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.

Results from pooled Phase III studies of ulipristal acetate for emergency contraception.

BACKGROUND: Ulipristal acetate (UPA) is a new effective option to prevent unintended pregnancies up to 5 days after unprotected intercourse. We used pooled data from two Phase III studies to refine our understanding of the efficacy of UPA by time from unprotected intercourse and the effects of other factors on pregnancy rates. STUDY DESIGN: Data from two Phase III studies were pooled to create a larger analysis population. Analyses were performed on the first participation of 2183 women. RESULTS: A total of 41 women became pregnant despite the use of UPA, yielding an overall proportion pregnant of 1.9% (1.3%-2.5%). Proportions of pregnant women were higher among those with further acts of unprotected intercourse in the same cycle and among obese women. These varied from 1.3% (0.9%-2.0%) among nonobese women who had no further acts of unprotected intercourse (n=1704) to 8.3% (0.2%-38.5%) among obese women who had subsequent unprotected intercourse (n=12). CONCLUSIONS: UPA is effective and safe in preventing pregnancy after unprotected intercourse. Its effectiveness is lower among women who have subsequent unprotected intercourse and among obese women.

Centchroman: is unsupervised long-term use warranted? Case report.

OBJECTIVES: Centchroman (Ormeloxifene) is a synthetic non-steroidal compound used as an oral and a post-coital contraceptive. It is currently under trial for treatment of breast cancer and postmenopausal osteoporosis. Centchroman has been reported to induce only minimal side effects and no hormonal imbalance. CASE: A young woman who used centchroman for a long time in an unsupervised fashion presented with menorrhagia, which was controlled with norethisterone. Her massively enlarged uterus showed extensive decidual changes in a hyperplastic endometrium, and diffuse microglandular cervical hyperplasia. CONCLUSIONS: The case suggests a prominent oestrogenic effect of centchroman on the uterus. This could be a significant adverse effect related to prolonged therapy. Lengthy intake of centchroman requires medical surveillance and long-term studies are needed.

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.

Mifepristone: where do we come from and where are we going? Clinical development over a quarter of a century.

Administration of mifepristone followed by the prostaglandin, misoprostol, has been used successfully in the medical termination of pregnancy for over 25 years, and the method is registered in 35 countries. Single doses of mifepristone are also effective as an emergency postcoital contraceptive. Mifepristone administered for 3 months or longer to women with uterine leiomyomas, is associated with a reduction in pain and bleeding with improvement in quality of life and decrease in fibroid size. Mifepristone is also effective in decreasing pain in women with endometriosis. In both these conditions, serum estradiol levels are in the range of those in the early follicular phase. A daily dose of at least 2 mg mifepristone blocks ovulation. In contrast, weekly administration of 25 or 50 mg does not consistently block ovulation but has contraceptive potential by delaying endometrial development. Mifepristone in a dose of 200 mg, administered 48 h after the Luteinizing Hormone (LH) surge, also acts as a contraceptive, but this strategy is not practical for widespread use. Administration of mifepristone for 4-6 months or longer may lead to endometrial thickening. Endometrial histology reveals cystic glandular dilation together with admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histological pattern does not represent endometrial hyperplasia.

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.

Ectopic pregnancy following levonorgestrel emergency contraception: a case report.

Use of levonorgestrel as emergency contraception is a safe and effective measure to prevent unwanted pregnancy. However, ectopic gestation in case of failure is a known risk. Access to levonorgestrel without a prescription in many countries has made it impossible to estimate the exact incidence of this potential adverse event. Thus, spontaneous reporting of cases serves to alert physicians to this possibility. We present a case of ectopic pregnancy following use of levonorgestrel emergency contraception. To our knowledge, this is the first case report from India following introduction of levonorgestrel emergency contraception in 2001.

Anticoncepción hormonal de emergencia y embarazo ectópico: caso clínico / Emergency contraception and ectopic pregnancy: clinical case

El riesgo de embarazo ectópico después de anticoncepción de emergencia es un hecho conocido y con el aumento de la demanda por este método, es esperable un mayor número de casos en el futuro. Se presenta un caso de embarazo ectópico después del fracaso de la anticoncepción de emergencia con levonorgestrel.

