Our goal was to evaluate short-term (3 months) and long-term (1 year) treatment of vulvar lichen sclerosus, by comparing topical application of testosterone propionate 2% in petrolatum with the corticosteroid clobetasol dipropionate 0.05%.
There were 20 women in each treatment group. The patients' symptoms and the gynecologist's examination findings were recorded before treatment, at 3 months, and at 1 year after initiation of therapy.
The symptomatic (subjective) effect of clobetasol treatment was similar to that of testosterone at the 3-month follow-up (p < or = 0.34), although objectively the signs of lichen sclerosus had improved more in the clobetasol group (p < or = 0.033). Both symptoms and signs were significantly more improved in the clobetasol-treated group at the 1-year follow-up examination (p < or = 0.02). Seventy percent of women treated by testosterone discontinued treatment because of a lack of response, whereas only 10% of the women treated with clobetasol stopped the treatment for that reason (p < or = 0.00042).
Clobetasol is more effective than testosterone in the treatment of women with lichen sclerosus, especially in the long term.
The binding capacity of plasma testosterone-estradiol-binding globulin (TeBG) and testosterone (T) levels were measured in four women with proved polycystic ovaries and three women with a clinical diagnosis of polycystic ovarian disease before, during, and after administration of norethindrone, 2 mg., and mestranol, 0.1 mg. (N + M)...
The response of the binding capacity of plasma testosterone-estradiol-binding globulin (TeBG) to 2 mg norethindrone and .1 mg mestranol in polycystic ovarian disease was investigated. TeBG and testosterone levels were measured in 4 women with proved polystic ovaries and 3 women with a clinical diagnosis of polystic ovarian disease before, during, and after norethindrone plus mestranol treatment. TeBG was increased within 4 days after treatment was begun. TeBG was significantly elevated (p less than .05) and testosterone was significantly suppressed (p less than .05) relative to pretreatment levels by 9-12 days after treatment was started. Both levels remained markedly different from pretreatment levels during the 12-day posttreatment period. All 7 women responded to treatment with a decrease in plasma levels of both total and free testosterone.
Norethindrone 0.35 mg. was taken daily by 154 women for a total of 1,888 months in a study of continuous low-dosage progestin as an oral contraceptive method. Pregnancy rates of 0.6 per 100 woman-years for correct use and 1.3 per 100 woman-years for total use were obtained. A high incidence of menstrual irregularity and/or amenorrhea was noted but the incidence of nausea and weight gain was low. There was no significant difference in oral glucose tolerance tests done in 18 women before and after taking norethindrone for 6+ months, and other serum determinations done in 19 women showed a significant rise in alkaline phosphatase and albumin along with a significant decrease in SGOT.
This study was undertaken to investigate the effect of daily ingestion of 0.5 mg. of lynestrenol on some parameters of the hypothalamic-pituitary-ovarian axis. Daily plasma concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol-17-beta (estradiol; E2-17beta), and progesterone (P) were determined by specific radioimmunoassays during one control and one treatment cycle of seven normally ovulating women. One of the volunteers was followed throughout 84 days of treatment. The following changes were observed during medication: (1) the midcycle FSH/LH peak was abolished, with a trend toward reduced LH values during the second half of the treatment cycles; (2) progesterone was significantly, though variably, reduced whereas estradiol showed little difference between control and treatment cycles; (3) during prolonged treatment two difference cyclic response patterns were observed in the same individual. It is concluded that daily administration of 0.5 mg. of lynestrenol exerts a profound effect at the central level, which contributes to the satisfactory contraceptive efficacy of this compound. A hypothetic blockade of estradiol receptors at the pituitary and/or hypothalamic level is discussed.
Abortion was successfully induced by intravaginal insertion of a silicone rubber device impregnated with an 0.5% concentration of 15(S)-15-methyl-prostaglandin F2alpha methyl ester in 20 of 25 patients by prostaglandin alone and in an additional three patients by prostaglandin with a concomitant oxytocin infusion. The mean abortion time for the 23 successful abortions was 15.46 hours. Uterine activity was monitored in six patients and uterine response to the vaginal insertion of the prostaglandin-impregnated device was characterized by a gradual rise in amplitude of contractions and intrauterine baseline tonus accompanied by a rapid increase in the frequency of contractions. Induction of abortion by intravaginal administration of a silicone rubber device impregnated with prostaglandin eliminates the hazards associated with intra-amniotic instillation and offers the advantage of a single administration with the option of reversibility if a patient should be hypersensitive to the drug.
