Estrogen does not cause breast cancer

“OOPHORECTOMY OR SALPINGECTOMY—WHICH MAKES MORE SENSE?”
William H. Parker, MD (March 2014)

Estrogen does not cause breast cancer
Excellent article by Dr. Parker, with one exception—he continues to promulgate the erroneous misconception that estrogen is what causes breast cancer. He repeats the inaccurate early conclusion of the Women’s Health Initiative (WHI) in 2002 that reported an increased risk of breast cancer. Yet review of that early data suggested that progestin was responsible for the increase, because patients taking estrogen alone had a lower breast cancer risk. Indeed, final and comprehensive review of the WHI studies in 2011 indicates that the estrogen-only arm of the study demonstrated lower breast cancer risks than the placebo group; that distinction continued in the post-intervention period as well.

We need to stop perpetuating the misconception that estrogen causes breast cancer, as the idea continues to be a major deterrent for patients to take estrogen during menopause, to the detriment of their health.

Rafael Haciski, MD
Naples, Florida

‡‡Dr. Parker responds:
Dr. Haciski is absolutely right about the fact that the estrogen-only arm of the WHI found a lower risk of breast cancer. The point I was trying to make, perhaps unsuccessfully, was that, in response to the 2002 WHI publication findings of an increased risk of breast cancer after estrogen and progesterone administration, the rate of oophorectomy declined. One interpretation of this trend toward ovarian conservation is that it reflected women deciding to keep their own ovarian hormones, rather than take exogenous hormones associated with health-related risks. While the 2004 WHI estrogen-only publication found a trend toward lower breast cancer risk, this association was not fully confirmed until 2012.¹ Even now, many women find the WHI estrogen-progestin and the estrogen-only publications confusing. It was not my intention to add to that confusion.

Reference

1. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

“UPDATE ON MINIMALLY INVASIVE GYNECOLOGY”
Amy Garcia, MD (April 2014) 

Terminology is important: A cesarean scar pregnancy is not an ectopic pregnancy
I read with great interest the excellent “Update on minimally invasive gynecology,” by Amy Garcia, MD, co-member of OBG Management’s Board of Editors. In it she gives an excellent definition and discussion of an increase in the epidemic of cesarean scar defects (CSD). Her update focuses on intermenstrual bleeding when the menstrual blood presumably collects in the defect and comes out externally, and unpredictably, as old dark blood. I strongly agree with how she managed her clinical case, as I too have had success in such cases using the lowest dosed birth control pills.

My concern, however, is for a potentially fatal outcome because of our use of the term “cesarean scar ectopic pregnancy,” which she mentions as being an additional clinical outcome as described in the review article by Tower and colleagues.¹ The strictest definition of ectopic pregnancy is “a pregnancy that occurs outside the uterus.” Many clinicians, however, refer to any pregnancy outside the normal endometrial cavity as being “ectopic.” Regardless of the definition used, I am aware of cases when this nomenclature has been responsible (at least in part) for maternal mortality.

Here is a scenario: A clinician gets an imaging report that there is a cesarean scar ectopic pregnancy. The patient is then treated with a methotrexate protocol² for the ectopic pregnancy, even though the sac size is small and there is no embryo or cardiac activity.

This patient did not actually have a cesarean scar ectopic pregnancy. Ninety-eight percent of ectopic pregnancies are tubal and these are the ones in which methotrexate has been studied adequately and used. Cesarean scar pregnancies (and, in my opinion, cervical pregnancies as well as cornual pregnancies) are very different from “garden variety” tubal ectopic pregnancies, and should not automatically be plugged into existing methotrexate protocols. In my experience, the existing methotrexate protocols do not work for cesarean scar pregnancies, and place these women at risk for potential harm, such as severe hemorrhage.

We should be meticulous in referring to these as cesarean scar pregnancies—not cesarean scar ectopic pregnancies—to help keep well-meaning clinicians from being misled.

Steven R. Goldstein, MD
Professor, Department of Obstetrics and Gynecology
New York University School of Medicine, New York, New York

References

1. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications.
J Minim Invasive Gynecol. 2013;20(5):562–572.

2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479–1485.

