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espanolAntecedentes: el levonorgestrel (LNG) es un agonista del receptor de progesterona que se utiliza tanto en la anticoncepcion hormonal regular como en la de emergencia; sin embargo, sus efectos sobre el endometrio como anticonceptivo siguen siendo ampliamente desconocidos y estan bajo debate publico. Objetivo: Analizar los efectos del LNG o mifepristona (MFP), un antagonista del receptor de progesterona y tambien conocido como RU-486, administrado en el momento de la rotura del foliculo (FR) sobre el transcriptoma endometrial durante el periodo receptivo del ciclo menstrual. Metodos: Se estudiaron diez mujeres voluntarias ovulatorias durante dos ciclos menstruales, un ciclo de control y un ciclo de tratamiento consecutivo; en este ultimo caso, las mujeres fueron asignadas aleatoriamente a dos grupos de 5 mujeres cada uno, recibiendo una dosis de LNG (1,5 mg) o MFP (50 mg) el dia de la RF por ecografia. Se tomaron biopsias de endometrio 6 dias despues de la administracion del farmaco y se prepararon para el analisis de microarrays. Resultados: El analisis funcional genomico en el grupo tratado con LNG mostro como activada la implantacion y decidualizacion del embrion con funciones biologicas, mientras que estas funciones biologicas en el grupo T-MFP se predijeron como inhibidas. Conclusiones: La administracion de LNG como anticonceptivo hormonal de emergencia resulto en un perfil de expresion genica endometrial asociado a receptividad. Estos resultados coinciden en el concepto de que el LNG no afecta la receptividad endometrial y / o la implantacion de embriones cuando se utiliza como anticonceptivo de emergencia. EnglishBackground: 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.

Emergency contraceptive (EC) pills may be less effective for women with higher body mass index (BMI), but little is known about public response to the fact that EC may lose efficacy as weight increases. In November 2013, European authorities changed the label for a levonorgestrel EC product to warn of a reduction in effectiveness for women with higher BMI, garnering significant media coverage in the United States. Ulipristal acetate (UPA) EC may be more effective than levonorgestrel for women with BMI levels designated as obese. Among 8,019 women who received UPA from the online pharmacy KwikMed from 2011 to 2015 and self-reported their height, weight and reasons for seeking UPA online, we analyzed changes in the proportion of women in different BMI categories before and after the label change. For the 25 month-period after the label change, the proportion of women in the obese category rose by 26.7 percentage points relative to the 35 months before (B=0.2665, p

Unplanned or unintended pregnancy remains a significant challenge for adolescents; many teens who plan ahead but opt not to choose long-acting reversible contraceptive methods have high failure rates with condom usage, oral contraceptives, and other less long-acting methods. Emergency contraception (EC) remains a necessity for those adolescents seeking a second chance to prevent the unintended consequences of unplanned sexual activity. At present, 5 postcoital methods remain available as EC globally: intrauterine devices, ulipristal acetate, a selective progesterone modulator, mifepristone; levonorgestrel, and ethinyl estradiol plus levonorgestrel or norgestrel (rarely used now that progestin only methods are more readily available).

Background The days just prior to ovulation are the most crucial for emergency contraception (EC) efficacy. Ulipristal acetate (UPA) and levonorgestrel's (LNG) capacity to inhibit follicular rupture have never been compared directly at this time of the cycle. Study Design Raw data from three pharmacodynamics studies with similar methodology were pooled to allow direct comparison of UPA, LNG and LNG+meloxicam's ability to prevent ovulation when administered orally in the advanced follicular phase, with a leading follicle of ≥18 mm. Results Forty eight LNG-treated (1.5 mg) cycles, 31 LNG (1.5 mg) + meloxicam (15 mg), 34 UPA (30 mg) cycles and 50 placebo cycles were compared. Follicle rupture was delayed for at least 5 days in 14.6%, 38.7%, 58.8% and 4% of the LNG-, LNG+meloxicam-, UPA- and placebo-treated cycles, respectively. UPA was more effective than LNG and placebo in inhibiting follicular rupture (p=.0001), while LNG, when administered at this time of the cycle, was not different than placebo. The addition of meloxicam improved the efficacy of LNG in preventing follicular rupture (p=.0292 vs. LNG; p=.0001 vs. placebo; non-significant vs. UPA). UPA was effective in preventing rupture in the 5 days following treatment, even when administered at the time of the luteinizing hormone (LH) surge (UPA 79%, LNG 14% and placebo 10%). None of the treatments were effective when administered on the day of the LH peak. The median time from treatment to rupture was 6 days during the ulipristal cycles and 2 days in the placebo and LNG/LNG+meloxicam cycles (p=.0015). Conclusion Although no EC treatment is 100% effective in inhibiting follicular rupture when administered in the late follicular phase, UPA is the most effective treatment, delaying ovulation for at least 5 days in 59% of the cycles. LNG is not different from placebo in inhibiting follicular rupture at this advanced phase of the cycle. No treatment was effective in postponing rupture when administered on the day of LH peak.

Recent trials on emergency contraception (EC) have indicated that levonorgestrel (LNG) used alone has fewer side-effects and is more efficacious than the Yuzpe regimen (high dose combined oral contraceptive pills). However, the experienced side-effects and acceptability may vary between different groups or societies.The primary objective of this study was to determine side-effects and acceptability of two emergency contraceptive pill (ECP) regimens among users in Kampala, Uganda.Randomized clinical trial.A total of 337 women were enrolled in a double blind randomized clinical trial. Women requesting ECPs within 72 hours after unprotected sexual intercourse received either LNG or the Yuzpe regimen. The women returned for follow-up after three days and a follow-up interview was performed after one year.Levonorgestrel had significantly fewer side-effects than the Yuzpe regimen (p0.001). There was a significant association between having worries about the method and experiencing side-effects (p0.001). Most women (81%) were prime users of EC. The majority would recommend ECP to other clients.Levonorgestrel is a superior option to the Yuzpe regimen and should be promoted as the recommended ECP. Having worries about ECP may influence experience of the side-effects. Correct information is critical in promotion of ECP use.

