Análisis y consideraciones técnicas acerca de dispositivos intrauterinos de levonorgestrel para la evaluación de productos similares y genéricos / Analysis and technical considerations about levonorgestrel intrauterine devices for the evaluation of generic and similar products

Los dispositivos intrauterinos hormonales de levonorgestrel son métodos anticonceptivos seguros y eficaces. Al igual que los medicamentos convencionales, una vez expirada la patente, las autoridades regulatorias de salud pueden aprobar el registro de productos similares. El objetivo de ello es disminuir los costos, considerando el elevado precio del producto original. Este tipo de productos están regulados y se aplican requisitos generales similares a los medicamentos tradicionales para demostración de seguridad y eficacia. Las propiedades mecánicas únicas del producto de referencia plantean un gran desafío a los productos similares. El presente artículo analiza de manera comparativa las características de los diversos sistemas intrauterinos hormonales de levonorgestrel, disponibles en el mercado. La autoridad sanitaria y los diversos centros clínicos deben considerar que en este tipo de productos no hay, hasta la fecha en el mundo, genéricos intercambiables y que por lo tanto, se debe decidir la intercambiabilidad de éstos sobre la base de estudios de bioequivalencia in vivo, luego de la demostración de equivalencia farmacéutica in vitro, tal y como sugiere la FDA, o en su defecto deberían ser registrados como productos nuevos, con estudios clínicos apropiados que demuestren seguridad y eficacia.

Levonorgestrel hormonal intrauterine systems are safe and effective contraceptive methods. Like conventional drugs, once the patent expires, health regulatory authorities can approve the registration of similar products. The objective of this is to reduce costs, considering the high price of the original product. These types of products are regulated as drugs and similar general requirements apply to traditional drugs for demonstration of safety and efficacy. The unique mechanical properties of the reference product pose a great challenge to similar products. This article comparatively analyzes the characteristics of the various levonorgestrel hormonal intrauterine systems available on the market. Therefore, the health authority and clinical centers must consider that up to date, there are no interchangeable generics in this type of products worldwide. Thus, their interchangeability must be decided on the basis of in vivo bioequivalence studies after the demonstration of in vitro pharmaceutical equivalence, as suggested by the FDA. Without that, they should be registered as new products, with appropriate clinical studies that demonstrate safety and efficacy.

Continuation rates of the 52-mg levonorgestrel-releasing intrauterine system according to the primary reason for its use / Taxas de continuação com o sistema intrauterino de liberação de levonorgestrel de 52mg de acordo com o motivo principal de seu uso

Abstract Objective To evaluate whether continuation rates with the 52-mg levonorgestrelreleasing intrauterine system (LNG-IUS) up to 5 years after placement differed between women using the method exclusively for contraception and those using the device for medical reasons alone. Methods A retrospective cohort study was conducted in a family planning clinic with 5,034 LNG-IUS users: 4,287 using the method exclusively for contraception and 747 for medical reasons alone. The continuation rate at 1 to 5 years of use was calculated by life table analysis. Results Initially, the continuation rate was significantly higher in the contraception group: 85.8 versus 83.4 and 77.4 versus 76.0 per 100 women-years in the 1st and 2nd years of use, respectively. There were more discontinuations due to bleeding/spotting in the medical reasons group in the first two years. The discontinuation rate according to reason for use was not significantly different from the third to the fifth year of use. No women discontinued due to amenorrhea in either group. Conclusion The continuation rate was significantly higher in the contraception group in the first two years of use. Amenorrhea was not a reason for discontinuation in either group, suggesting that counselling in this respect was adequate. Nevertheless, counselling could perhaps have been better with regards to the expected long period of bleeding and spotting in the first two years after placement.

