Ovarian cysts: presence and persistence with use of a 13.5mg levonorgestrel-releasing intrauterine system.

OBJECTIVE: The aim of this study was to assess the presence of ovarian cysts in women using a new low-dose levonorgestrel-releasing intrauterine contraceptive system (LNG-IUS 13.5mg [total content]). STUDY DESIGN: A Phase 3 study assessed LNG-IUS 13.5mg use in healthy women with regular menstrual cycles who requested contraception. Transvaginal ultrasonography was performed at screening, baseline, and 3, 6, 9, 12, 18, 24, 30, and 36 months after placement. RESULTS: A total of 1432 women, mean age 27.2±4.8 years, were studied. A total of 10,446 transvaginal ultrasound examinations were performed over 3 years. Ovarian cysts were present in 1.6, 1.1, 2.3, 2.1, 2.4, 2.0, 2.1, 2.2, 1.9, and 2.1% of participants at screening, baseline, and Months 3, 6, 9, 12, 18, 24, 30, and 36, respectively. One hundred first-time ovarian cysts were identified from baseline through Month 9. The size distribution through Month 12 was ≤30 mm (13%), >30 to ≤50 mm (74%), >50 to ≤80 mm (11%), and >80 mm (0%). The overall persistence of ovarian cysts from one examination to the next in Year 1 was 12% (11/90 with follow-up). Cyst persistence was 36% from baseline to 3 months, 13% from 3 to 6 months, 10% from 6 to 9 months, and 0% from 9 to 12 months. The likelihood of cyst persistence increased for cysts >50mm (36%) as compared to those ≤50 mm (8%). CONCLUSION: Ovarian cysts were present in 1.6% of women at screening, 2.0 to 2.4% of LNG-IUS 13.5mg users during Year 1, and 1.9 to 2.1% during Years 2 and 3. The majority were >30 to ≤50 mm in size. The small and diminishing number of persistent cysts-decreasing to 0% from 9 to 12 months-suggests that they were functional in nature. IMPLICATIONS: Transvaginal ultrasound follow-up of women during a 3-year clinical trial of LNG-IUS 13.5mg showed that ovarian cysts were present in 1.6% of participants at screening and 1.1-2.4% at each subsequent visit. Eighty-eight percent were ≤5cm, with none >8cm. No ovarian cysts persisted beyond Month 9, suggesting a functional etiology.

Stopping menopausal hormone therapy: if breast cancer really decreased, why did colorectal cancer not increase?

OBJECTIVE: The Women's Health Initiative (WHI) study of postmenopausal hormone therapy (HT) found that estrogen plus progestogen therapy (EPT) decreased colorectal cancer risk. Thus, the decline in EPT use from 2002 to 2003 should have precipitated an increase in the incidence of colorectal cancer. We tested this prediction using the SEER 9 epidemiologic database. METHODS: We analyzed WHI data concerning the effects of EPT and estrogen therapy (ET) on colorectal cancer risks. We also examined HT prescription sales data, as well as SEER 9 colorectal cancer incidences from 2001 to 2004. RESULTS: In the WHI study, the incidence of colorectal cancer was comparable in EPT placebo-users, ET users, and ET placebo-users, but significantly lower in EPT users. Assuming that 30% of eligible women used HT in 2001, the decline in EPT sales from 2002 to 2003 of 63% should have increased the incidence of colorectal cancer by 2.8% in the overall population at risk. However, the SEER 9 colorectal cancer incidence fell by 5.9% in this population, which is comparable to the 6.7% decrease observed for invasive breast cancer from 2002 to 2003. CONCLUSIONS: Declining EPT use from 2002 to 2003 should have precipitated an increase in the incidence of colorectal cancer, but the opposite trend was seen in the SEER 9 database during this time. The incidences of invasive breast cancer and colorectal cancer both declined by a similar amount from 2002 to 2003, despite the results of the WHI study predicting opposing trends for the two different types of cancer. Thus, the SEER 9 findings are fundamentally incompatible with expectations from the WHI findings. This implies that reductions in HT use from 2002 to 2003 cannot account for the contemporaneous changes in invasive breast cancer and colorectal cancer incidences. Alternative explanations must be found.

Burden of illness of hypertension among women using menopausal hormone therapy: a US perspective.

