Drug Seller Provision Practices and Knowledge of Misoprostol in Bangladesh.

CONTEXT: In Bangladesh, prior to the availability of the approved combination regimen of mifepristone and misoprostol for menstrual regulation (MR), drug seller provision of misoprostol-only regimens for MR without a prescription was widespread but service quality was poor. Examining provider practices relating to misoprostol-only provision in Bangladesh may increase understanding of misoprostol use and provision in other low-resource, legally restrictive settings. METHODS: In 2013-2014, a countrywide cross-sectional knowledge, attitudes and practice survey was conducted among 777 randomly selected drug sellers; data were analyzed descriptively. Logistic regression was used to test the associations between exposure to three interventions designed to improve drug seller practice (nongovernmental organization [NGO]-led training, a call center and in-shop training from pharmaceutical company representatives) and correct knowledge of the misoprostol-only MR regimen. RESULTS: Almost all (97%) of the drug sellers reported providing medications intended for MR; misoprostol-only was more commonly sold than the combination regimen (96% vs. 26%). Nine percent had received NGO-led training, 62% had received in-shop training from a pharmaceutical company representative and 27% had used the call center. Overall, 19% of drug sellers knew the correct misoprostol-only MR regimen, and 74% wanted more information about this regimen. Correct regimen knowledge was positively associated with receipt of NGO training and call center utilization (odds ratios, 2.0 and 1.9, respectively). CONCLUSIONS: NGO-led training and call centers should be considered in other settings in which misoprostol alone is provided off-label for pregnancy termination.

RESUMEN Contexto: En Bangladesh, antes de que el régimen combinado de mifepristona y misoprostol fuera aprobado para la regulación menstrual (RM), la provisión sin receta de regímenes de misoprostol solo para RM por parte de vendedores de medicamentos estuvo muy generalizada, pero la calidad de servicio era deficiente. Examinar las prácticas de los proveedores relacionadas con la provisión de misoprostol solo en Bangladesh podría aumentar la comprensión sobre el uso y la provisión de misoprostol en otros entornos de bajos recursos restringidos legalmente. Métodos: Entre 2013 y 2014, se realizó una encuesta transversal de conocimientos, actitudes y prácticas en todo el país entre 777 vendedores de medicamentos seleccionados al azar; los datos fueron analizados descriptivamente. Se utilizó regresión logística para evaluar las asociaciones entre la exposición a tres intervenciones diseñadas para mejorar las prácticas de los vendedores de medicamentos (capacitación conducida por una organización no gubernamental [ONG], un centro de atención telefónica y capacitación en el negocio por parte de representantes de las compañías farmacéuticas), así como el conocimiento correcto del régimen de misoprostol solo usado para RM. Resultados: Casi la totalidad (97%) de los vendedores de medicamentos informaron que estaban vendiendo medicamentos para RM; que la venta de misoprostol solo era más común que el régimen combinado (96% vs 26%). El nueve por ciento había recibido capacitación impartida por ONG, el 62% había recibido capacitación en su negocio de un representante de una compañía farmacéutica y el 27% había utilizado el centro de llamadas. En general, el 19% de los vendedores de medicamentos conocía el régimen correcto de RM basado en misoprostol solo y el 74% quería más información sobre ese régimen. El conocimiento correcto del régimen se asoció positivamente con la recepción de capacitación de las ONG y la utilización del centro de atención telefónica (razón de probabilidades, 2.0 y 1.9, respectivamente). Conclusiones: La capacitación conducida por ONG y el uso del centro de atención telefónica deberían considerarse en otros entornos restringidos en los que el misoprostol solo se proporciona sin autorización para la interrupción del embarazo.