We sought to determine the effects of the intramuscular maternal administration of betamethasone to the pregnant baboon at 0.7 of gestation on fetal blood pressure and heart rate.
We treated pregnant baboons at 0.7 of gestation with intramuscular betamethasone (n = 4), at a weight-adjusted dose equivalent to the daily dose administered to women in preterm labor or with saline solution (n = 5). Four injections were given at 12-hour intervals. Fetal and maternal blood pressure and heart rate were recorded continuously. Within-group differences and between-group differences were analyzed with repeated measures analysis of variance.
Fetal blood pressure increased significantly after betamethasone treatment. Fetal heart rate, maternal blood pressure, and heart rate did not change.
Exposure of the developing primate fetus to exogenous glucocorticoid at 0.7 of gestation elevates fetal blood pressure. These findings confirm and extend the observations in the fetal sheep. Further studies are needed to evaluate the mechanisms that are involved and possible long-term consequences of these cardiovascular effects of antenatal glucocorticoid exposure in the fetal primate.
Exposure to glucocorticoid levels inappropriately high for current maturation alters fetal hypothalamo-pituitary-adrenal axis (HPAA) development. In an established fetal sheep model, we determined whether clinical betamethasone doses used to accelerate fetal lung maturation have persistent effects on fetal HPAA hypotensive-stress responses.
Pregnant ewes received saline (n = 6) or betamethasone (n = 6); 2 × 110 μg/kg body weight doses injected 24 hours apart (106/107 and 112/113 days' gestational age, term 150 days). Basal adrenocorticotropin (ACTH) and cortisol and responses to fetal hypotension were measured before and 5 days after the first course and 14 days after the second course.
Basal ACTH and cortisol were similar with treatment. HPAA responses to hypotension increased after the second but not first course and ACTH/cortisol ratio increased indicating central HPAA effects.
Results demonstrate latency in the emergence of fetal HPAA hyperresponsiveness following betamethasone exposure that may explain hyperresponsiveness in full-term but not preterm neonates.
Our purpose was to test the hypothesis that a long-term physiologic elevation of plasma cortisol would not alter the basal plasma concentrations of immunoreactive and bioactive corticotropin, yet it would evoke an increase in the ratio of bioactive to immunoreactive corticotropin secreted during stress. We define immunoreactive corticotropin (i.e., immunoreactive corticotropin-like activity) as that material obtained from plasma that displaces the binding of tracer quantities of iodine 125-labeled corticotropin from antisera directed toward the 6-24 portion of the corticotropin (1-39) molecule, whereas bioactive corticotropin (i.e., bioactive corticotropin-like activity) is defined as that material obtained from plasma that stimulates the secretion of corticosterone from dispersed rat adrenal cells in comparison to known concentrations of synthetic corticotropin (1-39).
We studied the plasma immunoreactive and bioactive corticotropin response to hemorrhage in eight vehicle- and 10 cortisol-treated fetal sheep at 101 +/- 1 days of gestation. At 94 +/- 1 days of gestation each fetus began receiving a 6-day continuous infusion of either vehicle or cortisol. During the last 10 minutes of the infusion about 30% of the estimated blood volume was withdrawn from the fetuses.
Basal plasma cortisol was significantly higher in the cortisol group (20.6 +/- 2.3 ng/ml vs 2.7 +/- 0.3 ng/ml). Basal plasma immunoreactive ACTH and bioactive corticotropin were not significantly different between groups. In both groups the plasma immunoreactive corticotropin significantly increased during hemorrhage, although the increase in the cortisol group (32 +/- 8 to 40 +/- 8 pg/ml) was significantly less than that in the vehicle group (45 +/- 14 to 86 +/- 28 pg/ml). In contrast, plasma bioactive corticotropin increased significantly during hemorrhage in the vehicle group (10 +/- 1 to 16 +/- 3 pg/ml) alone.
In the early-gestation fetal sheep a chronic elevation of plasma cortisol does not significantly lower basal plasma immunoreactive and bioactive corticotropin. Nevertheless, it (1) attenuates the immunoreactive corticotropin response and (2) abolishes the bioactive corticotropin response to hemorrhage. It is possible that some of the negative feedback effects of plasma cortisol on corticotropin release occur at the posttranslational level.