Millions of women each year start or continue to use some type of hormonal contraceptive method. Choosing a method may be anxiety provoking. In this article, we review some of the latest advances in and options for hormonal contraception, including extended-dose oral contraceptives, the vaginal ring, injectable methods, and emergency contraception. Nurses can facilitate women's decision making for healthy reproductive options.

For emergency contraceptive, the rapid delivery of levonorgestrel (LNG) to plasma is desirable, furthermore, a sustained delivery of LNG along with rapid absorption will be necessary. The pharmacokinetics and pharmacodynamics of LNG entrapped in different kinds of liposome formulations via nasal administration in rats were evaluated and compared with LNG suspension via the oral route. The relative bioavailabilities of these liposome formulations via nasal administration were 100% or higher than 100%. The Cmax and Tmax values of sterylglucoside (SG) and chitosan-contained formulations by nasal administration were 416.84 ng/mL and 1.02 hr, 227.97 ng/mL and 2.02 hr, respectively, compared with that of 334.94 ng/mL and 1.89 hr of oral suspension. Fully 100% contraception was observed for all the formulations. SG could promote the absorption of LNG via the nasal route and may provide a rapid onset of action of LNG for emergency contraception. Chitosan could retain LNG in the nasal cavity for long contact time to sustain delivery of LNG. The rapid onset and sustained delivery of LNG can be achieved via the nasal route using liposomes as the vehicle.

Antiepileptic drugs that induce hepatic enzyme activity may alter the metabolism of most hormonal methods of contraception, and this affects the contraceptive regime. This effect should be considered in the choice of both the treatment of the epilepsy and the choice of contraceptive method. This review considers these interactions and offers advice about their management.

Background While the use of emergency contraception (EC) is becoming more widespread in Australia, little is known about the reasons for, and the social context of, this use. Methods In order to explore the use of EC from the perspective of users, a qualitative study was conducted with women presenting to one of three health care settings in Melbourne, Australia for EC. Results Thirty-two women ranging in age from 18 to 45 years were interviewed. While a number of themes were discussed with the women, this paper reports on four ‘types of users’ of EC identified from the data. ‘Controllers’ experienced failure of their contraceptive method and were very uncomfortable needing EC. They changed their contraceptive strategy in an attempt to avoid needing EC in the future. ‘Thwarted controllers’ were similar to controllers except that they could not improve their contraceptive strategy due to medical or social limitations. ‘Risk takers’ saw the use of EC as a component of their overall contraceptive strategy. They did not rely on EC regularly, but were comfortable to use it occasionally when the need arose. A final group of women were ‘caught short’ by a sexual experience that was unplanned and therefore they did not manage to use their chosen contraceptive strategy. Conclusions The findings from this study challenge the assumptions that are often made about the users of EC and highlight the need to acknowledge the different ways that women make sense of, and make decisions about, contraception.

BACKGROUND: In January 2001, emergency hormonal contraception was made available for women over the age of 16 years directly from a pharmacist without prescription. It is of interest whether this change in the UK has led to any improvements or deterioration in the service provided for the women who need it. METHODS: Self-completed, anonymous questionnaires were distributed to women requesting emergency hormonal contraception through a single group of pharmacies located throughout England, Wales and Scotland. RESULTS: A total 419 women returned completed questionnaires. A greater proportion of women were able to take emergency contraception within 24 h when they obtained their tablets directly from a pharmacy without a prescription (64% versus 46%, P = 0.029). Women who obtained their drugs directly from the pharmacist were just as well informed, just as likely to arrange regular follow-up and generally preferred this system, although they disliked having to pay. CONCLUSION: Making emergency hormonal contraception available without prescription has improved services to women who need them, but these improvements are quantitatively minimal, preventing only five additional pregnancies per 10 000 users.

The effect of aromatase inhibitors on the implantation process is not well known. This study examined the anti-implantation action in rats of a nonsteroidal aromatase inhibitor of high specific activity, fadrozole hydrochloride (Fad). Continuous subcutaneous infusion of Fad at 300 microg/day from Day 1 (the day of sperm detection) through Day 7 of pregnancy using a mini-osmotic pump was found to delay the initiation of implantation by 1 or 2 days with no negative effects on embryonic viability. The Fad treatment delayed preimplantation embryo development and zona shedding by embryos. The treatment also delayed the period of maximum sensitivity to a decidualizing stimulus (intraluminal infusion of sesame oil) by 2 days. The results show that continuous treatment with Fad has multiple anti-implantation effects in rats.

Objective To describe and evaluate the training and support provided to the first cohort of community pharmacists to supply progestogen-only emergency contraception (POEC) under a Patient Group Direction (PGD) in Lambeth, Southwark and Lewisham, London. Design The study comprised (a) a systematic analysis of written and oral data from pharmacists before and during training, and at 5 and 13-14 months after launch; (b) analysis of telephone calls to clinical support and (c) analysis of written pharmacy records. Subjects A total of 20/22 pharmacists in the first training cohort; 6/23 pharmacists who applied but were not accepted were also followed up. Results A formal course with role-play was a successful training method, and the course also served as a team-building exercise. Subsequent interviews demonstrated that pharmacists had understood the concept of client confidentiality and gained confidence over time in the use of the PGD. The on-call consultants received 152 calls in the first 12 months of the scheme. Over 80% of the calls concerned clinical criteria (notably including 22% that were queries about oral contraceptives). Frequency ranged from one to eight calls per week with 28% made at weekends. In over half (60%) of the calls the pharmacist was subsequently able to make a supply. Queries over client management resulted in several changes in the protocol. The primary expressed concern for all pharmacists at all time points was how clients might 9misuse9 or 9abuse9 the service, and this remained a concern despite the fact that it also applies to other routes of supply of POEC. However, the PGD cohort was more positive on local benefits than pharmacists who were not selected. Conclusions Training and support have enabled this often-underused group of professionals to participate in an extended reproductive health service. Mobile phones are an essential support tool.

