Expert Commentary

Objective

The Bethesda 2001 Workshop updated the 1991 Bethesda System terminology for reporting results of cervical cytology. This effort represents a focus on broad participation utilizing an Internet bulletin board to collect data prior to the workshop.

Method and Results

Eight months before the workshop convened, 9 forum groups of 6 to 10 persons developed recommendations for discussion. These recommendations were posted on the Internet to encourage discussion and commentary. More than 400 cytopathologists, gynecologists, epidemiologists, family physicians, attorneys, and patient advocates from 44 professional societies and 20 countries participated in the workshop.

After more than 1,000 comments were submitted via the bulletin board, the workshop convened in Bethesda, Maryland, from April 30 to May 2, 2001. The most clinically relevant changes to the Bethesda System are listed below.

• Specimen adequacy.
  • eliminates “satisfactory but limited by” (absence of endocervical cells is not considered unsatisfactory)
    
  
  
• General categorization.
  • “within normal limits” was changed to “negative for intraepithelial lesion”
    
  
  
• Interpretation/result.
  • “diagnosis” was replaced by “interpretation” or “result”
    
  
  
• Epithelial cell abnormalities.
  • ASCUS was replaced by ASC-US or ASC-H (cannot exclude HSIL)
    
  • 2-tiered LSIL and HSIL classifications remain
    
  • AGUS classification was significantly revised and changed to AGC, endocervical endometrial, or glandular cells NOS (not otherwise specified)
    
  • endometrial cells will be noted if present in women over the age of 40 rather than only postmenopausal patients
    
  
  

Who May Be Affected?

Physicians managing patients with cytologic abnormalities.

Expert Commentary

The wide range of participants lends significance to this extraordinary effort to correct and simplify the Bethesda System recommendations. First, a 6-month Internet survey generated many recommendations. This was followed by the actual workshop, which provided another opportunity to finalize the system. The process was deemed so successful that the American Society for Colposcopy and Cervical Pathology and the American College of Obstetricians and Gynecologists used a similar process when the workshop for the management of cytologic abnormalities was held later in 2001.

Overall, this is a kinder and gentler system. Elimination of “satisfactory but limited by” was a major improvement. Narrowing the ASCUS classification to ASC-US and ASC-H makes it possible to use multiple triage methods such as immediate colposcopy, HPV testing, or repeating the smear unless the report is ASC-H, which requires immediate evaluation.

Bottom Line

Physicians who manage patients with cytologic abnormalities will be better served by the Bethesda 2001 System.

Objective

The Bethesda 2001 Workshop updated the 1991 Bethesda System terminology for reporting results of cervical cytology. This effort represents a focus on broad participation utilizing an Internet bulletin board to collect data prior to the workshop.

Method and Results

Eight months before the workshop convened, 9 forum groups of 6 to 10 persons developed recommendations for discussion. These recommendations were posted on the Internet to encourage discussion and commentary. More than 400 cytopathologists, gynecologists, epidemiologists, family physicians, attorneys, and patient advocates from 44 professional societies and 20 countries participated in the workshop.

After more than 1,000 comments were submitted via the bulletin board, the workshop convened in Bethesda, Maryland, from April 30 to May 2, 2001. The most clinically relevant changes to the Bethesda System are listed below.

• Specimen adequacy.
  • eliminates “satisfactory but limited by” (absence of endocervical cells is not considered unsatisfactory)
    
  
  
• General categorization.
  • “within normal limits” was changed to “negative for intraepithelial lesion”
    
  
  
• Interpretation/result.
  • “diagnosis” was replaced by “interpretation” or “result”
    
  
  
• Epithelial cell abnormalities.
  • ASCUS was replaced by ASC-US or ASC-H (cannot exclude HSIL)
    
  • 2-tiered LSIL and HSIL classifications remain
    
  • AGUS classification was significantly revised and changed to AGC, endocervical endometrial, or glandular cells NOS (not otherwise specified)
    
  • endometrial cells will be noted if present in women over the age of 40 rather than only postmenopausal patients
    
  
  

Who May Be Affected?

Physicians managing patients with cytologic abnormalities.

Expert Commentary

The wide range of participants lends significance to this extraordinary effort to correct and simplify the Bethesda System recommendations. First, a 6-month Internet survey generated many recommendations. This was followed by the actual workshop, which provided another opportunity to finalize the system. The process was deemed so successful that the American Society for Colposcopy and Cervical Pathology and the American College of Obstetricians and Gynecologists used a similar process when the workshop for the management of cytologic abnormalities was held later in 2001.

Overall, this is a kinder and gentler system. Elimination of “satisfactory but limited by” was a major improvement. Narrowing the ASCUS classification to ASC-US and ASC-H makes it possible to use multiple triage methods such as immediate colposcopy, HPV testing, or repeating the smear unless the report is ASC-H, which requires immediate evaluation.

Bottom Line

Physicians who manage patients with cytologic abnormalities will be better served by the Bethesda 2001 System.

Objective

The Bethesda 2001 Workshop updated the 1991 Bethesda System terminology for reporting results of cervical cytology. This effort represents a focus on broad participation utilizing an Internet bulletin board to collect data prior to the workshop.

Method and Results

Eight months before the workshop convened, 9 forum groups of 6 to 10 persons developed recommendations for discussion. These recommendations were posted on the Internet to encourage discussion and commentary. More than 400 cytopathologists, gynecologists, epidemiologists, family physicians, attorneys, and patient advocates from 44 professional societies and 20 countries participated in the workshop.

After more than 1,000 comments were submitted via the bulletin board, the workshop convened in Bethesda, Maryland, from April 30 to May 2, 2001. The most clinically relevant changes to the Bethesda System are listed below.

• Specimen adequacy.
  • eliminates “satisfactory but limited by” (absence of endocervical cells is not considered unsatisfactory)
    
  
  
• General categorization.
  • “within normal limits” was changed to “negative for intraepithelial lesion”
    
  
  
• Interpretation/result.
  • “diagnosis” was replaced by “interpretation” or “result”
    
  
  
• Epithelial cell abnormalities.
  • ASCUS was replaced by ASC-US or ASC-H (cannot exclude HSIL)
    
  • 2-tiered LSIL and HSIL classifications remain
    
  • AGUS classification was significantly revised and changed to AGC, endocervical endometrial, or glandular cells NOS (not otherwise specified)
    
  • endometrial cells will be noted if present in women over the age of 40 rather than only postmenopausal patients
    
  
  

Who May Be Affected?

Physicians managing patients with cytologic abnormalities.

Expert Commentary

The wide range of participants lends significance to this extraordinary effort to correct and simplify the Bethesda System recommendations. First, a 6-month Internet survey generated many recommendations. This was followed by the actual workshop, which provided another opportunity to finalize the system. The process was deemed so successful that the American Society for Colposcopy and Cervical Pathology and the American College of Obstetricians and Gynecologists used a similar process when the workshop for the management of cytologic abnormalities was held later in 2001.

Overall, this is a kinder and gentler system. Elimination of “satisfactory but limited by” was a major improvement. Narrowing the ASCUS classification to ASC-US and ASC-H makes it possible to use multiple triage methods such as immediate colposcopy, HPV testing, or repeating the smear unless the report is ASC-H, which requires immediate evaluation.

Bottom Line

Physicians who manage patients with cytologic abnormalities will be better served by the Bethesda 2001 System.

THE QUESTION:

Does prolonged use of oral contraceptives delay planned conception?

Past studies

Several earlier studies have shown that women who stop oral contraceptives (OCs) have a short-term decrease in fertility that begins the first month after discontinuing use and lasts up to a year. It took 3 months to several years for pregnancy rates to equal those of comparison groups.^1-5

A smaller study of women discontinuing associated with longer intervals from discontinuation to conception.⁶ Additional investigations have shown a decrease in fertility rates after OCs, but have not controlled as well for other factors such as age (OC users tend to be older than non-users). Still, multiple studies indicate that the rate of post-pill amenorrhea is low, and therefore unlikely to affect pregnancy rates.^7-8

This study

This investigation is part of a larger study of environmental and genetic influences on pregnancy outcome. The study enrolled 85% of couples in southwest England expecting a child during the study period. Researchers collected information on various aspects of the women’s health, including tobacco use, alcohol consumption, body size, and occupational and educational status. The study population included a total of 12,106 couples—8,497 of which had planned pregnancies.

Researchers found the pregnancy rate at 1 year was significantly higher for OC users than for non-users. Although the absolute difference was not large (89.5% of women using OCs for more than 5 years versus 85.4% of never-users), it is consistently related to the length of exposure. Stepwise regression analysis showed that the higher pregnancy rates persisted even when other factors, such as smoking and maternal age, were considered.

Find this study

Farrow A, Hull MGR, Northstone K, Taylor H, Ford WCL, Golding J. Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception. Human Reprod. 2002;17:2754-2761.

Who may be affected by these findings?

Current OC users planning future pregnancy.

Expert commentary

The ideal contraceptive would be highly effective and readily reversible; planned pregnancy would not be delayed or prevented. However there are persistent beliefs that women need a break from prolonged use of OCs before they are able to conceive. Post-OC amenorrhea is presented as a usually reversible complication of OC use that may delay conception. Unfortunately, the alternative may be a contraceptive with a higher failure rate (leading to unplanned pregnancy) or one with fewer noncontraceptive benefits.

The women in the comparison group included users of other contraceptives as well as women who used no contraception at all. Other studies of post-OC fertility have used various comparison groups. Several have suggested that OCs may decrease the rate of upper genital infection.^9,10 Thus, OC users may have a higher subsequent fertility rate, since users of nonhormonal methods may experience more tubal infertility.

The current study does not demonstrate a dip in fertility, but it doesn’t address the possibility of a short-term decrease with prompt recover y. Still, the findings strongly support the thesis that pregnancy rates for women who stop OC use are the same, if not higher, than rates for women using no contraceptives or another birth control method.

Bottom line

Women who want to become pregnant should discontinue contraception when they are ready, and OC users shouldn’t anticipate a longer period from discontinuation to conception.

Dr. Borgatta reports no financial relationship with any companies whose products are mentioned in this article.

THE QUESTION:

Does prolonged use of oral contraceptives delay planned conception?

Past studies

Several earlier studies have shown that women who stop oral contraceptives (OCs) have a short-term decrease in fertility that begins the first month after discontinuing use and lasts up to a year. It took 3 months to several years for pregnancy rates to equal those of comparison groups.^1-5

A smaller study of women discontinuing associated with longer intervals from discontinuation to conception.⁶ Additional investigations have shown a decrease in fertility rates after OCs, but have not controlled as well for other factors such as age (OC users tend to be older than non-users). Still, multiple studies indicate that the rate of post-pill amenorrhea is low, and therefore unlikely to affect pregnancy rates.^7-8

This study

This investigation is part of a larger study of environmental and genetic influences on pregnancy outcome. The study enrolled 85% of couples in southwest England expecting a child during the study period. Researchers collected information on various aspects of the women’s health, including tobacco use, alcohol consumption, body size, and occupational and educational status. The study population included a total of 12,106 couples—8,497 of which had planned pregnancies.

Researchers found the pregnancy rate at 1 year was significantly higher for OC users than for non-users. Although the absolute difference was not large (89.5% of women using OCs for more than 5 years versus 85.4% of never-users), it is consistently related to the length of exposure. Stepwise regression analysis showed that the higher pregnancy rates persisted even when other factors, such as smoking and maternal age, were considered.

Find this study

Farrow A, Hull MGR, Northstone K, Taylor H, Ford WCL, Golding J. Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception. Human Reprod. 2002;17:2754-2761.