Efficacy study of suppressive vaginal metronidazole in reducing recurrent symptomatic episodes of bacterial vaginosis.
Multicenter prospective study with initial 10-day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks.
Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2%) responded clinically and were randomly assigned. During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR] 0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68, CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18%, respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02).
Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.
Our purpose was to investigate the temporal relationship between delta4-androstenedione-induced preterm switching of myometrial activity patterns from contractures to contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey.
Eight rhesus monkeys (132 to 136 days' gestation) were instrumented under halothane with femoral artery and vein catheters and uterine electromyogram electrodes. At 138 to 142 days' gestation baseline maternal femoral artery blood samples for estradiol and oxytocin measurement were taken at 30-minute intervals for 7 hours, starting 2 hours before the onset of darkness. The day after baseline sampling a continuous intravenous delta4-androstenedione infusion (0.3 mg . kg-1 .hr-1 in 10% intralipid at 0.25 ml . hr-1) was started in four monkeys, while four monkeys were infused intravenously with intralipid alone. The sampling regimen was then repeated at 1 and 3 days after the start of the delta4-androstenedione or intralipid infusion. Contractions were counted and estradiol and oxytocin were measured by radioimmunoassay.
Androstenedione promoted a premature nocturnal increase in myometrial contractions in conjunction with an increase in maternal plasma concentrations of estradiol and oxytocin, which were of similar magnitude to those measured in spontaneous term labor. The increase in maternal estradiol preceded the increase in maternal oxytocin levels and myometrial contractions. The onset of the increase in maternal plasma oxytocin was closely associated with the appearance of myometrial contractions after delta4-androstenedione treatment. In contrast, no sustained premature contractions or changes in estradiol and oxytocin occurred in intralipid-treated monkeys.
We conclude that in the 0.8 gestation rhesus monkey (1) the increase in maternal plasma estradiol precedes the increase in maternal plasma oxytocin after delta4-androstenedione treatment and (2) delta4-androstenedione-induced preterm myometrial contractions are closely associated in time with physiologic increases in maternal plasma oxytocin concentrations.
This study was undertaken to assess the effectiveness of transvaginal ultrasound-guided ovarian interstitial laser-coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS).
Nineteen anovulatory women with clomiphene citrate-resistant PCOS underwent ultrasound-guided transvaginal ovarian interstitial YAG-laser treatment. In this study, serum hormonal level, spontaneous ovulation rate, and pregnancy rate were assessed.
With a spontaneous ovulation rate of 84.2%, 16 of 19 cases ovulated regularly during the 6-month postoperative period. The mean serums luteinizing hormone and serum testosterone levels in the second, fourth, and sixth postoperative months were significantly lower than preoperative levels: 5.87 +/- 2.04 IU/L versus 13.17 +/- 3.03 IU/L (P < .001) and 2.98 +/- 1.79 nmol/L versus 5.49 +/- 3.23 nmol/L (P < .001), respectively. The mean luteinizing hormone/follicle-stimulating hormone ratio was also significantly lower postoperatively at 1.09 +/- 0.30 compared with the preoperative 2.85 +/- 1.14 (P < .001). There was a cumulative pregnancy rate at 6 months of 32.3% (6/19) among the subjects. No significant operative complications were encountered.
The ultrasound-guided transvaginal ovarian interstitial laser treatment may be an effective new method to manage anovulation in PCOS patients.
We sought to determine whether downward trends in inflation-adjusted salaries (1989-99) continued for obstetrics and gynecology faculty.
Data were gathered from the Faculty Salary Survey from the Association of American Medical Colleges for academic years 2001 through 2009. We compared median physician salaries adjusted for inflation according to rank and specialty.
While faculty compensation increased by 24.8% (2.5% annually), change in salaries was comparable to the cumulative inflation rate (21.3%). Salaries were consistently highest among faculty in gynecologic oncology (P < .001), next highest among maternal-fetal medicine specialists (P < .001), and were not significantly different between general obstetrics-gynecology and reproductive-endocrinology-infertility. Inflation-adjusted growth of salaries in general obstetrics-gynecology was not significantly different from that in general internal medicine and pediatrics.