Context Since January 2001, women aged over 16 years in the UK have been able to purchase progestogen-only emergency hormonal contraception from pharmacists without prescription. This paper outlines the context in which these changes took place, including contraceptive choices in the UK, changes within the pharmacy profession and political pressures. Observations We chart the multisectoral developments required to make emergency contraception (EC) available without prescription in the UK, from clinical research findings and results on the views and behaviour of health care professionals and users of EC, through to professional and policy developments, including challenges during and after this process. Discussion Lessons learnt from the innovative experience of the deregulation of EC in the UK apply to other regions currently considering similar change. We extrapolate internationally applicable lessons including the importance of stakeholder partnership, transparency and cautious pace of change, and the vital role of professional groups. Conclusion Although this change brought a new element of reproductive choice to some women, significant barriers to access to EC still remain for young women and women unable to afford the high price (£24/€37/$39) of pharmacy purchase in the UK.

The introduction of widespread nonprescription delivery of hormonal emergency contraception (EC) calls for development of innovative tools to provide information to and gather feedback from EC users. Individuals seeking confidential information on sexual health and contraception are increasingly turning to the Internet as the resource of choice. This study employed analytical software and manual content analysis to examine the use of a website dedicated to an EC product (www.norlevo.com) over the course of 2 years. Frequency of visits to and pageviews of the site increased consistently over the 2-year time period, and the bulk of the visitors to the site were EC users seeking responses to frequently asked questions. The most common concern raised by users was the occurrence of spotting and menstrual bleeding following EC use. This analysis reveals that within the context of nonprescription access to hormonal EC, a website can constitute a potent educational tool for health professionals and EC users and provide a valuable source of post-marketing feedback on product use.

Objective The purpose of this study was to provide evidence about the mechanism of action of the Yuzpe method of emergency contraception by examining effectiveness by cycle day of intercourse relative to ovulation. Methods Through a literature search, we identified eight studies that present the number of women treated and outcome of treatment by cycle day of unprotected intercourse relative to expected day of ovulation. Using five sets of external estimates of conception probabilities by cycle day of intercourse among women not using contraception, we assessed and compared the effectiveness of the Yuzpe regimen by whether intercourse occurred on or before the second day before ovulation or afterward, and whether intercourse occurred on or before the first day before ovulation or afterward. Results In 36 of the 45 pairs of estimates of effectiveness, based on eight separate studies and the eight studies combined and five different sets of conception probabilities by cycle day, effectiveness was higher—and in most cases substantially higher—when intercourse occurred on or before the second day before ovulation (day −2) than when it occurred later. When data were stratified by whether intercourse occurred on or before the day before ovulation (day −1), effectiveness was greater when intercourse occurred early in 43 of 45 pairs. Conclusions These results suggest that one hypothesized mechanism of action of the Yuzpe method, inhibiting implantation of a fertilized egg, is unlikely to be the primary mechanism of action.

In the 1960s, high-dose estrogen was identified as a highly effective emergency contraceptive but was associated with a high frequency of nausea and vomiting. The combination of low-dose estrogen and a progestin (the Yuzpe regimen) is highly effective and much better tolerated. Recently, a progestin-only regimen containing levonorgestrel was found to be more effective than the Yuzpe regimen and caused significantly less nausea and vomiting. Danazol, an antigonadotropin, is well tolerated but has questionable efficacy. Mifepristone has several pharmacologic actions that make it highly effective with an adverse-effect profile similar to that of the Yuzpe regimen. Progress has been made in the last 3 years toward increasing the number of emergency contraceptives that are accessible to women in the United States, and several highly effective options are available. The most effective and well-tolerated regimen available is levonorgestrel. However, the barriers to access and low patient and provider awareness limit the impact of emergency contraception on the rate of unintended pregnancies.

Objective To describe the provision of emergency contraception and confidentiality for the under 169s by general practitioners (GPs) in Avon, in order to inform the development of a health promotion intervention in schools in Avon. Design Confidential postal questionnaire survey. Setting All principals in general practice in Avon Health Authority, South West England. Subjects Five hundred and eighty general practice principals were sent the questionnaire. Results Four hundred and eighty-six (84%) principals in general practice responded to the questionnaire. Only three (0.6%) GPs did not provide hormonal emergency contraception. Nearly half (232, 47.7%) would fit the intrauterine device (IUD) as emergency contraception. Fitting an IUD was associated with female gender of the GP (OR = 2.34, 95% CI 1.53-3.71), and whether the GP had a family planning qualification (OR = 4.55, 95% CI 2.41-8.60). Three hundred and fifty-two (72%) respondents would provide emergency contraception on a Sunday if requested to do so by a 14-year-old who reported having had unprotected sex the night before. Practice nurses in 26 (5%) of the respondent9s practices were available to provide advice and tablets for patients requesting hormonal emergency contraception. However, 74 (21%) respondents employed a family planning trained practice nurse who was not involved in any way in the provision of emergency contraception. Practice nurses remain an under used resource in this area. Conclusion Our findings suggest that most GPs provide hormonal emergency contraception. Only eight (1.6%) of respondents would need to ask for parental consent prior to providing hormonal emergency contraception to a 14-year old-girl. Young people need to be informed of GPs widespread adherence to current confidentiality guidelines.

