Massive acute pulmonary embolism. The deceivingly nonspecific manifestations.
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Acute Disease↗
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Clinical diagnosis and management of the patient with deep venous thromboembolism and acute pulmonary embolism.
Pulmonary embolism is the third most common acute cause of death in the United States. There are approximately 500,000 cases annually in this country, leading to death in 50,000. Subjective symptoms and objective findings can oftentimes be confusing and nonspecific. A pulmonary embolism is defined as an occlusion of one or more pulmonary vessels by material that has traveled there from outside of the lung and is usually caused by a dislodged thrombus that originated in the deep veins of the legs or pelvis. Risk factors include older age, prior thromboembolism, immobility, cancer, chronic disease, congestive heart failure, pelvic and lower extremity surgery, varicosities, obesity, and oral contraception. This article will discuss current modalities that are used in the evaluation of deep venous thromboembolism and pulmonary embolism and include ventilation/perfusion scan, ultrasonography, impedance plethysmography, pulmonary angiography, and newer tests including D-dimer assays and spiral computed tomography. Medical management including simple and complex decision making, anticoagulation, and thrombolytic therapy will also be discussed. An ounce of prevention is worth a pound of gold--identification of risk factors and the use of appropriate therapeutic measures can reduce an individual's risk for deep venous thromboembolism and pulmonary embolism.
Anticoagulants↗
Measuring contraceptive effectiveness: a conceptual framework.
We present a conceptual model that outlines the four measures of how well a contraceptive method works: 1) efficacy, 2) effectiveness, 3) perfect-use pregnancy rate, and 4) typical-use pregnancy rate. Moreover, we illustrate how four variables influence these measures: 1) capacity to conceive, 2) frequency and timing of intercourse, 3) degree of compliance, and 4) inherent protection of the method. Because of inter-individual as well as intra-individual variability of the first three variables, generalizing results from a contraceptive clinical trial to other populations is problematic. There is a hierarchy of generalizability of the four outcome measures, with the typical-use pregnancy rate the least generalizable but the easiest to measure, and efficacy the most generalizable but the most difficult to measure. These four variables should be considered in the design and analysis of future contraceptive clinical trials. Finally, this article illustrates why the terms "pregnancy rate" and "failure rate" are not synonymous and why we recommend that the latter term not be used.
Clinical Trials as Topic↗
[Contraception using an intrauterine device inserted 1 month after delivery].
The authors report their experience of mechanical contraception using an intra-uterine device placed one month after delivery. The fact that perforation did not occur and there were no serious infectious complications, as well as that the method was well tolerated, that there was only 4.7% per year expulsions, and few failures (Pearl 2.96% per year) shows that this is a worth-while contraceptive method to recommend to women who have just delivered.
Adult↗
Case studies in wildlife immunocontraception: wild and feral equids and white-tailed deer.
Non-lethal management methods are required for wild equids that are protected by law and for deer inhabiting areas where lethal controls are not legal or safe. Single or multiple inoculations of porcine zona pellucida (PZP) vaccine have been delivered to wild horses and deer by means of darts. Contraceptive efficacy in horses after two inoculations ranged from 90% to 100%, and after a single inoculation ranged from 19% to 28%. Mares given a controlled-release form of the vaccine had foaling rates ranging from 7% to 20%. No detectable changes in social organization or behaviours among treated horses occurred. Contraceptive effects were reversible after 4 consecutive years of treatment but 5-7 years of treatment resulted in ovulation failure and decreased urinary oestrogen concentrations. Among deer, two inoculations were 70-100% effective in preventing fawns, but one inoculation yielded a contraceptive efficacy of < or = 20%, with pregnancies occurring late in the breeding season; a single annual booster inoculation reduced fertility to 20% in the second year. Energy costs of extended breeding seasons were less than those resulting from pregnancy. After two years of treatment, ovaries appeared normal. These studies suggest that PZP immunocontraception can be successfully applied to certain free-roaming populations of wild horses and deer.
Animals↗
A multicenter efficacy and safety study of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol.
The study reported herein is the primary efficacy and safety study conducted to support U.S. registration of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol. A large multicenter study enrolled 1,221 women at 50 centers in the United Kingdom. A total of 11,656 cycles of exposure was accumulated, corresponding to approximately 879 women-years of use. Contraceptive efficacy was high; no subject conceived as a result of method failure. The product was generally well tolerated with excellent cycle control, causing fewer than 2% of the subjects to discontinue because of bleeding irregularities. The study medication demonstrated no adverse effects on cervical cytology, blood pressure, body weight or laboratory variables, while pre-existing benign breast disease generally improved. The study did not identify any medication-related adverse experiences. This study confirmed that the monophasic oral contraceptive with 150 micrograms desogestrel and 30 micrograms ethinylestradiol is a safe and effective oral contraceptive with excellent cycle control and patient acceptability.