RÉSUMÉ Contexte: Au Bangladesh, avant la disponibilité du traitement homologué au mifépristone associé au misoprostol pour la régulation menstruelle (RM), la prestation par les vendeurs de médicaments des traitements de RM au misoprostol seul sans ordonnance était répandue, mais la qualité du service était faible. L'examen des pratiques de prestation relatives à la fourniture de misoprostol seul au Bangladesh peut aider à mieux cerner l'usage et l'offre de ce médicament dans d'autres contextes à faibles ressources soumis à des lois restrictives. Méthodes: En 2013­2014, une étude transversale sur les connaissances, les attitudes et les pratiques à l'échelle du pays a été menée auprès de 777 vendeurs de médicaments sélectionnés aléatoirement, pour analyse descriptive des données. La régression logistique a servi au test des associations entre l'exposition à trois interventions conçues pour améliorer la pratique des vendeurs de médicaments (formation sous la conduite d'organisations non gouvernementales [ONG], établissement d'un centre d'appels et formation par des représentants de laboratoires pharmaceutiques) et la connaissance correcte du traitement de RM à base de misoprostol seul. Résultats: Presque tous les vendeurs de médicaments (97%) ont déclaré vendre des médicaments destinés à la RM. Le misoprostol seul était vendu plus fréquemment que le traitement d'association (96% vs 26%). Neuf pour cent avaient bénéficié d'une formation par une ONG, 62% d'une formation locale assurée par un représentant de laboratoire pharmaceutique et 27% avaient eu recours au centre d'appels. Globalement, 19% des vendeurs avaient une connaissance correcte du traitement de RM à base de misoprostol seul et 74% désiraient plus d'information à ce sujet. La connaissance correcte du traitement était associée positivement à l'obtention d'une formation par une ONG et au recours au centre d'appels (RC, 2,0 et 1,9, respectivement). Conclusions: La formation sous la conduite d'une ONG et l'établissement d'un centre d'appels doivent être envisagés dans d'autres contextes sujets à une législation restrictive dans lesquels le misoprostol seul est proposé hors indication pour l'interruption d'une grossesse.

Feasibility of assessing the safety and effectiveness of menstrual regulation medications purchased from pharmacies in Bangladesh: a prospective cohort study.

OBJECTIVE: To assess the feasibility of following up women who purchase mifepristone+misoprostol or misoprostol-only from pharmacies in order to measure the safety and effectiveness of self-administration of menstrual regulation. STUDY DESIGN: A prospective cohort study followed women purchasing mifepristone+misoprostol or misoprostol-only from pharmacies in Bangladesh. Participants were recruited by pharmacy workers either in person or indirectly via the purchaser of the drugs. End users were contacted by phone 2 weeks after recruitment, screened and interviewed. RESULTS: Study recruitment rates by pharmacy workers were low (30%, 109 of 642 women informed about the study), but 2-week follow-up rates were high (87%). Of the 109 end users interviewed, 87 purchased mifepristone+misoprostol and 20 misoprostol-only, while 2 women did not know what drugs they had purchased. Mean self-reported number of weeks of pregnancy was 5.7 weeks. Information provision by pharmacy workers was inadequate (40.4% received none, 8.7% received written information or pictures). A total of 80.5% of mifepristone+misoprostol users were sold the correct regimen versus 9 out of 20 misoprostol-only users. A total of 68.8% did not report experiencing any complications (70.0% misoprostol-only; 69.0% mifepristone+misoprostol users, p=1.0). A total of 94.3% of mifepristone+misoprostol users and 75% of misoprostol-only users reported that they were not pregnant at day 15 (p=.020). However, 7.3% of all users sought additional treatment. CONCLUSIONS: Challenges in assessing outcomes of self-managed menstrual regulation medications purchased from pharmacies must be overcome through further development of this methodology. Interventions are urgently needed to ensure that women have access to correct dosages, accurate information and necessary referrals. IMPLICATIONS: This paper assesses the outcomes of women who self-manage menstrual regulation medications purchased from pharmacies. The methodology requires further development, but our study provides preliminary positive evidence on the safety and effectiveness of self-management despite low information provision from pharmacy workers.

Provision of menstrual regulation with medication among pharmacies in three municipal districts of Bangladesh: a situation analysis.

