Oral contraception and its possible protection against rheumatoid arthritis.
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A significantly higher prevalence of a protective concentration of anti-HBs was achieved at 1 and 2 months among 132 healthy medical students who received an accelerated vaccination schedule with a recombinant hepatitis B vaccine (Engerix-B) than among 120 medical students who received a conventional regimen. With the accelerated schedule, however, 60% students at 1 month and 27% at 2 months were still unprotected (anti-HBs titre less than 10.0 IU/l). Additional passive immunisation should therefore continue to be offered if the accelerated schedule is adopted for post-exposure prophylaxis.
OBJECTIVE: To evaluate the safety and contraceptive efficacy of magainin-A in monkeys. DESIGN: Controlled laboratory study. SETTING: Department of Immunology, National Institute for Research in Reproductive Health, Parel, Mumbai, India. ANIMAL(S): Male and female bonnet monkeys (Macaca radiata). INTERVENTION(S): Animals were treated intravaginally with 1 mg of magainin-A before attempted conception, as well as daily for 14 days to assess local and systemic toxicity. MAIN OUTCOME MEASURE(S): Suitability of magainin-A for the control of pregnancy and sexually transmitted infections. RESULT(S): Complete sperm immobilization was observed within 20 seconds after the exposure to magainin-A (800-1,000 microg) in vitro. Intravaginal administration of 1 mg of magainin-A blocked conception in monkeys. When magainin-A was administered intravaginally for 14 consecutive days, no treatment-related abnormalities were observed in menstrual cycle length, vaginal epithelial cell morphology, and hematologic/serum biochemical profiles. The peptide inhibited the growth of sexually transmitted infection-causing pathogens but not HIV-1 and HIV-2. CONCLUSION(S): Magainin-A can be used as an effective and safe intravaginal contraceptive compound with additional protection against sexually transmitted infection-causing pathogens.
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OBJECTIVES: The objective of the study is to evaluate the effects of levonorgestrel transferred through breast milk on thyroid stimulating hormone (TSH) and luteinizing hormone (LH) levels in full breast-fed infants. METHODS: Forty healthy postpartum women and their male newborns were recruited for the study. Women were randomly allocated to two study groups: Group 1, IUD users and group 2, Norplant users. Blood and milk samples were collected on the day of IUD or Norplant insertion and 3 and 6 months later for TSH and levonorgestrel measurements. RESULTS: The results disclosed a significant decrease in TSH levels, and a negative relationship between LNG levels and TSH concentration in breast feeding infants at 3 months after implant insertion. The lowest TSH levels were observed at 6 months in the women from group 2. CONCLUSIONS: The overall data indicate that the LNG levels transferred to fully breast-fed infants through breast milk from Norplant users significantly modified their TSH levels.
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Leukocytes are critical mediators of endometrial remodeling, but the mechanisms by which leukocyte subpopulations enter the uterus are currently unknown. Endometrial leukocytes have no genomic progesterone receptors; thus, we hypothesized that leukocyte migration is induced indirectly by progesterone-regulated chemokines. Fractalkine (CX3CL1), a chemotactic membrane-bound adhesion factor, and its receptor (CX3CR1) were assessed by immunohistochemistry in endometrial samples across the menstrual cycle, in early pregnancy, and in women using progestin-only contraceptives. Fractalkine was localized predominantly to glandular epithelial and decidualized stromal cells, with the highest staining intensity in the secretory phase and early pregnancy. It was also detected in subpopulations of endometrial leukocytes (macrophages and uterine NK cells), with maximal numbers during the proliferative phase and early pregnancy. CX3CR1 was similarly colocalized to the glandular epithelium and decidualized stromal cells, with the highest expression in the secretory phase. CX3CR1-positive leukocytes (macrophages and neutrophils) were in greatest abundance during the menstrual phase. In the endometrium of women using progestin-only contraceptives, immunoreactive fractalkine was markedly reduced in the glandular epithelium, but was increased in decidualized stroma and infiltrating leukocytes. These findings support a number of roles for fractalkine in the endometrium, in the secretory phase, in early pregnancy, and when influenced by progestin-only contraceptives.
Silicones have an adverse effect on human health well beyond that suggested by the recent superficial public controversy. The evidence for immune responses to injected/implanted silicones is extensive, detailed, often very specific, and not at all new. Comprehending the immunopathogenicity, realized and potential, of silicone has grown as our general understanding of the immune system has developed. Several major issues in furthering this comprehension pertain to the nature of the essential epitope, special risk of silicones to women, and definition of the chronic disease complex so evident clinically, one defying classification within currently traditional disease categories and states. The commentary presented here emphasizes the immunopathic evidence, explores the question of the essential epitope, estimates the minimal threshold of silicone load for immune reactivity, presents a profile of autoantibodies for siliconosis, and calls attention to specific silicone-based female contraceptive modalities. The silicone content of personal care products, not always revealed by retail package labeling, is explored as a potential sensitizing factor in the environment.