Who may be affected by these findings?

Current OC users planning future pregnancy.

Expert commentary

The ideal contraceptive would be highly effective and readily reversible; planned pregnancy would not be delayed or prevented. However there are persistent beliefs that women need a break from prolonged use of OCs before they are able to conceive. Post-OC amenorrhea is presented as a usually reversible complication of OC use that may delay conception. Unfortunately, the alternative may be a contraceptive with a higher failure rate (leading to unplanned pregnancy) or one with fewer noncontraceptive benefits.

The women in the comparison group included users of other contraceptives as well as women who used no contraception at all. Other studies of post-OC fertility have used various comparison groups. Several have suggested that OCs may decrease the rate of upper genital infection.^9,10 Thus, OC users may have a higher subsequent fertility rate, since users of nonhormonal methods may experience more tubal infertility.

The current study does not demonstrate a dip in fertility, but it doesn’t address the possibility of a short-term decrease with prompt recover y. Still, the findings strongly support the thesis that pregnancy rates for women who stop OC use are the same, if not higher, than rates for women using no contraceptives or another birth control method.

Bottom line

Women who want to become pregnant should discontinue contraception when they are ready, and OC users shouldn’t anticipate a longer period from discontinuation to conception.

Dr. Borgatta reports no financial relationship with any companies whose products are mentioned in this article.

THE QUESTION:

Does prolonged use of oral contraceptives delay planned conception?

Past studies

Several earlier studies have shown that women who stop oral contraceptives (OCs) have a short-term decrease in fertility that begins the first month after discontinuing use and lasts up to a year. It took 3 months to several years for pregnancy rates to equal those of comparison groups.^1-5

A smaller study of women discontinuing associated with longer intervals from discontinuation to conception.⁶ Additional investigations have shown a decrease in fertility rates after OCs, but have not controlled as well for other factors such as age (OC users tend to be older than non-users). Still, multiple studies indicate that the rate of post-pill amenorrhea is low, and therefore unlikely to affect pregnancy rates.^7-8

This study

This investigation is part of a larger study of environmental and genetic influences on pregnancy outcome. The study enrolled 85% of couples in southwest England expecting a child during the study period. Researchers collected information on various aspects of the women’s health, including tobacco use, alcohol consumption, body size, and occupational and educational status. The study population included a total of 12,106 couples—8,497 of which had planned pregnancies.

Researchers found the pregnancy rate at 1 year was significantly higher for OC users than for non-users. Although the absolute difference was not large (89.5% of women using OCs for more than 5 years versus 85.4% of never-users), it is consistently related to the length of exposure. Stepwise regression analysis showed that the higher pregnancy rates persisted even when other factors, such as smoking and maternal age, were considered.

Find this study

Farrow A, Hull MGR, Northstone K, Taylor H, Ford WCL, Golding J. Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception. Human Reprod. 2002;17:2754-2761.

Who may be affected by these findings?

Current OC users planning future pregnancy.

Expert commentary

The ideal contraceptive would be highly effective and readily reversible; planned pregnancy would not be delayed or prevented. However there are persistent beliefs that women need a break from prolonged use of OCs before they are able to conceive. Post-OC amenorrhea is presented as a usually reversible complication of OC use that may delay conception. Unfortunately, the alternative may be a contraceptive with a higher failure rate (leading to unplanned pregnancy) or one with fewer noncontraceptive benefits.

The women in the comparison group included users of other contraceptives as well as women who used no contraception at all. Other studies of post-OC fertility have used various comparison groups. Several have suggested that OCs may decrease the rate of upper genital infection.^9,10 Thus, OC users may have a higher subsequent fertility rate, since users of nonhormonal methods may experience more tubal infertility.

The current study does not demonstrate a dip in fertility, but it doesn’t address the possibility of a short-term decrease with prompt recover y. Still, the findings strongly support the thesis that pregnancy rates for women who stop OC use are the same, if not higher, than rates for women using no contraceptives or another birth control method.

Bottom line

Women who want to become pregnant should discontinue contraception when they are ready, and OC users shouldn’t anticipate a longer period from discontinuation to conception.

Dr. Borgatta reports no financial relationship with any companies whose products are mentioned in this article.

The question:

Does dexamethasone-clomiphene citrate (CC) treatment improve ovulation rates in CC-resistant patients with polycystic ovary syndrome?

Past studies

This paper pays homage to the pioneering work of Riddick and colleagues who, almost 20 years ago, demonstrated that dexamethasone (DEX) therapy increased the rate of ovulation and conception in clomiphene citrate (CC)-resistant anovulatory patients with normal serum dehydroepiandrosterone sulfate (DHEAS) levels.¹ Since then, several mechanisms have been proposed to explain this phenomenon, including the ability of glucocorticoids to lower hypothalamo-pituitary luteinizing hormone (LH) secretion,^2,3 suppress adrenal androgen production,⁴ and therefore reduce circulating androgen levels in hyperandrogenic women.^5,6 Reducing ovarian androgen production while suppressing circulating DHEAS as a prehormone for ovarian steroidogenesis⁴ presumably lowers elevated intrafollicular androgen levels, which appear to impair folliculogenesis.

This study

Parsanezhad et al examined the efficacy of DEX in conjunction with CC for inducing ovulation in CC-resistant polycystic ovary syndrome (PCOS) patients. Two hundred thirty infertile PCOS patients who failed to ovulate during CC therapy (250 mg/day orally for 5 days) and human chorionic gonadotropin (hCG) administration (10,000 units, intramuscularly) were randomized to CC (200 mg/day, cycle days 5-9) with or without DEX (2 mg/day, cycle days 5-14). Serum DHEAS levels, semen analysis, postcoital testing, and hysterosalpingography were normal in all cases. Basal serum hormone levels were measured before CC therapy (cycle days 3-5). Clinicians performed ultrasound-timed hCG administration on cycle days 16 and 17, and serum hormone determinations 1 week later. Treatment persisted for a maximum of 6 cycles.

Eighty-eight percent of PCOS patients receiving combined DEX-CC therapy ovulated, as determined by serum progesterone values, compared with 20% of PCOS patients receiving CC alone. Participants receiving DEX-CC therapy also demonstrated significant decreases in serum levels of LH, DHEAS, and testosterone, with a significant increase in serum progesterone concentrations. In addition, 40.5% and 4.2% of PCOS patients conceived while receiving CC with and without DEX, respectively. The authors conclude that the combination of DEX and CC in the treatment of CC-resistant anovulatory PCOS patients should be considered before gonadotropin therapy or surgical intervention.

Find this study

Parsanezhad EM, Alborzi S, Motazedian S, Omrani G. Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. Fertil Steril. 2002;78:1001-1004.

Who may be affected by these findings?

CC-resistant PCOS patients who have difficulty conceiving.

Expert commentary

This study confirms the previous observation that DEX therapy can increase the rate of ovulation and conception in CC-resistant anovulatory patients with normal serum DHEAS levels.¹ While 88% of the PCOS patients receiving combined DEX-CC therapy in this study ovulated and had “regular ” menstrual cycles, the proportion of women resuming normal menstrual cyclicity on a monthly basis is not addressed. Using weekly serum progesterone measurements, the ratio of luteal phase weeks to total observed weeks (with a ratio of 0.5 denoting a 4-week ovulatory menstrual cycle)⁷ along with a description of menstrual cycle intervals (by days) would address this important question.

In addition, the authors do not discuss the proportion of patients who experienced side effects from intermittent DEX therapy or the rate of patient dropout over the study interval, leaving some practical aspects of this DEX administration unresolved. The authors do recommend that clinicians use combined DEX-CC therapy to treat CC-resistant anovulatory PCOS patients before gonadotropin therapy or surgical intervention, but this is not new. What is new, however, is how this recommendation fits with other advice regarding the use of insulin sensitizers in similar PCOS patients to reduce ovarian hyperandrogenism for ovulation induction.^7,8 This issue is crucial because reversal of hyperinsulinemia in anovulatory PCOS women receiving insulin sensitizers may improve both ovulation and pregnancy outcome by ameliorating possible adverse effects of insulin excess on oocyte development.^9,10

Bottom line

Future studies examining the safety, side effects, and efficacy of these agents will determine whether combined DEX-CC therapy for treating CC-resistant anovulatory PCOS patients may be a possible alternative to insulin sensitizers.

Dr. Dumesic reports no financial relationship with any companies whose products are mentioned in this article.

The question:

Does dexamethasone-clomiphene citrate (CC) treatment improve ovulation rates in CC-resistant patients with polycystic ovary syndrome?

Past studies

This paper pays homage to the pioneering work of Riddick and colleagues who, almost 20 years ago, demonstrated that dexamethasone (DEX) therapy increased the rate of ovulation and conception in clomiphene citrate (CC)-resistant anovulatory patients with normal serum dehydroepiandrosterone sulfate (DHEAS) levels.¹ Since then, several mechanisms have been proposed to explain this phenomenon, including the ability of glucocorticoids to lower hypothalamo-pituitary luteinizing hormone (LH) secretion,^2,3 suppress adrenal androgen production,⁴ and therefore reduce circulating androgen levels in hyperandrogenic women.^5,6 Reducing ovarian androgen production while suppressing circulating DHEAS as a prehormone for ovarian steroidogenesis⁴ presumably lowers elevated intrafollicular androgen levels, which appear to impair folliculogenesis.

This study

Parsanezhad et al examined the efficacy of DEX in conjunction with CC for inducing ovulation in CC-resistant polycystic ovary syndrome (PCOS) patients. Two hundred thirty infertile PCOS patients who failed to ovulate during CC therapy (250 mg/day orally for 5 days) and human chorionic gonadotropin (hCG) administration (10,000 units, intramuscularly) were randomized to CC (200 mg/day, cycle days 5-9) with or without DEX (2 mg/day, cycle days 5-14). Serum DHEAS levels, semen analysis, postcoital testing, and hysterosalpingography were normal in all cases. Basal serum hormone levels were measured before CC therapy (cycle days 3-5). Clinicians performed ultrasound-timed hCG administration on cycle days 16 and 17, and serum hormone determinations 1 week later. Treatment persisted for a maximum of 6 cycles.

Eighty-eight percent of PCOS patients receiving combined DEX-CC therapy ovulated, as determined by serum progesterone values, compared with 20% of PCOS patients receiving CC alone. Participants receiving DEX-CC therapy also demonstrated significant decreases in serum levels of LH, DHEAS, and testosterone, with a significant increase in serum progesterone concentrations. In addition, 40.5% and 4.2% of PCOS patients conceived while receiving CC with and without DEX, respectively. The authors conclude that the combination of DEX and CC in the treatment of CC-resistant anovulatory PCOS patients should be considered before gonadotropin therapy or surgical intervention.

Find this study

Parsanezhad EM, Alborzi S, Motazedian S, Omrani G. Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. Fertil Steril. 2002;78:1001-1004.

Who may be affected by these findings?

CC-resistant PCOS patients who have difficulty conceiving.

Expert commentary

This study confirms the previous observation that DEX therapy can increase the rate of ovulation and conception in CC-resistant anovulatory patients with normal serum DHEAS levels.¹ While 88% of the PCOS patients receiving combined DEX-CC therapy in this study ovulated and had “regular ” menstrual cycles, the proportion of women resuming normal menstrual cyclicity on a monthly basis is not addressed. Using weekly serum progesterone measurements, the ratio of luteal phase weeks to total observed weeks (with a ratio of 0.5 denoting a 4-week ovulatory menstrual cycle)⁷ along with a description of menstrual cycle intervals (by days) would address this important question.