OBJECTIVE: To estimate the burden of illness (BOI) of hypertension in a cohort of women receiving menopausal hormone therapy (HT). METHODS: Patients with at least one prescription for menopausal HT were selected from the PharMetrics database during the period July 1, 2003, to June 30, 2005. Hormone therapy patients were divided into those with and without hypertension. The nonhypertensive cohort was propensity score-matched to the hypertensive cohort, controlling for patient demographics, overall comorbidities, and type of HT use. The BOI of hypertension in the menopausal HT cohort was defined as the difference in average annual total healthcare expenditures per person between the cohorts. RESULTS: The prevalence of menopausal HT use was 9.75% among potentially eligible patients in this commercially insured sample. Hypertension was the most common comorbidity in the menopausal HT cohort, with a prevalence of 34%. Hormone therapy patients with hypertension (n = 106,729) had significantly higher average annual healthcare expenditures compared to matched HT patients without hypertension ($8908 vs. $5960 per person per year; difference of $2948; p < 0.001). CONCLUSIONS: Hypertension is the most common comorbidity among menopausal HT users in the United States. The annual BOI of hypertension is both substantial and significant when compared to matched patients without hypertension, averaging $2948 per patient per year.

The breast cancer "plunge" after initial publication of the WHI results: an alternative explanation.

From 2002 to 2003, the breast cancer incidence in the United States, as reported by the National Cancer Institute's Surveillance Epidemiology and End Results (SEER 9) database, appeared to decrease by 6.7%. This phenomenon has been attributed to a reduction in the use of menopausal hormone therapies after the initial publication of the Women's Health Initiative (WHI) study results in July of 2002. However, attempts to draw a causal association between the use of menopausal hormone therapies and the incidence of breast cancer have not accounted for the facts that prescriptions of estrogen-plus-progestin menopausal therapies, which are associated with increased rates of breast cancer, fell by 53% from 2002 to 2003, while prescriptions of estrogen-only therapies fell by only 27%. To address this issue, we analyzed the effects of the higher rate of discontinuation of estrogen-plus-progestin menopausal therapies relative to estrogen-only treatments during the 2002-2003 time period, based upon the effects of different types of menopausal hormone therapies on breast cancer incidence as determined by the WHI interventional hormone trials. This approach demonstrates that the relative persistence with menopausal estrogen-only therapies - as compared to estrogen-plus-progestin therapies - can explain the reduction in breast cancer incidence from 2002 to 2003. In addition, we point out the incompatibility of the breast cancer incidence rates found in the two WHI interventional hormone trials and the rates reported in the SEER 9 database. Based on these findings, we conclude - as previously demonstrated in the estrogen-only arm of the WHI interventional hormone trials - that menopausal estrogen-only use is not responsible for increasing the risk of breast cancer in menopausal women and may, in fact, be protective. Additional studies are still needed to better define the relationship between different types of menopausal hormone therapies and the incidence of breast cancer.

Prevalence and opinions of hormone therapy prior to the Women's Health Initiative: a multinational survey on four continents.

OBJECTIVE: Hormone therapy (HT) is a well-established form of treatment for menopausal symptoms worldwide. Since 2002 when the initial findings of the Women's Health Initiative (WHI) were published, the use of HT has decreased dramatically. This investigation was conducted immediately prior to the initial publication of the WHI and Million Women's Study results and quantifies menopausal women's prevalence of symptoms across nine countries on four continents. In addition, it investigates women's positive and negative motivations for HT use as well as their acceptance of various forms and routes of administration. METHODS: Using national representative population panels and quota samples in nine countries on four continents, 10,297 women aged 40-70 years were recruited between April and June 2002. A validated survey was administered to determine which symptoms women suffered from the most and what their desires were regarding the use and effects of HT. RESULTS: Self-reported symptoms did not differ significantly among menopausal women in Europe, North America, Latin America, and Indonesia. However, the prevalence of HT ever-use ranged from a high of 50% in France to a low of 1.8% in Indonesia (U.S. rate 43%). Oral pills had the highest acceptance rate in all countries. CONCLUSIONS: Women in all parts of the world suffer from symptoms associated with menopause, and many desire treatment. This study was conducted prior to the publication of the initial WHI and Million Women Study results, thereby providing a benchmark of patient attitudes about menopausal symptoms and the acceptability of different types and delivery modes of HT.

A computerized method for accurately predicting fetal macrosomia up to 11 weeks before delivery.