The risk of ectopic pregnancy after emergency contraception is known and with the increased use of this treatment, we might expect more cases in the future. One case of ectopic pregnancy after failure of emergency contraception with levonorgestrel is presented.

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.

A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency contraception.

OBJECTIVE: To compare the efficacy, patient acceptability and adverse effects of low-dose mifepristone (10 mg) with the levonorgestrel regimen (2 doses of 750 microg given 12 hours apart) for emergency contraception. METHODS: This randomized controlled trial compared mifepristone (10 mg) to levonorgestrel (2 doses of 750 microg given 12 hours apart) in the context of emergency contraception within 120 hours of unprotected intercourse. The primary outcome measure was unintended pregnancy. Secondary outcomes included adverse effects experienced by women, acceptability of the method of emergency contraception used, and the timing of the first menstrual cycle after treatment. RESULTS: The total number of women recruited was 2,065. The crude pregnancy rates were 1.3% and 2.0% for mifepristone and levonorgestrel (P = .46), with 77% and 64% of expected pregnancies prevented, respectively. Women receiving mifepristone were more likely to have a delayed onset of the subsequent menstrual cycle after treatment (P < .001), whereas those having levonorgestrel were more likely to have an early onset of the subsequent menstrual cycle (P < .001). Acceptability levels were high for both methods, with 94% of women receiving mifepristone and 91% receiving levonorgestrel expressing satisfaction. There was no difference in adverse effects (nausea, vomiting, breast tenderness, abdominal pain, lethargy, headache, hot flushes, and dizziness) experienced by women in the 2 groups. CONCLUSION: This study suggests that a small dose of mifepristone is not less effective than levonorgestrel for emergency contraception. Both regimens were highly acceptable to women.

Tolerability of levonorgestrel emergency contraception in adolescents.

OBJECTIVE: We evaluated the tolerability of emergency contraception in adolescents. Study design In this descriptive study, 1 0.75 mg levonorgestrel tablet was administered to 52 females aged 13-16 with instructions to take the second tablet 12 hours later (unprotected intercourse was not an entry requirement). Participants kept diaries of side effects and menstrual patterns. We assessed correct use, side effects caused by treatment, and impact on menstrual cycle. RESULTS: Virtually all participants used the drug correctly, with no serious adverse events. Minor expected side effects occurred, including nausea, fatigue, and vomiting. There was no difference in reporting of side effects by age. Adolescents' mean duration of menses was comparable pre- and post-treatment (5.3 vs 5.0 days; P=.146), and onset of menses was within the expected range. Ninety percent of participants reported they would recommend emergency contraception to a friend or relative if needed. CONCLUSION: Adolescents tolerated the medication well, experiencing transient side effects.

[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.

[Emergency contraception with levonorgestrel in adolescents]. / Speshna kontratseptsiia s Levonorgestrel pri momicheta.

OBJECTIVE: The aim of the study was to asses effectiveness and adverse reactions in adolescent girls received Postinor (0.75 mg Levonorgestrel) for emergency contraception. METHOD: Forty-two teenage girls with established regular menstrual cycles for 24 months period and 128 intercourses are included. Excluding criteria are: clinical data for gynecological endocrine diseases, other contraceptive methods used and contraindication for using gestagens. The girls received tablets Postinor containing 0.75 mg levonorgestrel in dosage 1 or 2 pills after non-protected sexual contact. Before the study the girls are examined for their knowledge about fertile period of the menstrual cycle, opportunities of hormonal contraception and about their ability to make adequate decisions in unpredicted situations and complications of the unprotected or inadequate protected intercourse. RESULTS: No one pregnancy occurred during the study period. Main first adverse reactions after receiving Postinor were nausea (12.4%) and intermenstrual bleeding (30.9%), persisting up to three days. Systemic adverse reactions reported from the women were breast tenderness (11.2%), dizziness (6.5%) and headache (5.6%). These side effects were mild and did not require treatment. CONCLUSION: Emergency contraception with Levonorgestrel is effective, with less contraindications compared with other emergency contraception methods. Postinor is available and reliable contraceptive medication.