DL-Centchroman (67/20; INN: Ormeloxifene) synthesized at the Central Drug Research Institute, Lucknow, is a nonsteroidal once-a-week oral contraceptive. It was introduced in Delhi in July, 1991, marketed in India in 1992 as Saheli and Choice-7 (Hindustan Latex Ltd., Thiruvananthapuram) and Centron (Torrent Pharmaceuticals India Ltd., Ahmedabad), and included in the National Family Welfare Programme in 1995.5 According to post-marketing surveillance, approximately 100,000 women were using this pill and approximately 1100,000 menstrual cycles were covered until 1996. It is a unique need-oriented contraceptive being effective when taken immediately after coitus or routinely as a weekly pill and has the advantage of less frequent administration. Its contraceptive action is quickly reversible. It has long terminal serum halflife of 168 hr in women and exhibits duration of anti-implantation/estrogen antagonistic action of 120 hr, despite a short (24.1 hr) serum halflife, in the rat. In lactating women, it is excreted in milk in quantities considered unlikely to cause any deleterious effect on suckling babies. In phase II and III multicentric trials as a contraceptive, children born of method-and-user failure pregnancies showed normal milestones, without any congenital anomaly. Reports of its promising action in the management of certain hormone-related clinical disorders are available. It has an excellent therapeutic index and is considered safe for chronic administration.

The effectiveness of postcoital contraception can only be estimated. The most commonly used method of calculation compares the expected pregnancy rate in the exposed population to the resultant pregnancies after treatment. Estimation of the fertile period and the day of ovulation are critical to calculate the expected pregnancies. The aim of this study was to improve the accuracy of calculations by evaluating the hormonal status on the day of contraceptive treatment. A total of 483 consecutive women requesting postcoital contraception was included in a prospective observational trial. A blood sample was obtained at the moment of consultation to measure serum luteinizing hormone, estradiol, and progesterone concentrations. An ethinylestradiol-levonorgestrel combination (100 micrograms/500 mg for two doses, 12 h apart) was then prescribed. The fertile period was estimated according to previous hormonal studies in the normal cycling population. Of 483 women, 64 (13.25%) women were excluded because they presented irregular menstrual cycles and 37 (7.6%) women were lost to follow-up. Two pregnancies occurred in the remaining 382 women. Following Wilcox's and Trussell's methods, 21.1 and 17.75 pregnancies should be expected, yielding an overall treatment effectiveness of 90.52% (95% confidence interval [CI] 62.58%-97.6%) and 88.73% (95% CI 55.93%-97.12%), respectively. Hormonal data were available in 356 women; 303 of whom presented with regular cycles. Hormonal information in this group restricted the number of exposed cases to 88 women. Of the women included in Trussell's method of analysis, only 51 (51.5%; p0.05) were at risk using hormonal data. Fifty-six percent (95% CI 34.9%-75.6%) of women with luteinizing hormone levels20 IU/L were not between days-1 and +1 of the cycle. Hormonal studies suggest that methods based on pregnancy risk calculated by cycle day do not faithfully reflect the real exposure.

The purpose of this study was to provide new estimates of the effectiveness of the Yuzpe method of emergency contraception and to offer correctly computed estimates of the confidence intervals for estimated effectiveness rates. Through a literature search, seven studies that present the number of women treated and outcome of treatment by cycle day of unprotected intercourse relative to expected day of ovulation were identified. Probabilities of conception by cycle day of intercourse among women not using contraception and the associated variance-covariance matrix from five other datasets were estimated, and these external estimates were used to assess the effectiveness of the Yuzpe regimen. The 40 estimates of effectiveness, based on seven separate studies and the seven studies combined and five different sets of conception probabilities by cycle day, ranged from a low of 44.2% to a high of 88.7%. The preferred point estimate is that emergency contraceptive pills reduce the risk of pregnancy by 75.4%, with a 95% confidence interval extending from 65.6% to 82.4%. True effectiveness is likely to be at least 75% because treatment failures (observed pregnancies) include women who were already pregnant when treated and women who became pregnant after being treated.

Wide availability of hormonal postcoital contraception (HPC) is likely to reduce the incidence of unplanned pregnancies. The two most common indications for HPC are unprotected intercourse and 'condom accidents'. The combined estrogen/progestogen HPC described by Yuzpe is the most widely used method. It is given within 72 h of unprotected intercourse. The efficacy of combined HPC is high. The crude failure rate is 1-5 per 100 woman-months while the true reduction in pregnancy risk is over 75%. Efficacy is not influenced by the exposure-treatment interval within the 72-h 'window'. The mechanisms of action is multifocal and depends on the cycle phase at which treatment is instituted. Data are presented suggesting a consistent endometrial effect. None of the side-effects of HPC are serious. When HPC fails, there is so far no evidence of an adverse effect of the treatment on the outcome of pregnancy. Counselling should include all the above together with discussion of possible side-effects such as nausea and vomiting. The clinician should ensure that the woman uses an effective contraceptive thereafter. There is renewed interest in progestogen-only postcoital contraception. Varying doses of levonorgestrel have been used. The efficacy of some regimens is similar to that of the combined HPC. Danazol has not proved to be as effective. Antiprogestins hold the greatest promise of emergency contraception with high efficacy and low side-effects.

