curves converge after age 65. Thus, Parker and colleagues conclude that “ovarian conservation until age 65 benefits long-term survival.”
Other factors may influence survival
GUZICK: Ovarian conservation reduces hip fracture3 but increases breast cancer, at least up until age 50.6 Such factors are included in the Parker analysis, but the main drivers of the model are heart disease and ovarian cancer. The conceptual framework for the model, and the pattern of the results, are clear strengths of this study.
MENZIN: Parker et al noted that their study did not address the benefits of oophorectomy among women with known or possible hereditary predisposition to ovarian cancer. Nevertheless, being aware of this major risk factor and its relevance to an informed consent discussion of hysterectomy is important, especially given the recognized benefits of risk-reducing surgery in this setting.
For women whose risk of ovarian cancer is equivalent to that of the general population, the decision is more complex. Hysterectomy, even with ovarian conservation, itself appears to reduce the risk of ovarian cancer by 10% to 40%—probably because abnormal-appearing ovaries are usually removed at hysterectomy.7,8 The prognosis of ovarian cancer in conserved ovaries appears equivalent to that in women without hysterectomy,9 although several studies suggest that 5% to 15% of ovarian cancers might have been prevented by oophorectomy at the time of prior hysterectomy for benign disease.
Why the Parker findings can’t be taken at face value
GUZICK: The estimated benefit of ovarian conservation in regard to heart disease was based on data acquired between 1976 and 1982 from the Nurses’ Health Study (NHS).2 This is problematic for several reasons. First, the relative risk of 2.2 was estimated in the NHS for coronary heart disease events, not deaths.2 It is not clear how Parker et al converted relative risk of events to relative risk of deaths, but apparently the risk estimate for events was applied to a baseline death rate. If so, then, because not all women with a cardiovascular event from 1976 to 1982 died of cardiovascular disease, the effect of oophorectomy is overstated.
Translating event effects to mortality effects is even more problematic when applied to contemporary medical practice. Women at risk of common cardiovascular problems such as hypertension and coronary artery disease now have the benefit of advances in diagnosis (blood pressure monitoring, biochemical markers, endothelial function tests, and coronary imaging) and treatment (eg, statins, antihypertensives, and coronary artery stents), which can reduce the likelihood of both cardiovascular events and deaths.
Finally, the relative risk for oophorectomy is based not on a randomized trial but on the observational, longitudinal NHS study,2 which may have been subject to selection bias. Were women who went against prevailing wisdom and retained their ovaries at the time of hysterectomy the same ones who had a prevention/wellness view of personal health? Did they follow a regimen of personal fitness and nutrition that reduced their risk of heart disease? In such a scenario, not captured by the statistical controls in the study,4 the dual facts of ovarian conservation and reduced heart disease are true but unrelated.
MENZIN: I agree that the modeling used by Parker and colleagues depends on several reference data sets that have their own potential biases and limitations. For example, the authors recognized that “no published data were found for coronary risk when oophorectomy was performed after menopause,” yet their study purportedly demonstrated that the excess mortality associated with oophorectomy between the ages of 50 and 65 years was primarily a result of coronary disease.
The clinical importance of postmenopausal hormone production has not been fully determined. Furthermore, the duration of effective estrogen production in conserved ovaries also can be hard to predict; almost 33% of women experience menopause within 2 years after hysterectomy with ovarian conservation.10
The Parker study focuses on mortality; however, the likelihood of medical or surgical intervention for benign or equivocal adnexal pathology also should be considered, along with the potential complexity of such treatments.
Women feel uninformed about their options
GUZICK: In my judgment, the fate of the ovaries in a woman undergoing hysterectomy for benign disease should be based on a thorough discussion with the patient that takes into account her individual risk profile and the psychological weight she attaches to the various outcomes. Key factors in the risk profile include age; menopausal status; family history of heart disease and breast and ovarian cancer; and biochemical, genetic, or imaging findings related to cancer, cardiovascular disease, and osteoporosis.
For example, a 45-year-old woman who is lean and normotensive with a favorable lipid profile, and who greatly fears the prospect of ovarian cancer because a friend died of the disease, may choose to have her ovaries removed. Whether this decision is “right” or “wrong” in general is hard to say, but for this patient the decision is acceptable. Her individual risk for cardiovascular disease and osteoporosis can be monitored more carefully and, if necessary, treated effectively early on. She can be given estrogen for vasomotor symptoms.
For postmenopausal women in their early to mid-50s, the situation is murkier, but a blanket recommendation still seems unwarranted. For women in their late 50s and older, although the Parker model shows a “visual” difference between projected survival curves until age 65, it is not clear whether such differences are statistically significant.
MENZIN: A critical point was highlighted in a recent description of interviews with women awaiting hysterectomy. Bhavnani and Clarke11 found that “many women felt inadequately informed about their treatment options and were unaware of important longer-term outcomes of oophorectomy.” Although the work by Parker and colleagues adds another dimension to the counseling of women considering hysterectomy for benign indications, the complexity of that counseling continues to evolve.
Ultimately, the Parker study demonstrates that oophorectomy does not provide a survival benefit over ovarian conservation. This does not mean oophorectomy is always unadvised. Equivalent treatment arms of randomized trials in oncology have demonstrated that quality of life can vary between alternate therapies. Parker and colleagues did not address this critical issue—one I believe to be at the core of every therapeutic decision and informed consent discussion.
In the end, we must individualize the operation to meet the goals and expectations of the patient.
GUZICK: I agree. A one-size-fits-all approach to clinical decision-making is rarely appropriate. The study by Parker et al provides a framework for women to determine which size is best for them.
The authors report no financial relationships relevant to this article.
It only seems that this controversy is coming to the fore for the first time. In reality, it has been hotly debated for decades. One camp favors oophorectomy to prevent ovarian cancer; the other, preservation of the ovaries to reduce the risk of heart disease and hip fracture.
What is the function of the postovulatory ovary?