Resumo Objetivo Avaliar a taxa de continuação até 5 anos de uso do sistema intrauterino liberador de 52-mg levonorgestrel por dia (SIU LNG) -IUS) é diferente entre mulheres que o usam exclusivamente como anticoncepcional que entre as que usam exclusivamente por razões médicas. Métodos Estudo retrospectivo realizado em uma clínica de Planejamento Familiar 5.034 usuárias de SIU LNG, 4.287 que optaram pelo método apenas como anticoncepcional e 747 que o usavamsomente por razoesmédicas. A taxa de continuação de um até cinco ano foi calculada por meio de análise de tabela de vida Resultados No início a taxa de continuação foi significativamente maior no grupo da anticoncepção: 85,8 versus 83,4 e 77,4 versus 76,0 por 100 anos-mulher no 1° e 2° ano de uso, respectivamente. Houve mais descontinuações por sangrado-manchado no grupo de razões médicas nos dos primeiros anos. A taxa de continuação não foi significativamente diferente desde o terceiro até o quinto ano de uso. Nenhuma mulher de ambos os grupos descontinuou por amenorreia. Conclusão A taxa de continuação foi significativamente maior no grupo de anticoncepção durante os dos primeiros anos de uso. Amenorreia não foi motivo de descontinuação em ambos os grupos, sugerindo que a orientação a esse respeito foi adequada. Entretanto, a orientação referente ao longo período de sangramentos irregulares nos dois primeiros anos após a inserção, precisaria ser melhorado.

Efectos adversos y motivos de retiro de implante subdérmico Jadelle® en usuarias de Policlínica de salud Sexual y Reproductiva del Hospital de Clínicas en período junio 2015- diciembre 2017 / Adverse effects and reasons of remove of subdermico implant Jadelle® in users of Sexual and Reproductive Health Clinics of Hospital de Clinicas in period june 2015-december 2017

INTRODUCCIÓN: La anticoncepción hormonal, a través de implantes subdérmicos, es uno de los métodos anticonceptivos reversibles de larga duración más eficaces en la actualidad que está disponible en nuestro país en forma gratuita en el sistema público. OBJETIVO: Reconocer los efectos adversos y los motivos de retiro del Implante Jadelle® en usuarias del Hospital de Clínicas, así como evaluar la información recibida por las usuarias al momento de la colocación. MATERIAL Y MÉTODOS: Un total de 160 pacientes participaron en el estudio a través de una encuesta previo consentimiento informado. Se utilizó la estadística descriptiva en números absolutos y porcentuales. Resultados: Previo al uso, recibieron información sobre los probables efectos adversos del método el 83% de ellas, y acerca de la efectividad del método el 89 %. En cuanto a efectos adversos los presentaron el 80,6% de las usuarias, siendo la irregularidad de la menstruación la causa más frecuente constituyendo un 61%. CONCLUSIONES: Es alta la frecuencia de pacientes que presentan efectos adversos y que solicitan retiro del implante antes del tiempo a causa de ello, 35% de las usuarias, siendo el principal motivo la irregularidad menstrual en un 43% de los casos. Es recomendable realizar un correcto asesoramiento previo a la colocación e incentivar a las pacientes a concurrir a los controles médicos, luego de la colocación, para brindar asesoramiento y tratamiento si se presentara algún efecto adverso, con el fin de obtener una mejor continuidad de uso del método.

INTRODUCTION: Hormonal contraception, through subdermal implants, is one of the most effective long active reversal contraceptive methods currently available in our country for free in the public system. OBJETIVE: Recognize the adverse effects and the reasons for its withdrawal in users of the Hospital de Clínicas as well as to evaluate the information received by the users at the time of placement. METHODOLOGY: A total of 160 patients participated in the work with prior informed consent through a survey. Descriptive statistics were used in absolute and percentage numbers. They received information on the probable adverse effects of the 83% pre-use method, about the effectiveness of the 89% method. RESULTS: Regarding adverse effects, they were present in 80.6% of the users; the being irregularity of menstruation is the most frequent, constituting 61%. Concluding that the frequency of patients presenting with adverse effects and requesting removal of the implant before the time is high because of it, 35% of the users who requested removal menstrual irregularities were the main reason for 43% of patients. CONCLUSIONS: It is advisable to make a correct advice prior to placement and encourage patients to attend medical controls, after placement, to provide advice and treatment if any adverse effect occurs, in order to give better use in terms of method time.

Analysis of the endometrial transcriptome at the time of implantation in women receiving a single post-ovulatory dose of levonorgestrel or mifepristone

Abstract Background: Levonorgestrel (LNG) is a progesterone receptor agonist used in both regular and emergency hormonal contraception; however, its effects on the endometrium as a contraceptive remain widely unknown and under public debate. Objective: To analyze the effects of LNG or mifepristone (MFP), a progesterone receptor antagonist and also known as RU-486, administered at the time of follicle rupture (FR) on endometrial transcriptome during the receptive period of the menstrual cycle. Methods: Ten volunteers ovulatory women were studied during two menstrual cycles, a control cycle and a consecutively treated cycle; in this last case, women were randomly allocated to two groups of 5 women each, receiving one dose of LNG (1.5 mg) or MFP (50 mg) the day of the FR by ultrasound. Endometrial biopsies were taken 6 days after drug administration and prepared for microarray analysis. Results: Genomic functional analysis in the LNG-treated group showed as activated the bio-functions embryo implantation and decidualization, while these bio-functions in the T-MFP group were predicted as inhibited. Conclusions: The administration of LNG as a hormonal emergency contraceptive resulted in an endometrial gene expression profile associated with receptivity. These results agree on the concept that LNG does not affect endometrial receptivity and/or embryo implantation when used as an emergency contraceptive.