Adolescent↗
Efficacy and side effects of immediate postcoital levonorgestrel used repeatedly for contraception. United Nations Development Programme/ United Nations Population Fund/World Health Organization/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Post-Ovulatory Methods of Fertility Regulation. vonhertzenh@who.ch.
We evaluated the efficacy and side effects of immediate postcoital administration of levonorgestrel 0.75 mg used repeatedly for contraception. A total of 295 healthy women with infrequent coitus were enrolled at 6 study sites. Each woman took levonorgestrel 0.75 mg by mouth immediately after intercourse during 6 months as her only method of contraception. We collected data on side effects and acceptability and calculated the Pearl index failure rates over 133 woman-years of use by standard methods. The Pearl index failure rate was 6.8 (95% CI 3.1-12.9) pregnancies per 100 woman-years of use. The overall probability of pregnancy per treated coital act was 1.4 per 1000. Approximately one-third of participants discontinued the study within 6 months (mainly for bleeding problems). Menstrual complaints were reported by 70% of women. Other complaints included (in decreasing order) nausea, breast tenderness, weakness, dizziness, headache, abdominal bloating, loss of libido, depression, and vomiting. High-dose levonorgestrel pills are unsuitable for regular postcoital contraception.
Adult↗
Contraception for the insulin-dependent diabetic woman: the view from one clinic.
Experience in a large diabetic clinic has confirmed the suspicion that insulin-dependent diabetic women are at considerably increased risk of thromboembolic disease if they take combined estrogen/progestogen oral contraceptive preparations. The most obvious alternative, an intrauterine device, is associated with an unexpectedly high failure rate, probably because of an unusual metabolic interaction with the diabetic endometrium. In a small group of diabetic women the progestogen-only pill was found to be a successful form of contraception not associated with any side effects except for menstrual irregularities. For most diabetic women the choice of contraceptive should therefore be between a progestogen-only pill and a mechanical method. Female sterilization and injectable progesterone each have their place in particular circumstances. Careful counseling of each patient is essential to ensure the best choice of contraceptive and correct application of the chosen method.
Adult↗
Current assessment of the use of intrauterine devices.
The need for effective, long-term contraception remains a significant issue. Intrauterine devices (IUDs) have evolved to the point where currently available devices are comparable, in safety and efficacy, to oral contraceptives. Due to concerns regarding previous devices, available IUDs remain largely underused by midwives and all other providers of reproductive health care. Recent medical data refute many of the medical-legal misconceptions. Currently available IUDs are safe and effective and represent a suitable contraceptive alternative for the appropriate patient.
Copper↗
Spermicides 2002: an overview.
The first-ever written prescription for a contraceptive (barrier method) tampon can be found in the Ebers Papyrus, a compendium of medical practices written in 1550 BC. Modern spermicides are produced in a variety of formulations, including gels, foams, creams, suppositories, pessaries, capsules, foaming tablets and films. Spermicides are relatively inexpensive and widely available over the counter. Most of the currently used spermicides contain the chemical agent (non-ionic detergent) nonoxynol-9. The spermicide 'as a commonly used method' has a very high failure rate (one pregnancy in every four women using this method of contraception for 1 year). Implementation of other, much more effective methods of contraception has made spermicides less and less popular, but recently their potential properties against HIV and STI pathogens (a cause of sexually transmitted diseases) have led to new attention for these products. These properties have been widely evaluated in clinical trials, but the final conclusion does not favor spermicides as the tool for the global fight against HIV/AIDS. There is an urgent need for the invention of a chemical product that, for dual protection, would be administered vaginally before sexual intercourse to kill HIV and other STI pathogens, and at the same time disable or kill sperm. The new era for barrier methods should begin from the development of novel microbicides.
Contraception↗
Evaluation of fusogenic trophoblast surface epitopes as targets for immune contraception.