Growth in salaries of physician faculty in obstetrics and gynecology increased from 2000-01 through 2008-09 with real purchasing power keeping pace with inflation.
We sought to determine whether our process improvement program led to increased postpartum diabetes screening rates among women with gestational diabetes mellitus (GDM).
In early 2009, we conducted obstetrics department staff education sessions, revised GDM patient care protocols, and developed an electronic system to trigger reminder calls to patients who had not completed diabetes mellitus screening by 3 months postpartum. We then evaluated the rates of postpartum glucose test order entry and completion for women with GDM delivering from July 2009 through June 2010 (n = 179) and July 2007 through June 2008 (n = 200).
After the program's implementation, the proportion of women receiving an order for a postpartum glucose test within 3 months of delivery increased from 77.5-88.8% (P = .004), and test completion increased from 59.5-71.5% (hazard ratio, 1.37; 95% confidence interval, 1.07-1.75).
Rates of postpartum diabetes testing can be improved with system changes and reminders.
Histologic chorioamnionitis has been associated with preterm birth and low birthweight. Our goal was to evaluate the relationship between polymorphonuclear cell and mononuclear cell placental infiltrations and adverse infant outcomes.
Data from women who were enrolled in a trial of antibiotics for prevention of mother-to-child transmission of HIV-1 and of preterm birth were analyzed. Women who had HIV and women who did not have HIV were assigned randomly to either metronidazole 250 mg and erythromycin 250 mg at 20 to 24 weeks of gestation 3 times daily for 7 days and metronidazole 250 mg and ampicillin 500 mg every 4 hours during labor or identical placebos. Women with HIV were offered nevirapine at delivery for the prevention of mother-to-child transmission. At delivery, various placental sites were evaluated for polymorphonuclear cell and mononuclear cell infiltration.
Polymorphonuclear and mononuclear cell infiltrations were common in the decidua (18% and 43%, respectively) and chorioamnion (28% and 34%, respectively). Gestational age and birthweight were lower among women with polymorphonuclear cell infiltrations, with these relationships generally stronger at earlier gestational age and birthweight. Mononuclear infiltrations were not associated with adverse outcomes. Neither polymorphonuclear cell nor mononuclear placental infiltrations were associated with mother-to-child transmission of HIV. Antibiotic use was not associated with reduced polymorphonuclear or mononuclear cell infiltrations.
Polymorphonuclear cell infiltrations were associated with preterm birth and decreased birthweight and gestational age. Antibiotic use was not associated with reductions in polymorphonuclear or mononuclear cell infiltrations. In this nevirapine-treated population, neither polymorphonuclear nor mononuclear cell infiltration was associated with the mother-to-child transmission of HIV.
The use of antibiotics to prevent preterm birth has achieved mixed results. Our goal in this study was to determine if antibiotics given prenatally and during labor reduce the incidence of preterm birth and histologic chorioamnionitis.
A double-blind randomized placebo-controlled trial of antibiotics to reduce preterm birth was conducted in 4 African sites. Both HIV-infected and uninfected pregnant women were given 2 courses of antibiotics, prenatally at 24 weeks (metronidazole 250 mg and erythromycin 250 mg tid orally for 7 days), and during labor (metronidazole 250 mg and ampicillin 500 mg q 4 hours) or identically appearing placebos. Two thousand ninety-eight HIV-infected and 335 HIV-uninfected women had evaluable end points, including gestational age determined by both obstetric and pediatric criteria and birth weight (BWT). Pre- and post-treatment rates of various sexually transmitted infections (STI) were determined and placentas were evaluated for histologic chorioamnionitis.
Comparing antibiotic versus placebo treated HIV-infected and uninfected women, there were few differences in mean gestational age at delivery, the percent of preterm births, the time between randomization and delivery, or BWT. Four weeks after the 24-week antibiotic/placebo course, bacterial vaginosis, and trichomoniasis were reduced by 49% to 61% in the antibiotic groups compared with the placebo groups. However, in both the HIV-infected and uninfected groups, the placentas showed no difference in the rate of histologic chorioamnionitis. There were significant differences between HIV-infected and uninfected women, with the former having less education, a history of more stillbirths, more STIs, and in this pregnancy, a lower BWT (2949 vs 3100 g, P < .0001).
