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.

Desogestrel+ethinylestradiol versus levonorgestrel +ethinyles tradiol Which one has better affect on acne, hirsutism, and weight change

To compare complications of third and second generation oral contraceptive pills [OCPs]. In a randomized clinical trial from October 2007 to October 2008, 100 healthy women of reproductive age referred to Amir Hospital Family Planning Clinic and some heath centers in Semnan, Iran were randomized in 2 equal groups. They received either a third generation OCP [150 micro g desogestrel [DSG] + 30 micro g ethinylestradiol [EE] or a second generation type [150 micro g levonorgestrel [LNG] + 30 micro g EE]. Six months later, changes of weight, acne, and hirsutism severity, as well as serum titers of sex hormone-binding globulin [SHBG] and free testosterone were compared between the 2 groups. Forty-five women were evaluated in the DSG+EE OCP group, and 46 women in the LNG+EE OCP group. The BMI was significantly higher in the second group [p=0.000] after 6 months duration. Likewise, the decrement of acne and hirsutism seventy was significantly higher in the DSG+EE users [p=0.000]. Mean changes of serum free testosterone [f=0.967] and SHBG [f=0.916] were comparable between the 2 groups. In comparison with the LNG+EE OCP, the DSG+EE OCP is a contraceptive pill that significantly decreases the severity of acne and hirsutism, without any significant change in weight

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...

Avaliação de protocolos para indução de inatividade ovariana em gatas domésticas / Evaluation of protocols for induction of inactivity ovarian in domestic cats

Os índices de prenhez após inseminação artificial em felídeos selvagens não são satisfatórios devido ao variável ambiente endócrino após a estimulação com gonadotropinas. O objetivo deste estudo consistiuem aumentar a taxa de sucesso em programas de inseminação artificial em gatas domésticas (animal modelo). As fêmeas (n=9) foram divididas em três grupos, cada um com três animais, sendo: 1) controle(C), somente 200 UI eCG/ 100 UI hCG ; 2) levonorgestrel oral (L)(0,075 mg) durante 37 dias + eCG/hCG; 3) etonogestrel (E), implante subdérmico durante 37 dias + eCG/hCG. Foram submetidas ao exame laparoscópico 29-39 horas após a administração de hCG para verificação da resposta ovariana e realização de esfregaço vaginal para monitoração da fase do ciclo estral. Foram coletadas amostras de fezes 60 dias antes e 60 dias após o tratamento com gonadotropinas para dosagem hormonal de estrógenos. Os resultados foram avaliados através do Teste ANOVA. Os níveis de significância mostraram que o Grupo E, em contraste com o Grupo C e o Grupo L, apresentou inibição satisfatória das concentrações de estrógenos durante a sua utilização. O grupo L não apresentou inibição ovariana durante o tratamento e diferença significativa em relação ao Grupo C. No exame laparoscópico todas as fêmeas dos grupos C, L e E apresentaram folículos e 77% das fêmeas apresentaram corpo lúteo. Também apresentaram células epiteliais superficiais anucleadas e nucleadas características de estro. Concluiu-se que a utilização de implantes de etonogestrel em gatas domésticas mostrou-se eficaz, possibilitando asua utilização prévia aos programas de inseminação artificial, aspiração folicular e também para a contracepção.

Reproductive success in endangered captive small felids species is veryl ow. Due to great variability in endocrine environment post gonadotropin treatment, after artificial insemination pregnancy rates are very low. Nowadays, ovarian activity controll improves the AI success in many species. In this study, new protocols were compared to improve the fertilization rates in artificial insemination programs in domestic cat. Female domestic cats were divided in three treatments: 1) control (eCG/hCG); 2) levonorgestrel (0.075 mg) orally during 37days + eCG/hCG; 3) etonogestrel subdermal implant during 37days + eCG/hCG: Laparoscopies were done 29-39 hours post hCG treatment to verify ovarian activity. Vaginal swabs were collected at laparoscopic procedures. Fecal samples were colected 60 days before, during and 60 days after the gonadotropin treatment for estradiol assay. Means comparisons were done by ANOVA test. Results demonstrated that etonogestrel (implant) and not oral levonorgestrel successfully suppressed ovarian activity. The levonorgestrel group didnot show ovarian inactivity during the administration, presenting oestradiol peaks and without significative diference comparing to control group. All females presented anuclear and nuclear superficial vaginal epithelial cells at laparoscopies. In conclusion, the etonogestrel implant used in the domestic cat was efficient and can be used previous to gonadotropin protocol in artificial insemination programs, follicular aspiration and contraception

