Mifepristone: a potential clinical agent based on its anti-progesterone and anti-glucocorticoid properties.

Nowadays, unwanted pregnancy is a major globe tragedy for millions of women, associated with significant direct and indirect costs, no matter for individuals or society. The progesterone receptor antagonist steroid, mifepristone has been widely and effectively using throughout the world for medical abortion, but to a lesser extent for emergency contraception. In this review, we hope to explore the role of mifepristone as a contraceptive, particularly for emergency contraception. Studies of mifepristone have also been expanding to the fields of endometriosis and uterine fibroids. Furthermore, this initially considered reproductive medicine has been investigated in some psychotic diseases and various disorders of hypercortisolism, because of its glucocorticoid receptor antagonism. Mifepristone was approved suitable for patients with hyperglycemia secondary to Cushing's syndrome by the United States Food and Drug Administration (FDA) in 2012. The aim of this article is to review published reports on the anti-progesterone and anti-glucocorticoid properties of mifepristone as a clinical agent. There is a new insight into systematically describing and evaluating the potential efficiency of mifepristone administrated in the field of endocrine and neuroendocrine, not only in obstetrics and gynecology.

Métodos anticonceptivos utilizados por población inmigrante y condicionantes que influyen en su elección en un área sanitaria de Zaragoza / Contraceptive methods used by immigrant populations and conditions that influence the choice in a health area in Zaragoza

Introducción. En los últimos años el porcentaje de mujeres inmigrantes ha aumentado provocando el surgimiento de necesidades específicas referentes a su salud sexual y reproductiva. El objetivo fue conocer los métodos anticonceptivos utilizados por ellas y los condicionantes que influyen en su elección. Estimar como indicadores de alerta: uso de píldora poscoital y prevalencia de abortos. Material y métodos. Estudio descriptivo transversal, mediante encuesta realizada en el primer trimestre del año 2011 en el Centro de Salud Delicias Sur (Zaragoza). La población diana fueron mujeres inmigrantes en edad fértil (15-45 años) que acudieron al centro, previo consentimiento informado. Muestreo accidental por cuotas. Resultados. La edad media fue de 29,35 años (IC al 95% = 27,95-30,75 años). El país de origen mayoritario fue Ecuador. Casi la mitad de las mujeres estaban solteras y trabajaban por cuenta ajena, y su nivel de instrucción era medio. La media de años de residencia en España fue de 5,68 años (IC al 95% = 4,99-6,37 años). Un 42% de las mujeres (IC al 95% = 32,62-51,83) no utilizaba ningún método anticonceptivo. El método más utilizado fue el preservativo, seguido de la píldora. Más de la mitad de las mujeres habían sido informadas en atención primaria. Un 32% (IC al 95% = 23,42-41,60) de ellas tenían un antecedente de aborto. Respecto al uso de la píldora poscoital (PPC), había recurrido a ella el 19,39% (IC al 95% = 12,46-28,10). Conclusiones. El 42% no utilizaba ningún método anticonceptivo y los indicadores de alerta sobre el fracaso de medidas preventivas en salud reproductiva son elevados (AU)

Background. The percentage of women immigrants in Spain has increased in these last years, resulting in the emergence of specific needs related to sexual and reproductive health. The objective of this article was to define the contraceptive methods used by immigrant women and the determining factors that influence their choice. To estimate the use of emergency post-coital contraception and prevalence of abortion. Methods. A descriptive cross-sectional study using a survey was carried out in the first quarter of 2011 at the "Centro de Salud Delicias Sur" in Zaragoza, Spain. The target population were immigrant women of childbearing age between 15 and 45 years who attended the clinic. Non probability sampling was used. Results. The mean age was 29.35 years (95% confidence interval (CI) = 27.95 to 30.75 years). The majority country of origin was Ecuador. Almost half the women were single and worked in paid employment. The educational level was considered as average. The average duration of residence in Spain was 5.68 years (95% CI = 4.99 to 6.37 years) and 42% of them (95% CI = 32.62 to 51.83) did not use any contraceptive method. The most used contraceptive method was the condom, followed by oral hormonal contraceptives. More than half of the women had been informed in Primary Care. Almost one third (32%) (95% CI = 23.42 to 41.60) of the women had a history of abortion. More than 19% of women (95% CI = 12.46 to 28.10) had used the emergency contraceptive method. Conclusion. Contraceptive methods were not used by 42% of women. The alert indicators on the failure of preventive measures in sexual health are still too high (AU)

Defining reality: the potential role of pharmacists in assessing the impact of progesterone receptor modulators and misoprostol in reproductive health.

Medical abortion is increasingly heralded as an ideal method for decreasing maternal mortality in health-care resource-deprived areas and as an answer to the shrinking pool of physicians willing to perform abortions. The advent of progesterone receptor modulators (PRMs) and the recent approval by the Food and Drug Administration of ella (ulipristal) as an emergency contraceptive put pharmacists in the center of abortion controversy. Pharmacists, worldwide, need to be aware of the controversy surrounding the introduction of PRMs, particularly with regard to the effect on health policy, their mechanism of action, associated adverse events, and common off-label uses. Once understood, genuine opportunity exists for pharmacists to serve a fundamental role in positively shaping public health policy.