In addition, the authors do not discuss the proportion of patients who experienced side effects from intermittent DEX therapy or the rate of patient dropout over the study interval, leaving some practical aspects of this DEX administration unresolved. The authors do recommend that clinicians use combined DEX-CC therapy to treat CC-resistant anovulatory PCOS patients before gonadotropin therapy or surgical intervention, but this is not new. What is new, however, is how this recommendation fits with other advice regarding the use of insulin sensitizers in similar PCOS patients to reduce ovarian hyperandrogenism for ovulation induction.^7,8 This issue is crucial because reversal of hyperinsulinemia in anovulatory PCOS women receiving insulin sensitizers may improve both ovulation and pregnancy outcome by ameliorating possible adverse effects of insulin excess on oocyte development.^9,10

Bottom line

Future studies examining the safety, side effects, and efficacy of these agents will determine whether combined DEX-CC therapy for treating CC-resistant anovulatory PCOS patients may be a possible alternative to insulin sensitizers.

Dr. Dumesic reports no financial relationship with any companies whose products are mentioned in this article.

The question:

Does dexamethasone-clomiphene citrate (CC) treatment improve ovulation rates in CC-resistant patients with polycystic ovary syndrome?

Past studies

This paper pays homage to the pioneering work of Riddick and colleagues who, almost 20 years ago, demonstrated that dexamethasone (DEX) therapy increased the rate of ovulation and conception in clomiphene citrate (CC)-resistant anovulatory patients with normal serum dehydroepiandrosterone sulfate (DHEAS) levels.¹ Since then, several mechanisms have been proposed to explain this phenomenon, including the ability of glucocorticoids to lower hypothalamo-pituitary luteinizing hormone (LH) secretion,^2,3 suppress adrenal androgen production,⁴ and therefore reduce circulating androgen levels in hyperandrogenic women.^5,6 Reducing ovarian androgen production while suppressing circulating DHEAS as a prehormone for ovarian steroidogenesis⁴ presumably lowers elevated intrafollicular androgen levels, which appear to impair folliculogenesis.

This study

Parsanezhad et al examined the efficacy of DEX in conjunction with CC for inducing ovulation in CC-resistant polycystic ovary syndrome (PCOS) patients. Two hundred thirty infertile PCOS patients who failed to ovulate during CC therapy (250 mg/day orally for 5 days) and human chorionic gonadotropin (hCG) administration (10,000 units, intramuscularly) were randomized to CC (200 mg/day, cycle days 5-9) with or without DEX (2 mg/day, cycle days 5-14). Serum DHEAS levels, semen analysis, postcoital testing, and hysterosalpingography were normal in all cases. Basal serum hormone levels were measured before CC therapy (cycle days 3-5). Clinicians performed ultrasound-timed hCG administration on cycle days 16 and 17, and serum hormone determinations 1 week later. Treatment persisted for a maximum of 6 cycles.

Eighty-eight percent of PCOS patients receiving combined DEX-CC therapy ovulated, as determined by serum progesterone values, compared with 20% of PCOS patients receiving CC alone. Participants receiving DEX-CC therapy also demonstrated significant decreases in serum levels of LH, DHEAS, and testosterone, with a significant increase in serum progesterone concentrations. In addition, 40.5% and 4.2% of PCOS patients conceived while receiving CC with and without DEX, respectively. The authors conclude that the combination of DEX and CC in the treatment of CC-resistant anovulatory PCOS patients should be considered before gonadotropin therapy or surgical intervention.

Find this study

Parsanezhad EM, Alborzi S, Motazedian S, Omrani G. Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. Fertil Steril. 2002;78:1001-1004.

Who may be affected by these findings?

CC-resistant PCOS patients who have difficulty conceiving.

Expert commentary

This study confirms the previous observation that DEX therapy can increase the rate of ovulation and conception in CC-resistant anovulatory patients with normal serum DHEAS levels.¹ While 88% of the PCOS patients receiving combined DEX-CC therapy in this study ovulated and had “regular ” menstrual cycles, the proportion of women resuming normal menstrual cyclicity on a monthly basis is not addressed. Using weekly serum progesterone measurements, the ratio of luteal phase weeks to total observed weeks (with a ratio of 0.5 denoting a 4-week ovulatory menstrual cycle)⁷ along with a description of menstrual cycle intervals (by days) would address this important question.

In addition, the authors do not discuss the proportion of patients who experienced side effects from intermittent DEX therapy or the rate of patient dropout over the study interval, leaving some practical aspects of this DEX administration unresolved. The authors do recommend that clinicians use combined DEX-CC therapy to treat CC-resistant anovulatory PCOS patients before gonadotropin therapy or surgical intervention, but this is not new. What is new, however, is how this recommendation fits with other advice regarding the use of insulin sensitizers in similar PCOS patients to reduce ovarian hyperandrogenism for ovulation induction.^7,8 This issue is crucial because reversal of hyperinsulinemia in anovulatory PCOS women receiving insulin sensitizers may improve both ovulation and pregnancy outcome by ameliorating possible adverse effects of insulin excess on oocyte development.^9,10

Bottom line

Future studies examining the safety, side effects, and efficacy of these agents will determine whether combined DEX-CC therapy for treating CC-resistant anovulatory PCOS patients may be a possible alternative to insulin sensitizers.

Dr. Dumesic reports no financial relationship with any companies whose products are mentioned in this article.

THE QUESTION:
Is duloxetine hydrochloride effective in the treatment of stress urinary incontinence (SUI)?

Past studies

Research has indicated that the neurotransmitters serotonin and norepinephrine are responsible for neural control of the lower urinary tract. Serotogenic agonists generally suppress parasympathetic activity and enhance sympathetic and somatic activity in the lower urinary tract—effects that promote urine storage.

This study

This double-blind, randomized, placebo-controlled study examined 553 women, ages 18 to 65, with at least a 3-month diagnosis of SUI. Subjects were assigned a 12-week course of either placebo (n=138) or duloxetine treatment at 1 of 3 daily doses: 20 mg (n=138), 40 mg (n=137), or 80 mg (n=140). The women were examined once every 4 weeks and asked to keep a diary documenting voiding episodes.

The diary entries revealed a decrease in incontinence episodes for all subjects. Patients taking placebo recorded a 41% decline, compared to 54% in women taking 20 mg/d of duloxetine, 59% for users on 40 mg of duloxetine, and 64% for women taking 80 mg of duloxetine. Among women taking the 80-mg dose, half experienced at least a 64% reduction in incontinence frequency and 67% noted at least a 50% decrease.

Researchers concluded that duloxetine is a safe and effective agent for treating SUI.

Find this study

Norton PA, Zinner NR, Yalcin I, Bump RC. July 2002 issue of American Journal of Obstetrics and Gynecology; abstract online at www3.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

Women suffering from SUI.

Expert commentary

The annual direct cost of female urinary incontinence in the United States is approximately $12.4 billion,¹ with $1.3 billion dedicated to treatment. Of that, surgical management accounts for nearly 80% (or $1 billion), while pharmacologic therapy utilizes only 9% ($114 million).¹ Thus, even with rising medication costs, medical incontinence management uses fewer health-care dollars than surgery. If more women can be effectively treated pharmacologically, therefore, we can conserve valuable health-care resources while reducing related costs, such as time off from work.

If more women can be treated pharmacologically, we can conserve valuable health-care resources.

Presently, there are agents available to treat urge incontinence, but no effective, tolerable medical therapies for stress incontinence. Alpha-1 agonists such as pseudoephedrine have been used for SUI, but the side effects of nervousness, dizziness, and insomnia have proved prohibitive.

SUI typically is treated either surgically or with physical therapy designed to strengthen pelvic-floor muscles. Recently, however, advances in the understanding of neuromuscular control of women’s “stress continence control system” has spurred the development of new drugs.²

In this study, duloxetine use was associated with significant decreases in incontinent episodes (as measured by diary entries). Quality-of-life measures also improved significantly. In addition, voiding intervals lengthened, indicating that women were not voiding more frequently to avoid incontinent episodes. This result may indicate duloxetine’s dual efficacy with the continence system: increasing bladder capacity and increasing striated urethral sphincter activity. A more recent analysis of a subgroup of patients with both stress and urge incontinence showed similar improvements.³

Interestingly, cough stress tests at 400 mL and pad tests failed to demonstrate any significant improvement in the study’s treated patients. However, these conflicting results may reflect inherent problems with assessing urinary incontinence treatments: A patient with 400 mL of urine in her bladder may leak with vigorous coughing in the upright position, but if she voids at 300 to 350 mL—a reasonable bladder capacity—she may never leak in “real life.”

Bottom line

Duloxetine hydrochloride appears to be a promising new pharmacologic agent to treat stress incontinence. However, clinicians must keep in mind that even when drugs seem efficacious in clinical trials, they may not yield the same results in clinical practice. Patients in this study completed weeklong diaries every 4 weeks, which, by itself, may improve bladder csontrol.

As mentioned by the authors, larger multinational trials are needed to further demonstrate duloxetine’s safety and efficacy in more diverse clinical settings.

THE QUESTION:
Is duloxetine hydrochloride effective in the treatment of stress urinary incontinence (SUI)?

Past studies

Research has indicated that the neurotransmitters serotonin and norepinephrine are responsible for neural control of the lower urinary tract. Serotogenic agonists generally suppress parasympathetic activity and enhance sympathetic and somatic activity in the lower urinary tract—effects that promote urine storage.

This study

This double-blind, randomized, placebo-controlled study examined 553 women, ages 18 to 65, with at least a 3-month diagnosis of SUI. Subjects were assigned a 12-week course of either placebo (n=138) or duloxetine treatment at 1 of 3 daily doses: 20 mg (n=138), 40 mg (n=137), or 80 mg (n=140). The women were examined once every 4 weeks and asked to keep a diary documenting voiding episodes.

The diary entries revealed a decrease in incontinence episodes for all subjects. Patients taking placebo recorded a 41% decline, compared to 54% in women taking 20 mg/d of duloxetine, 59% for users on 40 mg of duloxetine, and 64% for women taking 80 mg of duloxetine. Among women taking the 80-mg dose, half experienced at least a 64% reduction in incontinence frequency and 67% noted at least a 50% decrease.

Researchers concluded that duloxetine is a safe and effective agent for treating SUI.

Find this study

Norton PA, Zinner NR, Yalcin I, Bump RC. July 2002 issue of American Journal of Obstetrics and Gynecology; abstract online at www3.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

Women suffering from SUI.

Expert commentary

The annual direct cost of female urinary incontinence in the United States is approximately $12.4 billion,¹ with $1.3 billion dedicated to treatment. Of that, surgical management accounts for nearly 80% (or $1 billion), while pharmacologic therapy utilizes only 9% ($114 million).¹ Thus, even with rising medication costs, medical incontinence management uses fewer health-care dollars than surgery. If more women can be effectively treated pharmacologically, therefore, we can conserve valuable health-care resources while reducing related costs, such as time off from work.

If more women can be treated pharmacologically, we can conserve valuable health-care resources.

Presently, there are agents available to treat urge incontinence, but no effective, tolerable medical therapies for stress incontinence. Alpha-1 agonists such as pseudoephedrine have been used for SUI, but the side effects of nervousness, dizziness, and insomnia have proved prohibitive.