GUZICK: Some experts recommend conserving the ovaries to reduce the risk of heart disease. Why? The postovulatory ovary continues to produce androgens, which are converted to circulating estrogens. The androgens themselves are said to improve libido (itself a controversial assertion),1 and their conversion to estrogens may reduce the risk of heart disease2 and hip fracture.3
Parker and colleagues used a Markov decision-analysis model to estimate whether, on balance, the ovaries should be removed or conserved during hysterectomy for benign disease in women at least 40 years old. Using this model, ovarian conservation averted enough heart disease and hip fracture cases to more than offset new cases of ovarian and breast cancers.
About half of all women older than 40 will die of heart disease,4 while fewer than 1% will die of ovarian cancer.5 If women undergoing hysterectomy for benign disease are roughly 50 times more likely to die of heart disease than ovarian cancer, then clearly even a small protective effect of ovarian conservation on heart disease will outweigh the potential for ovarian cancer.
For the moment, let’s take the study by Parker and colleagues at face value. Given the high base rate of cardiovascular disease, it is not surprising that oophorectomy markedly diminishes the overall probability of survival at age 80 among women undergoing hysterectomy at age 50 to 54. The authors estimate that oophorectomy reduces this probability from 62% to 54%. Moreover, the estimated impact of oophorectomy on mortality varies by age. This effect is built into the model because of the age-associated increase in the base rate of ovarian cancer mortality and the estimate that the risk of coronary heart disease declines 6% each year oophorectomy is delayed after menopause.6
Significant differences in survival curves between groups of women undergoing ovarian removal or conservation are found between the ages of 40 and 54, and the curves converge after age 65. Thus, Parker and colleagues conclude that “ovarian conservation until age 65 benefits long-term survival.”
Other factors may influence survival
GUZICK: Ovarian conservation reduces hip fracture3 but increases breast cancer, at least up until age 50.6 Such factors are included in the Parker analysis, but the main drivers of the model are heart disease and ovarian cancer. The conceptual framework for the model, and the pattern of the results, are clear strengths of this study.
MENZIN: Parker et al noted that their study did not address the benefits of oophorectomy among women with known or possible hereditary predisposition to ovarian cancer. Nevertheless, being aware of this major risk factor and its relevance to an informed consent discussion of hysterectomy is important, especially given the recognized benefits of risk-reducing surgery in this setting.
For women whose risk of ovarian cancer is equivalent to that of the general population, the decision is more complex. Hysterectomy, even with ovarian conservation, itself appears to reduce the risk of ovarian cancer by 10% to 40%—probably because abnormal-appearing ovaries are usually removed at hysterectomy.7,8 The prognosis of ovarian cancer in conserved ovaries appears equivalent to that in women without hysterectomy,9 although several studies suggest that 5% to 15% of ovarian cancers might have been prevented by oophorectomy at the time of prior hysterectomy for benign disease.
Why the Parker findings can’t be taken at face value
GUZICK: The estimated benefit of ovarian conservation in regard to heart disease was based on data acquired between 1976 and 1982 from the Nurses’ Health Study (NHS).2 This is problematic for several reasons. First, the relative risk of 2.2 was estimated in the NHS for coronary heart disease events, not deaths.2 It is not clear how Parker et al converted relative risk of events to relative risk of deaths, but apparently the risk estimate for events was applied to a baseline death rate. If so, then, because not all women with a cardiovascular event from 1976 to 1982 died of cardiovascular disease, the effect of oophorectomy is overstated.
Translating event effects to mortality effects is even more problematic when applied to contemporary medical practice. Women at risk of common cardiovascular problems such as hypertension and coronary artery disease now have the benefit of advances in diagnosis (blood pressure monitoring, biochemical markers, endothelial function tests, and coronary imaging) and treatment (eg, statins, antihypertensives, and coronary artery stents), which can reduce the likelihood of both cardiovascular events and deaths.
Finally, the relative risk for oophorectomy is based not on a randomized trial but on the observational, longitudinal NHS study,2 which may have been subject to selection bias. Were women who went against prevailing wisdom and retained their ovaries at the time of hysterectomy the same ones who had a prevention/wellness view of personal health? Did they follow a regimen of personal fitness and nutrition that reduced their risk of heart disease? In such a scenario, not captured by the statistical controls in the study,4 the dual facts of ovarian conservation and reduced heart disease are true but unrelated.
MENZIN: I agree that the modeling used by Parker and colleagues depends on several reference data sets that have their own potential biases and limitations. For example, the authors recognized that “no published data were found for coronary risk when oophorectomy was performed after menopause,” yet their study purportedly demonstrated that the excess mortality associated with oophorectomy between the ages of 50 and 65 years was primarily a result of coronary disease.
The clinical importance of postmenopausal hormone production has not been fully determined. Furthermore, the duration of effective estrogen production in conserved ovaries also can be hard to predict; almost 33% of women experience menopause within 2 years after hysterectomy with ovarian conservation.10
The Parker study focuses on mortality; however, the likelihood of medical or surgical intervention for benign or equivocal adnexal pathology also should be considered, along with the potential complexity of such treatments.
Women feel uninformed about their options
GUZICK: In my judgment, the fate of the ovaries in a woman undergoing hysterectomy for benign disease should be based on a thorough discussion with the patient that takes into account her individual risk profile and the psychological weight she attaches to the various outcomes. Key factors in the risk profile include age; menopausal status; family history of heart disease and breast and ovarian cancer; and biochemical, genetic, or imaging findings related to cancer, cardiovascular disease, and osteoporosis.
For example, a 45-year-old woman who is lean and normotensive with a favorable lipid profile, and who greatly fears the prospect of ovarian cancer because a friend died of the disease, may choose to have her ovaries removed. Whether this decision is “right” or “wrong” in general is hard to say, but for this patient the decision is acceptable. Her individual risk for cardiovascular disease and osteoporosis can be monitored more carefully and, if necessary, treated effectively early on. She can be given estrogen for vasomotor symptoms.