Consecutive use of the 52 mg levonorgestrel-releasing intrauterine system: variations in bleeding patterns / Uso consecutivo do sistema intrauterino de levonorgestrel 52 mg: variações no padrão de sangramento

Abstract Objective Changes in bleeding patterns could influence the decisions of healthcare professionals to change the levonorgestrel-releasing intrauterine system (LNG-IUS) before 7 years of use, the recommended period of extended use. We evaluated changes in the bleeding patterns of users of the 52 mg LNG-IUS at the end of use of the first (IUS-1) and during the second device (IUS-2) use. Methods We performed an audit of the medical records of all women who used two consecutive LNG-IUSs at the Family Planning clinic. We evaluated the sociodemographic/gynecological variables, the length of use, and the bleeding patterns reported in the reference periods of 90 days before removal of the IUS-1 and at the last return in use of IUS-2. We used the McNemar test to compare bleeding patterns. Statistical significance was established at p < 0.05. Results We evaluated 301 women aged (mean ± SD) 32 (±6.1) years, with lengths of use of 68.9 (±16.8) and 20.3 (±16.7) months for the IUS-1 and IUS-2, respectively. No pregnancies were reported. Bleeding patterns varied significantly among women who used the IUS-2 for ≥ 7 months to 6 years when compared the bleeding patterns reported in IUS-1 use. Eighty-nine out of 221 (40%) women maintained amenorrhea and infrequent bleeding; 66 (30%) evolved to bleeding patterns with light flow, and 66 (30%) maintained or evolved to heavy flow patterns (p = 0.012). No differences were observed among the 80 women with ≤ 6 months of use. Conclusion Changes in bleeding patterns occur during the use of LNG-IUS and should not be decisive for the early replacement of the device.

Resumo Objetivo Variações no padrão de sangramento podem afetar a decisão de troca do sistema intrauterino de levonorgestrel (SIU-LNG) antes do período de uso estendido recomendado de 7 anos. Nós avaliamos mudanças no padrão de sangramento de usuárias ao final do uso do primeiro SIU-LNG 52 mg (SIU-1) e durante o uso do segundo dispositivo (SIU-2). Métodos Revisamos os prontuários de todas as mulheres que inseriram consecutivamente o SIU-LNG no ambulatório de Planejamento Familiar. Foram avaliadas as variáveis sociodemográficas/ginecológicas, o tempo de uso, e os padrões de sangramento relatados nos períodos de referência de 90 dias antes da remoção do SIU-1 e no último retorno em uso do SIU-2. Usamos o teste de McNemar para comparar os padrões de sangramento. A significância estatística foi estabelecida em p < 0,05. Resultados Analisamos os dados de 301 mulheres com idade (média ± desvio padrão [DP]) de 32 (±6,1) anos e tempo de uso de 68,9 (±16,8) e 20,3 (±16,7) meses para o SIU-1 e SIU-2, respectivamente. Nenhuma gravidez foi relatada. Os padrões de sangramento variaram significativamente durante o uso do SIU-2 (≥ 7 meses a 6 anos) em relação ao padrão relatado no SIU-1. Oitenta e nove das 221 (40%) mulheres mantiveram amenorreia e sangramento infrequente; 66 (30%) evoluíram para padrões de sangramento com fluxo leve e 66 (30%) mantiveram ou evoluíram para padrões de fluxo intenso (p = 0,012). Não foram observadas diferenças entre as 80 mulheres que utilizavam o SIU-2 há ≤ 6 meses. Conclusão Mudanças nos padrões de sangramento ocorrem durante o uso do LNG-IUS e não devem ser decisivas para a troca precoce do dispositivo.