SUI typically is treated either surgically or with physical therapy designed to strengthen pelvic-floor muscles. Recently, however, advances in the understanding of neuromuscular control of women’s “stress continence control system” has spurred the development of new drugs.²

In this study, duloxetine use was associated with significant decreases in incontinent episodes (as measured by diary entries). Quality-of-life measures also improved significantly. In addition, voiding intervals lengthened, indicating that women were not voiding more frequently to avoid incontinent episodes. This result may indicate duloxetine’s dual efficacy with the continence system: increasing bladder capacity and increasing striated urethral sphincter activity. A more recent analysis of a subgroup of patients with both stress and urge incontinence showed similar improvements.³

Interestingly, cough stress tests at 400 mL and pad tests failed to demonstrate any significant improvement in the study’s treated patients. However, these conflicting results may reflect inherent problems with assessing urinary incontinence treatments: A patient with 400 mL of urine in her bladder may leak with vigorous coughing in the upright position, but if she voids at 300 to 350 mL—a reasonable bladder capacity—she may never leak in “real life.”

Bottom line

Duloxetine hydrochloride appears to be a promising new pharmacologic agent to treat stress incontinence. However, clinicians must keep in mind that even when drugs seem efficacious in clinical trials, they may not yield the same results in clinical practice. Patients in this study completed weeklong diaries every 4 weeks, which, by itself, may improve bladder csontrol.

As mentioned by the authors, larger multinational trials are needed to further demonstrate duloxetine’s safety and efficacy in more diverse clinical settings.

THE QUESTION:
Is duloxetine hydrochloride effective in the treatment of stress urinary incontinence (SUI)?

Past studies

Research has indicated that the neurotransmitters serotonin and norepinephrine are responsible for neural control of the lower urinary tract. Serotogenic agonists generally suppress parasympathetic activity and enhance sympathetic and somatic activity in the lower urinary tract—effects that promote urine storage.

This study

This double-blind, randomized, placebo-controlled study examined 553 women, ages 18 to 65, with at least a 3-month diagnosis of SUI. Subjects were assigned a 12-week course of either placebo (n=138) or duloxetine treatment at 1 of 3 daily doses: 20 mg (n=138), 40 mg (n=137), or 80 mg (n=140). The women were examined once every 4 weeks and asked to keep a diary documenting voiding episodes.

The diary entries revealed a decrease in incontinence episodes for all subjects. Patients taking placebo recorded a 41% decline, compared to 54% in women taking 20 mg/d of duloxetine, 59% for users on 40 mg of duloxetine, and 64% for women taking 80 mg of duloxetine. Among women taking the 80-mg dose, half experienced at least a 64% reduction in incontinence frequency and 67% noted at least a 50% decrease.

Researchers concluded that duloxetine is a safe and effective agent for treating SUI.

Find this study

Norton PA, Zinner NR, Yalcin I, Bump RC. July 2002 issue of American Journal of Obstetrics and Gynecology; abstract online at www3.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

Women suffering from SUI.

Expert commentary

The annual direct cost of female urinary incontinence in the United States is approximately $12.4 billion,¹ with $1.3 billion dedicated to treatment. Of that, surgical management accounts for nearly 80% (or $1 billion), while pharmacologic therapy utilizes only 9% ($114 million).¹ Thus, even with rising medication costs, medical incontinence management uses fewer health-care dollars than surgery. If more women can be effectively treated pharmacologically, therefore, we can conserve valuable health-care resources while reducing related costs, such as time off from work.

If more women can be treated pharmacologically, we can conserve valuable health-care resources.

Presently, there are agents available to treat urge incontinence, but no effective, tolerable medical therapies for stress incontinence. Alpha-1 agonists such as pseudoephedrine have been used for SUI, but the side effects of nervousness, dizziness, and insomnia have proved prohibitive.

SUI typically is treated either surgically or with physical therapy designed to strengthen pelvic-floor muscles. Recently, however, advances in the understanding of neuromuscular control of women’s “stress continence control system” has spurred the development of new drugs.²

In this study, duloxetine use was associated with significant decreases in incontinent episodes (as measured by diary entries). Quality-of-life measures also improved significantly. In addition, voiding intervals lengthened, indicating that women were not voiding more frequently to avoid incontinent episodes. This result may indicate duloxetine’s dual efficacy with the continence system: increasing bladder capacity and increasing striated urethral sphincter activity. A more recent analysis of a subgroup of patients with both stress and urge incontinence showed similar improvements.³

Interestingly, cough stress tests at 400 mL and pad tests failed to demonstrate any significant improvement in the study’s treated patients. However, these conflicting results may reflect inherent problems with assessing urinary incontinence treatments: A patient with 400 mL of urine in her bladder may leak with vigorous coughing in the upright position, but if she voids at 300 to 350 mL—a reasonable bladder capacity—she may never leak in “real life.”

Bottom line

Duloxetine hydrochloride appears to be a promising new pharmacologic agent to treat stress incontinence. However, clinicians must keep in mind that even when drugs seem efficacious in clinical trials, they may not yield the same results in clinical practice. Patients in this study completed weeklong diaries every 4 weeks, which, by itself, may improve bladder csontrol.

As mentioned by the authors, larger multinational trials are needed to further demonstrate duloxetine’s safety and efficacy in more diverse clinical settings.

THE QUESTION:
Does depot medroxyprogesterone acetate decrease bone mineral density?

Past studies

A substantial number of studies, largely cross-sectional, have suggested that loss of bone mineral density (BMD) occurs in current users of the progestin-only injectable contraceptive depot medroxyprogesterone acetate (DMPA). This loss likely indicates that ovarian estradiol production is lowered during use of this contraceptive.

This study

In this prospective cohort evaluation, researchers assessed BMD in 183 DMPA users and 274 non-users over a 3-year period. Bone density in women ages 18 to 39 was measured via dual-energy x-ray absorptiometry every 6 months. The results indicated marked BMD loss among DMPA users when compared with those women who did not take DMPA. Specifically, women on DMPA experienced a loss of 1.12% femoral bone density per year and nonusers lost an annual 0.05%. Further, spine bone density loss among DMPA users was 0.87% per year, while non-users experienced a 0.40% gain.

However, the 110 women who discontinued DMPA during the study showed significant increases in BMD. Mean annualized gains were 1.41% and 1.03% at the spine and hip, respectively. Moreover, women who stopped DMPA injections for 30 months had bone density values similar to those of non-users.

The researchers concluded that DMPA use is strongly linked to BMD loss. However, if DMPA is discontinued, bone loss is reversible.

Find this study

Scholes D, LaCroix AZ, Ichikawa LE, et al. September 2002 issue of Epidemiology; abstract online at http://www. nichd.nih.gov/CPR/crh/crh.htm.

Who may be affected by these findings?

Women taking DMPA.

Expert commentary

The results of this important longitudinal study remind us that the skeleton is a dynamic organ and that cross-sectional observations may not adequately assess long-term clinical impact.

DMPA use is strongly linked to bone mineral density loss, but if discontinued, bone loss is reversible.

Premenopausal women whose endogenous estrogen levels decline, including DMPA users and lactating women, do experience short-term declines in BMD. However, this study (consistent with others assessing BMD following DMPA discontinuation) clarifies that bone loss is reversible following discontinuation of progestin-only injectable contraception. In fact, Orr-Walker’s study of postmenopausal women in New Zealand demonstrated that DMPA use in reproductive-aged women is not associated with postmenopausal osteopenia or osteoporosis.¹

No study has found any long-term impact of DMPA use on bone mineral density or fracture risk. BMD concerns should not prevent clinicians from prescribing DMPA to appropriate candidates.

It is important to note that DMPA users—and all women for that matter—should be encouraged to avoid smoking, consume adequate amounts of calcium, and engage in consistent weight-bearing exercises.

The bottom line

Clinicians providing contraceptive services should recognize that the use of the highly effective and convenient DMPA does not appear to cause a lasting negative impact on BMD. In fact, no study has found evidence of any long-term impact of DMPA use on BMD or fracture risk. High-priority areas for future research include assessment of BMD in adolescents following use of DMPA, in women who have used DMPA for extended periods of time, and in higher-risk DMPA users, including smokers and those with a positive family history of osteoporosis. Based on the current evidence, however—including the reassuring findings reported in this study—BMD concerns should not prevent clinicians from prescribing DMPA to appropriate candidates.

THE QUESTION:
Does depot medroxyprogesterone acetate decrease bone mineral density?

Past studies

A substantial number of studies, largely cross-sectional, have suggested that loss of bone mineral density (BMD) occurs in current users of the progestin-only injectable contraceptive depot medroxyprogesterone acetate (DMPA). This loss likely indicates that ovarian estradiol production is lowered during use of this contraceptive.

This study

In this prospective cohort evaluation, researchers assessed BMD in 183 DMPA users and 274 non-users over a 3-year period. Bone density in women ages 18 to 39 was measured via dual-energy x-ray absorptiometry every 6 months. The results indicated marked BMD loss among DMPA users when compared with those women who did not take DMPA. Specifically, women on DMPA experienced a loss of 1.12% femoral bone density per year and nonusers lost an annual 0.05%. Further, spine bone density loss among DMPA users was 0.87% per year, while non-users experienced a 0.40% gain.

However, the 110 women who discontinued DMPA during the study showed significant increases in BMD. Mean annualized gains were 1.41% and 1.03% at the spine and hip, respectively. Moreover, women who stopped DMPA injections for 30 months had bone density values similar to those of non-users.

The researchers concluded that DMPA use is strongly linked to BMD loss. However, if DMPA is discontinued, bone loss is reversible.

Find this study

Scholes D, LaCroix AZ, Ichikawa LE, et al. September 2002 issue of Epidemiology; abstract online at http://www. nichd.nih.gov/CPR/crh/crh.htm.

Who may be affected by these findings?

Women taking DMPA.

Expert commentary

The results of this important longitudinal study remind us that the skeleton is a dynamic organ and that cross-sectional observations may not adequately assess long-term clinical impact.

DMPA use is strongly linked to bone mineral density loss, but if discontinued, bone loss is reversible.

Premenopausal women whose endogenous estrogen levels decline, including DMPA users and lactating women, do experience short-term declines in BMD. However, this study (consistent with others assessing BMD following DMPA discontinuation) clarifies that bone loss is reversible following discontinuation of progestin-only injectable contraception. In fact, Orr-Walker’s study of postmenopausal women in New Zealand demonstrated that DMPA use in reproductive-aged women is not associated with postmenopausal osteopenia or osteoporosis.¹

No study has found any long-term impact of DMPA use on bone mineral density or fracture risk. BMD concerns should not prevent clinicians from prescribing DMPA to appropriate candidates.

It is important to note that DMPA users—and all women for that matter—should be encouraged to avoid smoking, consume adequate amounts of calcium, and engage in consistent weight-bearing exercises.

The bottom line

Clinicians providing contraceptive services should recognize that the use of the highly effective and convenient DMPA does not appear to cause a lasting negative impact on BMD. In fact, no study has found evidence of any long-term impact of DMPA use on BMD or fracture risk. High-priority areas for future research include assessment of BMD in adolescents following use of DMPA, in women who have used DMPA for extended periods of time, and in higher-risk DMPA users, including smokers and those with a positive family history of osteoporosis. Based on the current evidence, however—including the reassuring findings reported in this study—BMD concerns should not prevent clinicians from prescribing DMPA to appropriate candidates.

THE QUESTION:
Does depot medroxyprogesterone acetate decrease bone mineral density?

Past studies

A substantial number of studies, largely cross-sectional, have suggested that loss of bone mineral density (BMD) occurs in current users of the progestin-only injectable contraceptive depot medroxyprogesterone acetate (DMPA). This loss likely indicates that ovarian estradiol production is lowered during use of this contraceptive.