Cómo y cuándo el levonorgestrel previene el embarazo si se administra como anticonceptivo de emergencia / How and when levonorgestrel prevents pregnancy if it is administered as emergency contraceptive

En esta revisión se actualiza el mecanismo de acción del levonorgestrel (LNG) usado en anticoncepción de emergencia. El análisis crítico de la estimación de la eficacia anticonceptiva del LNG indica que su tasa de falla es más alta que la publicada. El LNG aumenta la viscosidad del moco cervical impidiendo que los espermatozoides del reservorio cervical vayan a renovar la población espermática en el sitio de fecundación. Diversos autores han documentado que LNG suprime el pico preovulatorio de gonadotrofinas e interfiere con el proceso ovulatorio en la mujer y en modelos animales. Administrado después de la ovulación en rata, en la mona Cebus apella y en la mujer, no interfiere con la implantación del embrión. Se concluye que LNG previene el embarazo solamente cuando se administra en un momento del ciclo menstrual en el cual puede impedir la fecundación y que el método falla cuando la administración es más tardía.

This review updates the mechanism of action of levonorgestrel (LNG) used for emergency contraception. A critical analysis of estimates of the contraceptive efficacy of LNG indicates that its failure rate is higher than previously reported. Under the effect of LNG, cervical mucus turns highly viscous and hinders the exit of sperm from the cervical reservoir needed to renew the sperm population at the site of fertilization. Several authors have documented that LNG suppresses the preovulatory surge of gonadotropins and interferes with the ovulatory process in women and in animal models. Administered after ovulation in the rat, in the Cebus apella monkey and women, LNG does not interfere with embryo implantation. In conclusion, LNG prevents pregnancy only when it is administered at a time of the menstrual cycle in which it can impede fertilization and the method fails when it is given at later stages of the cycle.

Variação de peso em usuárias de sistema intra-uterino liberador de levonorgestrel, DIU T-cobre e acetato de medroxiprogesterona no Brasil / Weight variation in users of the levonorgestrel-releasing intrauterine system, of the copper IUD and of medroxyprogesterone acetate in Brazil

OBJETIVO: Determinar a variação de peso corpóreo em mulheres usuárias de sistema intra-uterino liberador de 20 mg/dia de levonorgestrel (SIU-LNG, Mirena®) e compará-la com a variação de peso de usuárias de dispositivo intra-uterino T cobre 380A (DIU Tcu) e usuárias de acetato de medroxiprogesterona de depósito (AMP-D) ao longo de cinco anos. MÉTODOS: Foram analisadas 163 mulheres usuárias de SIU-LNG que tiveram a inserção do mesmo em 1998 durante a admissão para o estudo. Cada mulher foi pareada por peso (± 1kg) e por idade (± 1 ano) no início do estudo, com as usuárias de DIU Tcu e AMP-D. Todas as mulheres foram seguidas por até cinco anos. Nesse período foram medidos seus pesos e calculados os índices de massa corpórea (IMC). RESULTADOS: A média de idade das usuárias de SIU-LNG foi 27±6,7 anos, enquanto que das usuárias de DIU Tcu foi 28±6,6 anos e das usuárias de AMP-D foi de 26,9±6,5 anos. O peso inicial era 62,9 ± 0,8 kg, 62,8 ± 0,8 kg e 62,5 ± 0,9 kg para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente. O IMC no início do estudo era 25 (±0,3), 26,4 (±0,3) e 25,5 (±0,4) para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente. Foi observado um aumento de peso de 3,1 kg, 4,9 kg e 8,2 kg para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente, ao final do quinto ano (p=0,009). O IMC também apresentou um aumento em todos os grupos (IMC final de 26,3 ± 0,7, 28,5 ± 0,8 e 28,7 ± 1,3 para as usuárias de SIU-LNG, DIU Tcu e AMP-D, respectivamente). A análise multivariada mostrou que o uso de AMP-D e seu tempo de uso foram significativos em relação ao ganho de peso. CONCLUSAO: O uso de SIU-LNG não mostrou aumento significativo no ganho de peso ao longo dos cinco anos, bem como diferença na variação de peso quando comparado com o uso de DIU Tcu.

Male contraception: expanding reproductive choice.

The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable, safe and effective male contraceptive, scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen, thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently, a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view, while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men, using sperm surface epitopes not expressed in female reproductive tract as source, still requires considerable research efforts.

Effects of low dose oral contraceptives on serum total cholesterol, TAG, HDL-C & LDL-C levels in contraceptive users.