OBJECTIVE: The objective was to assess the provision of the combination of mifepristone-misoprostol for menstrual regulation (MR) in randomly selected urban pharmacies in Bangladesh. STUDY DESIGN: We conducted a cross-sectional survey among 553 pharmacy workers followed by 548 mystery client visits to the same pharmacies in 3 municipal districts during July 2014-December 2015. RESULTS: The survey found that 99% of pharmacy workers visited had knowledge of MR procedures but only two-thirds (67%) could state the legal time limit correctly; they mentioned misoprostol (86%) over mifepristone-misoprostol combination (78%) as a procedure of MR with medication (MRM); 36% reported knowing the recommended dosage of mifepristone-misoprostol combination; 70% reported providing information on effectiveness of the medicines; 50% reported recommending at least one follow-up visit to them; 63% reported explaining possible complications of using the medications; and 47% reported offering any post-MR contraception to their clients. In contrast, mystery client visits found that the mifepristone-misoprostol combination (69%) was suggested over misoprostol (51%) by the pharmacy workers; 54% provided the recommended dosage of mifepristone-misoprostol combination; 42% provided information on its effectiveness; 12% recommended at least one follow-up visit; 11% counseled on possible complications; and only 5% offered post-MR contraceptives to the mystery clients. CONCLUSIONS: We found knowledge gaps regarding recommended dosage for MRM and inconsistent practice in informing women on effectiveness, follow-up visits, possible complications and provision of post-MR contraceptives among the pharmacy workers, particularly during the mystery client visits. IMPLICATIONS: Pharmacy workers in Bangladesh need to be trained on legal time limits for MR services provision, on providing accurate information on disbursed medicine, and on proper referral mechanisms. A strong monitoring and regulatory system for pharmacy provision of MRM in pharmacies should be established.

An observational study of the fresh frozen plasma: red blood cell ratio in postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal death worldwide. Recent data from trauma patients and patients with hemorrhagic shock have suggested that an increased fresh frozen plasma:red blood cell (FFP:RBC) ratio may be of benefit in massive bleeding. We addressed this issue in cases of severe postpartum hemorrhage. METHODS: We reviewed data from all patients diagnosed with severe postpartum hemorrhage during a 4-year period (2006-2009). Patients who were treated with sulprostone and required transfusion within 6 hours of delivery were included in the study and were divided into 2 groups according to their response to sulprostone: bleeding controlled with sulprostone alone (sulprostone group) and bleeding requiring an additional advanced interventional procedure including arterial angiographic embolization and/or surgical procedures (arterial ligation, B-Lynch suture, or hysterectomy; intervention group). The requirement or no requirement for advanced procedures constituted the primary end point of the study. Propensity scoring was used to assess the effect of a high FFP:RBC ratio on bleeding control. RESULTS: Among 12,226 deliveries during the study period, 142 (1.1%) were complicated by severe postpartum hemorrhage. Bleeding was controlled with sulprostone alone in 90 patients (63%). Advanced interventional procedures were required for 52 patients (37%). Forty-one patients were transfused with both RBCs and FFP. The FFP:RBC ratio increased over the study period (P < 0.001), from 1:1.8 at the start to 1:1.1 at the end of the study period. After propensity score modeling (inverse probability of treatment weighting), a high FFP:RBC ratio was associated with lower odds for advanced interventional procedures (odds ratio [95% confidence interval], 1.25 [1.07-1.47]; P = 0.008). There were no deaths, severe organ dysfunction, or other complications as a consequence of severe postpartum hemorrhage. CONCLUSIONS: In this retrospective study, a higher FFP:RBC ratio was associated with a lower requirement for advanced interventional procedures in the setting of postpartum hemorrhage. The benefits of transfusion using a higher FFP:RBC ratio should be confirmed by randomized-controlled trials.

Effect of mifepristone on COX-2 both in eutopic and ectopic endometrium in mouse endometriotic model.