This study

In this prospective cohort evaluation, researchers assessed BMD in 183 DMPA users and 274 non-users over a 3-year period. Bone density in women ages 18 to 39 was measured via dual-energy x-ray absorptiometry every 6 months. The results indicated marked BMD loss among DMPA users when compared with those women who did not take DMPA. Specifically, women on DMPA experienced a loss of 1.12% femoral bone density per year and nonusers lost an annual 0.05%. Further, spine bone density loss among DMPA users was 0.87% per year, while non-users experienced a 0.40% gain.

However, the 110 women who discontinued DMPA during the study showed significant increases in BMD. Mean annualized gains were 1.41% and 1.03% at the spine and hip, respectively. Moreover, women who stopped DMPA injections for 30 months had bone density values similar to those of non-users.

The researchers concluded that DMPA use is strongly linked to BMD loss. However, if DMPA is discontinued, bone loss is reversible.

Find this study

Scholes D, LaCroix AZ, Ichikawa LE, et al. September 2002 issue of Epidemiology; abstract online at http://www. nichd.nih.gov/CPR/crh/crh.htm.

Who may be affected by these findings?

Women taking DMPA.

Expert commentary

The results of this important longitudinal study remind us that the skeleton is a dynamic organ and that cross-sectional observations may not adequately assess long-term clinical impact.

DMPA use is strongly linked to bone mineral density loss, but if discontinued, bone loss is reversible.

Premenopausal women whose endogenous estrogen levels decline, including DMPA users and lactating women, do experience short-term declines in BMD. However, this study (consistent with others assessing BMD following DMPA discontinuation) clarifies that bone loss is reversible following discontinuation of progestin-only injectable contraception. In fact, Orr-Walker’s study of postmenopausal women in New Zealand demonstrated that DMPA use in reproductive-aged women is not associated with postmenopausal osteopenia or osteoporosis.¹

No study has found any long-term impact of DMPA use on bone mineral density or fracture risk. BMD concerns should not prevent clinicians from prescribing DMPA to appropriate candidates.

It is important to note that DMPA users—and all women for that matter—should be encouraged to avoid smoking, consume adequate amounts of calcium, and engage in consistent weight-bearing exercises.

The bottom line

Clinicians providing contraceptive services should recognize that the use of the highly effective and convenient DMPA does not appear to cause a lasting negative impact on BMD. In fact, no study has found evidence of any long-term impact of DMPA use on BMD or fracture risk. High-priority areas for future research include assessment of BMD in adolescents following use of DMPA, in women who have used DMPA for extended periods of time, and in higher-risk DMPA users, including smokers and those with a positive family history of osteoporosis. Based on the current evidence, however—including the reassuring findings reported in this study—BMD concerns should not prevent clinicians from prescribing DMPA to appropriate candidates.

THE QUESTION:
Is self-sampling effective in cervical cancer screening?

Past studies

Prior research has shown selfcollected cervical cell samples to be of variable concurrence to clinician-collected samples.

This study

Researchers evaluated 1 selfand 1 clinician-collected sample from 253 women, ages 16 to 88, randomly selected from a population at high risk for cervical neoplasia. Participants collected self-samples by rotating a cotton swab against the vaginal epithelium, and possibly, the cervix. Next, a colposcopist collected samples with an Ayre’s spatula and endocervical brush, then conducted a colposcopy. All specimens were frozen. Polymerase chain reaction (PCR) studies tested for both low-risk (LR) and high-risk (HR) viral types.

Positive HPV results from self-sampling and physician sampling were 23% and 29%, respectively. While there was no significant difference in the overall results from self-collected samples compared with physician-collected specimens, the prevalence of HR HPV among self-collected samples was 17%, as opposed to 26% in physician-collected samples. Further, testing for HPV detection on self-collected samples resulted in 50% more missed diagnoses of cervical cancer than did samples collected with a spatula and endocervical brush, and in 33.3% more missed diagnoses of high-grade cervical intraepithelial neoplasia. Hence, the researchers concluded that a sample for cervical HPV detection collected with a spatula and endocervical brush provides better results for primary cervical cancer screening than does self-sampling with a cotton-tipped swab.

Find this study

Lorenzato FR, Singer A, Ho L, et al. May 2002 issue of the American Journal of Obstetrics and Gynecology; abstract online at www.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

All women screened for cervical cytology.

Expert commentary

There has been a marked decrease in invasive cervical cancer prevalence and mortality in countries where there are organized cytologic screening programs. Even so, an estimated 30% of US women with invasive cervical cancer had not had a Pap smear in at least 5 years, and 50% had never been screened. Moreover, developing countries have both health-care infrastructure deficiencies and cultural taboos that have thus far precluded universal screening.

Many women may find self-sampling to be a more convenient and comfortable way of screening for cervical cancer. Thus, if self-sampling could be substituted for clinician examinations, the detection of preinvasive cervical neoplasia cases could be substantially increased. This study, however, demonstrated a poor correlation with colposcopic and histologic diagnoses of high-grade squamous intraepithelial lesions and invasive cancer. Of note, this study’s conclusions differed from a similar project conducted in South Africa in which researchers found a high sensitivity but poor specificity in self-collected specimens.¹

Bottom line

Although self-sampling is promising, the present self-collection technique may provide a false sense of security for patients with high-grade lesions. Since these patients need more close monitoring than those with low-grade lesions, this method is not ready for widespread implementation. Further research aimed at improving the safety and efficacy of self-sampling is still needed.

THE QUESTION:
Is self-sampling effective in cervical cancer screening?

Past studies

Prior research has shown selfcollected cervical cell samples to be of variable concurrence to clinician-collected samples.

This study

Researchers evaluated 1 selfand 1 clinician-collected sample from 253 women, ages 16 to 88, randomly selected from a population at high risk for cervical neoplasia. Participants collected self-samples by rotating a cotton swab against the vaginal epithelium, and possibly, the cervix. Next, a colposcopist collected samples with an Ayre’s spatula and endocervical brush, then conducted a colposcopy. All specimens were frozen. Polymerase chain reaction (PCR) studies tested for both low-risk (LR) and high-risk (HR) viral types.

Positive HPV results from self-sampling and physician sampling were 23% and 29%, respectively. While there was no significant difference in the overall results from self-collected samples compared with physician-collected specimens, the prevalence of HR HPV among self-collected samples was 17%, as opposed to 26% in physician-collected samples. Further, testing for HPV detection on self-collected samples resulted in 50% more missed diagnoses of cervical cancer than did samples collected with a spatula and endocervical brush, and in 33.3% more missed diagnoses of high-grade cervical intraepithelial neoplasia. Hence, the researchers concluded that a sample for cervical HPV detection collected with a spatula and endocervical brush provides better results for primary cervical cancer screening than does self-sampling with a cotton-tipped swab.

Find this study

Lorenzato FR, Singer A, Ho L, et al. May 2002 issue of the American Journal of Obstetrics and Gynecology; abstract online at www.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

All women screened for cervical cytology.

Expert commentary

There has been a marked decrease in invasive cervical cancer prevalence and mortality in countries where there are organized cytologic screening programs. Even so, an estimated 30% of US women with invasive cervical cancer had not had a Pap smear in at least 5 years, and 50% had never been screened. Moreover, developing countries have both health-care infrastructure deficiencies and cultural taboos that have thus far precluded universal screening.

Many women may find self-sampling to be a more convenient and comfortable way of screening for cervical cancer. Thus, if self-sampling could be substituted for clinician examinations, the detection of preinvasive cervical neoplasia cases could be substantially increased. This study, however, demonstrated a poor correlation with colposcopic and histologic diagnoses of high-grade squamous intraepithelial lesions and invasive cancer. Of note, this study’s conclusions differed from a similar project conducted in South Africa in which researchers found a high sensitivity but poor specificity in self-collected specimens.¹

Bottom line

Although self-sampling is promising, the present self-collection technique may provide a false sense of security for patients with high-grade lesions. Since these patients need more close monitoring than those with low-grade lesions, this method is not ready for widespread implementation. Further research aimed at improving the safety and efficacy of self-sampling is still needed.

THE QUESTION:
Is self-sampling effective in cervical cancer screening?

Past studies

Prior research has shown selfcollected cervical cell samples to be of variable concurrence to clinician-collected samples.

This study

Researchers evaluated 1 selfand 1 clinician-collected sample from 253 women, ages 16 to 88, randomly selected from a population at high risk for cervical neoplasia. Participants collected self-samples by rotating a cotton swab against the vaginal epithelium, and possibly, the cervix. Next, a colposcopist collected samples with an Ayre’s spatula and endocervical brush, then conducted a colposcopy. All specimens were frozen. Polymerase chain reaction (PCR) studies tested for both low-risk (LR) and high-risk (HR) viral types.

Positive HPV results from self-sampling and physician sampling were 23% and 29%, respectively. While there was no significant difference in the overall results from self-collected samples compared with physician-collected specimens, the prevalence of HR HPV among self-collected samples was 17%, as opposed to 26% in physician-collected samples. Further, testing for HPV detection on self-collected samples resulted in 50% more missed diagnoses of cervical cancer than did samples collected with a spatula and endocervical brush, and in 33.3% more missed diagnoses of high-grade cervical intraepithelial neoplasia. Hence, the researchers concluded that a sample for cervical HPV detection collected with a spatula and endocervical brush provides better results for primary cervical cancer screening than does self-sampling with a cotton-tipped swab.

Find this study

Lorenzato FR, Singer A, Ho L, et al. May 2002 issue of the American Journal of Obstetrics and Gynecology; abstract online at www.us.elsevierhealth.com/ajog.

Who may be affected by these findings?

All women screened for cervical cytology.

Expert commentary

There has been a marked decrease in invasive cervical cancer prevalence and mortality in countries where there are organized cytologic screening programs. Even so, an estimated 30% of US women with invasive cervical cancer had not had a Pap smear in at least 5 years, and 50% had never been screened. Moreover, developing countries have both health-care infrastructure deficiencies and cultural taboos that have thus far precluded universal screening.

Many women may find self-sampling to be a more convenient and comfortable way of screening for cervical cancer. Thus, if self-sampling could be substituted for clinician examinations, the detection of preinvasive cervical neoplasia cases could be substantially increased. This study, however, demonstrated a poor correlation with colposcopic and histologic diagnoses of high-grade squamous intraepithelial lesions and invasive cancer. Of note, this study’s conclusions differed from a similar project conducted in South Africa in which researchers found a high sensitivity but poor specificity in self-collected specimens.¹

Bottom line

Although self-sampling is promising, the present self-collection technique may provide a false sense of security for patients with high-grade lesions. Since these patients need more close monitoring than those with low-grade lesions, this method is not ready for widespread implementation. Further research aimed at improving the safety and efficacy of self-sampling is still needed.

THE QUESTION:
Does the risk of uterine rupture and dehiscence increase with a previous cesarean delivery?

Past studies

Prior research has demonstrated that patients undergoing a trial of labor after a cesarean delivery have an increased risk (1 in 200) of uterine rupture and dehiscence (URD).

This study

This 10-year review and case-control study examined 25,718 deliveries at a regional medical center to describe complications and identify risk factors for URD. During this period, 11 uterine ruptures and 10 uterine dehiscences occurred, along with 1 maternal death and 3 neonatal deaths. Other complications included intrapartum nonreassuring fetal status (67%), 5-minute Apgar score of less than 7 (52%), maternal blood transfusion (24%), neonatal hypoxic injury (14%), hysterectomy (14%), and endometritis (10%).