The objectives of the study were to assess the suitability of a service for provision of emergency hormonal contraception by nurses.Retrospective analysis was carried out of data obtained from the case records of 500 consecutive women who attended ABACUS (a city center-based family planning clinic in Liverpool, UK) for emergency contraception during the 7th and 9th months of the first year (1994) of the service. Similar data were collected for 100 consecutive women during 1 month of the third year (June 1996). The number of women who received emergency hormonal contraception was noted. In particular, details pertaining to the reasons for referral to the doctor and the trend of referrals were noted.The results indicate that during the first year the nurses independently issued emergency hormonal contraception to 37% of the women. They referred the remaining 63% to the medical staff. One-third of referrals were for ongoing contraception, especially oral contraception. Another third of referrals appeared to be due to 'nurse anxiety', as no medical or other cause was found for these referrals. During the third year, nurses dispensed emergency hormonal contraception to 64% of women. Among the remaining 36% of women who were referred to the doctor, 19% needed hormonal contraception. Referral reflecting 'nurse anxiety' significantly declined (1%) compared to the first year of service.Ongoing contraception, particularly initiation of oral contraception, was one of the main reasons for referral during the first year. Referral due to 'nurse anxiety' significantly declined with continued experience and may have reflected initial anxiety and the learning curve. With increased experience over the first 2 years, the outcome of this service showed encouraging improvement. The nurses now dispense emergency hormonal contraception to a majority of women.

Steroid hormones from the testes promote attraction to estrous females and facilitate copulation in the male Syrian hamster. We compared the ability of testosterone (T) and MENT, a potent synthetic androgen that does not undergo 5 alpha-reduction, to maintain sexual behavior in castrated males. Steroid treatment was initiated immediately after castration at three levels by means of Alzet osmotic pumps in sexually experienced adult male hamsters. Daily doses were 5, 25, or 100 micrograms T and 1, 5, or 25 micrograms MENT (n = 5/group). Additional castrated males (n = 5) remained untreated. Sexual behavior was recorded during two 10-min tests before, and at 2, 4, 6, and 8 weeks after orchidectomy. MENT and T maintained equivalent levels of behavior at each corresponding dose of androgen (high, medium, or low). The low dose of T or MENT failed to sustain mating behavior. Eight weeks after castration, males receiving the high and medium doses of androgens continued to express intromissions and ejaculations at gonadally intact levels. However, only males receiving the high dose showed anogenital investigation at the same level as intact males. From these data, we conclude that MENT sustains mating behavior in the male hamster, and that chemoinvestigatory behavior requires higher levels of androgens than those necessary for copulation.

To evaluate the effect of treatment with ethinylesteradiol-levonorgestrel or danazol on ovarian function, gonadotrophin release and endometrial development during the time when a pregnancy may occur following unprotected intercourse.Women with regular menstrual cycles were followed during one control, one treatment and one follow-up month. The women obtained either a combination of 0.5 mg levonorgestrel and 0.1 mg ethinylestradiol (Yuzpe regimen: n = 16) or 600 mg danazol orally and repeated after 12 hours (n = 16). The treatment was administered on either cycle day (cd) 12 or day LH +2. An endometrial biopsy was obtained once on cd LH +6 to +8 in the subjects treated on cd LH +2 both in control and treatment cycles, and morphometric analysis was performed. The concentrations of LH, pregnandiol (P2G), and estrone (EIG) glucuronide were followed daily in morning urine during control and treatment cycles.Following treatment with the Yuzpe regimen on cd 12 the LH surge was either undetectable (three subjects), postponed to cd 16 to 22 (three subjects) or cd 38 to 39 (two subjects) with lower P2G and LH levels than in the control cycle. Following preovulatory treatment with danazol, no LH peak could be detected in four subjects and in the remaining four subjects the LH peak varied between cd 13 and cd 24. The mean area under the curve for LH was significantly lower, the levels of EIG were slightly higher and the P2G levels were unaffected in comparison with the control cycle. Neither of the two treatments administered on cd LH +2 affected the hormonal pattern and only a discreet effect on the development of the endometrium was seen after the EE/LNG treatment.The findings indicate that the contraceptive effect of postcoital treatment with EE/LNG and danazol is mainly due to an inhibition or delay of ovulation and insufficient corpus luteum function. The direct effect on the endometrium is limited, if any.

Spotting following the use of emergency contraception is not unusual, nor is anxiety in women waiting to see if the treatment has worked. It is not known whether such spotting should bring worry or relief. We, therefore, wished to see if there was any correlation between bleeding pattern and treatment outcome. Using data from a large multicenter efficacy trial, we examined bleeding patterns post-emergency contraception. The earlier in the cycle the pills were taken, the more likely the next bleed was to be early and the less likely it was to be on time. There was no observable difference in spotting rates between women who got pregnant and those who did not. The occurrence of spotting did not influence whether the next period was lighter or heavier.

There are little or no data on the risk of ectopic pregnancy following levonorgestrel treatment as an emergency contraception. We encountered three cases of ectopic pregnancy following the use of levonorgestrel administered peri- or postovulation. Here we report these cases and discuss the clinical and epidemiologic implications of this association. Health providers should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking levonorgestrel.

Periodic abstinence and coitus interruptus are the most popular methods of contraception in Poland. Recent studies have provided us with evidence that the so-called "menstrual calendar" may be much less effective than it was believed. In these circumstances, promotion and use of safe and truly effective contraceptives is very important for Polish women. Emergency contraception (EC) is a method which could be used even in cases when other contraception methods have failed. Mechanism of action of levonorgestrel used for EC and possible disturbances in the process of implantation of the blastocyst in the endometrium, remain the source of heated discussion among medical professionals. The latest publications provide us with evidence that the use of levonorgestrel in EC neither alters endometrial receptivity nor impedes implantation. Hormonal EC effectiveness is another hot topic of gynecological endocrinology and statistics. There is, however, no better, safer, and more ethically accepted method of preventing unwanted pregnancy for patients in need of postcoital contraception.

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.

