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Contraceptive choices in women with coagulation disorders.

When compared with older reports on the thromboembolic effects of high-dose oral contraceptives, new studies with low-dose oral contraceptives have a significantly reduced risk of thromboembolism. In the absence of risk factors such as smoking or inherited disorders predisposing to thrombosis, the modern low-dose oral contraceptive (< 50 micrograms of estrogen) is a safe and effective choice for contraception in women without symptoms who have family histories of sporadic thromboembolism. An intrauterine device or some form of barrier method is recommended for women who have a personal history of venous thrombus disease. The low-dose oral contraceptive may be a good choice in women taking oral anticoagulants because of the risk of teratogenic effects of anticoagulants and the risks of intraperitoneal bleeding associated with ovulation. In addition, oral contraceptives help diminish the excessive menstrual bleeding often seen in these women.

Blood Coagulation Disorders↗

Thromboembolic disease developing during oral contraceptive therapy in young females with antiphospholipid antibodies.

The role of oral contraceptives as a triggering factor for thrombosis in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA) has not yet been established. We describe the cases of three women aged 19, 29 and 48 years who developed venous thrombosis after 16 +/- 3.4 (mean +/- SD) cycles of oral contraceptives. They were all asymptomatic before taking the pill. Two patients subsequently developed venous and/or arterial recurrence of thrombosis. Laboratory studies performed after the diagnosis of thrombosis, showed the presence of LA and elevated levels of ACA (IgG and IgM) in all three patients. None of these patients had autoimmune diseases and therefore appeared to have a primary antiphospholipid antibody syndrome. The three patients belonged to a group of 45 young females who experienced their first thrombotic event while taking the pill. This group had a similar prevalence (8%) for antithrombin deficiency and antiphospholipid antibodies. We surmise that some of the women who developed venous thrombosis while taking the pill might have an undetected primary antiphospholipid syndrome.

Adult↗

The impact of oral contraception on chlamydial infection among patients with pelvic inflammatory disease.

The prevalence of oral contraceptive use in association with chlamydial pelvic inflammatory disease (PID) and the presence of anti-chlamydial IgG and IgA in a population of 144 hospitalized and outpatient subjects with a standard diagnosis of PID was studied. The rates of chlamydial PID and IgA detection were 15.3% (22/144) and 13.9% (20/144), respectively. After stratification for age, number of pregnancies, and lifetime sexual partners, the rates of chlamydial PID (odds ratio = 0.30, 95% CI = 0.10 - 0.89) and IgA detection (odds ratio = 0.23, 95% CI = 0.07 - 0.73) were lower among previous or current oral contraceptive users than in women who had never used birth control methods. Analyses of linear trend indicated a negative association between increasing duration of exposure to hormonal contraception and anti-chlamydial IgG and IgA. This study confirms that among patients with chlamydial PID, the frequency of oral contraceptive use is lower than that in patients with PID of other etiology. Serologic studies suggest a possible relationship between hormonal contraception and changes in immune response or susceptibility to chlamydial infection.

Adolescent↗

Fungal vulvovaginitis.

Fungal vulvovaginitis remains one of the most frequent conditions affecting the lower genital tract. Recent advances in the understanding of the pathophysiology of the condition have improved our ability to treat recurrent or persistent cases. More clinical data have become available on the optimal duration of treatment with some of the newer antifungal agents.

Antifungal Agents↗

Modification of functional serum antithrombin III assay for fibrometer. Results of examination of 50 patients.

The functional antithrombin III assay of von Kaulla is described and modified for the fibrometer with substitution of readily available Owren's buffer for previously described buffers. The assay is compared with immunological techniques on 50 hospital patients and comparable discrimination of normals and patients with thrombotic disease are shown. Normal values are 51.1+/-13.9 secs. Results in patients with thrombotic diseases are 16.7+/-1.8 secs.

Antithrombins↗

Variation in natural killer activity in peripheral blood during the menstrual cycle.

Natural killer activity was measured sequentially in normal female volunteers through their menstrual cycle. During the periovulatory period there was a significant fall in natural killer activity compared with in normal male volunteers. This variation was not apparent in women taking oral contraception. Cytotoxic activity was not related to oestradiol concentrations in individual women. The data support an interaction between immunological activity and sex hormones over the normal physiological range and would account for the described reduction in natural killer activity in pooled blood from female blood donors.

Adult↗

Ethinylestradiol and diethylstilbestrol induced antibodies and vascular thrombosis.

Antiethinylestradiol antibodies were demonstrated in several oral contraceptive users. The antibodies could be precipitated from serum immune complexes by 25% saturated ammonium sulfate. This test of serum precipitation was applied to a comparative study of 116 women on O.C and 65 men treated with diethylstilbestrol for a prostatic cancer. Controls without hormones were included in each group. The test was shown to discriminate among the estrogen users reactive and unreactive persons. 34% of women and 41% of men had high levels of precipitated immunoglobulins in 25% saturated ammonium sulphate. Study of the specificity of the Igs purified from the precipitates in reactive cases, showed that they were binding ethinylestradiol with an affinity constant consistent with an antigen antibody reaction. It is concluded that the oral ingestion of two different synthetic estrogen compounds may induce antiestrogen antibodies. The relation of these antibodies with the increased incidence of vascular thrombosis is considered.

Adolescent↗

An epidemiological study of the haemostatic and other effects of oral contraceptives.