Emergency contraception: past, present and future.

Women have been using emergency contraception (EC) for decades. Population studies have not shown that increased access to EC decreases abortion rates this is likely because of inconsistent and infrequent use even when it is available. Special populations, such as adolescents, have been shown to be just as good as their adult counterparts in comprehending EC instructions, and its use does not lead to more risky sexual practices or behaviors. There is little evidence on the administration of EC to victims of sexual assault, but what is available reveals more women who are victims of sexual assault should be offered EC as an option. Methods of EC include high doses of ethinyl estradiol; DES; Danzaol; combination ethinyl estradiol with a progestin; progestin alone and copper IUDs. This review describes the history of EC as well as newer medications such as the antiprogestins (gestrinone and uliprisatal acetate) and cyclooxygenase inhibitors(meloxifam). These methods have been added to the armamentarium and may prove to be more effective than current regimens. Finding a product that is highly effective with minimal side effects is a worthy goal, for it presents a woman with her last chance to prevent an unwanted pregnancy.

Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture.

BACKGROUND: Current methods of hormonal emergency contraception (EC) are ineffective in preventing follicular rupture when administered in the advanced pre-ovulatory phase. This study was designed to determine the capacity of ulipristal acetate (UPA), a selective progesterone receptor modulator developed for EC, to block follicular rupture when administered with a follicle of >or=18 mm. METHODS: This was a double-blind, crossover, randomized, placebo-controlled study. Thirty-five women contributed with UPA (30 mg. oral) and a placebo cycle. Serial blood sampling for luteinizing hormone (LH), estradiol and progesterone measurements and follicular monitoring by ultrasound were performed before and for 5 days following treatment. Follicular rupture inhibition was assessed in the overall study population and in subgroups of women stratified by when treatment was administered in relation to LH levels (before the onset of the LH surge, after the onset of the surge but before the LH peak or after the LH peak). RESULTS: Follicular rupture failed to occur for at least 5 days following UPA administration in 20/34 cycles [59%; 95% confidence interval (CI) (40.7-75.4%)], whereas rupture took place in all cycles within 5 days of placebo intake. When UPA was administered before the onset of the LH surge, or after the onset but before the LH peak, follicle rupture had not occurred within 5 days in 8/8 (100%) and 11/14 [78.6%; 95% CI (49.2-95.3)] cycles, respectively. In contrast, when UPA was given after the LH peak, follicle rupture inhibition was only observed in 1/12 [8.3%; 95% CI (0.2-38.5)] cycles. CONCLUSIONS: This study demonstrates that UPA can significantly delay follicular rupture when given immediately before ovulation. This new generation EC compound could possibly prevent pregnancy when administered in the advanced follicular phase, even if LH levels have already begun to rise, a time when levonorgestrel EC is no longer effective in inhibiting ovulation.

Emergency contraception, efficacy and public health impact.

PURPOSE OF REVIEW: Emergency contraception in the past two decades had been proven to be effective and well tolerated. Counseling and advance provision and prescription of emergency contraception have been embraced by professional organizations in practice guidelines for its potential to reduce the number of unintended pregnancies and abortions. Has emergency contraception lived up to that promise? RECENT FINDINGS: Mifepristone (not available in the USA) is the agent of choice. Emergency contraception has not reduced the number of unintended pregnancies. Acceptance by healthcare providers and the public has not been optimal, and multiple financial and healthcare system barriers to use emergency contraception continue to exist. The public health impact of emergency contraception has been disappointing. SUMMARY: Although emergency contraception may continue to be an important component of contraceptive practice, only increased access to more effective methods of contraception will change unintended pregnancy rates. The use of mifepristone for emergency contraception in the USA must be considered.

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...

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...(AU)

Update on medication abortion.

This article provides an overview of medication abortion in the United States 6 years after the approval of mifepristone (RU486; Mifeprex; Danco Laboratories, LLC, New York, NY) by the US Food and Drug Administration (FDA). The adoption of mifepristone is considered in the context of epidemiologic data on abortion, abortion access, and the safety of abortion. The risks of medication and aspiration abortion are discussed in the context of abortion-related mortality, recent experience with obstetric and gynecologic infection with Clostridium sordellii, and the limits of scientific knowledge on the incidence of this infection in women. Innovative protocols studied since FDA approval of mifepristone are presented, and implications for clinical practice are discussed.

[Emergency contraception with levonorgestrel for teenagers--efficacy, tolerability, and level of information awareness]. / Speshna kontratseptsiia pri tiineidzhuri s levonorgestrel--efektivnost, ponosimost, informiranost.