For postmenopausal women in their early to mid-50s, the situation is murkier, but a blanket recommendation still seems unwarranted. For women in their late 50s and older, although the Parker model shows a “visual” difference between projected survival curves until age 65, it is not clear whether such differences are statistically significant.
MENZIN: A critical point was highlighted in a recent description of interviews with women awaiting hysterectomy. Bhavnani and Clarke11 found that “many women felt inadequately informed about their treatment options and were unaware of important longer-term outcomes of oophorectomy.” Although the work by Parker and colleagues adds another dimension to the counseling of women considering hysterectomy for benign indications, the complexity of that counseling continues to evolve.
Ultimately, the Parker study demonstrates that oophorectomy does not provide a survival benefit over ovarian conservation. This does not mean oophorectomy is always unadvised. Equivalent treatment arms of randomized trials in oncology have demonstrated that quality of life can vary between alternate therapies. Parker and colleagues did not address this critical issue—one I believe to be at the core of every therapeutic decision and informed consent discussion.
In the end, we must individualize the operation to meet the goals and expectations of the patient.
GUZICK: I agree. A one-size-fits-all approach to clinical decision-making is rarely appropriate. The study by Parker et al provides a framework for women to determine which size is best for them.
The authors report no financial relationships relevant to this article.
1. Guzick DS, Hoeger K. Sex, hormones, and hysterectomies. N Engl J Med. 2000;343:730-731.
2. Colditz GA, Willett WC, Stampfer MJ, et al. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105-1110.
3. Melton LJ, 3rd, Khosla S, Malkasian GD, et al. Fracture risk after bilateral oophorectomy in elderly women. J Bone Miner Res. 2003;18:900-905.
4. National Cancer Institute, Statistical Research and Applications Branch. DevCan database: SEER 13 incidence and mortality, 2000–2002, released April 2005, based on the November 2004 submission. For more information see: http://srab.cancer.gov/devcan/. Accessed October 13, 2005.
5. American Heart Association. Heart disease and stroke statistics-2005 update. Available at: www.american-heart.org/presenter.jhtml?identifier=1200026. Accessed October 13, 2005.
6. Shairer C, Persson I, Falkeborn M, Naessen T, Troisi R, Brinton LA. Breast cancer risk associated with gynecologic surgery and indications for such surgery. Int J Cancer. 1997;70:150-154.
7. Parazzini F, Negri E, La Vecchia C, Luchini L, Mezzopane R. Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. Obstet Gynecol. 1993;81:363-366.
8. Chiaffarino F, Parazzini F, Decarli A, et al. Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer. Obstet Gynecol Surv. 2005;60:586-587.
9. Fine BA, Yazigi R, Risser R. Prognosis of ovarian cancer developing in the residual ovary. Gynecol Oncol. 1991;43:164-166.
10. Siddle N, Sarrel P, Whitehead M. The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function. A literature review. Fertil Steril. 1987;47:94-100.
11. Bhavnani V, Clarke A. Women awaiting hysterectomy: a qualitative study of issues involved in decisions about oophorectomy. BJOG. 2003;110:168-174.
1. Guzick DS, Hoeger K. Sex, hormones, and hysterectomies. N Engl J Med. 2000;343:730-731.
2. Colditz GA, Willett WC, Stampfer MJ, et al. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105-1110.
3. Melton LJ, 3rd, Khosla S, Malkasian GD, et al. Fracture risk after bilateral oophorectomy in elderly women. J Bone Miner Res. 2003;18:900-905.
4. National Cancer Institute, Statistical Research and Applications Branch. DevCan database: SEER 13 incidence and mortality, 2000–2002, released April 2005, based on the November 2004 submission. For more information see: http://srab.cancer.gov/devcan/. Accessed October 13, 2005.
5. American Heart Association. Heart disease and stroke statistics-2005 update. Available at: www.american-heart.org/presenter.jhtml?identifier=1200026. Accessed October 13, 2005.
6. Shairer C, Persson I, Falkeborn M, Naessen T, Troisi R, Brinton LA. Breast cancer risk associated with gynecologic surgery and indications for such surgery. Int J Cancer. 1997;70:150-154.
7. Parazzini F, Negri E, La Vecchia C, Luchini L, Mezzopane R. Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. Obstet Gynecol. 1993;81:363-366.
8. Chiaffarino F, Parazzini F, Decarli A, et al. Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer. Obstet Gynecol Surv. 2005;60:586-587.
9. Fine BA, Yazigi R, Risser R. Prognosis of ovarian cancer developing in the residual ovary. Gynecol Oncol. 1991;43:164-166.
10. Siddle N, Sarrel P, Whitehead M. The effect of hysterectomy on the age at ovarian failure: identification of a subgroup of women with premature loss of ovarian function. A literature review. Fertil Steril. 1987;47:94-100.
11. Bhavnani V, Clarke A. Women awaiting hysterectomy: a qualitative study of issues involved in decisions about oophorectomy. BJOG. 2003;110:168-174.
Q Is there a blood test for ovarian cancer?
Expert commentary
Ovarian cancer will strike 22,000 American women this year and ultimately kill 16,000.1 This cancer tends to exhibit few early symptoms, present at an advanced stage, and have low survival rates. As Mor and colleagues note, “Despite being one tenth as common as breast cancer, epithelial ovarian cancer is 3 times more lethal.” Although modest but significant gains have been achieved through advances in surgical and medical therapy, the holy grail of ovarian cancer investigation is an effective method of early detection.
Unlike breast or prostate cancer, ovarian cancer has a very low prevalence in the general population (50/100,000). Looking for a “needle in a haystack” requires a screening tool of exceptional sensitivity and specificity. The problem: Even a screening test with 99% specificity and 100% sensitivity would yield only 1 in 21 women with a positive screen who actually has the disease.2 Ultimately, confirming the validity of a positive screen requires surgery.