Factors V, VII and VIII (each determined by biological assay), fibrinogen, platelet count and adhesiveness, and fibrinolytic activity were measured in 234 white pre-menopausal women, of whom 57 (24%) were on oral contraceptives and 177 (76%) were not. Cholesterol, triglyceride and blood pressure levels were also recorded. In 20 of the women on oral contraceptives, and in an age-matched group of 20 who were not, prothrombin, factor X, antithrombin III and alpha 2-macroglobulin levels were determined, and factors VII and VIII were also measured immunologically. For the majority of the variables studied, the differences between those using and not using oral contraceptives were greater in younger than older women; in the case of factor VII (biological assay) and fibrinogen, the differences between the regression slopes on age were statistically significant, and mean values were substantially higher in those on oral contraceptives. There was also a significant difference between regression slopes on age for cholesterol. Mean levels of prothrombin, factors VII (immunological assay) and X, triglycerides and blood pressure were significantly higher, and mean levels of antithrombin III significantly lower, in those on oral contraceptives compared with those not. Overall, fibrinolytic activity was significantly higher in the women on oral contraceptives; this difference was, however, almost entirely due to the greatly increased fibrinolytic activity of the non-smokers on oral contraceptives, activity in the smokers on oral contraceptives being similar to that of the women not on these preparations. There were no significant differences in mean platelet count or adhesiveness, or in haemoglobin, packed cell volume, uric acid and blood sugar levels. Among the women on oral contraceptives, there was a significant negative correlation between factor VIII and fibrinolytic activity; this was largely due to five women all of blood groups A and B, in whom, besides high factor-VIII levels and poor fibrinolytic activity, other variables (e.g. fibrinogen) were raised in a direction that might be expected to favour thrombogenesis. It is possible that it is those women whose fibrinolytic activity does not increase in order to compensate for the effects of oral contraceptives on clotting factors, lipids and blood pressure, who are at special risk of thromboembolic episodes. The differential effects of oral contraceptives by age must be borne in mind in evaluating the effects of these preparations on the haemostatic and lipid systems.

Age Factors↗

Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection.

The severe adverse effects of gonococcal infection on human fertility suggests that Neisseria gonorrhoeae would exert powerful selection for the development of a protective immune response in humans. N. gonorrhoeae is an obligate human pathogen and must persist in humans to survive. Since it is an ecologically successful organism, it must have evolved strategies to evade any human immune response it elicits. In a longitudinal study among 243 women working as prostitutes and experiencing frequent gonococcal infection, younger women, women with HIV infection, and women with antibody to the gonococcal outer membrane protein 3 (Rmp) were at increased risk of infection (adjusted odds ratio 3.4, CI95% 1.1-10.4, P < 0.05). Rmp is highly conserved in N. gonorrhoeae and the blocking of mucosal defences may be one of its functions. As similar proteins occur in many gram negative mucosal pathogens, the enhancing effect of such proteins may be a general strategy whereby bacteria evade human immune responses.

Adult↗

[Focal peliosis of the adult liver in combination with glycogenosis type I (v.Gierke). A case report and review of the recent literature].

Peliosis hepatis is a condition characterized by blood-filled lesions in the liver that can be localized or diffuse in distribution. The predisposing factors for this condition include treatment with anabolic steroids, chemotherapeutic and oral contraceptive agents, catabolic metabolic conditions (e.g., hypoglycemia) and certain immunological disorders. This disease probably represents a non-specific immunological response to a variety of noxious agents and has been successfully induced in experimental animals. The increased tendency towards liver rupture following blunt trauma and resuscitation procedures may have important medicolegal consequences. We present a case of peliosis hepatis in a patient with type I glycogen storage disease (von Gierke).

Adult↗

[Effect of hormonal contraception on the course of lupus nephropathy].

Influence of oral contraceptive therapy on SLE activity was evaluated in 33 female patients with lupus nephropathy. Estroprogestative preparations containing either 50 micrograms (18 cases) or 30 micrograms (11 cases) of ethinylestradiol were used in 29 courses in 28 patients. Onset or exacerbation of clinical SLE activity occurred within 3 months after starting hormonal therapy in 13 cases, an overall incidence of lupus flare-up of 44 percent, involving major renal histological lesions in 5 cases. In contrast, of 16 patients receiving pure progestogen contraceptive therapy with either discontinuous normal dosage progestogens (9 cases) or continuous low-dose norsteroids (7 cases), only one developed clinical or immunological evidence of lupus exacerbation within 3 months of hormonal therapy. We conclude that oral contraceptive therapy using estrogens, even at low dosage, is associated with a high risk of SLE exacerbation. Pure progestogens, which have proven effective and devoid of such unfavorable effects, should be preferred in these patients when hormonal contraception is needed.

Contraceptives, Oral↗

Production of antisera against contraceptive steroids.

A four step synthesis of 6-(0-carboxymethyl) oximinoethynylestradiol is reported. This compound, 6-(0-carboxymethyl) oximinomestranol, the 3-(0-carboxymethyl) oximes of norethindrone and norgestrel and the 3-hemisuccinate of ethynylestradiol were synthesized and conjugated with bovine serum albumin. Rabbits were immunized at 3 dose levels of haptene (20, 66 and 200 nmoles) and eight weeks later with a booster containing 66 nmoles of haptene. The antibody titer and association constant of responding rabbits was nearly independent of dose although most antibody production occurred after the booster injection. Antibodies to mestranol crossreacted more than 100 percent with ethynylestradiol and to a small extent with norethindrone and norgestrel.

Animals↗