Métodos contraceptivos reversíveis de longa duração no Sistema Único de Saúde: o debate sobre a (in)disciplina da mulher / Long-acting reversible contraception methods in the Brazilian Unified National Health System: the debate on women's (in)discipline

Resumo Recentemente a Federação Brasileira das Associações de Ginecologia e Obstetrícia submeteu ao Ministério da Saúde uma solicitação para oferta no Sistema Único de Saúde de métodos contraceptivos reversíveis de longa duração (LARC), para jovens mulheres de 15 a 19 anos. Os dois dispositivos a serem incluídos seriam o implante subdérmico liberador de etonogestrel, com duração de três anos, e o sistema intrauterino liberador de levonorgestrel, com duração de cinco anos. O Ministério da Saúde abriu então consulta pública para avaliar tal introdução, terminando por decidir contrariamente à inclusão destes métodos na rede pública de saúde. O artigo discute as estratégias discursivas utilizadas para fundamentar e justificar a aceitação e aplicabilidade destes métodos em "populações especiais". O debate sobre o planejamento reprodutivo precisa compreender melhor as descontinuidades contraceptivas no uso de métodos, a centralidade da contracepção de emergência e o quanto as hierarquias de gênero dificultam uma prática contraceptiva segura. Ao contrário, a ênfase na (in)disciplina da mulher no tocante aos cuidados com a utilização de métodos contraceptivos de uso regular termina por reforçar sua condição de menoridade social.

Abstract Recently, the Brazilian Federation of Gynecology and Obstetrics Associations submitted a request to the Brazilian Ministry of Health for an introduction of long-acting reversible contraception (LARC) methods for young women aged 15 to 19 years in the Brazilian Unified National Health System. The two devices to be included were the etonogestrel-releasing subdermal implant (ENG implant), with a duration of three years, and the levonorgestrel-releasing intrauterine system (LNG-IUS), lasting five years. The Ministry of Health then launched a public inquiry to evaluate this introduction, deciding against the inclusion of these methods in the public health services. The article discusses the discursive strategies used to justify the acceptance and applicability of these methods in "special populations." The debate on family planning needs to understand fully the discontinuity of contraception in the use of such methods, the central concept of emergency contraception, and how gender hierarchies prejudice safe contraceptive practice. On the contrary, the emphasis on the (in)discipline of women regarding care with regular-use contraceptive methods effectively reinforces their condition of social minority.

A breve vida do Norplant® no Brasil: controvérsias e reagregações entre ciência, sociedade e Estado / The brief life of Norplant® in Brazil: controversies and reassemblages between science, society and State

Resumo Norplant® é a marca do primeiro implante hormonal subdérmico contraceptivo registrado no mundo, desenvolvido nos laboratórios do Population Council, organização internacional direcionada ao tema da fertilidade e crescimento populacional. O artigo revisita a trajetória deste contraceptivo no Brasil desde sua chegada, através de pesquisas clínicas, até sua proibição em 1986 pelo órgão brasileiro responsável por medicamentos na ocasião. Sua circulação gerou controvérsias relacionadas a práticas de pesquisa, efeitos colaterais e usos políticos do método. Este artigo concentra sua análise nas divergências relacionadas com as práticas de pesquisa. Utilizou-se a técnica de análise de controvérsia, revisitando as versões dos envolvidos, investigando suas compreensões e os efeitos que este objeto produziu em suas redes. O Norplant® provocou deslocamentos e associações entre grupos da sociedade, autoridades do Estado, cientistas e médicos, indústria, produtos farmacêuticos, procedimentos de pesquisas, instrumentos burocráticos, usuárias de contraceptivos. Estilos de pensamento médico científicos foram sacudidos e novas formas de pensar autonomia científica começaram a ser discutidas no país.

Abstract Norplant® is the brand name of the world's first registered subdermal hormonal contraceptive implant, developed by the laboratories of the Population Council, an international organisation working in the area of fertility and population growth. The article revisits the trajectory of this contraceptive in Brazil from its arrival through clinical trials to its eventual ban in 1986 by the Brazilian regulatory agency responsible for approving medications at the time. Its circulation generated controversies related to research practices, side effects and political uses of the drug as a birth control method. This article focuses its analysis on the divergences related to research practices. It uses a controversy analysis technique, reviewing the versions of those involved, investigating their understandings and the effects that this object generated in their networks. Norplant® provoked displacements and associations between civil society groups, State authorities, scientists and physicians, industry, pharmaceutical products, research procedures, bureaucratic instruments, and the female users of the contraceptives. Scientific styles of medical thought were shaken up and new forms of thinking about scientific autonomy began to be discussed in the country.