How technology is spurring progress
Recent developments in molecular biology have led to an explosion of new biomarkers. Microarray technology allows the rapid screening of proteins differentially expressed in cancer versus normal cells. Each of these proteins has the potential to be used for cancer screening.
With this new technology, Mor and colleagues at Yale University identified 4 markers that, when used together, achieved a sensitivity, specificity, and positive predictive value of 95%, with a negative predictive value of 94%. The markers are leptin, prolactin, osteopontin, and insulin-like growth factor-II. They successfully detected 23 of 24 patients with stage I and II disease. When compared with screening strategies based on proteomic patterns generated by mass spectroscopy, these markers are far less complex and expensive.3
Ovarian cancer screening strategies pursued over the past 20 years include the use of serum tumor markers such as CA 125, imaging modalities such as transvaginal sonography, or both. To date, no single test or combination of tests has achieved the high standards required for screening, even among high-risk populations. However, this may soon change.
The bottom line
Unfortunately, these markers do not yet meet the stringent requirements for population-based screening. To do so, they must be validated in a much larger population of patients and must have sensitivity and specificity well above current levels. When compared to CA 125 alone, however, they represent a remarkable improvement.
In the future, the authors predict the markers should “improve our ability to accurately detect premalignant change or early stage ovarian cancer in asymptomatic women at increased risk.”
The commentators report no financial relationships relevant to this article.
1. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30.
2. NIH Consensus Conference. Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA. 1995;273:491-497.
3. Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002;359:572-577.
Expert commentary
Ovarian cancer will strike 22,000 American women this year and ultimately kill 16,000.1 This cancer tends to exhibit few early symptoms, present at an advanced stage, and have low survival rates. As Mor and colleagues note, “Despite being one tenth as common as breast cancer, epithelial ovarian cancer is 3 times more lethal.” Although modest but significant gains have been achieved through advances in surgical and medical therapy, the holy grail of ovarian cancer investigation is an effective method of early detection.
Unlike breast or prostate cancer, ovarian cancer has a very low prevalence in the general population (50/100,000). Looking for a “needle in a haystack” requires a screening tool of exceptional sensitivity and specificity. The problem: Even a screening test with 99% specificity and 100% sensitivity would yield only 1 in 21 women with a positive screen who actually has the disease.2 Ultimately, confirming the validity of a positive screen requires surgery.
How technology is spurring progress
Recent developments in molecular biology have led to an explosion of new biomarkers. Microarray technology allows the rapid screening of proteins differentially expressed in cancer versus normal cells. Each of these proteins has the potential to be used for cancer screening.
With this new technology, Mor and colleagues at Yale University identified 4 markers that, when used together, achieved a sensitivity, specificity, and positive predictive value of 95%, with a negative predictive value of 94%. The markers are leptin, prolactin, osteopontin, and insulin-like growth factor-II. They successfully detected 23 of 24 patients with stage I and II disease. When compared with screening strategies based on proteomic patterns generated by mass spectroscopy, these markers are far less complex and expensive.3
Ovarian cancer screening strategies pursued over the past 20 years include the use of serum tumor markers such as CA 125, imaging modalities such as transvaginal sonography, or both. To date, no single test or combination of tests has achieved the high standards required for screening, even among high-risk populations. However, this may soon change.
The bottom line
Unfortunately, these markers do not yet meet the stringent requirements for population-based screening. To do so, they must be validated in a much larger population of patients and must have sensitivity and specificity well above current levels. When compared to CA 125 alone, however, they represent a remarkable improvement.
In the future, the authors predict the markers should “improve our ability to accurately detect premalignant change or early stage ovarian cancer in asymptomatic women at increased risk.”
The commentators report no financial relationships relevant to this article.
Expert commentary
Ovarian cancer will strike 22,000 American women this year and ultimately kill 16,000.1 This cancer tends to exhibit few early symptoms, present at an advanced stage, and have low survival rates. As Mor and colleagues note, “Despite being one tenth as common as breast cancer, epithelial ovarian cancer is 3 times more lethal.” Although modest but significant gains have been achieved through advances in surgical and medical therapy, the holy grail of ovarian cancer investigation is an effective method of early detection.
Unlike breast or prostate cancer, ovarian cancer has a very low prevalence in the general population (50/100,000). Looking for a “needle in a haystack” requires a screening tool of exceptional sensitivity and specificity. The problem: Even a screening test with 99% specificity and 100% sensitivity would yield only 1 in 21 women with a positive screen who actually has the disease.2 Ultimately, confirming the validity of a positive screen requires surgery.
How technology is spurring progress
Recent developments in molecular biology have led to an explosion of new biomarkers. Microarray technology allows the rapid screening of proteins differentially expressed in cancer versus normal cells. Each of these proteins has the potential to be used for cancer screening.
With this new technology, Mor and colleagues at Yale University identified 4 markers that, when used together, achieved a sensitivity, specificity, and positive predictive value of 95%, with a negative predictive value of 94%. The markers are leptin, prolactin, osteopontin, and insulin-like growth factor-II. They successfully detected 23 of 24 patients with stage I and II disease. When compared with screening strategies based on proteomic patterns generated by mass spectroscopy, these markers are far less complex and expensive.3
Ovarian cancer screening strategies pursued over the past 20 years include the use of serum tumor markers such as CA 125, imaging modalities such as transvaginal sonography, or both. To date, no single test or combination of tests has achieved the high standards required for screening, even among high-risk populations. However, this may soon change.
The bottom line
Unfortunately, these markers do not yet meet the stringent requirements for population-based screening. To do so, they must be validated in a much larger population of patients and must have sensitivity and specificity well above current levels. When compared to CA 125 alone, however, they represent a remarkable improvement.
In the future, the authors predict the markers should “improve our ability to accurately detect premalignant change or early stage ovarian cancer in asymptomatic women at increased risk.”
The commentators report no financial relationships relevant to this article.
1. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30.
2. NIH Consensus Conference. Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA. 1995;273:491-497.
3. Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002;359:572-577.
1. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30.
2. NIH Consensus Conference. Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. JAMA. 1995;273:491-497.
3. Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002;359:572-577.
Q Do androgen levels help diagnose low libido?
Expert commentary
In women, androgen insufficiency is generally defined as a cluster of symptoms and signs—diminished well-being, unexplained fatigue, decreased sexual desire, and thinning pubic hair—in the presence of decreased bioavailable testosterone and normal estrogen. However, we lack evidence that this syndrome can be diagnosed by measuring circulating androgens.
Davis and colleagues explored the question by randomly recruiting 1,423 women aged 18 to 75 from the electoral rolls of Victoria, Australia. Voting is mandatory in Australia, where every adult is on the rolls; thus, the study population represented a cross-section of the general female adult population in that country.
After exclusions, Davis et al measured circulating androgens and sexual function (by a self-reported scale) in 1,021 women. The objective: to determine whether women who reported “low sexual well-being” were more likely to have low serum androgen levels than women who did not.
No correlation between testosterone and libido
Davis and colleagues found no evidence that total or free testosterone levels help determine which women have low sexual function. Although significant associations were noted between low levels of dehydroepiandrosterone sulfate (DHEAS) and sexual dysfunction, Davis et al found no diagnostically useful reason to measure DHEAS. Most women with low DHEAS reported no sexual dysfunction, and most women with sexual dysfunction lacked low DHEAS.
The likelihood of a clinically useful association between women with low sexual function and a low androgen level was greatest when the proportion of women with low sexual function was small (less than the fifth percentile) and the normal range for the serum androgen level was relatively large, such as the DHEAS level among young women.1
Still no correlation in women at midlife
In the second study, Dennerstein et al used data collected over 8 years from the Melbourne Women’s Midlife Health Project, a prospective, longitudinal, population-based study of Australian women aged 45 to 55. They chose this age group because hormonal changes during the menopausal transition “do not occur in a vacuum.” Rather, the midlife years coincide with other transitions as children leave home and parents age. In addition, some women may lose or change sexual partners, some of whom have their own problems with sexual function. The authors wanted to determine whether women’s sexual function is more dependent on psychosocial and relationship factors than on actual hormone levels.
The study involved annual measurements of both sexual function (by questionnaire) and hormone levels. Data were available from 336 women.
The findings: Only estradiol levels had a direct effect on sexual function, and then only on sexual response and dyspareunia. However, estradiol levels were less important than prior levels of sexual function, a change in partners, or feelings for the partner. Testosterone and DHEAS levels did not correlate with sexual function.
So how do we diagnose low libido?
Although a correlation may exist between low levels of circulating androgens and sexual dysfunction,2 there is no consensus on the clinical utility of measuring androgens to diagnose it. These studies are consistent with others that have failed to find serum testosterone levels useful in diagnosing androgen insufficiency.3
One possibility may be that commercial assays for testosterone lack sufficient sensitivity and reliability to accurately measure the low levels of testosterone found in women, although the authors of both studies used reliable and reproducible methods.
Thus, for the time being, at least, androgen insufficiency syndrome remains a clinical diagnosis.
The commentators report no financial relationships relevant to this article.
1. Davison S, Bell R, Donath S, Montalto J, Davis S. Androgen levels in adult females: changes with age, menopause and oophorectomy. J Clin Endocrinol Metab. In press.
2. Turna B, Apaydin E, Semerci B, Altay B, Cikili N, Nazli O. Women with low libido: correlation of decreased androgen levels with female sexual function index. Int J Impot Res. 2005;17:148-153.
3. Bachmann G, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002;77:660-665.
Expert commentary
In women, androgen insufficiency is generally defined as a cluster of symptoms and signs—diminished well-being, unexplained fatigue, decreased sexual desire, and thinning pubic hair—in the presence of decreased bioavailable testosterone and normal estrogen. However, we lack evidence that this syndrome can be diagnosed by measuring circulating androgens.
Davis and colleagues explored the question by randomly recruiting 1,423 women aged 18 to 75 from the electoral rolls of Victoria, Australia. Voting is mandatory in Australia, where every adult is on the rolls; thus, the study population represented a cross-section of the general female adult population in that country.
After exclusions, Davis et al measured circulating androgens and sexual function (by a self-reported scale) in 1,021 women. The objective: to determine whether women who reported “low sexual well-being” were more likely to have low serum androgen levels than women who did not.
No correlation between testosterone and libido
Davis and colleagues found no evidence that total or free testosterone levels help determine which women have low sexual function. Although significant associations were noted between low levels of dehydroepiandrosterone sulfate (DHEAS) and sexual dysfunction, Davis et al found no diagnostically useful reason to measure DHEAS. Most women with low DHEAS reported no sexual dysfunction, and most women with sexual dysfunction lacked low DHEAS.
The likelihood of a clinically useful association between women with low sexual function and a low androgen level was greatest when the proportion of women with low sexual function was small (less than the fifth percentile) and the normal range for the serum androgen level was relatively large, such as the DHEAS level among young women.1
Still no correlation in women at midlife
In the second study, Dennerstein et al used data collected over 8 years from the Melbourne Women’s Midlife Health Project, a prospective, longitudinal, population-based study of Australian women aged 45 to 55. They chose this age group because hormonal changes during the menopausal transition “do not occur in a vacuum.” Rather, the midlife years coincide with other transitions as children leave home and parents age. In addition, some women may lose or change sexual partners, some of whom have their own problems with sexual function. The authors wanted to determine whether women’s sexual function is more dependent on psychosocial and relationship factors than on actual hormone levels.
The study involved annual measurements of both sexual function (by questionnaire) and hormone levels. Data were available from 336 women.
The findings: Only estradiol levels had a direct effect on sexual function, and then only on sexual response and dyspareunia. However, estradiol levels were less important than prior levels of sexual function, a change in partners, or feelings for the partner. Testosterone and DHEAS levels did not correlate with sexual function.