Summary Background Emergency contraception can prevent unintended pregnancies, but current methods are only effective if used as soon as possible after sexual intercourse and before ovulation. We compared the efficacy and safety of ulipristal acetate with levonorgestrel for emergency contraception. Methods Women with regular menstrual cycles who presented to a participating family planning clinic requesting emergency contraception within 5 days of unprotected sexual intercourse were eligible for enrolment in this randomised, multicentre, non-inferiority trial. 2221 women were randomly assigned to receive a single, supervised dose of 30 mg ulipristal acetate (n=1104) or 1·5 mg levonorgestrel (n=1117) orally. Allocation was by block randomisation stratified by centre and time from unprotected sexual intercourse to treatment, with allocation concealment by identical opaque boxes labelled with a unique treatment number. Participants were masked to treatment assignment whereas investigators were not. Follow-up was done 5–7 days after expected onset of next menses. The primary endpoint was pregnancy rate in women who received emergency contraception within 72 h of unprotected sexual intercourse, with a non-inferiority margin of 1% point difference between groups (limit of 1·6 for odds ratio). Analysis was done on the efficacy-evaluable population, which excluded women lost to follow-up, those aged over 35 years, women with unknown follow-up pregnancy status, and those who had re-enrolled in the study. Additionally, we undertook a meta-analysis of our trial and an earlier study to assess the efficacy of ulipristal acetate compared with levonorgestrel. This trial is registered with ClinicalTrials.gov, number NCT00551616. Findings In the efficacy-evaluable population, 1696 women received emergency contraception within 72 h of sexual intercourse (ulipristal acetate, n=844; levonorgestrel, n=852). There were 15 pregnancies in the ulipristal acetate group (1·8%, 95% CI 1·0–3·0) and 22 in the levonorgestrel group (2·6%, 1·7–3·9; odds ratio [OR] 0·68, 95% CI 0·35–1·31). In 203 women who received emergency contraception between 72 h and 120 h after sexual intercourse, there were three pregnancies, all of which were in the levonorgestrel group. The most frequent adverse event was headache (ulipristal acetate, 213 events [19·3%] in 1104 women; levonorgestrel, 211 events [18·9%] in 1117 women). Two serious adverse events were judged possibly related to use of emergency contraception; a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group. In the meta-analysis (0–72 h), there were 22 (1·4%) pregnancies in 1617 women in the ulipristal acetate group and 35 (2·2%) in 1625 women in the levonorgestrel group (OR 0·58, 0·33–0·99; p=0·046). Interpretation Ulipristal acetate provides women and health-care providers with an effective alternative for emergency contraception that can be used up to 5 days after unprotected sexual intercourse. Funding HRA Pharma.

OBJECTIVE:: To evaluate the efficacy and safety of ulipristal acetate as emergency contraception in women presenting 48-120 hours after receiving ulipristal acetate for unprotected intercourse. METHODS:: Women aged 18 years or older with regular cycles who presented for emergency contraception 48 to 120 hours after unprotected intercourse were enrolled in 45 Planned Parenthood clinics and treated with a single dose of 30 mg ulipristal acetate. Pregnancy status was determined by high-sensitivity urinary human chorionic gonadotropin testing and return of menses. RESULTS:: A total of 1241 women were evaluated for efficacy. Twenty-six were pregnant at follow-up for a pregnancy rate of 2.1% (95% confidence interval 1.4-3.1%). These results satisfy the protocol-defined statistical criteria for success because the pregnancy rate was lower than both the estimated expected pregnancy rate and a predefined clinical irrelevance threshold. In addition efficacy did not decrease over time: pregnancy rates were 2.3% (1.4-3.8%) 2.1% (1.0-4.1%) and 1.3% (0.1-4.8%) for intervals of 48 to 72 hours more than 72 to 96 hours and more than 96 to 120 hours respectively. Adverse events were mainly mild or moderate the most frequent being headache nausea and abdominal pain. Cycle length increased a mean of 2.8 days whereas the duration of menstrual bleeding did not change. CONCLUSION:: Ulipristal acetate is effective and well-tolerated for emergency contraception 48-120 hours after unprotected intercourse. LEVEL OF EVIDENCE:: II.

Based on the premise that testosterone, but not 7 alpha-methyl-androgens, is reduced at the 5 alpha-position in the prostate and seminal vesicles, the differential bioactivities of these androgens were investigated in castrated rats. The ability of 7 alpha-methyl-19-nortestosterone acetate (MENT) to increase the weights of ventral prostate and seminal vesicles of castrated rats was four times higher than that of testosterone, while its effect on the weights of bulbocavernosus plus levator ani muscles (muscle), was 10 times that of testosterone. MENT was also approximately 12 times more potent than testosterone in the suppression of serum gonadotropin levels. A dose of testosterone that maintains serum gonadotropin levels and muscle mass also maintains prostate and seminal vesicle weights in castrated rats. By contrast, a dose of MENT that maintains muscle and gonadotropins does not maintain prostate and seminal vesicles. The action of other 7 alpha-methylated androgens were similar to that of MENT. The importance of 5 alpha reductase in the differential action of testosterone and MENT on prostate was confirmed by using a 5 alpha-reductase inhibitor. The activity of testosterone was significantly suppressed in the ventral prostate and seminal vesicles but not on muscle by the 5 alpha-reductase inhibitor (N,N-diethyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide). The enzyme inhibitor, however, had no influence on the activity of MENT on either tissue. In contrast, cyproterone acetate, an antiandrogen that competitively binds to the androgen receptors, inhibited the action of MENT and of testosterone on the prostate as well as on the muscle. In conclusion, these observations show that 7 alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate. These findings suggest that 7 alpha-methylated androgens may offer some health benefits to men who require androgen treatment.

Contraceptive efficacy, cycle control and side effects of two types of 0.75 mg levonorgestrel tablets taken postcoitally during the periovulatory period of one cycle were studied in a multicenter trial involving 361 women. No significant differences were found between the two types of levonorgestrel pills in terms of contraceptive efficacy, cycle control and side effects. The failure rate observed (1.4% per treated cycle) was similar to that reported for other hormonal approaches to emergency postcoital contraception. Intermenstrual bleeding or spotting occurred in 11.5% of the cycles and anovulation as assessed from BBT charts in 14.4% of cycles. One or more side effects were reported by 22.2% of subjects. The relatively frequent occurrence of cycle disturbances and subjective side effects make it unlikely that the repeated postcoital use of levonorgestrel would be an acceptable routine method of contraception for most women.