‡‡Dr. Garcia responds:
While I can appreciate the comments from my co-editor, Dr. Goldstein, I believe he is defocusing the real issue regarding pregnancies occurring in scar defects caused by previous cesarean section. Rather than creating an issue with the semantics of “ectopic,” I would have preferred to read that Dr. Goldstein was emphasizing the potentially significant, if not fatal, complications and management of cesarean scar pregnancies as he did with co-authors Dr. Timor-Trisch and Dr. Monteagudo in a recent OBG Management article.¹

To clarify the terminology, I used “cesarean scar ectopic pregnancy” as it was quoted from the work of Tower and colleagues.² This terminology adequately describes the location of the pregnancy, as many cesarean scar defects are not just located in the isthmus of the uterus but in the cervix itself.³ And by all accounts a pregnancy at this location would be considered to be a cervical pregnancy, which ACOG defines as ectopic. The following definition of ectopic pregnancy is taken from Dr. Goldstein’s reference to ACOG Practice Bulletin #94: “Nearly all ectopic pregnancies (97%) are implanted within the fallopian tube, although implantation can occur within the abdomen, cervix, ovary, or uterine cornua.”⁴ Indeed if ACOG uses “ectopic” to describe a pregnancy within the cervix, then “cesarean scar ectopic pregnancy” should be adequate to describe the location of a potentially dangerous pregnancy.

Dr. Goldstein is concerned that our colleagues may become confused by the terminology “cesarean scar ectopic pregnancy” because the word “ectopic” might denote a less clinically significant scenario. Yet I say that anyone confused by the location of the pregnancy has not understood the part of the descriptive term that is “cesarean scar” regardless of the use of “ectopic.” Any clinician treating a patient with a cesarean scar pregnancy would benefit from Dr. ­Goldstein and his colleagues’ article for diagnosis and management of this critical and potentially life-threatening scenario.

References

1. Timor-Trisch IE, Monteagudo A, Goldstein SR. How to identify and manage cesarean scar pregnancy. OBG Manag. 2014;26(6):19–27. 

2. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications. J Minim Invasive Gynecol. 2013;20(5):562–572.

3. Garcia A. Update on minimally invasive gynecology. OBG Manag. 2014;26(4):18–32.

4. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol.  2008;111(6):1479–1485.

Totally painless birth: A new concept in obstetrical anesthesia and labor management

A recent review on epidural anesthesia for pain management during labor, which was published in the New England Journal of Medicine,¹ starts with the following case presentation: “A 30-year-old nulliparous woman at 39 weeks gestation is undergoing induction of labor for premature rupture of membranes. She is currently receiving an oxytocin infusion, and her cervical dilatation is 1 cm. Her obstetrician has ordered intermittent intravenous administration of Fentanyl for pain relief, but she feels nauseated, has been unable to rest, and describes her pain as 9 on scale of 10.”

The case we present in this letter sounds totally different: A 26-year-old multiparous woman at 39 weeks’ gestation is scheduled for induction of labor because of a decreased amount of amniotic fluid detected on prenatal ultrasonography. On admission, her cervix is 1-cm dilated and 60% effaced. She has no uterine contractions, and she describes her pain as 0 on the scale of 10. Anticipating a long induction and unwilling to experience any pain, the patient requests and is offered epidural anesthesia prior to oxytocin administration. Labor takes longer than expected but ultimately results in the birth of a healthy child. At no time during the course of labor and delivery does the mother experience any pain or discomfort, and she reports an extremely satisfying experience.

Traditionally, epidural anesthesia is administered upon maternal request when labor pain becomes difficult or intolerable. Many obstetricians discourage the use of epidural anesthesia prior to the onset of the active stage of labor, where the cervix is 4- to 6-cm dilated and the patient is in a great deal of pain.

This concept of administering an analgesic after the onset of pain is very different from the one where anesthesia is provided to patients prior to surgical procedures. No physician would begin a scheduled surgical procedure before confirming administration of adequate anesthesia. Why should labor be any different?

The pain of labor caused by uterine contractions and cervical dilatation is transmitted through visceral afferent nerves entering the spinal cord from T10 through L1. Perineal stretching transmits pain through the pudendal and sacral nerves. Epidural analgesia for labor and delivery involves injection of a local anesthetic agent and an opioid analgesic into the lumbar epidural space. The injected agents gradually diffuse across the dura into the subarachnoid cavity. In spinal analgesia, which is often combined with epidural analgesia, the medication is injected directly into the subarachnoid cavity, resulting in a more rapid effect.²

The American Society of Anesthesiologists and the American College of Obstetrics and Gynecology jointly state, “Labor causes severe pain for many women. There is no other circumstance where it is considered acceptable for an individual to experience severe pain, untreated. In the absence of medical contraindications, maternal request is a sufficient medical indication for pain relief during labor.”³

We decided to stretch this concept by allowing epidural anesthesia to be administered upon maternal consent in anticipation of pain, prior to onset. Our extensive literature search failed to find any comprehensive studies on the use of epidural anesthesia in anticipation of labor pain.