So how do we diagnose low libido?
Although a correlation may exist between low levels of circulating androgens and sexual dysfunction,2 there is no consensus on the clinical utility of measuring androgens to diagnose it. These studies are consistent with others that have failed to find serum testosterone levels useful in diagnosing androgen insufficiency.3
One possibility may be that commercial assays for testosterone lack sufficient sensitivity and reliability to accurately measure the low levels of testosterone found in women, although the authors of both studies used reliable and reproducible methods.
Thus, for the time being, at least, androgen insufficiency syndrome remains a clinical diagnosis.
The commentators report no financial relationships relevant to this article.
Expert commentary
In women, androgen insufficiency is generally defined as a cluster of symptoms and signs—diminished well-being, unexplained fatigue, decreased sexual desire, and thinning pubic hair—in the presence of decreased bioavailable testosterone and normal estrogen. However, we lack evidence that this syndrome can be diagnosed by measuring circulating androgens.
Davis and colleagues explored the question by randomly recruiting 1,423 women aged 18 to 75 from the electoral rolls of Victoria, Australia. Voting is mandatory in Australia, where every adult is on the rolls; thus, the study population represented a cross-section of the general female adult population in that country.
After exclusions, Davis et al measured circulating androgens and sexual function (by a self-reported scale) in 1,021 women. The objective: to determine whether women who reported “low sexual well-being” were more likely to have low serum androgen levels than women who did not.
No correlation between testosterone and libido
Davis and colleagues found no evidence that total or free testosterone levels help determine which women have low sexual function. Although significant associations were noted between low levels of dehydroepiandrosterone sulfate (DHEAS) and sexual dysfunction, Davis et al found no diagnostically useful reason to measure DHEAS. Most women with low DHEAS reported no sexual dysfunction, and most women with sexual dysfunction lacked low DHEAS.
The likelihood of a clinically useful association between women with low sexual function and a low androgen level was greatest when the proportion of women with low sexual function was small (less than the fifth percentile) and the normal range for the serum androgen level was relatively large, such as the DHEAS level among young women.1
Still no correlation in women at midlife
In the second study, Dennerstein et al used data collected over 8 years from the Melbourne Women’s Midlife Health Project, a prospective, longitudinal, population-based study of Australian women aged 45 to 55. They chose this age group because hormonal changes during the menopausal transition “do not occur in a vacuum.” Rather, the midlife years coincide with other transitions as children leave home and parents age. In addition, some women may lose or change sexual partners, some of whom have their own problems with sexual function. The authors wanted to determine whether women’s sexual function is more dependent on psychosocial and relationship factors than on actual hormone levels.
The study involved annual measurements of both sexual function (by questionnaire) and hormone levels. Data were available from 336 women.
The findings: Only estradiol levels had a direct effect on sexual function, and then only on sexual response and dyspareunia. However, estradiol levels were less important than prior levels of sexual function, a change in partners, or feelings for the partner. Testosterone and DHEAS levels did not correlate with sexual function.
So how do we diagnose low libido?
Although a correlation may exist between low levels of circulating androgens and sexual dysfunction,2 there is no consensus on the clinical utility of measuring androgens to diagnose it. These studies are consistent with others that have failed to find serum testosterone levels useful in diagnosing androgen insufficiency.3
One possibility may be that commercial assays for testosterone lack sufficient sensitivity and reliability to accurately measure the low levels of testosterone found in women, although the authors of both studies used reliable and reproducible methods.
Thus, for the time being, at least, androgen insufficiency syndrome remains a clinical diagnosis.
The commentators report no financial relationships relevant to this article.
1. Davison S, Bell R, Donath S, Montalto J, Davis S. Androgen levels in adult females: changes with age, menopause and oophorectomy. J Clin Endocrinol Metab. In press.
2. Turna B, Apaydin E, Semerci B, Altay B, Cikili N, Nazli O. Women with low libido: correlation of decreased androgen levels with female sexual function index. Int J Impot Res. 2005;17:148-153.
3. Bachmann G, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002;77:660-665.
1. Davison S, Bell R, Donath S, Montalto J, Davis S. Androgen levels in adult females: changes with age, menopause and oophorectomy. J Clin Endocrinol Metab. In press.
2. Turna B, Apaydin E, Semerci B, Altay B, Cikili N, Nazli O. Women with low libido: correlation of decreased androgen levels with female sexual function index. Int J Impot Res. 2005;17:148-153.
3. Bachmann G, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002;77:660-665.
Q Does treating gestational diabetes improve outcomes?
Expert Commentary
Gestational diabetes mellitus has occasionally seemed like a name looking for a disease. Screening recommendations and diagnostic criteria have been debated and changed, and it has appeared that, regardless of intervention, outcomes are the same.
This randomized trial sheds new light on the effectiveness of diagnosis and intervention, but some issues remain unclear—a fact pointed out in an editorial accompanying the study.1 My interpretation is similar to the one outlined in that editorial.
Nonstandard diagnostic criterion
Though the results are compelling and the randomized clinical trial model lends credence to the conclusions, the diagnostic test and criterion for diagnosing gestational diabetes (75-g glucose load with a 2-hour value >140 mg/dL) are not the standard in the United States, so the results may not be applicable in the US.
A real difference, or coincidence?
More adverse perinatal outcomes were reported among the “routine care” group than the intervention group. The authors did not clarify, however, whether the 5 perinatal deaths in the routine care group could be attributed to gestational diabetes or were coincidental. Also, although the difference in birth weight was statistically significant (mean weight of 3,335 g in the intervention group versus 3,482 g for routine care; P.001 i am unsure of the clinical importance this difference.>
Other variables listed under adverse outcomes included 5-minute Apgar scores of less than 7 and admission to the NICU, both of which can be based on highly subjective criteria. No information was offered about whether—and how—such decision-making was standardized.
Was it ethical to ignore screening?