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It has become more and more urgent to develop a safe, effective, recoverable and acceptable contraceptive for males. Decades of studies have made much progress on male hormonal contraception, one of the promising contraceptive methods. The principle is based on the suppression of pituitary gonadotropin and intratesticular testosterone, then the suppression of spermatogenesis, and the supplement of androgen to maintain the male characteristics and sexual function. There are many male hormonal contraceptive methods being studied include androgen, androgen combined with progesterone, GnRH antagonists combined with androgen, as well as immunological methods. To develop a safe and convenient androgen preparation with longer action and fewer side effects is also one of the key items of present research in this field.
The effect of sexual behavior on the risk for cervical dysplasia was evaluated in a case-control study. Cases (n = 257) had a histologically confirmed diagnosis of cervical dysplasia. Controls (n = 705) were sampled from the general population. A postal questionnaire was used to obtain information about, among other things, age at first sexual intercourse, number of sexual partners, current frequency of intercourse and contraceptive use. Information was also collected about other risk factors for cervical dysplasia, in order to adjust for possible confounding. We observed higher risks for cervical dysplasia (mild, moderate and severe) with increasing number of sexual partners. This effect appeared to be dependent on smoking behaviour. For women who reported more than six sexual partners, the adjusted odds ratio (aOR) was 9.1 (95% CI: 3.5-23.7) for non-smokers, and 26.4 (95% CI: 11.8-58.8) for women who smoked > or = 20 cigarettes per day. The effects of age at first sexual intercourse and current frequency of intercourse disappeared after adjustment for other risk factors. Use of oral contraceptives for > 10 years increased the risk (aOR = 2.3; 95% CI: 1.2-4.6). Thus, the number of sexual partners, especially in combination with smoking behaviour, appeared to be the most important risk factor for cervical dysplasia.
A method for the radioimmunoassay of ethynylestradiol in plasma is described. The sensitivity is 18 pg/ml, recovery 86.5%, and precision 10.9% (coefficient of variation). Normal women, five at each dose level, were given 50 or 80 mug ethynylestradiol or 50, 80, or 100 mug mestranol of uniform bioavailability. Peak plasma levels were consistently obtained in the 1-hour plasma sample with the former compound. With mestranol, the peak levels of ethynylestradiol were lower than with the same quantity of ethynylestradiol and the time-curve of plasma levels much more variable. With this procedure, it is now possible to study certain aspects of the pharmacokinetics of these clinically important compounds.
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The serum concentrations of 3-keto-desogestrel have been measured in 43 women who took a low-dose oral contraceptive containing 30 micrograms ethinyl estradiol (CAS 57-63-6) together with 150 micrograms desogestrel (CAS 54024-22-5) for a period of 3 months. Basic pharmacokinetic parameters, like Cmax, tmax and AUC, as well as the serum protein binding of 3-keto-desogestrel were determined on days 1, 10 and 21 of the first and the third treatment cycle, respectively. During cycle one, Cmax, AUC(0-4h) and AUC(0-24h) values on day 1 were 1.9 +/- 0.7 ng/ml, 3.9 +/- 1.3 ng.ml-1.h and 12.4 +/- 5.7 ng.ml-1.h, respectively. These values increased to 4.7 +/- 2.0 ng/ml, 12.1 +/- 5.6 ng.ml-1.h and 47.3 +/- 26.0 ng.ml-1.h on day 21. Within cycle 3, a similar, although less steep increase was observed for these parameters and there was practically no difference in the values of corresponding parameters on day 21 of both cycles. Throughout treatment, there was a redistribution of 3-keto-desogestrel with respect to the binding proteins albumin and sex hormone binding globulin (SHBG). During cycle 1, the free fraction decreased from 1.8% on day 1 to 1.1% on day 21, and the SHBG-bound fraction increased at the same time from 40% to 62%, mainly at the expense of the albumin-bound fraction. During cycle 3, there were only minor changes as compared to cycle one. The observed changes in the serum protein binding were related to an increase in SHBG levels during the treatment period.
Several reports indicate an association between oral contraceptives and increased infection rates. One mechanism that could explain this increased infection rate is a decrease in immune function. A study comparing T cell subsets showed no differences in numbers between oral contraceptive users and controls. In this study, natural killer cell activity was compared in women before and 3 and 6 months after oral contraceptive use. There was a statistically significant decrease in NK cell activity after three months. There was no further decrease by six months and the differences were no longer significant due to greater variability. No infections were reported during the study period. Thus, the observed reduction in NK activity was either physiologically insignificant or the previously reported increase in infections may be the result of non-immunological factors.
Five functional assays and two immunoassays for protein C (PC) were evaluated in parallel for the same plasma samples collected from healthy subjects, patients with congenital and acquired PC deficiencies or patients with conditions associated with high PC levels. For 7 patients starting warfarin therapy and for 15 patients during stabilized warfarin therapy, there were significant between-assay differences. For these groups immunoassays gave higher values than most functional assays and the latter also gave varied results, probably depending on their respective capacity for recognizing a carboxylated PC. On the other hand, there were no significant between-assay differences nor discrepancies between PC activity and antigen levels for healthy subjects (n = 39), patients with congenital PC deficiency (n = 10), myocardial infarction (n = 25), chronic liver disease (n = 19), disseminated intravascular coagulation (n = 35), in the post-operative period (n = 20) or in women taking oral contraceptives (n = 20). This comparison of PC assays indicates that PC levels measured by different functional or immunological assays are very close in the majority of clinical conditions, but not for patients on oral anticoagulants.