"Tabela Periódica" da Anticoncepção ­ uma ferramenta na escolha contraceptiva / "Periodic Table" of Contraception ­ a tool in the contraceptive choice

Estima-se que 40% das gestações no mundo sejam não planejadas. Em países de baixa renda, complicações no parto são a maior causa de morte entre mulheres de 15 a 19 anos. A disponibilidade de métodos contraceptivos reversíveis é necessária para o adequado planejamento reprodutivo. Entre os métodos reversíveis, os de longa ação (LARCs) são os mais efetivos. Métodos de curta ação (SARCs) são preferenciais para pacientes que desejam gestar a curto prazo e para as quais a gestação não será indesejada. O presente estudo é uma revisão narrativa da literatura, de artigos em inglês e português publicados entre 2009 e 2020, utilizando as bases de dados SciELO, Medline e Embase. O objetivo desta revisão é apresentar os LARCs e SARCs em uma tabela com dados comparativos que auxiliem na tomada de decisão do médico e da paciente e permita estabelecer estratégias para um planejamento familiar adequado.(AU)

It is estimated that 40% of pregnancies in the world are unplanned. In low-income countries, complications in childbirth are the major cause of death among women aged 15 to 19 years. The availability of reversible contraceptive methods is necessary for proper reproductive planning. Among the reversible methods, long-acting reversible contraception (LARCs) is the most effective. Short-acting reversible contraception (SARCs) methods are preferred for patients who wish to become pregnant in the short term and for whom pregnancy will not be undesirable. The present study is a narrative review of the literature, of articles in English and Portuguese published between 2009 and 2020, using the databases SciELO, Medline and Embase. The purpose of this review is to present the LARCs and SARCs in a table with comparative data that assist in the decision making of the doctor and the patient and allow to establish strategies for adequate family planning.(AU)

Management of isoniazid-monoresistant tuberculosis (Hr-TB) in Queensland, Australia: a retrospective case series.

OBJECTIVES: Drug-resistance represents a major threat in the fight against tuberculosis. Globally, isoniazid-monoresistant tuberculosis (Hr-TB) is twice as common as multidrug/rifampicin-resistant (MDR/RR)-TB. Recently updated WHO guidelines now recommend treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide and levofloxacin for at least six months. Our primary objective was to define the frequency, treatment and outcomes for Hr-TB in Queensland, Australia. We also sought to determine the frequency of fluoroquinolone use and whether its inclusion improved outcomes. METHODS: Retrospective case series of tuberculosis notifications in Queensland between 2000 and 2017 with at least low-level isoniazid resistance and preserved susceptibility to other first-line oral agents. RESULTS: Hr-TB was identified in 7.2% of all notifications. Where outcomes were assessable (163/198), 76.1% were treated with first-line agents only and 11.0% received at least six months of a fluoroquinolone-containing regimen (consistent with recent WHO guidelines). Favourable outcomes were achieved in 95.7%, comparable to fully susceptible disease (94.9%). Inclusion of a fluoroquinolone did not significantly improve outcomes compared with a regimen containing first-line agents only, although these cases were more likely to have high-level resistance. Previous treatment made an unfavourable outcome more likely. CONCLUSIONS: Hr-TB is prevalent in Queensland. Treatment outcomes in our cohort were comparable to fully susceptible disease. The current WHO-recommended regimen did not confer advantage over an appropriately constructed regimen containing first-line agents only. Our findings suggest that, in a well-resourced setting with good programmatic management, the addition of a fluoroquinolone may not substantially improve outcomes - potentially allowing these agents to be reserved for more extensively resistant disease.

Comparative randomized study on the sexual function and quality of life of women on contraceptive vaginal ring containing ethinylestradiol/etonogestrel 3.47/11.00mg or 2.7/11.7mg.

The objective of the study was to evaluate the sexual function and quality of life (QoL) of healthy women on a new contraceptive vaginal ring (CVR) containing ethinylestradiol (EE) 3.47 mg and etonogestrel (ENG) 11.00 mg (study group) manufactured with a new polymer composition compared to EE 2.7 mg/ENG11.7 mg CVR (control group). Fifty-eight women were randomly allocated to the study group and the control group. The Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS) and the Short Form-36, were used to assess sexual function, sexual distress and QoL, respectively. The study included two follow-ups, at 90 days and at 180 days. The control group reported more adverse events, mainly breakthrough bleeding, than the study group. The sexual function scores in the women in the study group improved with respect to those of the control group both at the 1st (FSFI, p = .009; FSDS, p = .001) and at the 2nd (FSFI, p = .001; FSDS, p = .002) follow-up. QoL of the study group improved at the 1st follow-up (p < .05) and 2nd (p < .01) follow-up. The control group improved their QoL at the 2nd follow-up (p < .01). The more gradual EE release of the new polymer composition could justify the behavioral differences of the women of the two groups.