US practitioners would not ignore the results of a gestational diabetes screening test, as in this study (neither practitioners nor patients were made aware of the diagnosis). Thus, the findings shed little light on real-world practices of US ObGyns.
We also lack information on the cost (in dollar terms and morbidity) of any false-positive results.
Stick to ACOG guidelines
Gestational diabetes is an increasing problem, compounded by the obesity epidemic. Failing to screen patients, or ignoring a positive screen, would seem ill-advised, and glucose control would seem to be a prudent way to minimize maternal and perinatal morbidity. We need to determine the appropriate screening tools and diagnostic criteria, glucose values that should prompt intervention, and the optimal form of intervention, be it through diet alone or in combination with oral hypoglycemics or insulin.
Until these questions are resolved (probably not within this decade), I suggest we continue to follow ACOG guidelines for diagnosis and management.2
Dr. Legro has received grant support from the American Heart Association, Crown, General Mills, and Pfizer and is a consultant for Abbott and Ortho-McNeil. Dr. Greenberg and Dr. Repke report no financial relationships relevant to these articles.
Expert Commentary
Gestational diabetes mellitus has occasionally seemed like a name looking for a disease. Screening recommendations and diagnostic criteria have been debated and changed, and it has appeared that, regardless of intervention, outcomes are the same.
This randomized trial sheds new light on the effectiveness of diagnosis and intervention, but some issues remain unclear—a fact pointed out in an editorial accompanying the study.1 My interpretation is similar to the one outlined in that editorial.
Nonstandard diagnostic criterion
Though the results are compelling and the randomized clinical trial model lends credence to the conclusions, the diagnostic test and criterion for diagnosing gestational diabetes (75-g glucose load with a 2-hour value >140 mg/dL) are not the standard in the United States, so the results may not be applicable in the US.
A real difference, or coincidence?
More adverse perinatal outcomes were reported among the “routine care” group than the intervention group. The authors did not clarify, however, whether the 5 perinatal deaths in the routine care group could be attributed to gestational diabetes or were coincidental. Also, although the difference in birth weight was statistically significant (mean weight of 3,335 g in the intervention group versus 3,482 g for routine care; P.001 i am unsure of the clinical importance this difference.>
Other variables listed under adverse outcomes included 5-minute Apgar scores of less than 7 and admission to the NICU, both of which can be based on highly subjective criteria. No information was offered about whether—and how—such decision-making was standardized.
Was it ethical to ignore screening?
US practitioners would not ignore the results of a gestational diabetes screening test, as in this study (neither practitioners nor patients were made aware of the diagnosis). Thus, the findings shed little light on real-world practices of US ObGyns.
We also lack information on the cost (in dollar terms and morbidity) of any false-positive results.
Stick to ACOG guidelines
Gestational diabetes is an increasing problem, compounded by the obesity epidemic. Failing to screen patients, or ignoring a positive screen, would seem ill-advised, and glucose control would seem to be a prudent way to minimize maternal and perinatal morbidity. We need to determine the appropriate screening tools and diagnostic criteria, glucose values that should prompt intervention, and the optimal form of intervention, be it through diet alone or in combination with oral hypoglycemics or insulin.
Until these questions are resolved (probably not within this decade), I suggest we continue to follow ACOG guidelines for diagnosis and management.2
Dr. Legro has received grant support from the American Heart Association, Crown, General Mills, and Pfizer and is a consultant for Abbott and Ortho-McNeil. Dr. Greenberg and Dr. Repke report no financial relationships relevant to these articles.
Expert Commentary
Gestational diabetes mellitus has occasionally seemed like a name looking for a disease. Screening recommendations and diagnostic criteria have been debated and changed, and it has appeared that, regardless of intervention, outcomes are the same.
This randomized trial sheds new light on the effectiveness of diagnosis and intervention, but some issues remain unclear—a fact pointed out in an editorial accompanying the study.1 My interpretation is similar to the one outlined in that editorial.
Nonstandard diagnostic criterion
Though the results are compelling and the randomized clinical trial model lends credence to the conclusions, the diagnostic test and criterion for diagnosing gestational diabetes (75-g glucose load with a 2-hour value >140 mg/dL) are not the standard in the United States, so the results may not be applicable in the US.
A real difference, or coincidence?
More adverse perinatal outcomes were reported among the “routine care” group than the intervention group. The authors did not clarify, however, whether the 5 perinatal deaths in the routine care group could be attributed to gestational diabetes or were coincidental. Also, although the difference in birth weight was statistically significant (mean weight of 3,335 g in the intervention group versus 3,482 g for routine care; P.001 i am unsure of the clinical importance this difference.>
Other variables listed under adverse outcomes included 5-minute Apgar scores of less than 7 and admission to the NICU, both of which can be based on highly subjective criteria. No information was offered about whether—and how—such decision-making was standardized.
Was it ethical to ignore screening?
US practitioners would not ignore the results of a gestational diabetes screening test, as in this study (neither practitioners nor patients were made aware of the diagnosis). Thus, the findings shed little light on real-world practices of US ObGyns.
We also lack information on the cost (in dollar terms and morbidity) of any false-positive results.
Stick to ACOG guidelines
Gestational diabetes is an increasing problem, compounded by the obesity epidemic. Failing to screen patients, or ignoring a positive screen, would seem ill-advised, and glucose control would seem to be a prudent way to minimize maternal and perinatal morbidity. We need to determine the appropriate screening tools and diagnostic criteria, glucose values that should prompt intervention, and the optimal form of intervention, be it through diet alone or in combination with oral hypoglycemics or insulin.
Until these questions are resolved (probably not within this decade), I suggest we continue to follow ACOG guidelines for diagnosis and management.2
Dr. Legro has received grant support from the American Heart Association, Crown, General Mills, and Pfizer and is a consultant for Abbott and Ortho-McNeil. Dr. Greenberg and Dr. Repke report no financial relationships relevant to these articles.
Q Which drug is best for infertile PCOS patients—clomiphene or metformin?