OBJECTIVE: To improve the prediction of birth weight and fetal macrosomia by combining sonographically derived fetal biometric data with routinely recorded pregnancy-specific information. STUDY DESIGN: Retrospective data were obtained for 218 normal gravidas who had obstetrical ultrasonography performed within 11 weeks of delivery. Multiple regression was employed to derive a set of equations for predicting birth weight that used different combinations of ultrasonographic and pregnancy-specific variables. RESULTS: A set of 38 unique combination equations was derived to accurately predict birth weight up to 11 weeks before delivery. The equations use different combinations of ultrasonographic and pregnancy-specific variables, so that predictions are still possible in the face of missing data. When ultrasonographic measurements are taken within 3 weeks of delivery, fetal macrosomia is predicted with 75% sensitivity, 93% specificity, and 67% and 95% positive and negative predictive value, respectively. The equations are equally as accurate for primiparous and multiparous women from all racial groups. A jackknifing procedure was used to validate the predictive accuracy of the equations for use with new subjects. CONCLUSION: The combined approach of predicting fetal macrosomia using ultrasonographic fetal measurements and pregnancy-specific characteristics is superior to pre-existing approaches that rely on either method alone. The method can be used up to 11 weeks before delivery, allowing fetal macrosomia to be predicted reliably in low-risk populations sufficiently early for prospective clinical intervention to be undertaken.

Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risks.

OBJECTIVE: Over ten million women are either pregnant or lactating in the United States at any time. The risks of medication use for these women are unique. In addition to normal physiologic changes that alter the pharmacokinetics of drugs, there is the concern of possible teratogenic and toxic effects on the developing fetus and newborn. This article reviews the risks and pharmacokinetic considerations for 11 broad-spectrum antibiotics that can be used to treat routine and life-threatening infections during pregnancy and lactation. DATA SOURCES: Information from the U.S. Food and Drug Administration (FDA) product labels, the Teratogen Information Service, REPROTOX, Shepard's Catalog of Teratogenic Agents, Clinical Pharmacology, and the peer-reviewed medical literature was reviewed concerning the use of 11 antibiotics in pregnant and lactating women. The PubMed search engine was used with the search terms "[antibiotic name] and pregnancy," "[antibiotic name] and lactation," and "[antibiotic name] and breastfeeding" from January 1940 to November 2005, as well as standard reference tracing. METHODS OF STUDY SELECTION: One hundred twenty-four references had sufficient information concerning numbers of subjects, methods, and findings to be included. TABULATION, INTEGRATION, AND RESULTS: The teratogenic potential in humans ranged from "none" (penicillin G and VK) to "unlikely" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, and rifampin) to "undetermined" (clindamycin, gentamicin, and vancomycin). Assessments were based on "good data" (penicillin G and VK), "fair data" (amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin, and rifampin), "limited data" (clindamycin and gentamicin), and "very limited data" (vancomycin). Significant pharmacokinetic changes occurred during pregnancy for the penicillins, fluoroquinolones and gentamicin, indicating that dosage adjustments for these drugs may be necessary. With the exception of chloramphenicol, all of these antibiotics are considered compatible with breastfeeding. CONCLUSION: Health care professionals should consider the teratogenic and toxic risk profiles of antibiotics to assist in making prescribing decisions for pregnant and lactating women. These may become especially important if anti-infective countermeasures are required to protect the health, safety, and survival of individuals exposed to pathogenic bacteriologic agents that may occur from bioterrorist acts.

Evaluating medical student obstetrics and gynecology clerkship performance: which assessment tools are most reliable?

OBJECTIVE: This study was undertaken to investigate medical student performance on an obstetrics and gynecology (Ob-Gyn) core clerkship to determine the most discriminating measures of student performance. STUDY DESIGN: Four-hundred twenty-one clinical clerks were assessed with the use of 46 performance indicators in 4 different categories. Final Scores were weighted: (1) Clinical Performance = 60%, (2) Formal Presentation = 10%, (3) Oral Examination = 10%, and (4) National Board of Medical Examiners (NBME) Subject Test score = 20%. RESULTS: A total of 17,023 scores were examined. Final Scores were normally distributed. Clinical Performance and Formal Presentation scores were highly skewed, explaining 35% and 5% of the Final Score variance, respectively. Oral Examination scores were slightly skewed, explaining 17% of the variance. The NBME Subject Test score was the only normally distributed performance indicator and, despite comprising only 20% of Final Scores, was the most highly correlated ( R = 0.86), explaining 74% of the variance. CONCLUSION: Despite their minor weighting in our grading system, NBME Subject Test scores were very highly correlated with overall clinical clerkship performance. By combining written Subject Test and Oral Examination scores, 91% of the variance in Final Scores can be explained.

Preventing ectopic pregnancies: how often does transperitoneal transmigration of sperm occur in effecting human pregnancy?