In theory, neuraxial local anesthetic in clinically relevant doses affect only skeletal muscles, not smooth muscles; therefore, this agent should not significantly decrease the amplitude or frequency of contractions in the myometrium.⁴ Randomized controlled trials of the effects of analgesia during labor do not exist since it is impossible to randomly assign women to a placebo group (no pain relief). Most trials have compared the use of epidural analgesia with that of systemic narcotics. In one large trial, 992 multiparous women were randomly assigned to either epidural analgesia or midwifery support supplemented by intramuscular narcotic injections. When pain was rated on a scale of 0–100 (100 is high), the median score before the study interventions was 80 in the group of patients who did not receive an epidural analgesia. With the administration of epidural analgesia, the median score was 27.⁵

Clinicians and patients also have been concerned about whether the use of epidural analgesia increases the risk of cesarean delivery. The results of three randomized controlled trials demonstrated that early administration of epidural analgesia does not increase the rate of cesarean delivery among women with spontaneous or induced labor as compared with early initiation of opioids.^6–8 The fact that early epidural placement does not appear to increase the incidence of cesarean delivery is encouraging for our ongoing study but doesn’t necessarily mean that epidural analgesia prior to the onset of pain (preventive epidural) will have the same outcome. More research is needed.

Boris M. Petrikovsky, MD, PhD; Elya Kozlov, MD; Matthew Ackert, MD; Ralph Ruggiero, MD; and Crystal Behofsits, DO
Wyckoff Heights Medical Center, Brooklyn NY

References

1. Haukins GL. Epidural analgesia for labor and delivery. N Engl J Med. 2010;362(16):1502–1510.

2. Catterall WA, Mackie K. Local anesthetics. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, New York: McGraw-Hill; 2005;369–386.

3. American College of Obstetricians and Gynecologists. ACOG Committee Opinion #295: pain relief during labor. Obstet Gynecol. 2004;104(1):213.

4. Fanning RA, Campion DP, Collins CB, et al. A comparison of the inhibitory effects of bupivacaine and levobupivacaine on isolated human pregnant myometrium contractility. Anesth Analg. 2008;107(4):1303–1307.

5. Dickinson JE, Paech MJ, McDonald SJ, Evans SF. Maternal satisfaction with childbirth and intrapartum analgesia in nulliparous labor. Aust N Z J Obstet Gynecol. 2003;43(6):463–468.

6. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia in labor. N Engl J Med. 2005;352(7):655–665.

7. Ohel G, Gonen R, Vaida S, Barak S, Gaitini L. Early versus late initiation of epidural analgesia in labor: does it increase the risk of cesarean section? A randomized trial. Am J Obstet Gynecol. 2006:194(3):600–605.

8. Wong CA, McCarthy RJ, Sullivan JT, Scavone BM, Gerber SE, Yaghmour EA. Early compared with late neuraxial analgesia in nulliparous labor induction: a randomized controlled trial. Obstet Gynecol. 2009;113(5):1066–1074.  

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“OOPHORECTOMY OR SALPINGECTOMY—WHICH MAKES MORE SENSE?”
William H. Parker, MD (March 2014)

Estrogen does not cause breast cancer
Excellent article by Dr. Parker, with one exception—he continues to promulgate the erroneous misconception that estrogen is what causes breast cancer. He repeats the inaccurate early conclusion of the Women’s Health Initiative (WHI) in 2002 that reported an increased risk of breast cancer. Yet review of that early data suggested that progestin was responsible for the increase, because patients taking estrogen alone had a lower breast cancer risk. Indeed, final and comprehensive review of the WHI studies in 2011 indicates that the estrogen-only arm of the study demonstrated lower breast cancer risks than the placebo group; that distinction continued in the post-intervention period as well.

We need to stop perpetuating the misconception that estrogen causes breast cancer, as the idea continues to be a major deterrent for patients to take estrogen during menopause, to the detriment of their health.

Rafael Haciski, MD
Naples, Florida

‡‡Dr. Parker responds:
Dr. Haciski is absolutely right about the fact that the estrogen-only arm of the WHI found a lower risk of breast cancer. The point I was trying to make, perhaps unsuccessfully, was that, in response to the 2002 WHI publication findings of an increased risk of breast cancer after estrogen and progesterone administration, the rate of oophorectomy declined. One interpretation of this trend toward ovarian conservation is that it reflected women deciding to keep their own ovarian hormones, rather than take exogenous hormones associated with health-related risks. While the 2004 WHI estrogen-only publication found a trend toward lower breast cancer risk, this association was not fully confirmed until 2012.¹ Even now, many women find the WHI estrogen-progestin and the estrogen-only publications confusing. It was not my intention to add to that confusion.