Diethylstilboestrol is currently only available in Australia for oral use in dogs and cats. As an orally and systemically active non-steroidal oestrogen, DES has been widely used in small animal veterinary medicine for a variety of indications. A review of the literature reveals that many of the recommendations for use are founded on anecdotal or unreported clinical observations. While many of the uses may be valid, accurate determinations of optimum dosing regimens have not been defined. This is especially unfortunate in view of the potential toxicity of DES to small animals. Nevertheless, particularly in cases of low-dose intermittent administration, oral DES appears indicated at least until data on alternative safe and effective interventions become available.

Emergency postcoital contraception prevents pregnancy, but it must be prescribed by a doctor and taken within 72 hours of intercourse. It has been proposed that emergency contraception be made available without a prescription. We undertook a study to learn how women might behave if given a supply of emergency contraceptive pills to keep at home.We assigned 553 women to be given a replaceable supply of hormonal emergency contraceptive pills to take home (the treatment group) and 530 women to use emergency contraception obtained by visiting a doctor (the control group). The frequency of use of emergency contraception, the use of other contraceptives, and the incidence of unwanted pregnancy were determined in both groups of women one year later.The results for 549 women in the treatment group and 522 women in the control group were available for analysis. Three hundred seventy-nine of the women in the treatment group (69 percent) and 326 of the women in the control group (62 percent) contributed detailed information at follow-up. One hundred eighty of the women in the treatment group (47 percent) used emergency contraception at least once. Among those who returned the study questionnaire, 98 percent used emergency contraception correctly. There were no serious adverse effects. Eighty-seven women in the control group (27 percent) used emergency contraception at least once (P0.001 for the comparison with the treatment group). The women in the treatment group were not more likely to use emergency contraception repeatedly. Their use of other methods of contraception was no different from that of the women in the control group. There were 18 unintended pregnancies in the treatment group and 25 in the control group (relative risk, 0.7; 95 percent confidence interval, 0.4 to 1.2).Making emergency contraception more easily obtainable does no harm and may reduce the rate of unwanted pregnancies.The feasibility of providing women with a supply of emergency contraception to keep on hand in the event of unprotected intercourse was investigated in a comparative study involving 1071 women 16-44 years of age recruited from a family planning clinic and hospital in Edinburgh, Scotland, in 1994-96. 549 women (treatment group) were given a replaceable supply of hormonal emergency contraceptive pills to take home and 522 women (controls) were counseled about the method and instructed to call their physician if it was needed. Emergency contraception was used on a total of 387 occasions during the 4-month study period (248 times by women in the treatment group and 139 times by controls). The women in the treatment group were significantly more likely to use emergency contraception on only one occasion during the study period than those in the control group (36% vs. 14%, p 0.001), but not more likely to use it more than once (12% vs. 13%). Use of other fertility control methods did not differ between study groups. There were 18 unintended pregnancies in the treatment group and 25 in the control group (relative risk, 0.7; 95% confidence interval, 0.4-1.2). 79% of women in the treatment group and 61% of controls believed emergency contraception should be available without a prescription. Support for this strategy was highest among women with a history of an induced abortion prior to study entry. These findings suggest that making emergency contraception more available has the potential to reduce the rate of unintended pregnancies.

Background: The purpose of this study was to determine whether East Asian women had more side effects and a higher discontinuation rate than Caucasian women when choosing to use hormonal contraceptives. Study Design: This was an observational cohort study of usual care using questionnaires for 2 months after being given hormonal contraceptives following an abortion in Vancouver, Canada. Results: In the first month, 73 (64.4%) of the 110 East Asian and 86 (80.4%) of the 107 Caucasian women took any of the sample provided (p=.020). In the second month, 52 (47.3%) of the East Asian and 62 (57%) of the Caucasian women used the prescription to buy and take their hormonal contraception (p=.12). Total side effects were similar, but there was more nausea in the East Asian women (23.3% vs. 8.1%) (p=.03) and more acne in the Caucasian women (8.2% vs. 20.9%) (p=.05). Conclusions: There may be both physiological and cultural differences leading East Asian women to use less hormonal contraception.

Emergency contraception is indicated when no birth control is used or in case of contraception failure. To day, two methods of emergency contraception are available. The hormonal method consists in taking a tablet of levonorgestrel 1.5 mg (NorLevo), as soon as possible following the contraceptive failure since its efficiency decreases rapidly as time goes by. No contraindication is associated with this contraceptive; however, it cannot be used as a regular contraception method since it is not 100% efficient (from 95.5 to 89% according to the authors). Apparently, this contraceptive acts by delaying ovulation. Mechanical contraceptives, such as intra-uterine devices, are extremely efficient (99.5%) and can be used up to 5 days after the estimated ovulation date. However, surveys conducted by the Inserm have revealed that in France, women are not aware of or lack of knowledge about emergency contraception and have many misconceptions. Moreover, many of them do not use emergency contraception since they do not feel concerned by the risk of pregnancy following contraception failure.