Activation of cardiac renin-angiotensin system and plasminogen activator inhibitor-1 gene expressions in oral contraceptive-induced cardiometabolic disorder.

CONTEXT: Clinical studies have shown that combined oral contraceptive (COC) use is associated with cardiometabolic disturbances. Elevated renin-angiotensin system (RAS) and plasminogen activator inhibitor-1 (PAI-1) have also been implicated in the development of cardiometabolic events. OBJECTIVE: To determine the effect of COC treatment on cardiac RAS and PAI-1 gene expressions, and whether the effect is circulating aldosterone or corticosterone dependent. METHODS: Female rats were treated (p.o.) with olive oil (vehicle) or COC (1.0 µg ethinylestradiol and 10.0 µg norgestrel) daily for six weeks. RESULTS: COC treatment led to increases in blood pressure, HOMA-IR, Ace1 mRNA, Atr1 mRNA, Pai1 mRNA, cardiac PAI-1, plasma PAI-1, C-reactive protein, uric acid, insulin and corticosterone. COC treatment also led to dyslipidemia, decreased glucose tolerance and plasma 17ß-estradiol. CONCLUSION: These results demonstrates that hypertension and insulin resistance induced by COC is associated with increased cardiac RAS and PAI-1 gene expression, which is likely to be through corticosterone-dependent but not aldosterone-dependent mechanism.

Combined oral contraceptive-induced hypertension is accompanied by endothelial dysfunction and upregulated intrarenal angiotensin II type 1 receptor gene expression.

Combined oral contraceptive (COC) use is associated with increased risk of developing hypertension. Activation of the intrarenal renin-angiotensin system (RAS) and endothelial dysfunction play an important role in the development of hypertension. We tested the hypothesis that COC causes hypertension that is associated with endothelial dysfunction and upregulation of intrarenal angiotensin-converting enzyme 1 (Ace1) and angiotensin II type 1 receptor (At1r). Female Sprague-Dawley rats aged 12 weeks received (p.o.) olive oil (control) and a combination of 0.1 µg ethinylestradiol and 1.0 µg norgestrel (low COC) or 1.0 µg ethinylestradiol and 10.0 µg norgestrel (high COC) daily for 6 weeks. Blood pressure was recorded by tail cuff plethysmography. Expression of genes in kidney cortex was determined by quantitative real-time polymerase chain reaction. COC treatment led to increased blood pressure, circulating uric acid, C-reactive protein and plasminogen activator inhibitor-1, renal uric acid, and expression of renal Ace1 and At1r. COC treatment resulted in increased contractile responses to phenylephrine in endothelium-denuded aortic rings. Endothelium-dependent relaxation responses to acetylcholine, but not endothelium-independent relaxation responses to nitric oxide (NO) donation by sodium nitroprusside, were attenuated in COC-exposed rings. Impaired relaxation responses to acetylcholine were masked by the presence of NO synthase inhibitor (L-NAME) in the COC-exposed rings, whereas the responses to acetylcholine in the presence of selective cyclooxygenase-2 inhibitor (NS-398) were enhanced. These findings indicate that COC induces hypertension that is accompanied by endothelial dysfunction, upregulated intrarenal Ace1 and At1r expression, and elevated proinflammatory biomarkers.

Thrombotic microangiopathy caused by oral contraceptives in a kidney transplant recipient.

Thrombotic microangiopathy (TMA) after kidney transplantation has various aetiologies, including acute antibody-mediated rejection, bacterial or viral infection and immunosuppressive drugs, particularly calcineurin inhibitors. We present the case of a 28-year-old woman who developed TMA 30 months after the transplantation of an ABO-incompatible kidney from a living unrelated donor. The patient developed a sudden onset of allograft renal dysfunction and became uremic. She was transferred to our institution from a community hospital with strongly suspected acute allograft rejection. Intensive treatments for both T- and B-cell mediated acute rejection, including steroid pulse therapy, double-filtration plasmapheresis, antithymocyte globulin (1.5 mg/kg × 14 days) and rituximab (100 mg), were initiated during haemodialysis. However, her renal allograft function did not improve. Histopathological analysis 8 days after the treatment indicated TMA, despite the absence of apparent acute T-cell- or acute antibody-mediated rejection. There were no symptoms of infectious diseases, such as intestinal haemorrhagic colitis or viral infection. We concluded that the use of oral contraceptives, which had been initiated 3 weeks before TMA onset for the treatment of irregular vaginal bleeding, was the aetiologic agent.