La anticoncepción de emergencia es menos efectiva en mujeres con obesidad / Emergency contraception is less effective in women with obesity

La anticoncepción de emergencia se refiere al uso de medicación o a la inserción de un dispositivo intrauterino de cobre para prevenir el embarazo luego de una relación sexual no protegida o del fallo de un método anticonceptivo, en una mujer que no desea el embarazo. De entre las alternativas farmacológicas del método, se estima que el uso de levonorgestrel prevendría el 50% de los embarazos. A partir de una viñeta clínica, en la cual se describe el caso de una paciente obesa que resultó embarazada luego de utilizar anticoncepción hormonal de emergencia tras una relación sexual no protegida, se realizó una búsqueda bibliográfica para establecer la efectividad del método en pacientes con esta característica (obesidad). La búsqueda identificó un metaanálisis que relacionó al triple la probabilidad de embarazo en pacientes con índice de masa corporal superior a 30 kg/m2 que utilizaron anticoncepción de emergencia hormonal. (AU)

Emergency contraception refers to the use of medication or the insertion of a copper intrauterine device to prevent pregnancy after the occurance of unprotected sex intercourse or failure of a contraceptive method in a woman who does not desire pregnancy. Among the pharmacological alternatives of the method it is estimated that the use of levonorgestrel prevents 50% of pregnancies. From a clinical vignette, in which the case of an obese patient who became pregnant using hormonal emergency contraception after unprotected sex intercourse is described, a literature search was conducted to establish the effectiveness of the method in patients with this feature (obesity). The search identified a metaanalysis that shows an incresed probability (threetimes) of pregnancy in patients with body mass index greater than 30 kg/m2 that used hormonal emergency contraception. Emergency contraception is less effective in women with obesity. (AU)

5 años de Experiencia en la Utilización del Dispositivo Intrauterino liberador de Levonorgestrel / 5 years of experience in the use of the levonorgestrel-releasing intrauterine device

Objetivo: Determinar el índice de éxito y los factores asociados en el uso del dispositivo intrauterino liberador de levonorgestrel (DIU-LVN). Materiales y Métodos: Estudio prospectivo, analítico experimental. Se recogieron datos de las pacientes ingresadas en el Servicio de Ginecología del HCIPS de febrero del 2007 a febrero del 2012 que se colocaron DIU-LVN y se realizo seguimientoa través del consultas ambulatorias. Resultados: Un total de 190 casos fueron seleccionados de forma aleatoria de 440. 60 casos fueron realizados en los años 2007 y 2008 sin evaluación histeroscopica de la cavidad endometrial 380 casos en los años 2009, 2010 y 2011 con evaluación histeroscopica, no considerando aptas para colocación pacientes con miomas submucosos irresecables. Edad de colocación: media de 42,9 años. Motivos: 92,6% HUA (61,6% miomas, 9,5% submucosos). Patologías asociadas: 31,1% HTA, 23,7% Diabetes Mellitus (DM), 34,2% Hipotiroidismo, 7,9% Hipotiroidismo y DM asociados 2,6% Anticoaguladas, 2,6% Endometriosis. Considerando la posición del útero, la situación de RVF resulto en un RR de 0,75, (IC: 0,41-1,38) y P: 0,33. La presencia de miomas en las pacientes que mantienen su SIU-LVN registró un RR de 1,26 (IC: 0,82-2,95) y una P: 0,28; comparando el IMC, las que presentaron IMC mayor a 25 obtuvo un RR 1,6 (IC: 0, 72-1,87) con P: 0,5. La presencia de hipertensión resulto un RR 1,14 (IC: 0,74-1,74) con P: 0,55. 37,4% con HSC previa. Hallazgos: 8,4% miomas submucosos y 3,7% pólipos endometriales. 76,8% tenían biopsia endometrial previa: 12,1% con hiperplasia endometrial simple sin atipias, 4,2% pólipo endometrial y el 60,5% normal. La histerometría a la colocación: promedio 9 cm. 70,6% mantienen su dispositivo, 3,2% con descenso y recolocación del mismo dispositivo por histeroscopía, 19,4% expulsó el dispositivo y 10% se retiró voluntariamente. De las que no mantienen su SIU-LVN 15,8% tuvieron una histerectomía, 2,6% se recoloco por segunda vez luego de una expulsión (todas mantienen su dispositivo), 2,6% fueron sometidas a una miomectomia por histeroscopía, 4,2% cambiaron a ACO, 3,7% entraron en menopausia, y 68,9% abandonaron tratamiento. Una tasa de éxito total del 76,3%, desglosada por año, éxito: 2007-2008 del 25%, 2009 del 69,5%, 2010 del 72% y 2011 Conclusión: Consideramos que estos dispositivos constituyen una opción más segura y de menor costo, con un buen índice de éxito, y una gran aceptación por parte de las pacientes y evita someterlas a procedimientos quirúrgicos mayores. Una evaluación histeroscópica previa a la colocación del dispositivo permite una mejor selección de las pacientes para colocación del dispositivo mejorando su tasa de éxito global. Aunque el dispositivo haya sido expulsado espontáneamente o se encuentre descendido, una segunda colocación o una reubicación por histeroscopía ha demostrado excelentes resultados. Palabras Claves: Dispositivo intrauterino, levonorgestrel, Mirena