URD was independently associated with a fetal weight of greater than 8.8 lb, nonreassuring fetal status, oxytocin administration, and previous cesarean delivery. On the other hand, internal fetal monitoring was associated with a reduced risk of URD. The researchers concluded that in order to reduce the risk of URD, a delivery plan must include a cesarean history and fetal macrosomia assessment, along with the judicious use of oxytocin and intrapartum monitoring for nonreassuring fetal status.

Find this study

Diaz SD, Jones JE, Seryakov M, Mann WJ. April 2002 issue of the Southern Medical Journal; abstract online at www.medscape.com/viewarticle/432436.

Who may be affected by these findings?

Gravidas and practitioners contemplating vaginal birth after cesarean (VBAC).

Expert commentary

In the past decade, the issue of VBAC has dominated the obstetrics field. Attempts to lower cesarean-delivery rates have been fueled largely by concerns regarding cost of care. While the promotion of VBAC may save insurance companies money, the risks of a trial of labor cannot be ignored and must be thoroughly examined.

Specific factors estimating the risks or benefits of vaginal birth after cesarean remain controversial.

This study suggests that birth weight and oxytocin use may increase the risk of URD. However, these findings have not been supported by other studies.^1,2 Perhaps it is because this retrospective study harbors many limitations. For example, only symptomatic dehiscences were “discovered.” It is likely that a significant number of successful and uncomplicated VBACs sustained some degree of “bloodless dehiscence.” These, however, could not be accounted for unless routine inspection of the lower uterine segment was performed after each delivery. Another limitation of this study is the absence of labor management standards. The authors concluded that use of internal monitoring reduced the likelihood of URD, but this reduction could be a proxy for the more judicious use of uterotonic agents. Further, we do not have data regarding “decision-to-incision” intervals once fetal distress or URD was recognized.

It is important to note that the issue involved here is not one of equivalent risk, but rather, of acceptable risk, which can be determined only by the patient and her physician. At present, I’m inclined to agree with a New England Journal of Medicine editorial suggesting that if the safety of the fetus is the only consideration, elective repeat cesarean (ERC) should be the delivery of choice.³ Clearly, not every patient or clinician will see it this way.

Bottom line

The current study underscores the complexity of this issue. But while its conclusions may not be not unanimously agreed upon, the patient and the practitioner would be well advised to recognize that VBAC does indeed increase the risk of URD. Further, they should note that specific factors estimating the risks or benefits of VBAC remain controversial.

While these matters continue to be debated, facilities need to adopt a plan wherein rapid accomplishment of an emergency cesarean can occur and neonatal resuscitation personnel are immediately available.

THE QUESTION:
Does the risk of uterine rupture and dehiscence increase with a previous cesarean delivery?

Past studies

Prior research has demonstrated that patients undergoing a trial of labor after a cesarean delivery have an increased risk (1 in 200) of uterine rupture and dehiscence (URD).

This study

This 10-year review and case-control study examined 25,718 deliveries at a regional medical center to describe complications and identify risk factors for URD. During this period, 11 uterine ruptures and 10 uterine dehiscences occurred, along with 1 maternal death and 3 neonatal deaths. Other complications included intrapartum nonreassuring fetal status (67%), 5-minute Apgar score of less than 7 (52%), maternal blood transfusion (24%), neonatal hypoxic injury (14%), hysterectomy (14%), and endometritis (10%).

URD was independently associated with a fetal weight of greater than 8.8 lb, nonreassuring fetal status, oxytocin administration, and previous cesarean delivery. On the other hand, internal fetal monitoring was associated with a reduced risk of URD. The researchers concluded that in order to reduce the risk of URD, a delivery plan must include a cesarean history and fetal macrosomia assessment, along with the judicious use of oxytocin and intrapartum monitoring for nonreassuring fetal status.

Find this study

Diaz SD, Jones JE, Seryakov M, Mann WJ. April 2002 issue of the Southern Medical Journal; abstract online at www.medscape.com/viewarticle/432436.

Who may be affected by these findings?

Gravidas and practitioners contemplating vaginal birth after cesarean (VBAC).

Expert commentary

In the past decade, the issue of VBAC has dominated the obstetrics field. Attempts to lower cesarean-delivery rates have been fueled largely by concerns regarding cost of care. While the promotion of VBAC may save insurance companies money, the risks of a trial of labor cannot be ignored and must be thoroughly examined.

Specific factors estimating the risks or benefits of vaginal birth after cesarean remain controversial.

This study suggests that birth weight and oxytocin use may increase the risk of URD. However, these findings have not been supported by other studies.^1,2 Perhaps it is because this retrospective study harbors many limitations. For example, only symptomatic dehiscences were “discovered.” It is likely that a significant number of successful and uncomplicated VBACs sustained some degree of “bloodless dehiscence.” These, however, could not be accounted for unless routine inspection of the lower uterine segment was performed after each delivery. Another limitation of this study is the absence of labor management standards. The authors concluded that use of internal monitoring reduced the likelihood of URD, but this reduction could be a proxy for the more judicious use of uterotonic agents. Further, we do not have data regarding “decision-to-incision” intervals once fetal distress or URD was recognized.

It is important to note that the issue involved here is not one of equivalent risk, but rather, of acceptable risk, which can be determined only by the patient and her physician. At present, I’m inclined to agree with a New England Journal of Medicine editorial suggesting that if the safety of the fetus is the only consideration, elective repeat cesarean (ERC) should be the delivery of choice.³ Clearly, not every patient or clinician will see it this way.

Bottom line

The current study underscores the complexity of this issue. But while its conclusions may not be not unanimously agreed upon, the patient and the practitioner would be well advised to recognize that VBAC does indeed increase the risk of URD. Further, they should note that specific factors estimating the risks or benefits of VBAC remain controversial.

While these matters continue to be debated, facilities need to adopt a plan wherein rapid accomplishment of an emergency cesarean can occur and neonatal resuscitation personnel are immediately available.

THE QUESTION:
Does the risk of uterine rupture and dehiscence increase with a previous cesarean delivery?

Past studies

Prior research has demonstrated that patients undergoing a trial of labor after a cesarean delivery have an increased risk (1 in 200) of uterine rupture and dehiscence (URD).

This study

This 10-year review and case-control study examined 25,718 deliveries at a regional medical center to describe complications and identify risk factors for URD. During this period, 11 uterine ruptures and 10 uterine dehiscences occurred, along with 1 maternal death and 3 neonatal deaths. Other complications included intrapartum nonreassuring fetal status (67%), 5-minute Apgar score of less than 7 (52%), maternal blood transfusion (24%), neonatal hypoxic injury (14%), hysterectomy (14%), and endometritis (10%).

URD was independently associated with a fetal weight of greater than 8.8 lb, nonreassuring fetal status, oxytocin administration, and previous cesarean delivery. On the other hand, internal fetal monitoring was associated with a reduced risk of URD. The researchers concluded that in order to reduce the risk of URD, a delivery plan must include a cesarean history and fetal macrosomia assessment, along with the judicious use of oxytocin and intrapartum monitoring for nonreassuring fetal status.

Find this study

Diaz SD, Jones JE, Seryakov M, Mann WJ. April 2002 issue of the Southern Medical Journal; abstract online at www.medscape.com/viewarticle/432436.

Who may be affected by these findings?

Gravidas and practitioners contemplating vaginal birth after cesarean (VBAC).

Expert commentary

In the past decade, the issue of VBAC has dominated the obstetrics field. Attempts to lower cesarean-delivery rates have been fueled largely by concerns regarding cost of care. While the promotion of VBAC may save insurance companies money, the risks of a trial of labor cannot be ignored and must be thoroughly examined.

Specific factors estimating the risks or benefits of vaginal birth after cesarean remain controversial.

This study suggests that birth weight and oxytocin use may increase the risk of URD. However, these findings have not been supported by other studies.^1,2 Perhaps it is because this retrospective study harbors many limitations. For example, only symptomatic dehiscences were “discovered.” It is likely that a significant number of successful and uncomplicated VBACs sustained some degree of “bloodless dehiscence.” These, however, could not be accounted for unless routine inspection of the lower uterine segment was performed after each delivery. Another limitation of this study is the absence of labor management standards. The authors concluded that use of internal monitoring reduced the likelihood of URD, but this reduction could be a proxy for the more judicious use of uterotonic agents. Further, we do not have data regarding “decision-to-incision” intervals once fetal distress or URD was recognized.

It is important to note that the issue involved here is not one of equivalent risk, but rather, of acceptable risk, which can be determined only by the patient and her physician. At present, I’m inclined to agree with a New England Journal of Medicine editorial suggesting that if the safety of the fetus is the only consideration, elective repeat cesarean (ERC) should be the delivery of choice.³ Clearly, not every patient or clinician will see it this way.

Bottom line

The current study underscores the complexity of this issue. But while its conclusions may not be not unanimously agreed upon, the patient and the practitioner would be well advised to recognize that VBAC does indeed increase the risk of URD. Further, they should note that specific factors estimating the risks or benefits of VBAC remain controversial.

While these matters continue to be debated, facilities need to adopt a plan wherein rapid accomplishment of an emergency cesarean can occur and neonatal resuscitation personnel are immediately available.

THE QUESTION:
Can acetaminophen and NSAIDs reduce the risk of ovarian, breast, or colon cancer?

Past studies

Prior research has shown that long-term exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of developing colon cancer. Studies also have shown that extended acetaminophen use is associated with a decreased risk of ovarian cancer, though some reports have contradicted those findings. The results with regard to breast cancer risk remain unclear.

This study

The researchers explored a possible association between acetaminophen or NSAID exposure and the risk of developing ovarian, breast, and colon cancer in women ages 50 to 89. Participants included 483 women with ovarian cancer and 1,877 women matched for age, years of medical history recorded, general practice attended, and calendar time; 3,706 breast cancer patients and 14,155 matched control subjects; and 635 women with colon cancer and 2,434 matched control subjects.

Regular acetaminophen exposure (30 prescriptions or more) was associated with a slightly decreased risk of developing breast cancer (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-1.0) but not ovarian (OR, 1.0; 95% CI, 0.6-1.5) or colon (OR, 1.0; 95% CI, 0.7-1.4) cancer. On the other hand, regular NSAID exposure was linked to a reduced risk of colon cancer (OR, 0.5; 95% CI, 0.3-0.9) but not ovarian (OR, 1.1; 95% CI, 0.7-1.8) or breast cancer (OR, 1.0; 95% CI, 0.8-1.1).

Find this study

Meier CR, Schmitz S, Hershel J. March 2002 issue of Pharmacotherapy; abstract online at www.medscape.com/viewarticle/430206.

Who may be affected by these findings?

Women who are at high risk for breast, ovarian, or colon cancer.

Expert commentary

Ovarian cancer affects approximately 26,000 US women annually and takes the lives of 15,000. While it is not one of the most common cancers in women, it is one of the most lethal because the vast majority of patients present at advanced stages of the disease. To date, no screening method has been proven effective for ovarian cancer.

Breast cancer is the most common cancer in US women, excluding skin cancers, accounting for 31% of all cancers. Colon cancer is the third most common cancer, with 75,000 US women diagnosed annually.