Randomized Controlled Trials for the Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease. Several treatment modalities are available, but most of them lack high-quality evidence. A systematic search was performed to identify all randomized controlled trials for the treatment of HS in order to review and evaluate the evidence. Recommendations for future randomized controlled trials include using validated scores, inclusion of patient rated outcomes, and thorough report of side effects. Evidence for long-term treatment and benefit/risk ratio of available treatment modalities is needed in order to enhance evidence-based treatment in daily clinical practice. Combining surgery with antiinflammatory treatment warrants further investigation.

Effect of obesity on the effectiveness of hormonal contraceptives: an individual participant data meta-analysis.

OBJECTIVE: The objective of this investigation was to assess the potential effect of obesity on the effectiveness of hormonal contraceptives (HCs). STUDY DESIGN: A meta-analysis was conducted using individual participant data directly from the Phase 3 clinical trials of combination oral contraceptives (COCs) rather than extracting summary data from literature. Trials selected were reviewed by the US Food and Drug Administration (FDA) between 2000 and 2012, conducted in North America, had more than six 28-day cycle equivalents of exposure, and had readily retrievable participant-level data. Contraceptive effectiveness was measured by the Pearl Index (PI: the number of pregnancies per 100 woman-years) in women aged 18-35 at risk of unintended pregnancy. The incidence rate ratio (IRR), a ratio of PIs for obese women (defined as body mass index [BMI] ≥30 kg/m(2)) compared to non-obese women (BMI <30 kg/m(2)) was calculated. A Cox proportional-hazard regression model with fixed and random-effects were used to estimate hazard ratios (HRs) for unintended pregnancy in obese women compared to non-obese women. RESULTS: Seven clinical trials with COCs (N=14,024: 2707 obese and 11,317 non-obese women) met the inclusion criteria for the meta-analysis. The PI for each trial varied: 2.05-5.08 for obese and 1.84-3.80 for non-obese women. The pooled PI estimated using direct weighted average method was 3.14 (95% CI: 2.33-4.22) for obese and 2.53 (95% CI: 1.88-3.41) for non-obese women. The pooled IRRs estimated using direct weighted average and Mantel-Haenszel adjustment methods were comparable: 1.37 (95% CI: 1.02-1.84) and 1.43 (95% CI: 1.07-1.92), respectively. The overall HR of 1.44 (95% CI: 1.06-1.95; p=.018) in the meta-analysis suggested a 44% higher pregnancy rate during COC use for obese women after adjusting for age and race. IMPLICATIONS STATEMENT: Obesity may increase the risk of unintended pregnancy in women using COCs; more data on obese women from ongoing and future Phase 3 clinical trials are necessary to allow further evaluation of this topic. CONCLUSIONS: Results of this meta-analysis suggest that obese women may have a higher pregnancy rate during COC use compared to non-obese women. Future analysis should assess differences in pharmacodynamics or compliance that could potentially account for the observed difference in unintended pregnancy rates.

Influence of thermally oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum cholesterol and triglycerides in young pigs.

To evaluate the effect of feeding thermally oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum fatty acid and cholesterol concentration in young pigs, 102 barrows (6.67 ± 0.03 kg BW) were divided into 3 groups and randomly assigned to dietary treatments in a 4 × 3 factorial arrangement. The main factors were lipid source (n = 4; corn oil [CN], canola oil [CA], poultry fat [PF], and tallow [TL]) and lipid peroxidation level (n = 3; original lipids [OL], slow oxidation [SO] through heating at 95°C for 72 h, or rapid oxidation [RO] through heating at 185°C for 7 h). Pigs were provided ad libitum access to diets in group pens for 28 d followed by controlled feed intake in metabolism crates for 10 d. On d 39, all pigs were euthanized for liver samples to determine liver weight, lipid profile, and gene expression patterns. Lipid oxidation analysis indicated that compared with the OL, SO and RO of lipids had a markedly increased concentrations of primary and secondary peroxidation products, and the increased lipid peroxidation products in CN and CA were greater than those in PF and TL. After a 28-d ad libitum feeding period, pigs fed RO lipids tended to have reduced ADFI (P = 0.09) and ADG (P < 0.05) compared with pigs fed OL, and pigs fed CA had reduced G:F (P < 0.05) compared with pigs fed all other lipids. Pigs fed RO lipids tended to have increased relative liver weight (P = 0.09) compared with pigs fed OL. Liver triglyceride concentration (LTG) in pigs fed OL was greater (P < 0.05) than in pigs fed SO lipids and tended to be greater (P < 0.07) than in pigs fed SO. The reduced LTG were consistent with increased (P < 0.05) mRNA expression of PPARα factor target genes (acyl-CoA oxidase, carnitine palmitoyltransferase 1, and mitochondrial 3-hydroxy-3-methylglutary-CoA synthase) in pigs fed SO and RO lipids compared with pigs fed OL. Pigs fed CN or CA tended to have increased LTG (P = 0.09) compared with pigs fed TL. Liver cholesterol concentration in pigs fed CN was less (P < 0.05) than in pigs fed PF and tended to be less (P = 0.06) than in pigs fed TL, whereas pigs fed CA had a reduced (P < 0.05) liver cholesterol compared with pigs fed PF or TL. In conclusion, feeding thermally oxidized lipids negatively affected growth performance and LTG of young pigs, which was associated with an upregulation of fatty acid catabolism pathways.