Objective: To determine the success rate and associated factors in the use of levonorgestrel-releasing intrauterine system (LVN-RIS). Materials and Methods: Prospective study. 190 cases were selected at random for study from 440 to who the SIU-LVN where applied in the Gynecology Service of the HCIPS from February 2007 to February. Two groups where created: one with supposed high risk of failure of the treatment and one group with supposed high chances of success. The monitoring was done through the outpatient visits. Results: A total of 190 cases were selected at random from 440. 60 cases were performed in 2007 and 2008 without hysteroscopic evaluation of the endometrial cavity 380 cases in 2009, 2010 and 2011 with hysteroscopic evaluation, considered not suitable for LVN-RIS patients with unresectable submucosal fibroids. Placement age: mean 42.9 years. Diagnosis: HUA 92.6% (61.6% fibroids, submucosal 9.5%). Associated diseases: hypertension 31.1%, 23.7% diabetes mellitus (DM), hypothyroidism 34.2%, 7.9% hypothyroidism and 2.6% associated DM anticoagulated, 2.6% endometriosis. Considering the position of the uterus, the situation of RVF resulted in an RR of 0.75 (CI: 0.41 to 1.38) and P: 0.33. The presence of fibroids in patients who maintain their LVN-IUS showed a RR of 1.26 (CI: 0.82 to 2.95) and P: 0.28, comparing BMI, who had BMI greater than 25 RR was 1.6 (CI: 0, 72 to 1.87) with Q: 0.5. The presence of hypertension resulted RR 1.14 (CI: 0.74 to 1.74) with P = 0.55. 37.4% with previous HSC. Findings: 8.4% and 3.7% submucosal fibroids endometrial polyps. 76.8% had prior endometrial biopsy: 12.1% with simple endometrial hyperplasia without atypia, endometrial polyp 4.2% and 60.5% normal results. Hysterometry: mean of 9 cm. Patients who maintain their LVN-RIS: 70.6%, 3.2% with descended device and repositioning of the same by hysteroscopy, 19.4% expelled the device and 10% withdrew voluntarily. Of those who do not maintain their LVN-RIS 15.8% had a hysterectomy, 2.6% was repositioned for the second time after an expulsion (all keep their device), 2.6% underwent a myomectomy by hysteroscopy, 2% moved to oral contraceptives, 3.7% entered menopause, and 68.9% abandoned treatment. A total success rate of 76.3%. Success by year: 2007-2008: 25%; 2009: 69.5%; 2010: 72% and 2011: 83%. Conclusion: We believe that these devices are a safe and cheap treatment option, with a good success rate, and a high acceptance by patients, and avoid subjecting them to major surgical procedures. Hysteroscopic evaluation prior the placement of the device allows a better patient selection and improves its overall success rate. Even is this device descend or is expelled spontaneously, a second placement or relocation by hysteroscopy shows excellent results. Keywords: levonorgestrel releasing intrauterine system, Mirena

Efficacy of levonorgestrel intrauterine system [LNG-IUS] for abnormal uterine bleeding and contraception