Syncytial trophoblast fusion is an essential step in the process of implantation. This project is aimed at the immunological inhibition of syncytial trophoblast fusion as a novel approach to contraception. Fusion-inhibiting recombinant antibodies were generated and used together with autoantibodies from patients with repetitive in vitro fertilization (IVF) failure that were shown to inhibit syncytial fusion and are expected to inhibit implantation, to generate anti-idiotypic peptides. These peptides mimic trophoblast epitopes essential for syncytial fusion and are, therefore, considered specific immunogens for the generation of antibodies that will inhibit implantation. To verify their physiological role in humans, 300 anti-idiotypic peptides were tested for their binding capacity to patient autoantibodies associated with repetitive IVF failure, habitual abortion and preeclampsia. Of these, only three peptides were found to selectively bind to autoantibodies of patients with repetitive IVF failure and were considered safe and efficient enough for evaluation in preclinical and clinical studies required for the development of immune contraceptives. When used as immunogens, these peptides are expected to elicit an antibody response inhibiting syncytial fusion and thus implantation. Furthermore, the action of these antibodies needs to be restricted to the stage of syncytium formation at the time of implantation so as not to cause complications of pregnancy in those cases where they fail to have a contraceptive effect. To exclude potential side effects on other systems, toxicological experiments in animals are in progress.
Amino Acid Sequence↗
Optimizing therapy of seizures in women who use oral contraceptives.
There is no evidence that oral contraceptives (OCs) increase seizure activity, and OC use in the setting of antiepileptic drug (AED) treatment provides pregnancy prevention at among the highest rates of any available contraceptive method. One concern, however, is the increased risk for OC failure with the use of cytochrome P450 3A4 enzyme-inducing AEDs, such as phenobarbital, carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine. Felbamate induces metabolism of only the progestogenic component, whereas topiramate induces metabolism of only the estrogenic component. There is preliminary evidence that lamotrigine induces the metabolism of a progestin, levonorgestrel. It is unclear whether the estrogenic or the progestogenic component is more clinically important in preventing pregnancy. To ensure maximal pregnancy prevention, it is therefore recommended that women taking enzyme-inducing AEDs should receive OCs containing at least 50 mug of ethinyl estradiol and that low-dose formulations in general should not be used. AEDs that do not induce cytochrome P450 3A4 enzymes, including valproic acid, gabapentin, levetiracetam, tiagabine, vigabatrin, zonisamide, and pregabalin, do not interact with OCs. There are no concerns regarding the treatment of seizures or increased pregnancy risk with the use of OCs and these non-enzyme-inducing AEDs. Lamotrigine levels, however, are reduced by 50% in the setting of OC use. Therefore, women with epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs are started and for toxicity when OCs are discontinued. Dose adjustment to maintain clinical stability may be necessary in these settings. The placebo or pill-free week of the OC regimen may also be a period when clinical toxicity can occur. Even with the considerations discussed in this review, OCs are a reasonable contraceptive option for women with epilepsy taking AEDs.
Anticonvulsants↗
[Prevalence and prognostic significance of major risk factors and some reproductive system changes in the development of atherosclerosis and ischemic heart disease in women of child-bearing age].
AIM: To conduct a long-term epidemiological trial to specify prevalence and significance of risk factors (RF) of atherosclerosis (AS) and IHD related and unrelated with reproductive system in fertile women. MATERIAL AND METHODS: 962 premenopausal women entered the trial. They were examined for RF of IHD and AS as well as some conditions of the reproductive system induced by oral contraceptives, replacement hormonal therapy, postmorbid period of OPH-gestosis, uterine myoma, ovarian failure. Plasma lipids were also measured. RESULTS: Most prevalent risk factors contributing to development of IHD and AS were the following: obesity (21.2%), arterial hypertension (10.3%), uterine myoma (5.61%), ovarian hypofunction including castration (4.78%), diabetes mellitus + low glucose tolerance (3.95%), gestosis in the past without residual hypertension (1.25%), smoking (1.87%), hypercholesterolemia (1.14%), inheritance (1.14%), hormonal contraception (0.98%). CONCLUSION: Between the incidence of AS and IHD and duration of the conditions studied a functional relation exists due to disorders of lipid metabolism and high arterial pressure.
Adult↗
Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives.