Reference

1. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

“UPDATE ON MINIMALLY INVASIVE GYNECOLOGY”
Amy Garcia, MD (April 2014) 

Terminology is important: A cesarean scar pregnancy is not an ectopic pregnancy
I read with great interest the excellent “Update on minimally invasive gynecology,” by Amy Garcia, MD, co-member of OBG Management’s Board of Editors. In it she gives an excellent definition and discussion of an increase in the epidemic of cesarean scar defects (CSD). Her update focuses on intermenstrual bleeding when the menstrual blood presumably collects in the defect and comes out externally, and unpredictably, as old dark blood. I strongly agree with how she managed her clinical case, as I too have had success in such cases using the lowest dosed birth control pills.

My concern, however, is for a potentially fatal outcome because of our use of the term “cesarean scar ectopic pregnancy,” which she mentions as being an additional clinical outcome as described in the review article by Tower and colleagues.¹ The strictest definition of ectopic pregnancy is “a pregnancy that occurs outside the uterus.” Many clinicians, however, refer to any pregnancy outside the normal endometrial cavity as being “ectopic.” Regardless of the definition used, I am aware of cases when this nomenclature has been responsible (at least in part) for maternal mortality.

Here is a scenario: A clinician gets an imaging report that there is a cesarean scar ectopic pregnancy. The patient is then treated with a methotrexate protocol² for the ectopic pregnancy, even though the sac size is small and there is no embryo or cardiac activity.

This patient did not actually have a cesarean scar ectopic pregnancy. Ninety-eight percent of ectopic pregnancies are tubal and these are the ones in which methotrexate has been studied adequately and used. Cesarean scar pregnancies (and, in my opinion, cervical pregnancies as well as cornual pregnancies) are very different from “garden variety” tubal ectopic pregnancies, and should not automatically be plugged into existing methotrexate protocols. In my experience, the existing methotrexate protocols do not work for cesarean scar pregnancies, and place these women at risk for potential harm, such as severe hemorrhage.

We should be meticulous in referring to these as cesarean scar pregnancies—not cesarean scar ectopic pregnancies—to help keep well-meaning clinicians from being misled.

Steven R. Goldstein, MD
Professor, Department of Obstetrics and Gynecology
New York University School of Medicine, New York, New York

References

1. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications.
J Minim Invasive Gynecol. 2013;20(5):562–572.

2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479–1485.

‡‡Dr. Garcia responds:
While I can appreciate the comments from my co-editor, Dr. Goldstein, I believe he is defocusing the real issue regarding pregnancies occurring in scar defects caused by previous cesarean section. Rather than creating an issue with the semantics of “ectopic,” I would have preferred to read that Dr. Goldstein was emphasizing the potentially significant, if not fatal, complications and management of cesarean scar pregnancies as he did with co-authors Dr. Timor-Trisch and Dr. Monteagudo in a recent OBG Management article.¹

To clarify the terminology, I used “cesarean scar ectopic pregnancy” as it was quoted from the work of Tower and colleagues.² This terminology adequately describes the location of the pregnancy, as many cesarean scar defects are not just located in the isthmus of the uterus but in the cervix itself.³ And by all accounts a pregnancy at this location would be considered to be a cervical pregnancy, which ACOG defines as ectopic. The following definition of ectopic pregnancy is taken from Dr. Goldstein’s reference to ACOG Practice Bulletin #94: “Nearly all ectopic pregnancies (97%) are implanted within the fallopian tube, although implantation can occur within the abdomen, cervix, ovary, or uterine cornua.”⁴ Indeed if ACOG uses “ectopic” to describe a pregnancy within the cervix, then “cesarean scar ectopic pregnancy” should be adequate to describe the location of a potentially dangerous pregnancy.

Dr. Goldstein is concerned that our colleagues may become confused by the terminology “cesarean scar ectopic pregnancy” because the word “ectopic” might denote a less clinically significant scenario. Yet I say that anyone confused by the location of the pregnancy has not understood the part of the descriptive term that is “cesarean scar” regardless of the use of “ectopic.” Any clinician treating a patient with a cesarean scar pregnancy would benefit from Dr. ­Goldstein and his colleagues’ article for diagnosis and management of this critical and potentially life-threatening scenario.

References

1. Timor-Trisch IE, Monteagudo A, Goldstein SR. How to identify and manage cesarean scar pregnancy. OBG Manag. 2014;26(6):19–27. 

2. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications. J Minim Invasive Gynecol. 2013;20(5):562–572.

3. Garcia A. Update on minimally invasive gynecology. OBG Manag. 2014;26(4):18–32.

4. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol.  2008;111(6):1479–1485.

Totally painless birth: A new concept in obstetrical anesthesia and labor management

A recent review on epidural anesthesia for pain management during labor, which was published in the New England Journal of Medicine,¹ starts with the following case presentation: “A 30-year-old nulliparous woman at 39 weeks gestation is undergoing induction of labor for premature rupture of membranes. She is currently receiving an oxytocin infusion, and her cervical dilatation is 1 cm. Her obstetrician has ordered intermittent intravenous administration of Fentanyl for pain relief, but she feels nauseated, has been unable to rest, and describes her pain as 9 on scale of 10.”

The case we present in this letter sounds totally different: A 26-year-old multiparous woman at 39 weeks’ gestation is scheduled for induction of labor because of a decreased amount of amniotic fluid detected on prenatal ultrasonography. On admission, her cervix is 1-cm dilated and 60% effaced. She has no uterine contractions, and she describes her pain as 0 on the scale of 10. Anticipating a long induction and unwilling to experience any pain, the patient requests and is offered epidural anesthesia prior to oxytocin administration. Labor takes longer than expected but ultimately results in the birth of a healthy child. At no time during the course of labor and delivery does the mother experience any pain or discomfort, and she reports an extremely satisfying experience.

Traditionally, epidural anesthesia is administered upon maternal request when labor pain becomes difficult or intolerable. Many obstetricians discourage the use of epidural anesthesia prior to the onset of the active stage of labor, where the cervix is 4- to 6-cm dilated and the patient is in a great deal of pain.

This concept of administering an analgesic after the onset of pain is very different from the one where anesthesia is provided to patients prior to surgical procedures. No physician would begin a scheduled surgical procedure before confirming administration of adequate anesthesia. Why should labor be any different?

The pain of labor caused by uterine contractions and cervical dilatation is transmitted through visceral afferent nerves entering the spinal cord from T10 through L1. Perineal stretching transmits pain through the pudendal and sacral nerves. Epidural analgesia for labor and delivery involves injection of a local anesthetic agent and an opioid analgesic into the lumbar epidural space. The injected agents gradually diffuse across the dura into the subarachnoid cavity. In spinal analgesia, which is often combined with epidural analgesia, the medication is injected directly into the subarachnoid cavity, resulting in a more rapid effect.²

The American Society of Anesthesiologists and the American College of Obstetrics and Gynecology jointly state, “Labor causes severe pain for many women. There is no other circumstance where it is considered acceptable for an individual to experience severe pain, untreated. In the absence of medical contraindications, maternal request is a sufficient medical indication for pain relief during labor.”³

We decided to stretch this concept by allowing epidural anesthesia to be administered upon maternal consent in anticipation of pain, prior to onset. Our extensive literature search failed to find any comprehensive studies on the use of epidural anesthesia in anticipation of labor pain.

In theory, neuraxial local anesthetic in clinically relevant doses affect only skeletal muscles, not smooth muscles; therefore, this agent should not significantly decrease the amplitude or frequency of contractions in the myometrium.⁴ Randomized controlled trials of the effects of analgesia during labor do not exist since it is impossible to randomly assign women to a placebo group (no pain relief). Most trials have compared the use of epidural analgesia with that of systemic narcotics. In one large trial, 992 multiparous women were randomly assigned to either epidural analgesia or midwifery support supplemented by intramuscular narcotic injections. When pain was rated on a scale of 0–100 (100 is high), the median score before the study interventions was 80 in the group of patients who did not receive an epidural analgesia. With the administration of epidural analgesia, the median score was 27.⁵

Clinicians and patients also have been concerned about whether the use of epidural analgesia increases the risk of cesarean delivery. The results of three randomized controlled trials demonstrated that early administration of epidural analgesia does not increase the rate of cesarean delivery among women with spontaneous or induced labor as compared with early initiation of opioids.^6–8 The fact that early epidural placement does not appear to increase the incidence of cesarean delivery is encouraging for our ongoing study but doesn’t necessarily mean that epidural analgesia prior to the onset of pain (preventive epidural) will have the same outcome. More research is needed.

Boris M. Petrikovsky, MD, PhD; Elya Kozlov, MD; Matthew Ackert, MD; Ralph Ruggiero, MD; and Crystal Behofsits, DO
Wyckoff Heights Medical Center, Brooklyn NY

References

1. Haukins GL. Epidural analgesia for labor and delivery. N Engl J Med. 2010;362(16):1502–1510.

2. Catterall WA, Mackie K. Local anesthetics. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, New York: McGraw-Hill; 2005;369–386.