OBJECTIVE: To study the influence of mifepristone on the expression of cyclooxygenase 2 (COX-2) protein and COX-2 mRNA and then to evaluate the mechanism. METHODS: After the establishment of 30 mice endometriosis models, the mice were randomly divided into six groups with 5 mice each group and assigned to experimental and control groups of 1-, 4- and 6-week circle according to whether mifepristone (0.13 mg d(-1)) was taken or not. Small animal optical imaging system was used to detect the fluorescent intensity of the ectopic tissue. Reverse transcript-polymerase chain reaction and western blot was used to examine COX-2 protein and COX-2 mRNA expression. ELISA was used to examine concentration of PGE(2) in serum. RESULT(S): Mifepristone could not affect the fluorescent intensity of the ectopic endometrium after it was taken 1, 4, and 6 (P > 0.05). However, it could decrease the transcription of COX-2 mRNA in the 1 and 4 week groups (P < 0.05), while the difference in the 6 week group was not significant (P > 0.05). It could decrease the expression of COX-2 protein after it was taken 4 and 6 weeks (P < 0.05). The serous PGE(2) in the trial groups was lower than that in the control groups, but the difference was not significant (P > 0.05). CONCLUSION(S): This study showed that mifepristone could not affect the size of the ectopic endometrium, but it could decrease the transcription of COX-2 gene and then reduce the expression of COX-2 protein and its product PGE(2) which is an important factor which mediate pain. This maybe another mechanism that mifepristone takes effect through anti-inflammatory path.

Uterine leiomyoma causing menometrorrhagia with a concomitant mature teratoma in a 15-year-old child: a case report and review of the literature.

Uterine leiomyoma is the most common uterine tumor in adult females but is rare in the pediatric population with only 10 previous cases reported. We describe the unique case of a 15-year-old girl who presented with abdominal pain and menometrorrhagia and was found to have a uterine leiomyoma as well as a mature ovarian teratoma that required surgical resection. We review diagnostic imaging and optimal management for the 2 gynecologic masses in this teenage girl.

Incidence and management of postpartum haemorrhage following the dissemination of guidelines in a network of 16 maternity units in France.

BACKGROUND: In France obstetric haemorrhage is the leading cause of maternal death. The aim of this study was to evaluate if the management of postpartum haemorrhage at individual maternity units followed guidelines established by the Aurore Network. METHODS: A descriptive study was carried out in 16 maternity units of the Aurore network between October 2004 and September 2005. Cases and data were prospectively identified and collected. RESULTS: Postpartum haemorrhage occurred in 1144 of 21 350 deliveries, an overall incidence of 5.4+/-0.3%. Of these, 316 cases were rated as severe. Diagnosis was clinical in 82.5% of severe cases and 77.5% of non-severe cases; the remainder were detected by postpartum laboratory tests. Uterotonic agents were given prophylactically to 46.7% of the 896 patients following vaginal delivery. In cases in which postpartum haemorrhage was due to uterine atony, 83.1% of women underwent examination of the uterine cavity and 96.3% received oxytocin, which proved therapeutic. Sulprostone was administered to 39.5% cases of persistent postpartum haemorrhage. A uterotonic was given prophylactically to 85.4% of the 247 patients at caesarean delivery. Oxytocin was therapeutic in 94.8% of cases of uterine atony. Sulprostone was administered in 84.4% of cases of persistent postpartum haemorrhage. CONCLUSION: The regional guidelines issued by the Aurore network were only partially followed. More effective guideline dissemination and implementation is required to improve the prevention and management of confirmed haemorrhage.

Tratamiento con metformina en pacientes con síndrome de ovario poliquístico, no obesa, no insulinorresistentes y durante el embarazo / Metformin treatment and pregnancy outcome in non-obese, non-insulinresistant patients with policystic ovarian syndrome