The good news: the evolution of chemoprevention strategies. For example, oral contraceptive (OC) use may decrease a woman’s chance of developing ovarian cancer by up to 60%,¹ and tamoxifen has been used to prevent breast cancer in high-risk individuals. In addition, numerous studies have reported a lower risk of colorectal cancer with regular aspirin use.²

Now, researchers are exploring the chemoprophylactic use of NSAIDs and other COX-2 inhibitors, as well as acetaminophen, at the cellular and clinical level. These agents have been associated with a 24% reduction in breast cancer risk.³

Unlike NSAIDs, acetaminophen is a poor inhibitor of cyclooxygenase. Rather, its mechanism of action may be through an antigonadotropic effect. The agent has a phenol ring similar to estradiol and an acetyl group similar to progesterone, indicating a potential sex-steroid antagonist property.⁴

This study confirms previous reports that regular acetaminophen use does not decrease the risk of ovarian or colon cancer, while NSAID exposure does decrease the risk of colon cancer. One caveat: The study only utilized prescription data in a national research database. Nonprescription use of these drugs was not accounted for. Thus, this study potentially underestimates the use and impact of these medications.

Bottom line

Clearly, the use of acetaminophen and NSAIDs for the prevention of ovarian, breast, and colon cancers requires further investigation. Knowledge of how these agents prevent cancer may lead to the development of more effective chemoprophylactic medications. At this time, OC use to reduce the risk of ovarian cancer is the best chemoprevention strategy we have.

THE QUESTION:
Can acetaminophen and NSAIDs reduce the risk of ovarian, breast, or colon cancer?

Past studies

Prior research has shown that long-term exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of developing colon cancer. Studies also have shown that extended acetaminophen use is associated with a decreased risk of ovarian cancer, though some reports have contradicted those findings. The results with regard to breast cancer risk remain unclear.

This study

The researchers explored a possible association between acetaminophen or NSAID exposure and the risk of developing ovarian, breast, and colon cancer in women ages 50 to 89. Participants included 483 women with ovarian cancer and 1,877 women matched for age, years of medical history recorded, general practice attended, and calendar time; 3,706 breast cancer patients and 14,155 matched control subjects; and 635 women with colon cancer and 2,434 matched control subjects.

Regular acetaminophen exposure (30 prescriptions or more) was associated with a slightly decreased risk of developing breast cancer (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-1.0) but not ovarian (OR, 1.0; 95% CI, 0.6-1.5) or colon (OR, 1.0; 95% CI, 0.7-1.4) cancer. On the other hand, regular NSAID exposure was linked to a reduced risk of colon cancer (OR, 0.5; 95% CI, 0.3-0.9) but not ovarian (OR, 1.1; 95% CI, 0.7-1.8) or breast cancer (OR, 1.0; 95% CI, 0.8-1.1).

Find this study

Meier CR, Schmitz S, Hershel J. March 2002 issue of Pharmacotherapy; abstract online at www.medscape.com/viewarticle/430206.

Who may be affected by these findings?

Women who are at high risk for breast, ovarian, or colon cancer.

Expert commentary

Ovarian cancer affects approximately 26,000 US women annually and takes the lives of 15,000. While it is not one of the most common cancers in women, it is one of the most lethal because the vast majority of patients present at advanced stages of the disease. To date, no screening method has been proven effective for ovarian cancer.

Breast cancer is the most common cancer in US women, excluding skin cancers, accounting for 31% of all cancers. Colon cancer is the third most common cancer, with 75,000 US women diagnosed annually.

The good news: the evolution of chemoprevention strategies. For example, oral contraceptive (OC) use may decrease a woman’s chance of developing ovarian cancer by up to 60%,¹ and tamoxifen has been used to prevent breast cancer in high-risk individuals. In addition, numerous studies have reported a lower risk of colorectal cancer with regular aspirin use.²

Now, researchers are exploring the chemoprophylactic use of NSAIDs and other COX-2 inhibitors, as well as acetaminophen, at the cellular and clinical level. These agents have been associated with a 24% reduction in breast cancer risk.³

Unlike NSAIDs, acetaminophen is a poor inhibitor of cyclooxygenase. Rather, its mechanism of action may be through an antigonadotropic effect. The agent has a phenol ring similar to estradiol and an acetyl group similar to progesterone, indicating a potential sex-steroid antagonist property.⁴

This study confirms previous reports that regular acetaminophen use does not decrease the risk of ovarian or colon cancer, while NSAID exposure does decrease the risk of colon cancer. One caveat: The study only utilized prescription data in a national research database. Nonprescription use of these drugs was not accounted for. Thus, this study potentially underestimates the use and impact of these medications.

Bottom line

Clearly, the use of acetaminophen and NSAIDs for the prevention of ovarian, breast, and colon cancers requires further investigation. Knowledge of how these agents prevent cancer may lead to the development of more effective chemoprophylactic medications. At this time, OC use to reduce the risk of ovarian cancer is the best chemoprevention strategy we have.

THE QUESTION:
Can acetaminophen and NSAIDs reduce the risk of ovarian, breast, or colon cancer?

Past studies

Prior research has shown that long-term exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of developing colon cancer. Studies also have shown that extended acetaminophen use is associated with a decreased risk of ovarian cancer, though some reports have contradicted those findings. The results with regard to breast cancer risk remain unclear.

This study

The researchers explored a possible association between acetaminophen or NSAID exposure and the risk of developing ovarian, breast, and colon cancer in women ages 50 to 89. Participants included 483 women with ovarian cancer and 1,877 women matched for age, years of medical history recorded, general practice attended, and calendar time; 3,706 breast cancer patients and 14,155 matched control subjects; and 635 women with colon cancer and 2,434 matched control subjects.

Regular acetaminophen exposure (30 prescriptions or more) was associated with a slightly decreased risk of developing breast cancer (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-1.0) but not ovarian (OR, 1.0; 95% CI, 0.6-1.5) or colon (OR, 1.0; 95% CI, 0.7-1.4) cancer. On the other hand, regular NSAID exposure was linked to a reduced risk of colon cancer (OR, 0.5; 95% CI, 0.3-0.9) but not ovarian (OR, 1.1; 95% CI, 0.7-1.8) or breast cancer (OR, 1.0; 95% CI, 0.8-1.1).

Find this study

Meier CR, Schmitz S, Hershel J. March 2002 issue of Pharmacotherapy; abstract online at www.medscape.com/viewarticle/430206.

Who may be affected by these findings?

Women who are at high risk for breast, ovarian, or colon cancer.

Expert commentary

Ovarian cancer affects approximately 26,000 US women annually and takes the lives of 15,000. While it is not one of the most common cancers in women, it is one of the most lethal because the vast majority of patients present at advanced stages of the disease. To date, no screening method has been proven effective for ovarian cancer.

Breast cancer is the most common cancer in US women, excluding skin cancers, accounting for 31% of all cancers. Colon cancer is the third most common cancer, with 75,000 US women diagnosed annually.

The good news: the evolution of chemoprevention strategies. For example, oral contraceptive (OC) use may decrease a woman’s chance of developing ovarian cancer by up to 60%,¹ and tamoxifen has been used to prevent breast cancer in high-risk individuals. In addition, numerous studies have reported a lower risk of colorectal cancer with regular aspirin use.²

Now, researchers are exploring the chemoprophylactic use of NSAIDs and other COX-2 inhibitors, as well as acetaminophen, at the cellular and clinical level. These agents have been associated with a 24% reduction in breast cancer risk.³

Unlike NSAIDs, acetaminophen is a poor inhibitor of cyclooxygenase. Rather, its mechanism of action may be through an antigonadotropic effect. The agent has a phenol ring similar to estradiol and an acetyl group similar to progesterone, indicating a potential sex-steroid antagonist property.⁴

This study confirms previous reports that regular acetaminophen use does not decrease the risk of ovarian or colon cancer, while NSAID exposure does decrease the risk of colon cancer. One caveat: The study only utilized prescription data in a national research database. Nonprescription use of these drugs was not accounted for. Thus, this study potentially underestimates the use and impact of these medications.

Bottom line

Clearly, the use of acetaminophen and NSAIDs for the prevention of ovarian, breast, and colon cancers requires further investigation. Knowledge of how these agents prevent cancer may lead to the development of more effective chemoprophylactic medications. At this time, OC use to reduce the risk of ovarian cancer is the best chemoprevention strategy we have.

Ob/Gyns are seeing more patients than ever before. According to a recent ACOG survey, the typical Ob/Gyn averages 95 office visits per week. Physicians also are devoting more time to administrative duties and less time to hospital rounds and clinic visits compared with recent years. Clearly, these changes make it harder for doctors to spend quality time with each of their patients.

But enhancing the patient-doctor relationship need not be difficult. In most cases, subtle gestures can have an enormous impact on patient satisfaction and continuity of care. Here, we depart from our usual Pearls focus, the recommendations of a single physician, to offer pointers from a number of Ob/Gyns located throughout the United States. They share pearls on topics ranging from the first-time Pap experience to making patients feel more comfortable during an office visit.

New patients. Take a picture of every patient and staple it to the inside of her chart. This will help you remember each woman, especially when you are communicating via phone or e-mail. It also will help you notice new hairstyles or other changes, so that you can comment on them. The familiarity often comforts patients. —Sunita Giyanani, MD, Vineland, NJ

First-timers. When I encounter a young woman who is nervous about having her first Pap smear, I begin the procedure by asking: “Do you know that muscle you’d squeeze together if you wanted to stop urinating?” When she responds affirmatively, I tell her to squeeze that muscle. Then I tell her to relax. While showing her the speculum, I then say: “I’m going to place this little speculum on the back of that muscle. All I want you to do is think ‘loose’ with regard to that muscle, and everything will be okay.” It works like magic. —John Hannig, MD, Escondido, Calif

The loud gravida. From time to time, I encounter an inconsolable “screamer” in early labor, a patient who is creating noise so piercing and persistent that staff members find it virtually impossible to do their jobs. To stop the screaming or lessen its intensity, I tell the patient: “Don’t scream. You’ll wake up the babies in the nursery!” I don’t know whether this appeals to the patient’s maternal instincts or not, but it works every time. —David Schneider, MD, Bedford, Ind

Comforting the patient. Never speak to your patient with your hand on the door. She will not only feel rushed but that what she is saying is unimportant. Instead, sit down in the office or examining room. This will convey that you are truly listening and put her at ease. —Angelica Zaid, MD, Encinitas, Calif

Ob/Gyns are seeing more patients than ever before. According to a recent ACOG survey, the typical Ob/Gyn averages 95 office visits per week. Physicians also are devoting more time to administrative duties and less time to hospital rounds and clinic visits compared with recent years. Clearly, these changes make it harder for doctors to spend quality time with each of their patients.

But enhancing the patient-doctor relationship need not be difficult. In most cases, subtle gestures can have an enormous impact on patient satisfaction and continuity of care. Here, we depart from our usual Pearls focus, the recommendations of a single physician, to offer pointers from a number of Ob/Gyns located throughout the United States. They share pearls on topics ranging from the first-time Pap experience to making patients feel more comfortable during an office visit.