3. American College of Obstetricians and Gynecologists. ACOG Committee Opinion #295: pain relief during labor. Obstet Gynecol. 2004;104(1):213.

4. Fanning RA, Campion DP, Collins CB, et al. A comparison of the inhibitory effects of bupivacaine and levobupivacaine on isolated human pregnant myometrium contractility. Anesth Analg. 2008;107(4):1303–1307.

5. Dickinson JE, Paech MJ, McDonald SJ, Evans SF. Maternal satisfaction with childbirth and intrapartum analgesia in nulliparous labor. Aust N Z J Obstet Gynecol. 2003;43(6):463–468.

6. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia in labor. N Engl J Med. 2005;352(7):655–665.

7. Ohel G, Gonen R, Vaida S, Barak S, Gaitini L. Early versus late initiation of epidural analgesia in labor: does it increase the risk of cesarean section? A randomized trial. Am J Obstet Gynecol. 2006:194(3):600–605.

8. Wong CA, McCarthy RJ, Sullivan JT, Scavone BM, Gerber SE, Yaghmour EA. Early compared with late neuraxial analgesia in nulliparous labor induction: a randomized controlled trial. Obstet Gynecol. 2009;113(5):1066–1074.  

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“OOPHORECTOMY OR SALPINGECTOMY—WHICH MAKES MORE SENSE?”
William H. Parker, MD (March 2014)

Estrogen does not cause breast cancer
Excellent article by Dr. Parker, with one exception—he continues to promulgate the erroneous misconception that estrogen is what causes breast cancer. He repeats the inaccurate early conclusion of the Women’s Health Initiative (WHI) in 2002 that reported an increased risk of breast cancer. Yet review of that early data suggested that progestin was responsible for the increase, because patients taking estrogen alone had a lower breast cancer risk. Indeed, final and comprehensive review of the WHI studies in 2011 indicates that the estrogen-only arm of the study demonstrated lower breast cancer risks than the placebo group; that distinction continued in the post-intervention period as well.

We need to stop perpetuating the misconception that estrogen causes breast cancer, as the idea continues to be a major deterrent for patients to take estrogen during menopause, to the detriment of their health.

Rafael Haciski, MD
Naples, Florida

‡‡Dr. Parker responds:
Dr. Haciski is absolutely right about the fact that the estrogen-only arm of the WHI found a lower risk of breast cancer. The point I was trying to make, perhaps unsuccessfully, was that, in response to the 2002 WHI publication findings of an increased risk of breast cancer after estrogen and progesterone administration, the rate of oophorectomy declined. One interpretation of this trend toward ovarian conservation is that it reflected women deciding to keep their own ovarian hormones, rather than take exogenous hormones associated with health-related risks. While the 2004 WHI estrogen-only publication found a trend toward lower breast cancer risk, this association was not fully confirmed until 2012.¹ Even now, many women find the WHI estrogen-progestin and the estrogen-only publications confusing. It was not my intention to add to that confusion.

Reference

1. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

“UPDATE ON MINIMALLY INVASIVE GYNECOLOGY”
Amy Garcia, MD (April 2014) 

Terminology is important: A cesarean scar pregnancy is not an ectopic pregnancy
I read with great interest the excellent “Update on minimally invasive gynecology,” by Amy Garcia, MD, co-member of OBG Management’s Board of Editors. In it she gives an excellent definition and discussion of an increase in the epidemic of cesarean scar defects (CSD). Her update focuses on intermenstrual bleeding when the menstrual blood presumably collects in the defect and comes out externally, and unpredictably, as old dark blood. I strongly agree with how she managed her clinical case, as I too have had success in such cases using the lowest dosed birth control pills.

My concern, however, is for a potentially fatal outcome because of our use of the term “cesarean scar ectopic pregnancy,” which she mentions as being an additional clinical outcome as described in the review article by Tower and colleagues.¹ The strictest definition of ectopic pregnancy is “a pregnancy that occurs outside the uterus.” Many clinicians, however, refer to any pregnancy outside the normal endometrial cavity as being “ectopic.” Regardless of the definition used, I am aware of cases when this nomenclature has been responsible (at least in part) for maternal mortality.

Here is a scenario: A clinician gets an imaging report that there is a cesarean scar ectopic pregnancy. The patient is then treated with a methotrexate protocol² for the ectopic pregnancy, even though the sac size is small and there is no embryo or cardiac activity.