Despite reducing the rate of vaginal infections, the antibiotic regimen used in this study did not reduce the rate of preterm birth, increase the time to delivery, or increase BWT. Failure of this regimen to reduce the rate of histologic chorioamnionitis may explain the reason the antibiotics failed to reduce preterm birth.
Our purpose was to assess the functional morphologic features of the ovarian cortex surrounding benign cysts.
Fifty-four specimens (13 mature teratomas, nine benign cystadenomas, and 32 endometriomas) were obtained from the area of maximum distention of the ovarian cortex overlying benign cysts from 48 patients. The type and number of follicles were scored on a semiquantitative scale (0 to 4). Alterations of the cortical stroma that were related to the primary tumor were investigated. The vascular network was assessed by means of monoclonal antibodies directed against endothelial cells (anti-VW, QBEND/10) and scored on a scale from 0 to 2. The chi 2 and Mann-Whitney U test were used for statistical analysis.
Morphologic patterns similar to those of the normal ovarian cortex were observed in the cortical tissue surrounding mature teratomas, benign cystomas, and endometriomas in 92%, 77%, and 19% (p < 0.01) of specimens, respectively, and a regular vascular network was observed in 84%, 78%, and 22% (p < 0.01). Although microscopic endometriosis was observed surrounding the endometrioma in the stroma of 82% of specimens, stromal alterations related to the ovarian tumor were absent in the cortex surrounding mature teratomas and cystadenomas.
The study shows that the ovarian cortex, which is stretched and thinned by the growth of a benign tumor, is not morphologically altered in the presence of teratomas or benign cystadenomas. Endometriomas are associated with microscopic stromal implants and reduced follicular number and activity.
Preterm birth and stillbirth are among the greatest health burdens associated with pregnancy and childbirth. Fifteen million babies are born preterm each year, causing about 1 million deaths annually and lifelong problems for many survivors; 3 million stillbirths also occur annually. Worldwide, the number of women and children who die during pregnancy and childbirth exceeds the total number of births in the United States. New approaches could provide a greater understanding of prematurity, stillbirth, and maternal complications of pregnancy and childbirth. Integrated multidisciplinary investigations of the mother, fetus, and newborn in different contexts and populations could elucidate the biological pathways that result in adverse outcomes and how to prevent them. Descriptive research can determine the burden of disease, while more mechanistic discovery research could explore the physiology and pathophysiology of pregnancy and childbirth. Together, this research can lead to the development and delivery of new and much more effective interventions, even in low-resource settings. Recent surveys of researchers and funders reveal a striking lack of consensus regarding priority areas for research and the development of interventions. While researchers enumerate unanswered questions about pregnancy and childbirth, they lack consensus on priorities. Funders are equally uncertain about research and development projects that need to be undertaken, and many are hard-pressed to support research on the complex problems of pregnancy and childbirth given competing priorities. This lack of consensus provides an opportunity to engage with funders and researchers to recognize the importance of understanding healthy pregnancies and the consequences of adverse pregnancy outcomes. A strategic alliance of funders, researchers, nongovernmental organizations, the private sector, and others could organize a set of grand challenges centered on pregnancy and childbirth that could yield a substantial improvement in reproductive health.
The objective of this investigation was to identify genes that confer susceptibility to polycystic ovary syndrome.
Nineteen subjects with polycystic ovary syndrome, hirsutism, and elevated plasma androgen levels and 46 fertile, female control subjects were studied. Alleles at the human leukocyte antigen DQA1 locus were identified with dot-blot hybridizations with allele-specific oligonucleotide probes. Associations between human leukocyte antigen DQA1 alleles and polycystic ovary syndrome were examined with logistic regression analysis.
The frequency of the human leukocyte antigen DQA1*0501 was 0.50 and 0.26 in subjects with polycystic ovary syndrome and control subjects, respectively (corrected for multiple comparisons, p = 0.067). Homozygosity for this allele was also increased among subjects with polycystic ovary syndrome (p = 0.054). The odds ratios for having polycystic ovary syndrome associated with the *0501 allele and the *0501/*0501 homozygous genotype were 2.8 and 5.8, respectively.
These data suggest that a polycystic ovary syndrome susceptibility allele is linked to human leukocyte antigen and that the susceptibility allele is recessive.
The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed:
Cox JT, Castle PE, Behrens CM, et al; and the ATHENA HPV Study Group. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol 2013;208:184.e1-11.