Expert Commentary
While metaanalysis suggests metformin improves ovulatory frequency in women with PCOS, until now the question of whether it helps achieve and maintain pregnancy has been explored only in small trials. The superiority of metformin for primary treatment of PCOS-related anovulatory infertility over standard-of-care clomiphene citrate was a matter of speculation (partly because metformin therapy was often reserved for “clomiphene failure”).
Palomba et al are to be commended for their study design (double-dummy, double-blind, randomized controlled trial) and choice of pregnancy as the primary outcome—a quantum leap forward for clinical trials involving PCOS. They studied 100 nonobese (BMI
Twice the pregnancy rate
The pregnancy rate after 6 months was significantly higher in the metformin group (69%) than in the clomiphene group (34%), and the abortion rate was significantly lower with metformin (10% versus 38% for clomiphene). There also was a trend toward a better live birth rate with metformin (84% versus 56% with clomiphene).
Intriguingly, ovulation and fecundity rates improved progressively with metformin and were highest during the sixth month of treatment, whereas an opposite trend was noted with clomiphene.
Flaws may limit credibility
Several imperfections mark this trial. Although it was billed as double-dummy, the dummy used for both clomiphene and metformin was described as “polyvitamin tablets similar in appearance to metformin and/or CC.” A true dummy is identical in appearance to the medication; any suggestion that a medication is inactive will lead to unblinding, potentially biasing the results.
Another problem: 10% of metformin patients and 6% of clomiphene patients were excluded from the analyses, in some cases for vague reasons (eg, significant weight loss). An intention-to-treat analysis including all randomized patients would have been more appropriate, although pregnancy rates would have been lower.
Finally, this comparatively large sample size is not nearly large enough to detect a significant difference in the ultimate pregnancy goal: a live birth.
Metformin best in nonobese women
This study reinforces the use of metformin as first-line therapy for PCOS in nonobese women with anovulatory infertility. It is too soon to extrapolate results to an obese PCOS population, which is more characteristic of the United States.
Expert Commentary
While metaanalysis suggests metformin improves ovulatory frequency in women with PCOS, until now the question of whether it helps achieve and maintain pregnancy has been explored only in small trials. The superiority of metformin for primary treatment of PCOS-related anovulatory infertility over standard-of-care clomiphene citrate was a matter of speculation (partly because metformin therapy was often reserved for “clomiphene failure”).
Palomba et al are to be commended for their study design (double-dummy, double-blind, randomized controlled trial) and choice of pregnancy as the primary outcome—a quantum leap forward for clinical trials involving PCOS. They studied 100 nonobese (BMI
Twice the pregnancy rate
The pregnancy rate after 6 months was significantly higher in the metformin group (69%) than in the clomiphene group (34%), and the abortion rate was significantly lower with metformin (10% versus 38% for clomiphene). There also was a trend toward a better live birth rate with metformin (84% versus 56% with clomiphene).
Intriguingly, ovulation and fecundity rates improved progressively with metformin and were highest during the sixth month of treatment, whereas an opposite trend was noted with clomiphene.
Flaws may limit credibility
Several imperfections mark this trial. Although it was billed as double-dummy, the dummy used for both clomiphene and metformin was described as “polyvitamin tablets similar in appearance to metformin and/or CC.” A true dummy is identical in appearance to the medication; any suggestion that a medication is inactive will lead to unblinding, potentially biasing the results.
Another problem: 10% of metformin patients and 6% of clomiphene patients were excluded from the analyses, in some cases for vague reasons (eg, significant weight loss). An intention-to-treat analysis including all randomized patients would have been more appropriate, although pregnancy rates would have been lower.
Finally, this comparatively large sample size is not nearly large enough to detect a significant difference in the ultimate pregnancy goal: a live birth.
Metformin best in nonobese women
This study reinforces the use of metformin as first-line therapy for PCOS in nonobese women with anovulatory infertility. It is too soon to extrapolate results to an obese PCOS population, which is more characteristic of the United States.
Expert Commentary
While metaanalysis suggests metformin improves ovulatory frequency in women with PCOS, until now the question of whether it helps achieve and maintain pregnancy has been explored only in small trials. The superiority of metformin for primary treatment of PCOS-related anovulatory infertility over standard-of-care clomiphene citrate was a matter of speculation (partly because metformin therapy was often reserved for “clomiphene failure”).
Palomba et al are to be commended for their study design (double-dummy, double-blind, randomized controlled trial) and choice of pregnancy as the primary outcome—a quantum leap forward for clinical trials involving PCOS. They studied 100 nonobese (BMI
Twice the pregnancy rate
The pregnancy rate after 6 months was significantly higher in the metformin group (69%) than in the clomiphene group (34%), and the abortion rate was significantly lower with metformin (10% versus 38% for clomiphene). There also was a trend toward a better live birth rate with metformin (84% versus 56% with clomiphene).
Intriguingly, ovulation and fecundity rates improved progressively with metformin and were highest during the sixth month of treatment, whereas an opposite trend was noted with clomiphene.
Flaws may limit credibility
Several imperfections mark this trial. Although it was billed as double-dummy, the dummy used for both clomiphene and metformin was described as “polyvitamin tablets similar in appearance to metformin and/or CC.” A true dummy is identical in appearance to the medication; any suggestion that a medication is inactive will lead to unblinding, potentially biasing the results.
Another problem: 10% of metformin patients and 6% of clomiphene patients were excluded from the analyses, in some cases for vague reasons (eg, significant weight loss). An intention-to-treat analysis including all randomized patients would have been more appropriate, although pregnancy rates would have been lower.
Finally, this comparatively large sample size is not nearly large enough to detect a significant difference in the ultimate pregnancy goal: a live birth.
Metformin best in nonobese women
This study reinforces the use of metformin as first-line therapy for PCOS in nonobese women with anovulatory infertility. It is too soon to extrapolate results to an obese PCOS population, which is more characteristic of the United States.