This patient did not actually have a cesarean scar ectopic pregnancy. Ninety-eight percent of ectopic pregnancies are tubal and these are the ones in which methotrexate has been studied adequately and used. Cesarean scar pregnancies (and, in my opinion, cervical pregnancies as well as cornual pregnancies) are very different from “garden variety” tubal ectopic pregnancies, and should not automatically be plugged into existing methotrexate protocols. In my experience, the existing methotrexate protocols do not work for cesarean scar pregnancies, and place these women at risk for potential harm, such as severe hemorrhage.

We should be meticulous in referring to these as cesarean scar pregnancies—not cesarean scar ectopic pregnancies—to help keep well-meaning clinicians from being misled.

Steven R. Goldstein, MD
Professor, Department of Obstetrics and Gynecology
New York University School of Medicine, New York, New York

References

1. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications.
J Minim Invasive Gynecol. 2013;20(5):562–572.

2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479–1485.

‡‡Dr. Garcia responds:
While I can appreciate the comments from my co-editor, Dr. Goldstein, I believe he is defocusing the real issue regarding pregnancies occurring in scar defects caused by previous cesarean section. Rather than creating an issue with the semantics of “ectopic,” I would have preferred to read that Dr. Goldstein was emphasizing the potentially significant, if not fatal, complications and management of cesarean scar pregnancies as he did with co-authors Dr. Timor-Trisch and Dr. Monteagudo in a recent OBG Management article.¹

To clarify the terminology, I used “cesarean scar ectopic pregnancy” as it was quoted from the work of Tower and colleagues.² This terminology adequately describes the location of the pregnancy, as many cesarean scar defects are not just located in the isthmus of the uterus but in the cervix itself.³ And by all accounts a pregnancy at this location would be considered to be a cervical pregnancy, which ACOG defines as ectopic. The following definition of ectopic pregnancy is taken from Dr. Goldstein’s reference to ACOG Practice Bulletin #94: “Nearly all ectopic pregnancies (97%) are implanted within the fallopian tube, although implantation can occur within the abdomen, cervix, ovary, or uterine cornua.”⁴ Indeed if ACOG uses “ectopic” to describe a pregnancy within the cervix, then “cesarean scar ectopic pregnancy” should be adequate to describe the location of a potentially dangerous pregnancy.

Dr. Goldstein is concerned that our colleagues may become confused by the terminology “cesarean scar ectopic pregnancy” because the word “ectopic” might denote a less clinically significant scenario. Yet I say that anyone confused by the location of the pregnancy has not understood the part of the descriptive term that is “cesarean scar” regardless of the use of “ectopic.” Any clinician treating a patient with a cesarean scar pregnancy would benefit from Dr. ­Goldstein and his colleagues’ article for diagnosis and management of this critical and potentially life-threatening scenario.

References

1. Timor-Trisch IE, Monteagudo A, Goldstein SR. How to identify and manage cesarean scar pregnancy. OBG Manag. 2014;26(6):19–27. 

2. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications. J Minim Invasive Gynecol. 2013;20(5):562–572.

3. Garcia A. Update on minimally invasive gynecology. OBG Manag. 2014;26(4):18–32.

4. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: Medical management of ectopic pregnancy. Obstet Gynecol.  2008;111(6):1479–1485.

Totally painless birth: A new concept in obstetrical anesthesia and labor management

A recent review on epidural anesthesia for pain management during labor, which was published in the New England Journal of Medicine,¹ starts with the following case presentation: “A 30-year-old nulliparous woman at 39 weeks gestation is undergoing induction of labor for premature rupture of membranes. She is currently receiving an oxytocin infusion, and her cervical dilatation is 1 cm. Her obstetrician has ordered intermittent intravenous administration of Fentanyl for pain relief, but she feels nauseated, has been unable to rest, and describes her pain as 9 on scale of 10.”

The case we present in this letter sounds totally different: A 26-year-old multiparous woman at 39 weeks’ gestation is scheduled for induction of labor because of a decreased amount of amniotic fluid detected on prenatal ultrasonography. On admission, her cervix is 1-cm dilated and 60% effaced. She has no uterine contractions, and she describes her pain as 0 on the scale of 10. Anticipating a long induction and unwilling to experience any pain, the patient requests and is offered epidural anesthesia prior to oxytocin administration. Labor takes longer than expected but ultimately results in the birth of a healthy child. At no time during the course of labor and delivery does the mother experience any pain or discomfort, and she reports an extremely satisfying experience.