Intároducción:el síndrome de ovario poliquístico (SOP) se caracteriza por anovulación crónica e hiperandrogenismo y en nuestro medio afecta el 12% de las mujeres. No existen dudas de la función que cumple la metformina en pacientes con SOP, obesidad e insulinorresistencia (IR), sin embargo, al no conocer íntegramente su mecanismo de acción, no estamos en condiciones de predecir cual es su rol en el grupo de no obesas, no IR. Se trata del 80% de nuestras pacientes con diagnóstico de PCO que solo presentan oligoamenorrea-anovulación y ovarios ecográficamente poliquísticos. Objetivo: investigar la efectividad de la metformina en la restauración de los ciclos menstruales y la ovulación, así como también en el logro del embarazo en mujeres con SOPQ no obesas, no IR, y reportar la evolución de los embarazos con metformina. Materiales y métodos: se realizó un trabajo prospectivo, desde julio de 2005 a marzo de 2007, en 59 pacientes con diagnóstico de SOP, según los criterios del Consenso de Rotterdam, todas con deseo de fertilidad, oligomenorreicas-anovuladoras, no obesas, no IR (mediana del peso: 60kg, mediana de talla:165 cm, BMI 22,8 de mediana. Indice HOMA:143 de mediana) El estudio se dividió en 3 etapas. En la primera etapa se utilizó metformina en dosis crecientes hasta la dosis de 1700mg/día, durante 6 meses. En la segunda, se sumó citrato de clomifeno, 50 mg/día entre el 5º y 9º días. La tercera etapa la constituyó el seguimiento de embarazos con el uso de metformina. Resultados: se observó un franco cambio en el ritmo menstrual y en la ovulación, con eumenorrea en un 72% de los casos post-metformina y dosaje de progesterona dentro de rango ovulatorio en el día 21 del ciclo. La tasa de embarazo global fue del 52,5% (31/59), de los que el 74% fue solo con metformina, más un 25,8% con el agregado de citrato de clomifeno. El 58% de embarazos (18/31) ocurrió en los 2 primeros meses. De los 31 embarazos, se logró seguimiento completo de 24, ...

Tratamiento con metformina en pacientes con síndrome de ovario poliquístico, no obesa, no insulinorresistentes y durante el embarazo / Metformin treatment and pregnancy outcome in non-obese, non-insulinresistant patients with policystic ovarian syndrome

Intároducción:el síndrome de ovario poliquístico (SOP) se caracteriza por anovulación crónica e hiperandrogenismo y en nuestro medio afecta el 12% de las mujeres. No existen dudas de la función que cumple la metformina en pacientes con SOP, obesidad e insulinorresistencia (IR), sin embargo, al no conocer íntegramente su mecanismo de acción, no estamos en condiciones de predecir cual es su rol en el grupo de no obesas, no IR. Se trata del 80% de nuestras pacientes con diagnóstico de PCO que solo presentan oligoamenorrea-anovulación y ovarios ecográficamente poliquísticos. Objetivo: investigar la efectividad de la metformina en la restauración de los ciclos menstruales y la ovulación, así como también en el logro del embarazo en mujeres con SOPQ no obesas, no IR, y reportar la evolución de los embarazos con metformina. Materiales y métodos: se realizó un trabajo prospectivo, desde julio de 2005 a marzo de 2007, en 59 pacientes con diagnóstico de SOP, según los criterios del Consenso de Rotterdam, todas con deseo de fertilidad, oligomenorreicas-anovuladoras, no obesas, no IR (mediana del peso: 60kg, mediana de talla:165 cm, BMI 22,8 de mediana. Indice HOMA:143 de mediana) El estudio se dividió en 3 etapas. En la primera etapa se utilizó metformina en dosis crecientes hasta la dosis de 1700mg/día, durante 6 meses. En la segunda, se sumó citrato de clomifeno, 50 mg/día entre el 5º y 9º días. La tercera etapa la constituyó el seguimiento de embarazos con el uso de metformina. Resultados: se observó un franco cambio en el ritmo menstrual y en la ovulación, con eumenorrea en un 72% de los casos post-metformina y dosaje de progesterona dentro de rango ovulatorio en el día 21 del ciclo. La tasa de embarazo global fue del 52,5% (31/59), de los que el 74% fue solo con metformina, más un 25,8% con el agregado de citrato de clomifeno. El 58% de embarazos (18/31) ocurrió en los 2 primeros meses. De los 31 embarazos, se logró seguimiento completo de 24, ... (AU)

Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome.

BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS: Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS: Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS: Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.

Meningioma: current treatment options and future directions.

Benign meningiomas can be observed if not symptomatic or growing. When treatment is indicated, the options are surgery, radiosurgery, fractionated radiation therapy, or a combination of these modalities. Except in certain cases, such as large tumors that require debulking for relief of symptoms, we do not recommend the routine use of combination therapy. Intracranial meningiomas have usually been treated with surgical resection with an expected durable local control of 80% to 90% when a gross total resection (GTR) is obtained. Patients who have inoperable disease, refuse surgery, undergo less than a GTR, or who have aggressive histology should instead be considered candidates for radiation therapy or radiosurgery. While benign meningiomas can be successfully treated definitively or postoperatively with either fractionated radiation therapy or single fraction radiosurgery, atypical or malignant lesions are best treated with fractionated radiation therapy with conventional dosimetric margins. The role of systemic therapy is not yet defined, but multiple agents are being investigated in early phase trials for patients with recurrent or progressive disease after standard therapy has failed.

Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol.

In this two centre study, the efficacy of 200 mg mifepristone orally followed 48 h later by 0.4 mg misoprostol orally for menstrual regulation was investigated. The dose of mifepristone was taken the day before the expected day of menstruation. Each volunteer was planned to participate for up to 6 months. A plasma beta human chorionic gonadotrophin (HCG) was measured on the day of mifepristone intake. The study was disrupted prematurely due to low efficacy. In 125 treatment cycles the overall pregnancy rate was 17.6% (22 pregnancies) and the rate of continuing pregnancies (failure) was 4.0%. Eight women discontinued the study due to bleeding irregularities which were seen in 15 cycles (12%). These effects on bleeding pattern made the timing of treatment day difficult. Late luteal phase treatment with a combination of mifepristone and misoprostol is not adequately effective for menstrual regulation.

PIP: A 2-center study was undertaken to examine the efficacy, safety and acceptability of a once-a-month administration of a combination of 200 mg mifepristone and 0.4 mg misoprostol for menstrual regulation in the late luteal phase. About 24 women from Shanghai and 8 from Stockholm were administered 200 mg mifepristone taken orally before or on the day of menstruation, followed by 0.4 mg misoprostol taken orally after 48 hours. Urine samples were collected during 3 days before to 4 days after ovulation for an analysis of luteinizing hormone. In addition, a plasma beta human chorionic gonadotrophin was measured immediately before intake of mifepristone. Volunteers were to participate for 6 months, but the study was disrupted prematurely due to low efficacy. In 125 treatment cycles, the total pregnancy rate was 17.6% (22 pregnancies) and the failure pregnancy rate was 4.0%. Discontinuation of the study among 8 women was due to bleeding disturbances seen in 15 cycles (12%). In conclusion, late luteal phase treatment with a combination of mifepristone and misoprostol was not effective enough to be used for menstrual regulation.

[Mifegyne (RU-486)]. / Mifegyne (RU-486).

The substance Mifegyne, an antigestagen, can profoundly influence progesterone-dependent situations given the relevant indications and preconditions.

RU 486 (mifepristone). A short overview of its mechanisms of action and clinical uses at the end of 1996.