This study was done to appraise the effects of low-dose oral contraceptives (OC(s)) containing synthetic estrogen ethinyl estradiol and synthetic progestin levonorgestrel on serum total cholesterol, TAG, HDL-C and LDL-C levels. 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 OCP users for last one-year group, three-year groups and five-year group. The results showed that there were no significant differences on most of the study parameters between users and non-users women. But there was a significant accession of serum triacylglycerol only in OCP user groups. The results hint that low-dose oral contraceptives regimens partly impaired the lipid metabolism. So, the safeness of low-dose OCP used in National Population Control Program is further inspired. The value of studied parameters for serial longer continuation of OCP uses need to be renegotiated.

Alleviation of the climacteric symptoms with oral sequential hormone replacement therapy.

The efficacy of the oral hormone replacement therapy (HRT) preparation estradiol valerate/levonorgestrel (EV/LNG, Klimonorm) in the alleviation of the menopausal complaints of peri- and postmenopausal Thai women was studied in a prospective, open, uncontrolled phase IV clinical trial. Of the 50 peri- or postmenopausal women screened, 39 completed the study. From them 31 were postmenopausal and 8 perimenopausal. The participants received EV/LNG over a period of 6 cycles. The Menopause Rating Scale II (MRS II) was used to assess the effect of EV/LNG on the menopausal symptoms. The changes in the main parameters of the MRS II during the treatment with EV/LNG showed that the general score decreased by 34.9 per cent after 3 months and was kept at the same value after 6 months of treatment. The somato-vegetative complaints decreased by 32.5 per cent after 3 months and by 35 per cent after 6 months. The psychological complaints decreased by 34.1 per cent after 3 months and by 32.9 per cent after 6 months. The urogenital complaints decreased by 29.3 per cent after 3 months, and remained at the same level after 6 months of treatment. In conclusion, the 6-months administration of the oral HRT preparation estradiol valerate/levonorgestrel caused a considerable alleviation of the climacteric symptoms in menopausal women.

Mecanismo de accion del levonorgestrel en la anticoncepcion de emergencia

En esta revisión se actualiza el mecanismo de acción del levonorgestrel (LNG) usado en anticoncepción de emergencia. El análisis crítico de la estimación de la eficacia anticonceptiva del LNG indica que su tasa de falla es más alta que la publicada. El LNG aumenta la viscosidad del moco cervical impidiendo que los espermatozoides del reservorio cervical vayan a renovar la población espermática en el sitio de fecundación. Diversos autores han documentado que LNG suprime el pico preovulatorio de gonadotrofinas e interfiere con el proceso ovulatorio en la mujer y en modelos animales. Administrado después de la fecundación en rata y Cebus apella, no interfiere con la implantación del embrión. Se concluye que LNG previene el embarazo solamente cuando se administra en un momento del ciclo menstrual en el cual puede impedir la fecundación y que el método falla cuando la administración es más tardía.

Mecanismos de acción del Levonorgestrel utilizado como método de anticoncepción de emergencia / Mechanisms of action of levonorgestrel used as a method of emergency contraception

En su boletín N°51 de 1999, el UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, principal iniciativa de la OMS en el campo de salud reproductiva, reconoce que a la fecha “no existe información sobre el modo de acción del levonorgestrel en dosis de dos tabletas de 0.75 mg dadas con un intervalo de 12 horas”, y que se están llevando a efecto investigaciones sobre el efecto de esta régimen sobre los distintos eventos que llevan a la fertilización y al establecimiento del embarazo. Croxatto (2001), en la revisión más reciente sobre el tema disponible en la literatura, concluye tambien que “Existen pocos estudios diseñados para buscar el mecanismo de acción del levonorgestrel en la contracepción de emergencia y su modo de acción preciso sigue siendo desconocido”.

Fine structure of prolactin cell of female albino rat as affected by some antifertility drugs--a comparative electron microscopic study.

One antioestrogenic compound as well as some antifertility drugs have been administered to female albino rats over a period of six months to study their long term effects on fine structures in PRL cell. Almost in all the cases, the dynamics of hormone synthesis and secretion have been affected. Fine structure is suggestive of activation of synthetic machinery of the cell. The cell picture under the estradiol valerate regimen presents a transitional stage progressing towards involution due to accelerated cell cycle. Sparse granulation, frequent granule extrusion and misplaced exocytosis under the influence of tamoxifen citrate or levonorgestrel + ethinyloestradiol are similar to those observed in adenomatous PRL cell. Fine structural correlates of stepped up synthesis are also observed following chronic progesterogenic influences of progesterone and norethisterone heptanoate, but the magnitude of the change is on a lower scale. All the fine structural changes have been discussed in the context of ultrastructural pathology.