A synthetic androgen 7alpha-Methyl-19-nortestosterone (MENT) has a potential for therapeutic use in 'androgen replacement therapy' for hypogonadal men or as a hormonal male-contraceptive in normal men. Its tissue distribution, excretion and metabolic enzyme(s) have not been reported. Therefore, the present study tested the distribution and excretion of MENT in Sprague-Dawley rats castrated 24h prior to the injection of tritium-labeled MENT ((3)H-MENT). Rats were euthanized at different time intervals after dosing, and the amount of radioactivity in various tissues/organs was measured following combustion in a Packard oxidizer. The radioactivity (% injected dose) was highest in the duodenal contents in the first 30min of injection. Specific uptake of the steroid was observed in target tissues such as ventral prostate and seminal vesicles at 6h, while in other tissues radioactivity equilibrated with blood. Liver and duodenum maintained high radioactivity throughout, as these organs were actively involved in the metabolism and excretion of most drugs. The excretion of (3)H-MENT was investigated after subcutaneous injection of (3)H-MENT into male rats housed in metabolic cages. Urine and feces were collected at different time intervals (up to 72h) following injection. Results showed that the radioactivity was excreted via feces and urine in equal amounts by 30h. Aiming to identify enzyme(s) involved in the MENT metabolism, we performed in vitro metabolism of (3)H-MENT using rat and human liver microsomes, cytosol and recombinant cytochrome P(450) (CYP) isozymes. The metabolites were separated by thin-layer chromatography (TLC). Three putative metabolites (in accordance with the report of Agarwal and Monder [Agarwal AK, Monder C. In vitro metabolism of 7alpha-methyl-19-nortestosterone by rat liver, prostate, and epididymis. Endocrinology 1988;123:2187-93]), [i] 3-hydroxylated MENT by both rat and human liver cytosol; [ii] 16alpha-hydroxylated MENT (a polar metabolite) by both rat and human hepatic microsomes; and [iii] 7alpha-methyl-19-norandrostenedione (a non-polar metabolite) by human hepatic microsomes, were obtained. By employing chemical inhibitors and specific anti-CYP antibodies, (3)H-MENT was found to be metabolized specifically by rat CYP 2C11 and 3-hydroxysteroid dehydrogenase (3-HSD) enzymes whereas in humans it was accomplished by CYP 3A4, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and 3-HSD enzymes.

Unintended and teenage pregnancies are major public health concerns in the United States. Emergency contraception is used to prevent pregnancy after failure of a contraceptive method or after unprotected intercourse. Expanded use of emergency contraception has the potential to reduce unintended pregnancy and induced abortions, while reducing state and federal healthcare expenditures. The recent approval of Plan B as an over-the-counter medication for individuals over 18 years of age should improve access to this medication. However, there are still widespread misconceptions about the mechanisms and implications of emergency contraception. Expanded access to emergency contraception is associated with increased use, but not associated with decreased efficacy, increased sexual risk-taking behavior, or less consistent use of traditional birth control methods. This review is designed to provide clinicians with information regarding the use of emergency contraception for reproductive age patients. It includes a brief description of methods of use, mechanisms of action, and side effect profiles of the most commonly used methods of emergency contraception, levonorgestrel and the Yuzpe method.

Emergency contraception has the potential to greatly reduce the number of unintended pregnancies occurring each year in the United States. Emergency contraception is a safe and effective intervention to which all women should have easy access in the event of an act of unprotected intercourse. Methods of emergency contraception include combined hormone oral contraceptive pills, progestin-only oral contraceptive pills, a dedicated progestin-only emergency contraceptive product, and insertion of a copper intrauterine device. Barriers exist to the increased use of emergency contraception, including the prescription-only status of all of the methods and lack of accurate knowledge on the part of health care providers and consumers. This article provides an overview of the clinical management of emergency contraception.

To elicit women’s preferences for routes of supply for emergency hormonal contraception (EHC). The objectives were to identify which attributes of services women regard as important and to identify how women trade off reductions in one attribute for an improvement in another. A stated preference discrete choice experiment. Women attending sexual health services in a Primary Care Trust in the North West of England were invited to complete a self-completion questionnaire. Each respondent completed a questionnaire containing nine pair-wise choices. Demographic data were also collected. Conditional logit models were used to analyse the data. Women’s preferences for, and trade-offs between, the attributes of opening hours, medical staff seen, cost of EHC, length of wait for an appointment, privacy of consultation and attitude of staff. Two hundred and sixty-nine women attending clinics (mean age 23.8 years, SD±8.69) completed the questionnaire. Almost two thirds of the sample had previously used EHC. All six attributes of EHC services were statistically significant factors influencing women’s preferences for the supply of EHC. A significant proportion of women indicated on at least one occasion that they would risk pregnancy rather than choose one of the services offered to them. These results suggest that the way in which a service is configured and presented to women is likely to influence which service is chosen. In this study, women prioritised visiting a service where they would be treated in a sympathetic and non-judgemental manner. They also prioritised privacy. The results also suggest that if women are dissatisfied with aspects of an EHC service, they may choose not to visit it, thereby risking an unwanted pregnancy.

AIMS: To evaluate differences in the time taken to access progestogen-only emergency hormonal contraception (EHC) by young women from family planning (FP) or community pharmacy settings. METHODS: An observational study of 203 women requesting EHC from FP clinics and community pharmacies in South-west Kent Primary Care Trust (PCT) from December 2002 to October 2003. RESULTS: Access to EHC from community pharmacy was significantly faster than from FP clinics (16 h vs. 41 h, P

The aim of this study was to profile the users of emergency contraception (EC) attending general practices and a general practice out-of-hours co-operative service using a pre-piloted questionnaire. Questionnaires were offered to 171 women and completed by 144 (84.2%). Mean age was 24.4 years (Standard Deviation = 6.7, range 14 to 51). Most were single, 116 (80.6%). Those who had no regular partner at the time of seeking EC were more likely to haveor =6 lifetime sexual partners than those in stable relationships (OR: 3.5; CI: 1.14-10.86, p0.03). At the time of seeking EC 121 (84.0%) were using some method of contraception. Ninety-three (64.6%) presented within 24 hours of sexual intercourse. Concerns about condoms were the commonest reason for seeking EC. For 55 (38.2%) this was their first time to use EC. Thirty-three (22.9%) were drunk at the time of intercourse.