OBJECTIVE: Transperitoneal transmigration of sperm constitutes the mechanism by which ectopic pregnancies occur in unilaterally obstructed fallopian tubes. This study was undertaken to determine how often sperm transmigrate across the peritoneal cavity to effect human pregnancy. DESIGN: In women with non-communicating rudimentary uterine horn pregnancies, the ratio of total uterine horn pregnancies to prior contralateral hemi-uterine pregnancies was calculated to infer the overall transperitoneal sperm transmigration rate. The prior parity frequency distribution was also determined to calculate the best-fit per-pregnancy probability of attaining a rudimentary horn pregnancy with each subsequent gestation using maximum likelihood estimation. SETTING: 20th century. SAMPLE: Non-communicating rudimentary uterine horn pregnancies reported from 40 countries. METHODS: Two hundred and seventy-two cases were identified using manual and computerised searches of Index Medicus, Excerpta Medica, the Index-Catalogue of the Library of the Surgeon-General's Office and standard reference tracing. MAIN OUTCOME MEASURES: The ratio of total prior non-rudimentary uterine horn pregnancies to rudimentary uterine horn pregnancies and the frequency distribution of prior maternal parities. RESULTS: Prior to the incident 272 uterine horn pregnancies, the number of observed pregnancies was 292 (ratio = 0.93), implying an aggregate sperm transmigration rate of 0.48. Using the prior parity frequency distribution, the best-fit probability of attaining a rudimentary horn gestation per-pregnancy was 0.51 (95% CI 0.48-0.56). CONCLUSIONS: Intraperitoneal sperm transmigration occurs approximately half the time in effecting spontaneous human pregnancies. To minimise the risk of ectopic tubal pregnancy in woman with unilaterally damaged fallopian tubes, salpingectomy should be the preferred surgical treatment, rather than attempting tubal salvage and repair.

Hemoglobin, altitude and birth weight: does maternal anemia during pregnancy influence fetal growth?

OBJECTIVE: To investigate the relationship between maternal hemoglobin concentration, altitude and birth weight. STUDY DESIGN: Birth weights in 235 term pregnancies were investigated for their dependence on maternal hemoglobin concentration after other maternal and pregnancy-specific influences on fetal weight were taken into account. The additional predictive value of hemoglobin concentration on birth weight was assessed using multiple regression. Using published data, the relationship of hemoglobin concentration to altitude was determined, as was the effect of increasing altitude on birth weight. The quantitative effect of hemoglobin concentration on birth weight was correlated with the effect of altitude on hemoglobin concentration to assess whether this could account for the known decrease in birth weight with increasing altitude. RESULTS: Birth weights ranged from 2,220 to 4,850 g (mean, 3,505+/-443), and hemoglobin concentrations ranged from 9.3 to 13.5 g/dL (mean, 11.6+/-0.8). Apart from other known predictive variables, the variation in maternal hemoglobin concentrations at constant altitude independently explained 2.6% of the variance in birth weight (r=-.18, P=.003). Term birth weight was reduced by 89 g for each 1.0 g/dL increase in hemoglobin concentration (P<.01). For every 1,000-m increase in altitude, hemoglobin concentration increased by 1.52 g/dL and birth weight decreased by 117 g. CONCLUSION: Birth weight correlates negatively with maternal hemoglobin concentration. This is consistent with the well-known effect of high-altitude exposure during pregnancy, which increases both hematocrit and blood viscosity and lowers birth weight. The quantitative effect on birth weight of increasing maternal hemoglobin concentration at constant altitude is within 13% of the change in birth weight that can be attributed to the change in hemoglobin concentration associated with increases in altitude.

Prediction of term birth weight in Hispanic women using an equation based on maternal characteristics.

OBJECTIVE: To test the accuracy of a birth weight prediction equation based on maternal characteristics in Hispanic women. STUDY DESIGN: A previously published birth weight prediction equation based on maternal and pregnancy-specific characteristics was used to predict birth weights for 283 normal Caucasian women of Hispanic ethnicity. The accuracy of these birth weight estimates was compared to a similarly selected group of 233 non-Hispanic Caucasian gravidas who were located 2500 miles away. RESULTS: Birth weight predictions for Hispanic women were accurate to within +/- 8.4% (+/- 287 g). The percentages of birth weights predicted to within +/- 15 and +/- 10% of actual values were 84 and 68%, respectively. These results were no different than those that were obtained for non-Hispanic Caucasian gravidas. CONCLUSIONS: A previously derived birth weight prediction equation based on maternal and pregnancy-specific characteristics alone successfully predicts term birth weight in normal Hispanic gravidas to within +/- 8.4% (+/- 287 g).

