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Rheumatoid arthritis, the contraceptive pill, and androgens.

Evidence is accumulating that low androgen concentrations are a cause of rheumatoid arthritis. This would explain a number of established features of the epidemiology of the disease. These include: (a) the variation of disease activity with pregnancy; (b) the variation of age at onset by sex; (c) the variation by sex with HLA-B15; (d) the association with bone mineral density; and (e) the differing time trends in incidence rates by sex. It is argued, moreover, that if one makes a plausible assumption--namely, that women who choose oral contraceptives have high androgen concentrations at the time they first make this choice--then an explanation becomes available for the confusion about the relation between rheumatoid arthritis and oral contraception. Grounds are adduced for that assumption. If this line of reasoning is substantially correct it also has implications for the relations between rheumatoid arthritis and smoking and consumption of alcohol.

Adult↗

Contraceptive vaccine: new hope for the overcrowded world?

The overall rate of fertilization in humans has contributed to sustained increases in the world population and the added urgency of the need to develop new, effective contraceptive strategies. One potential approach to preventing fertility is to disrupt sperm-egg interaction or embryonic-maternal communication during early pregnancy with immunological reagents. This has lead to the principal concept of "contraceptive vaccine" which may become available in the near future.

Contraception↗

Association of melasma with thyroid autoimmunity and other thyroidal abnormalities and their relationship to the origin of the melasma.

Melasma is localized hyperpigmentation over the forehead, upper lips, cheeks, and chin. In this study, evidence suggesting an association between autoimmune thyroid disorders and melasma and the relationship of thyroid disorders to the origin of melasma is presented. A total of 108 nonpregnant women, aged 20-56 yr, were divided into 2 groups for the purpose of this study: 1) melasma, 84 patients; 2) control group, 24 patients from the Dermatology Clinic matched for age and sex. Microsomal thyroid autoantibodies (MCHA) were sought in all subjects. TRH-TSH tests were performed in patients with melasma and in those women with goiter and/or positive MCHA tests from the control group. Studies were completed with serum T4, T3, and antithyroglobulin antibody (TGHA) measurements in all patients with thyroid abnormalities. In patients with melasma, the frequency of thyroid disorders (58.3%) was 4 times greater than in the control group. The MCHA-negative patients had 1) simple goiter (13.1%), 2) Plummer's disease (2.4%), and 3) TSH hyperresponse to TRH in nongoitrous patients (10.7%). Patients with positive MCHA tests (32.1%) were divided into 2 subgroups. One comprised those women with an apparently normal thyroid gland and thyroid function (n = 7), while the other included all patients with goiter and/or subclinical hypothyroidism (n = 20). Regarding the origin of the melasma, it was found that 70% of women who developed melasma during pregnancy or while using oral contraceptives had thyroid abnormalities compared to 39.4% of patients with idiopathic melasma. Subjects from the control group had a 12.5% incidence of thyroid abnormalities, and only 8.3% had positive MCHA. Estrogen, progesterone, or both could be the triggering factor in the development of melasma in women who have a particular predisposition toward both melasma and thyroid autoimmunity. Patients with idiopathic melasma had a lower frequency of thyroid abnormalities, suggesting that there may be different genetic patterns linked to autoimmune thyroid disease. We conclude that there is a true association between thyroid autoimmunity and melasma, mostly in women whose melasma develops during pregnancy or after ingestion of oral contraceptive drugs.

Adult↗

Immunogenicity and the vascular risk of oral contraceptives.

Data concerning circulating immune complexes were obtained for women who had had a pulmonary embolism, myocardial infarction, or cerebral thrombosis, and for 224 healthy controls. In women with pulmonary embolism who had used oral contraceptives concentrations of circulating immune complexes were significantly higher than in healthy controls (regardless of oral contraceptive use), or in those with pulmonary embolism who had never used these preparations. Concentrations of circulating immune complexes were not raised in myocardial infarction, but these women had major risk factors for ischaemic heart disease. The group of patients with cerebral thrombosis without risk factors tended to have high concentrations of circulating immune complexes. The data provide some confirmation that immunological mechanisms may play a role in thrombotic episodes associated with oral contraceptives, especially when they occur in the absence of risk factors for vascular disease.

Adolescent↗

Shingles, allergies, family medical history, oral contraceptives, and other potential risk factors for systemic lupus erythematosus.

The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.

Adult↗

Effect of varying dosages and adjuvants on antibody response in squirrel monkeys (Saimiri sciureus) immunized with the porcine zona pellucida Mr = 55,000 glycoprotein (ZP3).