OBJECTIVE: Assessment of efficacy and side effects of emergency contraception for teenagers with levonorgestrel (LNG) and the level of users' informedness about possibilities and practical application. METHODS: The subjects are healthy girls (n = 49) with regular menstrual cycles at the age between 15 and 19, having had one unprotected or faultily protected sexual intercourse. All of them have administered 0.75 mg LNG within the 72nd hour, repeated after 12 hours. The data have been processed by variational analysis. RESULTS: One pregnancy was registered of a girl with firstintake at the 67th hour - pregnancy rate - 2,0%. The most frequent side effect was nausea - 26,5%, folowed by breast tenderness - 22,4% and fatigue - 20,4%. An up to 7th day delay in menstrual cycle is non significantly more frequent - 14,3%, followed by a delay of more than 7 days breakthrough bleeding - 8,2%. No significant changes were established in the lenght of the menstrual cycle. Emergency contraception is sought for after unprotected sexual intercourse in 69,4%, and condom failure problems in 30,6%. Only 18,4% have sufficient information about the possibilities and practical use of emergency contraception. CONCLUSION: LNG provides effective, highly tolerable contraception with a small number of side effects. Need is felt for serious popularization of the application of emergency contraception with teenagers.

[Present and potential uses of mifepristone in gynecology, obstetrics and other medical specialties]. / Utilisations actuelles et potentielles de la mifépristone en gynécologie-obstétrique et dans les autres disciplines médicales.

Mifepristone, a derivative of norethindrone, a first generation synthetic progestative, has a very potent antiprogestative activity and to a lesser degree antiandrogenic and antiglucocorticoid activities. This action makes it potentially useful in the treatment of multiple hormone dependent diseases in obstetrics-gynecology as well as in a variety of medical specialties such as neurology, ophthalmology, and oncology. Nevertheless, the label of abortive pill has incited numerous ethical and political debates concerning the permission to market this drug, and this has contributed to the delay in the assessment of the potential indications of mifepristone. Largely under-utilized in practice despite its increasing theoretical benefit, clinical studies should now de conducted. Thus, based on an international review of literature during the last ten years, we have shed light on the present and potential indications of mifepristone in medical practice.

Levonorgestrel and mifepristone in emergency contraception.

Research on new technologies by the Special Programme of Research, Development and Research Training in Human Reproduction at WHO has led to the development of two new methods for emergency contraception, the levonorgestrel regimen and a low-dose mifepristone regimen. In 4 years, the levonorgestrel regimen has already been approved in some 95 countries. We review this research and present combined data from our multinational trials and combined estimates of efficacy for mifepristone and for levonorgestrel separately. Data were available for 6283 women in 10 mg mifepristone groups and 4098 women in levonorgestrel groups. One of these studies compared the two methods, namely a randomized, double-blind trial in which we also investigated a single dose of 1.5 mg of levonorgestrel. Both levonorgestrel and mifepristone are effective for emergency contraception and prevent a high percentage of pregnancies when used within a few days after coitus. Mifepristone is associated with later return of menses compared to levonorgestrel.

Adolescent emergency contraception: attitudes and practices of certified nurse-midwives.

Teenage pregnancy has reached epidemic proportions in the United States with I million pregnancies and more than 500,000 live births occurring each year among women under the age of 20. The safety and efficacy of postcoital administration of oral contraceptives, commonly called "emergency contraception" (EC), have been well documented. However, EC is dramatically underused in the United States. Because low use of EC may be attributable, in part, to both lack of knowledge, as well as misinformation on the part of health care providers, further research in this area is warranted. Because midwives play a significant role in the provision of reproductive health care to adolescents, their attitudes about the use of EC among teens may impact the availability of emergency contraception options to these clients. This article presents results of a survey of certified nurse-midwives with respect to their attitudes, practices, and policies related to EC and provides recommendations specific to this provider population.

Mifepristone: contraceptive and non-contraceptive uses.

Mifepristone is an orally active progesterone antagonist. It can be used for both contraceptive and non-contraceptive clinical indications. It is a very effective drug for emergency contraception with a low incidence of side effects. There is a potential for mifepristone to be used as a once-a-month pill. There is a need, however, for a simple, inexpensive and accurate method to identify the luteinizing hormone surge before this method can be used in clinical practice. The daily administration of mifepristone offers promise as an effective method of contraception but more studies need to be done. The combination of mifepristone with a prostaglandin analogue is a well-established method for termination of pregnancy of up to 9 weeks. Recent data suggest that this combination may also be used up to 9-13 weeks of pregnancy. Although mifepristone is effective in dilating the cervix before vacuum aspiration, misoprostol is probably the drug of choice in most situations. In the second trimester, mifepristone is effective in shortening the abortion process induced by prostaglandin analogues. The combination of mifepristone and prostaglandin also offers a medical method for management of miscarriages. Mifepristone has been used for a number of other indications, but further studies are needed before such treatment can be recommended.