Ultrasonic prediction of term birth weight in Hispanic women. Accuracy in an outpatient clinic.

OBJECTIVE: To investigate the accuracy of ultrasonic fetal biometric algorithms for estimating term fetal weight. STUDY DESIGN: Ultrasonographic fetal biometric assessments were made in 74 Hispanic women who delivered at 37-42 weeks of gestation. Measurements were taken of the fetal biparietal diameter, head circumference, abdominal circumference and femur length. Twenty-seven standard fetal biometric algorithms were assessed for their accuracy in predicting fetal weight. Results were compared to those obtained by merely guessing the mean term birth weight in each case. RESULTS: The correlation between ultrasonically predicted and actual birth weights ranged from 0.52 to 0.79. The different ultrasonic algorithms estimated fetal weight to within +/- 8.6-15.0% (+/- 295-520 g) of actual birth weight as compared with +/- 13.6% (+/- 449 g) for guessing the mean birth weight in each case (mean +/- SD). The mean absolute prediction errors for 17 of the ultrasonic equations (63%) were superior to those obtained by guessing the mean birth weight by 3.2-5.0% (96-154 g) (P < .05). Fourteen algorithms (52%) were more accurate for predicting fetal weight to within +/- 15%, and 20 algorithms (74%) were more accurate for predicting fetal weight to within +/- 10% of actual birth weight than simply guessing the mean birth weight (P < .05). Ten ultrasonic equations (37%) showed significant utility for predicting fetal weight > 4,000 g (likelihood ratio > 5.0). CONCLUSION: Term fetal weight predictions using the majority of sonographic fetal biometric equations are more accurate, by up to 154 g and 5%, than simply guessing the population-specific mean birth weight.

Ultrasonographic prediction of term birth weight: how accurate is it?

OBJECTIVE: The purpose of this study was to investigate the accuracy of 25 ultrasonic algorithms for the estimation of term fetal weight and to compare these results to an equation that is based on maternal and pregnancy-specific characteristics alone. STUDY DESIGN: Ultrasonography was performed in 82 nondiabetic gravid women at 35 to 41 weeks of gestation. Fetal biparietal diameter, abdominal circumference, head circumference, and femur length were measured. Twenty-five ultrasonic fetal biometric algorithms and an equation that is based only on maternal characteristics were used to predict birth weight. RESULTS: The correlation between predicted and actual birth weight ranged from 0.44 to 0.79 for the ultrasonic algorithms and was 0.60 for the maternal characteristics equation. Ultrasonic algorithms had mean absolute prediction errors that ranged from +/-263 to 646 g (+/-7.5%-18.8%). Accuracy for the maternal characteristics equation was not statistically different from the best performing ultrasonic algorithms (+/-353 g, +/-10.4%). CONCLUSION: Term birth weight estimates that use ultrasonography are generally no more accurate than predictions that are based solely on quantitative assessment of maternal and pregnancy-specific characteristics.

Relationship of paternal factors to birth weight.

OBJECTIVE: To investigate the relationship between paternal characteristics and birth weight. STUDY DESIGN: A total of 241 gravidas with uncomplicated, singleton, term pregnancies were studied. Maternal demographic and pregnancy-specific characteristics were used to calculate the expected birth weight for each fetus using a previously validated birth weight prediction equation. The additional independent predictive value of 4 paternal variables was assessed using multiple regression. RESULTS: Before adjustment for other variables, paternal height and weight significantly correlated with birth weight, but paternal age and body mass index did not. After controlling for maternal and pregnancy-specific factors that are known to influence fetal weight, only paternal height was significant as a predictive variable. The proportion of variance in birth weight that could be independently explained by paternal height was 2%. A 10-g gain in fetal weight was associated with each centimeter of increase in paternal height (P < .02). Using the resulting combination equation that included paternal height as a variable, 31% of the variance in term birth weight could be explained, and birth weights could be accurately predicted to within +/- 8.3% (+/- 288 g). Fathers with heights 2 SD above and below the mean had the term birth weight of their offspring increased and diminished by 125 g, respectively. CONCLUSION: Paternal height explains an independent portion of the variance in term birth weight among normal newborns of up to 250 g that cannot be explained by other maternal or pregnancy-specific factors. Paternal age, weight and body mass index do not independently influence birth weight.