Traditionally, epidural anesthesia is administered upon maternal request when labor pain becomes difficult or intolerable. Many obstetricians discourage the use of epidural anesthesia prior to the onset of the active stage of labor, where the cervix is 4- to 6-cm dilated and the patient is in a great deal of pain.

This concept of administering an analgesic after the onset of pain is very different from the one where anesthesia is provided to patients prior to surgical procedures. No physician would begin a scheduled surgical procedure before confirming administration of adequate anesthesia. Why should labor be any different?

The pain of labor caused by uterine contractions and cervical dilatation is transmitted through visceral afferent nerves entering the spinal cord from T10 through L1. Perineal stretching transmits pain through the pudendal and sacral nerves. Epidural analgesia for labor and delivery involves injection of a local anesthetic agent and an opioid analgesic into the lumbar epidural space. The injected agents gradually diffuse across the dura into the subarachnoid cavity. In spinal analgesia, which is often combined with epidural analgesia, the medication is injected directly into the subarachnoid cavity, resulting in a more rapid effect.²

The American Society of Anesthesiologists and the American College of Obstetrics and Gynecology jointly state, “Labor causes severe pain for many women. There is no other circumstance where it is considered acceptable for an individual to experience severe pain, untreated. In the absence of medical contraindications, maternal request is a sufficient medical indication for pain relief during labor.”³

We decided to stretch this concept by allowing epidural anesthesia to be administered upon maternal consent in anticipation of pain, prior to onset. Our extensive literature search failed to find any comprehensive studies on the use of epidural anesthesia in anticipation of labor pain.

In theory, neuraxial local anesthetic in clinically relevant doses affect only skeletal muscles, not smooth muscles; therefore, this agent should not significantly decrease the amplitude or frequency of contractions in the myometrium.⁴ Randomized controlled trials of the effects of analgesia during labor do not exist since it is impossible to randomly assign women to a placebo group (no pain relief). Most trials have compared the use of epidural analgesia with that of systemic narcotics. In one large trial, 992 multiparous women were randomly assigned to either epidural analgesia or midwifery support supplemented by intramuscular narcotic injections. When pain was rated on a scale of 0–100 (100 is high), the median score before the study interventions was 80 in the group of patients who did not receive an epidural analgesia. With the administration of epidural analgesia, the median score was 27.⁵

Clinicians and patients also have been concerned about whether the use of epidural analgesia increases the risk of cesarean delivery. The results of three randomized controlled trials demonstrated that early administration of epidural analgesia does not increase the rate of cesarean delivery among women with spontaneous or induced labor as compared with early initiation of opioids.^6–8 The fact that early epidural placement does not appear to increase the incidence of cesarean delivery is encouraging for our ongoing study but doesn’t necessarily mean that epidural analgesia prior to the onset of pain (preventive epidural) will have the same outcome. More research is needed.

Boris M. Petrikovsky, MD, PhD; Elya Kozlov, MD; Matthew Ackert, MD; Ralph Ruggiero, MD; and Crystal Behofsits, DO
Wyckoff Heights Medical Center, Brooklyn NY

References

1. Haukins GL. Epidural analgesia for labor and delivery. N Engl J Med. 2010;362(16):1502–1510.

2. Catterall WA, Mackie K. Local anesthetics. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, New York: McGraw-Hill; 2005;369–386.

3. American College of Obstetricians and Gynecologists. ACOG Committee Opinion #295: pain relief during labor. Obstet Gynecol. 2004;104(1):213.

4. Fanning RA, Campion DP, Collins CB, et al. A comparison of the inhibitory effects of bupivacaine and levobupivacaine on isolated human pregnant myometrium contractility. Anesth Analg. 2008;107(4):1303–1307.

5. Dickinson JE, Paech MJ, McDonald SJ, Evans SF. Maternal satisfaction with childbirth and intrapartum analgesia in nulliparous labor. Aust N Z J Obstet Gynecol. 2003;43(6):463–468.

6. Wong CA, Scavone BM, Peaceman AM, et al. The risk of cesarean delivery with neuraxial analgesia in labor. N Engl J Med. 2005;352(7):655–665.

7. Ohel G, Gonen R, Vaida S, Barak S, Gaitini L. Early versus late initiation of epidural analgesia in labor: does it increase the risk of cesarean section? A randomized trial. Am J Obstet Gynecol. 2006:194(3):600–605.

8. Wong CA, McCarthy RJ, Sullivan JT, Scavone BM, Gerber SE, Yaghmour EA. Early compared with late neuraxial analgesia in nulliparous labor induction: a randomized controlled trial. Obstet Gynecol. 2009;113(5):1066–1074.  

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