Using the porcine zona pellucida Mr = 55,000 (ZP3) glycoprotein as immunogen, the effect of varying ZP3 dosages (50 micrograms, 25 micrograms, 5 micrograms) or adjuvants (200 micrograms ZP3 with either Freund's, A1[OH]3, or a muramyl dipeptide analog [MDP] on antibody response was evaluated in female squirrel monkeys. Although the dosage range investigated did result in dose-dependent titration profiles, antisera from all dosage groups demonstrated in vitro contraceptive potential. MDP was as effective an adjuvant as Freund's in eliciting high titers of antibodies demonstrating contraceptive potential. A1(OH)3 was not an effective adjuvant in this system. Fertility data, utilizing those monkeys in the dosage study, suggested that an RIA titer greater than 40% binding was necessary to prevent pregnancy. We conclude that in the squirrel monkey system, a 50 micrograms dosage of ZP3 should be adequate for inhibiting fertility and that MDP would serve as a satisfactory alternative adjuvant for Freund's.

Acetylmuramyl-Alanyl-Isoglutamine↗

The relationship of oral contraceptive use to rheumatoid arthritis.

Current use of oral contraceptives among 71 women aged 17 to 45 diagnosed for the first time as having definite or probable rheumatoid arthritis at Group Health Cooperative of Puget Sound was compared with oral contraceptive use among matched controls. Twenty-three percent of cases and 13% of controls were current users of oral contraceptives at the index date (relative risk estimate = 2.0, 95% CI = 0.97-4.21). We conclude that current oral contraceptive use was not protective against the development of rheumatoid arthritis in this population.

Adolescent↗

[Oral contraceptives :misunderstood etiology of erythema nodosum (author's transl)].

The cutaneous side effects of oral contraceptives are uncommon but their manifestations are many and varied. Erythema nodosum is rare, it is typical but the associated signs are few and do not permit the etiological diagnosis. The latter rests mainly on the spontaneous disappearance of the symptomatology when the prescription of oral contraceptivae is discontinued and on the relapse on resumption of the retake. The physiopathology, much controversed, causes immunological disorders on the predisposed individual. Only stopping oral contraceptives intake brings about the cure.

Adult↗

The effects of sex, menstrual cycle, and oral contraceptives on the number and activity of natural killer cells.

OBJECTIVES: The aim of this study was to study the impact of sex, the menstrual cycle, and the use of oral contraceptives (OC) on the number and activity of natural killer (NK) cells. METHODS: Both the number and the activity of NK cells were assessed per milliliter of blood, and NK activity (NKA) per NK cell and per lymphocyte was calculated. NKA was measured in each subject using a whole blood assay, which preserves the plasma and all blood cells, and using a washed blood assay, in which plasma is replaced with an artificial medium. The subjects were young (20-29 years old) women with a regular menstrual cycle (n = 39; 26 tested on both the follicular and the luteal phases), age-matched women who use OC (n = 26), and age-matched men (n = 20). RESULTS: Men showed markedly and significantly higher NKA than women with regular menstrual cycles or women using OC, who had the lowest levels of NKA. No significant differences in blood concentration of NK cell were found. Differences in NKA were of similar magnitude in the whole and washed blood assays per milliliter of blood, per NK cell, or per lymphocyte. The menstrual cycle had no significant effect on activity levels of NK cells, but during the periovulatory phase, the number of NK cells per milliliter of blood increased significantly. CONCLUSIONS: The observed differences are independent of the presence of serum factors during the in vitro assessment of NKA, but may be related to chronic exposure to sex steroids and to fluctuation in the NK cell expression of beta-adrenoceptors.

Adult↗

The use of birth control pills in women with medical disorders.

Since little absolute data exist in the form of large prospective studies in patients with specific illnesses who are on oral contraceptives, the clinician must rely on well-founded empiric decisions in prescribing the pill for these patients. The decision should be based on a firm understanding of the pathophysiology and laboratory effects of the oral contraceptives. This must be juxtaposed with an understanding of the efficacy and effects of the estrogen and progestational components of the birth control pill and their interactions with maintenance medications. In the final analysis, though, the clinician must rely on a trial and error method in treating these patients. It must be stressed, however, that these women require careful monitoring, both clinically and biochemically. It is comforting to note that in all diseases studied to date, the use of birth control pills has not precipitated a catastrophic change.

Arthritis, Rheumatoid↗

[The procedure for treating patients with genital endometriosis].

The article contains results of case follow-up of 84 female patients with genital endometriosis. In the above patients, different combination of enzyme therapy and surgical treatment were instituted depending on the site of endometriosis and gravity of the pathological process. On the basis of the secured findings criteria are recommended for the policy of treating patients with genital endometriosis.

Adjuvants, Immunologic↗