Immunomodulatory effects by oral contraceptives in normal and cholestatic female rats: role of cytokines.

Oral contraceptives (OC) may cause intrahepatic cholestasis or increase a pre-established liver damage. OC effects on hepatic injury biochemical markers remain contradictory and the role of cytokines in those processes is fairly unknown. Two doses, simple or double, of the OC combination ethinylestradiol/norgestrel were administered during 14 or 28 days to normal and cholestatic female rats. Liver damage markers and the cytokines tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) were determined in plasma and liver. OC caused ambiguous results on cholestasis indicators, even more in cholestatic rats. Necrosis rose during cholestasis while OC lowered it in normal rats. Fibrosis was induced by cholestasis but OC double dose or intake time diminished that. Cholestasis depleted glycogen while OC did not alter it. Double dose or time of administration of OC significantly elevated the lipid peroxidation. Cholestasis modified plasma and liver cytokines but OC remarkably altered them in normal and cholestatic animals. TNF-α as well as IL-10 were increased in both tissues by OC, such rise was higher in normal rats. TGF-ß was augmented by OC and more in cholestatic rats receiving double dose. Thus, OC modified most liver injury markers in normal rats although more pronouncedly in cholestatic ones, as well as increased hepatic oxidative stress. Liver fibrosis was decreased and corroborated by histological analysis even when TGF-ß is elevated by OC. OC strongly immunomodulate cytokines that mediate liver damage or worsen a prior hepatopathy; those processes are influenced by dose, administration time and OC formulation.

A comparison of the pharmacokinetic profile of an ascending-dose, extended-regimen combined oral contraceptive to those of other extended regimens.

Quartette (levonorgestrel [LNG]/ethinyl estradiol [EE] and EE) is an ascending-dose, extended-regimen combined oral contraceptive (COC) that consists of a constant dose of LNG 150 µg on days 1 to 84 with EE 20 µg on days 1 to 42, 25 µg on days 43 to 63, 30 µg on days 64 to 84, and 10 µg of EE monotherapy on days 85 to 91. A population pharmacokinetic (PK) model for EE was developed using nonlinear mixed-effects modeling to characterize the PK profile of EE administered in Quartette and other extended-regimen LNG/EE COCs. Model-predicted plasma concentration-time profiles demonstrated a stepwise increase in systemic exposure to EE during the first 84 days of the cycle following each EE dose change. Lower concentrations of EE were noted during the final 7-day period of EE 10 µg. Gradual increases in EE seen with Quartette may decrease the incidence of unscheduled bleeding frequently observed during early cycles of extended-regimen COCs.

Mood and physical symptoms improve in women with severe cyclical changes by taking an oral contraceptive containing 250-mcg norgestimate and 35-mcg ethinyl estradiol.

BACKGROUND: The purpose of this study was to investigate how women without and with different severity of premenstrual symptoms react to treatment with a combined oral contraceptive containing 250-mcg norgestimate/35-mcg ethinyl estradiol (EE). Focus was placed on mood and physical symptoms. STUDY DESIGN: This open, prospective study evaluated 24 women using norgestimate/EE for three cycles in a 21/7 regimen. Symptoms and bleeding pattern were captured by daily ratings on the Cyclicity Diagnoser scale. RESULTS: Women with severe premenstrual mood symptoms improved in summarized negative mood (p<.001) and summarized positive mood (p<.05), as well as in swelling (p<.05) and effect on daily life (p<.05). Women with no or mild or moderate symptoms did not show any significant improvement or deterioration in any symptom after 3 months of treatment. CONCLUSIONS: Norgestimate 250 mcg/EE 35 mcg significantly improved premenstrual summarized negative mood symptoms during 3 treatment months compared to pretreatment in women with severe premenstrual symptoms, together with improvement in positive symptoms, swelling and effect on daily life.