New patients. Take a picture of every patient and staple it to the inside of her chart. This will help you remember each woman, especially when you are communicating via phone or e-mail. It also will help you notice new hairstyles or other changes, so that you can comment on them. The familiarity often comforts patients. —Sunita Giyanani, MD, Vineland, NJ

First-timers. When I encounter a young woman who is nervous about having her first Pap smear, I begin the procedure by asking: “Do you know that muscle you’d squeeze together if you wanted to stop urinating?” When she responds affirmatively, I tell her to squeeze that muscle. Then I tell her to relax. While showing her the speculum, I then say: “I’m going to place this little speculum on the back of that muscle. All I want you to do is think ‘loose’ with regard to that muscle, and everything will be okay.” It works like magic. —John Hannig, MD, Escondido, Calif

The loud gravida. From time to time, I encounter an inconsolable “screamer” in early labor, a patient who is creating noise so piercing and persistent that staff members find it virtually impossible to do their jobs. To stop the screaming or lessen its intensity, I tell the patient: “Don’t scream. You’ll wake up the babies in the nursery!” I don’t know whether this appeals to the patient’s maternal instincts or not, but it works every time. —David Schneider, MD, Bedford, Ind

Comforting the patient. Never speak to your patient with your hand on the door. She will not only feel rushed but that what she is saying is unimportant. Instead, sit down in the office or examining room. This will convey that you are truly listening and put her at ease. —Angelica Zaid, MD, Encinitas, Calif

Ob/Gyns are seeing more patients than ever before. According to a recent ACOG survey, the typical Ob/Gyn averages 95 office visits per week. Physicians also are devoting more time to administrative duties and less time to hospital rounds and clinic visits compared with recent years. Clearly, these changes make it harder for doctors to spend quality time with each of their patients.

But enhancing the patient-doctor relationship need not be difficult. In most cases, subtle gestures can have an enormous impact on patient satisfaction and continuity of care. Here, we depart from our usual Pearls focus, the recommendations of a single physician, to offer pointers from a number of Ob/Gyns located throughout the United States. They share pearls on topics ranging from the first-time Pap experience to making patients feel more comfortable during an office visit.

New patients. Take a picture of every patient and staple it to the inside of her chart. This will help you remember each woman, especially when you are communicating via phone or e-mail. It also will help you notice new hairstyles or other changes, so that you can comment on them. The familiarity often comforts patients. —Sunita Giyanani, MD, Vineland, NJ

First-timers. When I encounter a young woman who is nervous about having her first Pap smear, I begin the procedure by asking: “Do you know that muscle you’d squeeze together if you wanted to stop urinating?” When she responds affirmatively, I tell her to squeeze that muscle. Then I tell her to relax. While showing her the speculum, I then say: “I’m going to place this little speculum on the back of that muscle. All I want you to do is think ‘loose’ with regard to that muscle, and everything will be okay.” It works like magic. —John Hannig, MD, Escondido, Calif

The loud gravida. From time to time, I encounter an inconsolable “screamer” in early labor, a patient who is creating noise so piercing and persistent that staff members find it virtually impossible to do their jobs. To stop the screaming or lessen its intensity, I tell the patient: “Don’t scream. You’ll wake up the babies in the nursery!” I don’t know whether this appeals to the patient’s maternal instincts or not, but it works every time. —David Schneider, MD, Bedford, Ind

Comforting the patient. Never speak to your patient with your hand on the door. She will not only feel rushed but that what she is saying is unimportant. Instead, sit down in the office or examining room. This will convey that you are truly listening and put her at ease. —Angelica Zaid, MD, Encinitas, Calif

THE QUESTION:
Does acyclovir prevent recurrent genital herpes and viral shedding in late pregnancy?

Past studies

These have shown acyclovir’s effectiveness in decreasing the viral load present in active lesions, thereby reducing the transmission rate. In addition, continuous acyclovir in the last 4 weeks of pregnancy may prevent recurrence at term and the need for cesarean delivery.

This study

This randomized trial from Paris assessed the efficacy of acyclovir in suppressing recurrent genital herpes simplex virus (HSV) in gravidas, reducing the need for cesarean delivery to prevent neonatal infection. Of the 288 women who presented during pregnancy with active genital HSV, 167 received acyclovir orally in a dose of 200 mg given 4 times daily from 36 weeks’ gestation to term. The other 121 participants received no treatment.

At the time of delivery, all women were examined for herpes lesions, and viral cultures were obtained from the vagina and cervix. Among the 167 patients treated with acyclovir, there were no cesarean deliveries due to genital HSV, whereas in the 121 untreated women, there were 15 cesarean deliveries. No infants developed HSV infection.

The authors concluded that acyclovir treatment beginning at 36 weeks’ gestation for women who have recurrent genital HSV infection in pregnancy reduces the incidence of cesarean deliveries and viral transmission.

Find this study

Braig et al, May 2001 issue of European Journal of Obstetrics, Gynecology, and Reproductive Biology; abstract online at www.elsevier.com/locate/ejogrb.

Who may be affected by these findings?

Gravidas with genital HSV infection.

Expert commentary

At present, cesarean section is the preferred mode of delivery to prevent neonatal herpes transmission. However, administering antiviral therapy to gravidas may be a better management option. Unfortunately, none of the antiherpetic medications, including acyclovir, valacyclovir, and famciclovir, are approved by the Food and Drug Administration (FDA) for use in pregnancy. This study and others have clarified the need to revise the current recommendations for managing gravidas infected with HSV. Until then, all pregnant women should be screened for genital herpes during labor. Also, internal fetal monitoring should be used with caution in patients with a history of genital HSV, as local neonatal infection may occur when utilizing the fetal scalp electrode.

Unfortunately, this study does not address the problem of infants who have asymptomatic mothers but develop HSV infection anyway, nor does it examine preventive methods during pregnancy. In order to achieve a significant reduction in neonatal HSV infection in the United States, universal screening during pregnancy for HSV antibodies, along with antenatal use of antiviral prophylaxis may be the next step. Universal screening for HSV requires the availability of reliable serology tests that distinguish between HSV-1 and HSV-2. Intervention methods then could be better aimed at these populations.

The bottom line

While there is no possibility of completely eliminating the sporadic occurrence of neonatal herpes transmission, administering acyclovir to women with genital HSV infection at 36 weeks’ gestation may greatly reduce the need for cesarean delivery and the incidence of viral transmission. In addition, antiviral treatment at term of all pregnant women with a history of HSV would save $183 per patient. On a national level, this amounts to $36.6 million annually.¹

THE QUESTION:
Does acyclovir prevent recurrent genital herpes and viral shedding in late pregnancy?

Past studies

These have shown acyclovir’s effectiveness in decreasing the viral load present in active lesions, thereby reducing the transmission rate. In addition, continuous acyclovir in the last 4 weeks of pregnancy may prevent recurrence at term and the need for cesarean delivery.

This study

This randomized trial from Paris assessed the efficacy of acyclovir in suppressing recurrent genital herpes simplex virus (HSV) in gravidas, reducing the need for cesarean delivery to prevent neonatal infection. Of the 288 women who presented during pregnancy with active genital HSV, 167 received acyclovir orally in a dose of 200 mg given 4 times daily from 36 weeks’ gestation to term. The other 121 participants received no treatment.

At the time of delivery, all women were examined for herpes lesions, and viral cultures were obtained from the vagina and cervix. Among the 167 patients treated with acyclovir, there were no cesarean deliveries due to genital HSV, whereas in the 121 untreated women, there were 15 cesarean deliveries. No infants developed HSV infection.

The authors concluded that acyclovir treatment beginning at 36 weeks’ gestation for women who have recurrent genital HSV infection in pregnancy reduces the incidence of cesarean deliveries and viral transmission.

Find this study

Braig et al, May 2001 issue of European Journal of Obstetrics, Gynecology, and Reproductive Biology; abstract online at www.elsevier.com/locate/ejogrb.

Who may be affected by these findings?

Gravidas with genital HSV infection.

Expert commentary

At present, cesarean section is the preferred mode of delivery to prevent neonatal herpes transmission. However, administering antiviral therapy to gravidas may be a better management option. Unfortunately, none of the antiherpetic medications, including acyclovir, valacyclovir, and famciclovir, are approved by the Food and Drug Administration (FDA) for use in pregnancy. This study and others have clarified the need to revise the current recommendations for managing gravidas infected with HSV. Until then, all pregnant women should be screened for genital herpes during labor. Also, internal fetal monitoring should be used with caution in patients with a history of genital HSV, as local neonatal infection may occur when utilizing the fetal scalp electrode.

Unfortunately, this study does not address the problem of infants who have asymptomatic mothers but develop HSV infection anyway, nor does it examine preventive methods during pregnancy. In order to achieve a significant reduction in neonatal HSV infection in the United States, universal screening during pregnancy for HSV antibodies, along with antenatal use of antiviral prophylaxis may be the next step. Universal screening for HSV requires the availability of reliable serology tests that distinguish between HSV-1 and HSV-2. Intervention methods then could be better aimed at these populations.

The bottom line

While there is no possibility of completely eliminating the sporadic occurrence of neonatal herpes transmission, administering acyclovir to women with genital HSV infection at 36 weeks’ gestation may greatly reduce the need for cesarean delivery and the incidence of viral transmission. In addition, antiviral treatment at term of all pregnant women with a history of HSV would save $183 per patient. On a national level, this amounts to $36.6 million annually.¹

THE QUESTION:
Does acyclovir prevent recurrent genital herpes and viral shedding in late pregnancy?

Past studies

These have shown acyclovir’s effectiveness in decreasing the viral load present in active lesions, thereby reducing the transmission rate. In addition, continuous acyclovir in the last 4 weeks of pregnancy may prevent recurrence at term and the need for cesarean delivery.

This study

This randomized trial from Paris assessed the efficacy of acyclovir in suppressing recurrent genital herpes simplex virus (HSV) in gravidas, reducing the need for cesarean delivery to prevent neonatal infection. Of the 288 women who presented during pregnancy with active genital HSV, 167 received acyclovir orally in a dose of 200 mg given 4 times daily from 36 weeks’ gestation to term. The other 121 participants received no treatment.

At the time of delivery, all women were examined for herpes lesions, and viral cultures were obtained from the vagina and cervix. Among the 167 patients treated with acyclovir, there were no cesarean deliveries due to genital HSV, whereas in the 121 untreated women, there were 15 cesarean deliveries. No infants developed HSV infection.

The authors concluded that acyclovir treatment beginning at 36 weeks’ gestation for women who have recurrent genital HSV infection in pregnancy reduces the incidence of cesarean deliveries and viral transmission.

Find this study

Braig et al, May 2001 issue of European Journal of Obstetrics, Gynecology, and Reproductive Biology; abstract online at www.elsevier.com/locate/ejogrb.

Who may be affected by these findings?

Gravidas with genital HSV infection.

Expert commentary

At present, cesarean section is the preferred mode of delivery to prevent neonatal herpes transmission. However, administering antiviral therapy to gravidas may be a better management option. Unfortunately, none of the antiherpetic medications, including acyclovir, valacyclovir, and famciclovir, are approved by the Food and Drug Administration (FDA) for use in pregnancy. This study and others have clarified the need to revise the current recommendations for managing gravidas infected with HSV. Until then, all pregnant women should be screened for genital herpes during labor. Also, internal fetal monitoring should be used with caution in patients with a history of genital HSV, as local neonatal infection may occur when utilizing the fetal scalp electrode.

Unfortunately, this study does not address the problem of infants who have asymptomatic mothers but develop HSV infection anyway, nor does it examine preventive methods during pregnancy. In order to achieve a significant reduction in neonatal HSV infection in the United States, universal screening during pregnancy for HSV antibodies, along with antenatal use of antiviral prophylaxis may be the next step. Universal screening for HSV requires the availability of reliable serology tests that distinguish between HSV-1 and HSV-2. Intervention methods then could be better aimed at these populations.

The bottom line

While there is no possibility of completely eliminating the sporadic occurrence of neonatal herpes transmission, administering acyclovir to women with genital HSV infection at 36 weeks’ gestation may greatly reduce the need for cesarean delivery and the incidence of viral transmission. In addition, antiviral treatment at term of all pregnant women with a history of HSV would save $183 per patient. On a national level, this amounts to $36.6 million annually.¹