To find out clinical response, side effects and patients' acceptability of levonorgestrel-releasing intrauterine system [LNG-IUS]. Observational study. Gynaecology Department of Shifa International Hospital, Islamabad, from June 2005 to May 2008. Adult women were enrolled in the study. In group-A, 57 married women were enrolled presented with abnormal uterine bleeding while in group-B, 16 married women attended for contraception. All women in group-A had thyroid stimulating hormone, pelvic ultrasound and outpatient endometrial biopsy. Detailed counselling was done before insertion. Outcome variables were improvement in bleeding pattern, safety profile, spontaneous expulsion rate and continuation at the end of one year. In group-A [abnormal bleeding] menstrual cycle became normal in 40.4% women in the first 3 months. At the end of one year, 50.9% women experienced normal cycle, 8.8% were oligomenorrhic and 12.3% were amenorrhic. In group-B [contraceptive group] all women started with normal cycles. At the end of 3 months 42% complained of vaginal spotting which reduced to 10% at the end of one year. Menstrual pattern at the end of one year showed normal cycles in 52%, oligomenorrhea in 19% and amenorrhea in 10% women. Vaginal spotting was experienced by 42% women at 3 months as main complaint which reduced to 10% at the end of one year, however, 7% women requested for removal of device at one year. LNG-IUS is an effective and acceptable treatment for abnormal uterine bleeding as well as for contraception. Vaginal spotting was the most frequent side effect experienced by both groups

Mecanismo de acción del levonorgestrel como anticoncepción de emergencia con principal énfasis en su acción sobre los espermatozoides / Mechanism of action of levonorgestrel as emergency contraception with principal emphasis in its spermatozoa action

A pesar de lo extendido del uso de la anticoncepción de emergencia (AE) con levonorgestrel (LNG) en el mundo, el mecanismo de acción continúa siendo discutido, lo que ha sido aprovechado para que grupos confesionales aaquen su uso, argumentando que la misma es abortiva. Actualmente, dos comprimido de LNG de 0,75 mg hasta 5 días posteriores al coito no protegido, ha sido recomendada y mostrada como eficaz para AE. El mecanismo de acción probablemente depende del momento de la toma en relación al día del ciclo menstrual. Cuando el LNG para AE es administrado antes del período ovulatorio, el mismo inhibe la ovulación en algunas mujeres y afecta el endometrio. Sin embargo la administración de LNG antes de la ruptura folicular no mostró tener influencia sobre la expresión de glicodelina-A en biopsias de endometrio tomadas 24 o 48 horas después de la toma de las píldoras de LNG. Los resultados de los estudios no apoyan la idea de que el LNG como AE causaría un efecto anti-implantatorio. Fue especulado que el LNG podría actuar sobre los espermatozoides. En estudios muy antiguos de la Argentina fue observado que la administración de 0,4 mg de LNG dado 3-10 horas post coito reducía el número de espermatozoides recuperados de la cavidad uterina, causaba alcalinización del fluido intrauterino, inmovilizaba los espermatozoides y aumentaba la viscosidad del moco cervical. Esto llevó a sugerir que la migración espermática a los lugares de fertilización podría esar comprometida después de la ingesta de LNG como AE. Sin embargo, nosotros hemos trabajado sobre esta hipótesis, pero no observamos efectos sobre reacción acrosomal después de la exposición in vitro al LNG de espermatozoides capacitados...

Contracepción de emergencia con Levonorgestrel / Emergency contraception with levonorgestrel

La contracepción de emergencia puede evitar el embarazo luego de un coito sin medidas contraceptivas o cuando éstas fallan. Se recomienda el levonorgestrel, un gestágeno sintético, en dosis única de 1.5 mg (alternativamente en dos dosis de 0.75 mg espaciadas 12 h). Su eficacia es moderada, pues impide aproximadamente 80% de los embarazos. La eficacia es mayor cuanto más precozmente se administre, pero puede darse hasta 5 días post-coito. La tolerancia es similar o superior a la de otros preparados empleados con igual propósito. Los efectos adversos comprenden náuseas, vómitos, cefalea, tensión mamaria y alteraciones transitorias en la siguiente menstruación. Se desconoce si el levonorgestrel aumenta la probabilidad de embarazo ectópico cuando el tratamiento fracasa. No se recomienda su empleo como contraceptivo habitual. Cuando se administra antes del pico preovulatorio de LH, el levonorgestrel generalmente bloquea o retrasa la ovulación. Puede asimismo afectar la migración de los espermatozoides en el tracto genital femenino e, indirectamente, la fertilización. Pese a haberse postulado reiteradamente, no existe evidencia de un efecto antiimplantatorio. El conocimiento del método es muy variable en diferentes sociedades, pero aun donde es bien conocido permanece subutilizado. Se ha propuesto proveer levonorgestrel por adelantado para promover su uso. En ensayos clínicos, tal provisión no afectó adversamente el comportamiento sexual ni el empleo de otros contraceptivos, pero tampoco redujo el número de embarazos o abortos. En consecuencia, el empleo de levonorgestrel debe considerarse un método de respaldo que no reemplaza el uso de contraceptivos más eficaces.