effect of norplant [long term contraceptive] on the uterus of female albino rats

To study noticeable changes in the status of endometrium of uterus in female albino rats with long term contraceptive Norplant. Design: Light microscopic study of uterus of female albino rats with Norplant therapy. Setting: Department of Anatomy, Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi. Subjects: Sixty Six adult female albino rats were divided into six group A, B, C, D, E and F, and each group comprising of six animals, group 'A' served as age-match control, group 'B', 'C', 'D', 'E' and 'F' received subdermal insertion of single rod of Norplant at the interval of 13 days respectively. All the animals were sacrificed at their schedule time and uterus was removed, processed for paraffin embedding and stained with H and E and also with special stains. All the observations were statistically analysed. In Norplant treated animals the thickness of endometrium demonstrated a highly significant increase in groups 'B', 'C', 'D', 'E' and 'F' when compared with age-matched controls. The height of epithelial cells showed a highly significant decrease, the connective tissue fibres also showed a marked increase. On the basis of present study, it is concluded that Norplant initiate cellular injury which causes damage to the tissue and produces fibrosis

O sistema anticonceptivo Norplant do ponto de vista das usuárias / The Norplant contraceptive system of users point of view

O objetivo da pesquisa foi conhecer a experiência e a opiniäo de um grupo de mulheres brasileiras que aceitaram experimentar o sistema anticoncepcional Norplant. Foram estudadas 280 mulheres, selecionadas em três clínicas de planejamento familiar em Campinas, Curitiba e Fortaleza. Houve poucas diferenças significativas entre as clínicas. A equimose foi a moléstia mais freqüentemente relacionada com a inserçäo (60%), e a coceira foi o sintoma local mais comumente mencionado (40%) durante o uso. A percentagem de mulheres que disseram que as cólicas menstruais, corrimento, dor de cabeça e nervosismo tinham diminuido com o uso do método foi maior do que a das que relataram aumento. Mais da metade das mulheres estudadas estiveram em amenorréia durante dois ou mais meses, ou menstruaram, sangraram e/ou mancharam durante dez ou mais dias em um mês. A grande maioria das usuárias (77,2%) considerou "boa ou "muito boa" sua experiência com o Norplant e 80,6% disse tê-lo recomendado a outra mulher

Cytoplasmic estrogen receptors in endometrium after long term use of contraceptive implant Norplant

In this work, endometrial biopsies from 31 ladies who had used contraceptive implants NORPLANT for 5 years were studied for detection of estrogen receptors. The biopsies were taken at the time of removal of the NORPLANT at the outpatient Family Planning Clinic of Assiut University Hospital. Age of patients varied between 28 and 45 years. All were multipara with regular menstruation except for 3 women who had irregular bleeding and one with ammenorrhea. Histochemcial immunoperoxidase staining method was used in formalin-fixed paraffin-embedded tissue sections for detection of cytoplasmic estrogen receptor complexes. Accordign to histopathological paterrn of endometrium our 31 cases were classified into: proliferative endometrium [15 cases], irregular secretory [11 cases] and suppressed endometrium [5 cases]. Serum concentrations of estradiol, progesterone, levonorgestrel and sex hormone binding globulin were measured in all cases. Progesterone serum concentration was higher in cases with both proliferative and suppressed endometrium

Hormonal levels and endometrial histology after prolonged use of the contraceptive implants Norplant [R]

The serum concentration of estradiol, progesterone [prog], levonorgestrel [LNG] and sex hormone binding globulin [SHPG] were measured and endometrial specimens were histologically examined in 50 women who had been using the contraceptive implants NORPLANTR for about five years. The hormonal levels obtained in different phases of the menstrual cycle suggested the occurrence of cyclic ovarian hormone production. However, prog. Concentration did not attain levels suggestive of normal corpus luteum function. The mean serum concentration of LNG was 0.3 +/- 0.15 [SD] ng/ml, a level similar to those reported for the earlier phases of NORPLANTR use. SHBG concentration was on the average 13.61 9.9 nmoL/L, lower than the mean value reported for normal women not using hormonal contraception. Again, endometerial patterns were suggestive of ovarian cyclisty. However, suppressed endo-metrium was found in 10, and irregular secretory pattern in 11 out of the 43 readable biopsies. Foci of cystic glandular hyperplasia were found in four specimens that showed otherwise proliferative endometrium.No evidence of malignant transformation were found in either the glandular or stromal elements. The results indicate that prolonged use of NORPLANT[R] does not result in a state of chronic hypoestrenism