Fragile X premutations are known to be a risk factor for diminished ovarian function at a relatively young age. We studied endocrine profiles of female fragile X family members (n = 79) at risk of premature ovarian failure (POF). Of these 79 women aged <40 years, 45 had menstrual cycles, and 34 were using oral contraceptives. Of the women with menstrual cycles, the premutation carriers had higher serum FSH concentrations than women who were not carrying the premutation. Even premutation carriers with regular cycles showed increased serum FSH concentrations. Moreover, premutation carriers using oral contraceptives also demonstrated increased serum FSH concentrations. Irrespective of whether oral contraceptives were used, a serum FSH concentration of > or =15 IU/l was more common in the premutation carriers than in the other women. One premutation carrier using oral contraceptives had a serum FSH concentration of >40 IU/l, the threshold that defines POF. We confirmed that premutation carriers with menstrual cycles demonstrate premature ovarian dysfunction. However, we also found endocrine signs of unrecognized ovarian dysfunction in premutation carriers using oral contraceptives, despite endocrine alterations by oral contraceptives. Premutation carriers may have a poorer prognosis for future pregnancy, either achieved spontaneously or by assisted reproductive technology. We recommend that premutation carriers should be counselled not to wait too long if they wish to start a family.
Adult↗
Successful pregnancy in a woman with acute myeloid leukemia treated with high-dose whole-body irradiation.
BACKGROUND: Although radiotherapy is an integral part of managing certain types of hematologic malignancies, its effect on the reproductive system are well established. We report a case of successful pregnancy in a patient who received high-dose whole-body irradiation (WBI) (1,575 cGy) as part of her treatment for acute myeloid leukemia (AML). CASE: A 26-year-old woman received high-dose cyclophosphamide accompanied by high-dose (1,575 cGy) WBI as part of her treatment for AML when she was 23 years of age. The patient received oral contraceptives before, during and after treatment. After WBI, the patient developed ovarian failure and amenorrhea, which was confirmed by hormonal evaluation. The amenorrhea persisted for one year. No recurrence of AML was found. The patient was placed on hormone replacement therapy (HRT) because of vasomotor changes. An unexpected pregnancy occurred 14 months later; HRT was discontinued. The patient delivered a normal female infant at 38 weeks of gestation. The infant was followed for eight months; her development appeared to be normal. CONCLUSION: In this case report, it is unclear whether pregnancy resulted from active folliculogenesis remote from radiation therapy or from possible ovarian protection rendered by the use of oral contraceptives. The benefit of oral contraceptives in protecting the ovary from radiation injury is unknown and remains an area for future research.
Adult↗
Double-blind, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day versus a 21-day low-dose oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene.
This prospective, double-blind, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day versus a 21-day oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene. Participants took trial medication daily for 28 days, either 23 tablets with active substances plus 5 placebo tablets or 21 tablets with active substances plus 7 placebo tablets. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 4,878 treatment cycles (23-day regimen: 2,362 cycles; 21-day regimen: 2,516 cycles) were obtained from 703 participants (23-day regimen, n = 342; 21-day regimen, n = 361). Both preparations proved to be effective contraceptives and provided good cycle control. One pregnancy because of method failure was recorded in each treatment group. This resulted in a study Pearl Index of 0.5 for each treatment. For the 23-day regimen, 36.0% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 37.1% in the 21-day regimen. In the 23-day regimen group, intracyclic bleeding episodes were reported by 42.4% of the participants in Cycle 1 but only in 14% in Cycle 7 and in the 21-day regimen group by 44.6% in Cycle 1 and only 17.3% in Cycle 7. Overall, intracyclic bleeding was reported in 21.9% of the 23-day regimen cycles and in 22.7% of the 21-day regimen cycles.A greater number of 23-day regimen participants had shorter withdrawal bleeding periods than with the 21-day regimen. In significantly (p <0.0001) more cycles in the 23-day regimen group, participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day regimen group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day regimen group was 4 days and in the 21-day regimen group 5 days. Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was low (23-day regimen, 6%; 21-day regimen, 4%). No serious vascular adverse events were reported. More than 75% of the women in both groups either lost more than 2 kg of weight or did not gain weight during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study.
Contraceptives, Oral↗
Current practice of family planning in China.
Current practice of family planning in China is based on the population policy and strategy of the country. Comprehensive contraceptive methods are provided in family planning clinics at all levels. Among the methods used, intrauterine devices and tubal sterilization are most popular. Vasectomy is popular in some provinces. Oral pills, injectables and subdermal implants occupy a small proportion. Incidence of abortion is high due to failure of methods and unprotected intercourse. Attention is paid to the adoption of emergency contraception to prevent unwanted pregnancy. Improvement in quality of care is the key to a successful family planning program. Basic research is essential for development of new contraceptive technology.
China↗
Premature ovarian failure.
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Autoimmune Diseases↗