Emergency contraception may avoid pregnancy after unprotected intercourse or when regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is recommended for emergency contraception as a single 1.5-mg dose or, alternatively, two 0.75-mg doses taken 12 h apart. Its efficacy is moderate, preventing about 80% of pregnancies. Efficacy is higher the earlier after unprotected intercourse the drug is taken, but it may be administered up to 5 days post-coitum. Tolerance is similar to, or better than, those of other oral emergency contraceptives. Adverse effects include nausea, vomiting, headache, breast tenderness and transient alteration of menstrual bleeding pattern. It is not known whether levonogestrel increases the risk of ectopic pregnancy when the treatment fails. Its use as an ongoing contraceptive method is discouraged. When given before the preovulatory LH peak, levonorgestrel blocks or delays ovulation. It may also affect sperm migration in the female reproductive tract and have an effect on fertilization. Although it has been often postulated, there is no evidence for an anti-implantatory effect. Acquaintance with the method is quite variable among different societies, but it remains underutilized even where it is well known. Advance provision of the drug has been proposed as a way to promote its use. In clinical trials, advance provision did not adversely modify sexual or regular contraceptive behavior, but it did not reduce pregnancy or abortion rate either. Therefore, emergency contraception with levonorgestrel should be regarded as a backup method which is not a substitute for the continued use of more effective contraceptive methods.

Comparison of cycle control and side effects between transdermal contraceptive patch and an oral contraceptive in women older than 35 years.

OBJECTIVE: To compare menstrual patterns and side effects between transdermal contraceptive patch and oral contraceptive use in Thai women over 35 years old. DESIGN: Open labeled randomized control trial. SETTING: Family Planning Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: Ninety-six women above the age of 35 years old were randomized to receive either transdermal contraceptive patch (n = 48) or oral contraceptive (n = 48). The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive contained with ethinyl estradiol (EE) 30 microg and levonorgestrel 150 microg. RESULTS: There were no statistically significant differences between the two groups in terms of cycle length. The mean duration in the transdermal contraceptive group was longer than the COC group with statistically significant difference. More patients in the COC group experienced spotting than the transdermal contraceptive group. Neither amenorrhea nor pregnancies occurred in both groups. CONCLUSION: Transdermal contraceptive patch provides reliable contraceptive efficacy. It also provides good cycle control equal to COC in Thai women aged above 35 years old. However, a higher incidence of minor adverse effects such as breast tenderness and nausea were demonstrated when compared to oral contraceptive containing with ethinyl estradiol (EE) 30 microg and levonorgestrel 150 microg.

Serum HDL-cholesterol in women using low dose oral contraceptives.

This study was done to appraise the effects of low-dose oral contraceptives (OCs) containing 30microgm ethinyl estradiol and 150microgm levonorgestrel on lipid metabolism by a lipid variable-serum HDL-cholesterol (HDL-C). HDL-C has been identified as a lipoprotein that protects against atherosclerosis and its levels are inversely proportional to the risk for developing ischemic coronary disease and venous thromboembolic disorders. Ninety young women within reproductive age group were picked for this study. Sixty women using low-dose oral contraceptives served as experimental group and thirty age matched hormonal contraceptive non users were selected for control group. Experimental group was again subdivided into OCs users for last one-year group, three-year group and five-year group. The result showed that there was no significant difference on serum HDL-cholesterol levels between users & non-users women. It is concluded that low-dose oral contraceptives regimens did not significantly affect the lipid metabolism. It can be safely used as contraceptive & non-contraceptive purposes. The value of studied parameter for serial longer duration of OCs uses needs to be assessed.

Laevonorgestrel intra-uterine system--a revolutionary intra-uterine device.

Laevonorgestrel intra-uterine system is a new hormone releasing long acting intra-uterine device. Besides being used as long acting contraceptive, it has multiple non-contraceptive benefits. It is the best choice for young women suffering from menorrhagia who want contraception along with preservation of fertility and for premenopausal women who want to avoid surgery. Moreover, it has been reported to be useful in patients with dysmenorrhoea, fibroids, endometriosis and adenomyosis and endometrial hyperplasia.