RU 486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in humans. The mechanism of action of RU 486 involves the intracellular receptors of the antagonized hormones progesterone and glucocorticosteroids. At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenyl-aminodimethyl group in the 11 beta-position with a specific region of the receptor binding pocket, and RU 486-induced transconformation in the ligand binding domain. These properties have consequences at different steps of the receptor function as compared with agonists. However, this cannot be limited to the RU 486-receptor interaction; for instance, a switch from an antagonistic property to an agonist activity is possible, depending on the intervention of other signaling pathways. Derivatives with only one of the two antagonistic properties (antiprogestin, antiglucocorticosteroid) would be desirable in spite of similarities between the steroid structures, receptors involved, and responsive machineries in target cells. Clinically, the RU 486 plus prostaglandin method is ready to be used on a large scale, and is close to being as practical and safe as any medical method of abortion may be. The early use of RU 486, as a contragestive--that is, for use by a woman as soon as she fears a pregnancy she does not want--will help to defuse the abortion issue. Research should now be conducted to define an efficient and convenient contraceptive method with RU 486 or other antiprogestins. The usefulness of RU 486 for obstetrical indications, including facilitation of difficult delivery, has to be assessed rapidly. Gynecological trials, particularly in leiomyomata, should also be systematically continued. The very preliminary results obtained with tumors, including breast cancers, do indicate that further studies are necessary.

RU486 (mifepristone): mechanisms of action and clinical uses.

RU486 (mifepristone) has proved to be a remarkably active antiprogesterone and antiglucocorticosteroid agent in human beings. The mechanism of action involves the intracellular receptors of the antagonized hormones (progesterone and glucocorticosteroids). At the molecular level, the most important features are high binding affinity to the receptor, interaction of the phenylaminodimethyl group in the 11 beta-position with a specific region of the receptor binding pocket, and RU486-induced transconformation differences in the ligand-binding domain. These particularities have consequences at different steps of the receptor function as compared with agonists. However, the reasoning cannot be limited to the RU486-receptor interaction, and, for instance, there is the possibility of a switch from antagonistic property to agonist activity, depending on the intervention of other signaling pathways. It would be desirable to have derivatives with only one of the two antagonistic properties (antiprogestin, antiglucocorticosteroid) in spite of similarities between steroid structures, receptors involved, and responsive machineries in target cells. Clinically, the RU486-plus-prostaglandin method is ready to be used on a large scale and is close to being as convenient and safe as any medical method of abortion may be. The early use of RU486 as a contragestive as soon as a woman fears a pregnancy she does not want will help to defuse the abortion issue. Research should now be conducted to define an efficient and convenient contraceptive method with RU486 or other antiprogestins. The usefulness of RU486 for obstetric indications, including facilitation of difficult delivery, has to be assessed rapidly. Gynecologic trials, particularly in leiomyomata, should be systemically continued. The very preliminary results obtained with tumors, including breast cancers, indicate that further studies are necessary.

Serum relaxin concentrations in women following the administration of 16,16-dimethyl-trans-delta 2-PGE1 methyl ester during early pregnancy.

Serum relaxin was estimated in 11 women during termination of first-trimester pregnancy with 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (16 DM-PGE1). Vaginal administration of 16 DM-PGE1 was associated with a significant increase in serum relaxin.

PIP: The effect of prostaglandin on relaxin secretion in early pregnancy has not been established. To gain more information on this process, the association between administration of a derivative of prostaglandin El (PGE1)--16,16-dimethyl-trans-delta2-PGE1 methyl ester (16 DM-PGE1)--on serum relaxin levels was investigated in 11 women presenting for 1st- trimester abortion. A vaginal suppository of 1 mg of 16 DM-PGE1 was inserted in the posterior vaginal fornix of study subjects every 3 hours for a maximum of 5 applications. Both relaxin and progesterone levels were measured by radioimmunoassay. 8 of the 11 subjects aborted. Mean basal concentrations of relaxin and progesterone were 1.1 + or - 0.2 and 21.9 + - 8.0 ng/ml, respectively. Serum relaxin levels were significantly increased over baseline levels 1, 2, 3, and 6 hours after 16 DM-PGE1 administration, even in subjects whose pregnancies were not terminated, but there was no effect on serum progesterone levels. Since relaxin is considered to provide an accurate indicator of luteal function, these results suggest that 16 DM-PGE1 is luteolytic in humans.

The missed menstrual period.

The most likely cause of a missed menstrual period in a woman of childbearing age is pregnancy, stress, or the effects of the pill. If fear of pregnancy is the basis of the problem, simply reassuring the patient that menstrual extraction is available may bring spontaneous resolution.