The effect of oral contraceptives on orthodontic tooth movement in rat.

INTRODUCTION: The purpose of this study was to investigate the effect of ethinyl estradiol/norgestrel - used in some oral contraceptives- on orthodontic tooth movement in Wistar rats. MATERIAL AND METHODS: Forty eight female three-month old Wistar rats with an average weight of 250 ± 25 gr were divided into two experimental and control groups. One week prior to appliance insertion and during the appliance therapy period, 100 mcg/kg/day of ethinyl estradiol and 1 mg/kg/days of norgestrel were administered to the experimental group by gavage; meanwhile the control group received an equivalent volume of Sodium Chloride 0.9 % (Saline). Maxillary central incisors were tipped distally by insertion of springs exerting 30 g force. Two, seven and fourteen days after spring insertion animals were sacrificed. The mesioincisal distance between maxillary incisors were measured. Subsequently, histological sections were prepared for histomorphometric studies. RESULTS: 14 days after force application the orthodontic tooth movement was significantly lower in the experimental group (p<0.05). The number of osteoclasts were significantly lower in the experimental group 2, 7 and 14 days after spring insertion (p<0.05). CONCLUSION: Ethinyl estradiol/norgestrel (oral contraceptives) can significantly decrease the amount of tooth movement in the linear phase.

Effects of chronic treatment with cyclooxygenase inhibitor, indomethacin on oral contraceptive-induced high blood pressure in female rats.

The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OC-induced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.

Comparative biochemical studies on steroidogenic compounds in chickens.

Comparative studies of the effects of Nordette and Lutofolone on 15 days old chicken were carried out to determine their effects on growth performance, biochemical parameters and an analysis of hormonal residues in the liver and muscle. Sixty chickens were equally divided into three groups. Group 1 was served as a control. Groups 2 and 3 were treated daily with Nordette (1 mg/kg B.W.) mixed in the ration and Lutofolone (0.5 mg/kg B.W.) orally via a bent stainless steel feeding tube, respectively, for 30 days (from the 15th till the 45th day old). Then these treated groups were left for another 15 days without any treatment. Blood samples were collected at 45 and 60 days old and used for biochemical studies, while liver and muscles were excised from each chicken and used to prepare tissue homogenate for estimation of hormonal residues (estrogen and progesterone). Both drugs caused a gain in body weight. They also increased several serum variables, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, creatine kinase (CK), creatinine and uric acid, and reduced total proteins, albumin and globulin levels at 30 days post-administration. Moreover, this study exhibited a significant increase in the levels of estrogen residues in the liver and muscle. Estrogen level was much higher in the liver than muscles. However, some of these findings were insignificant changed at 15 days post-stopping of the hormones. Data on the biochemical parameters and residue levels obtained from these results clearly indicate that anabolic agents may entail a special risk to the chickens and probably to the consumer.

Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients.

PURPOSE: To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle. MATERIALS AND METHODS: Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support. RESULTS: There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group. CONCLUSION: Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.

Mechanisms of action of hormonal emergency contraceptives.

Hormonal emergency contraceptives have been used to prevent unwanted pregnancy for more than 3 decades. The mechanisms of action of the regimen containing a combination of estrogen and progestin, known as the Yuzpe regimen, and those of the levonorgestrel regimen continue to be controversial, especially over the possibility that these regimens might act by interfering with implantation of the fertilized ovum. We performed a search of the PubMed (1949-July 2009) and EMBASE (1980-July 2009) databases to identify literature on the mechanisms of action of these contraceptive regimens, and data were extracted from pertinent English-language studies. We classified studies according to the approach taken by the investigators to study the actions of emergency contraceptives on pregnancy: an indirect method that uses statistical models to determine whether emergency contraceptives would be as effective as reported if they act only by disrupting ovulation; direct observation of the effects of emergency contraceptives on surrogate outcomes, including ovulation, sperm activity, hormonal levels, and endometrial receptivity to implantation; and analysis of directly observed pregnancy outcomes against statistical data. Acceptability of emergency contraceptives by women and clinicians may depend on personal opinions about when life or pregnancy begins. The evidence strongly supports disruption of ovulation as a mechanism of action. The data suggest that emergency contraceptives are unlikely to act by interfering with implantation, although the possibility has not been completely excluded. The data also suggest that emergency contraceptives are ineffective after ovulation. Women and clinicians who consider implantation or later events to be the beginning of pregnancy should be aware that emergency contraceptives are likely nonabortive by this definition of pregnancy.