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Estrogen, progesterone, and testosterone: can they be used to treat autoimmune diseases?

BACKGROUND: Sex hormones have marked immunomodulatory properties and may play important roles in the etiology of various autoimmune diseases. OBJECTIVE: To review the immunomodulatory effects of sex hormones, their roles in the etiology of autoimmune diseases, and their potential therapeutic applications. DISCUSSION: Progesterone and androgens suppress the immune system, prolactin stimulates it, and estrogens can do either. Rheumatoid arthritis tends to improve during pregnancy, during estrogen replacement therapy, and during treatment with estrogen-containing oral contraceptives. Systemic lupus erythematosus is aggravated by pregnancy and probably by estrogens. Therapy of rheumatoid arthritis with estrogens has not been promising, but testosterone replacement in men has shown modest benefits. In lupus, 19-nortestosterone has had little or no benefit, but danazol has been helpful in some patients, and encouraging preliminary results were obtained with dehydroepiandrosterone. CONCLUSIONS: We strongly recommend estrogen replacement therapy to prevent postmenopausal osteoporosis in women with rheumatoid arthritis. Younger women with rheumatoid arthritis can undergo pregnancy or use estrogen-containing contraceptives. Estrogens can be used in lupus only with great caution. Recommendations regarding other hormones and other diseases are less firm, but research is continuing in this area.

Animals↗

Family planning in Bali.

Despite low per capita income and little evidence of economic development, the response to the government-sponsored family planning program in Bali has been remarkably favorable. After five years of government involvement, a total of 29 percent of eligible women are estimated to be using program methods, including 25 percent who have accepted IUDs, and 4 percent more are estimated to be using nonprogram methods. This level of performance is higher than in most other developing areas of the world. A number of the factors that might help to explain the success of the program in Bali are identified, and the future prospects for continued success are assessed.

Adolescent↗

Advances in the understanding of risk factors for ovarian cancer.

The identification of risk factors for ovarian cancer is central to the goal of preventing deaths from this disease. Reproductive and hormonal history clearly modulate the risk of ovarian cancer. Continuous ovulation associated with nulliparity increases the likelihood of ovarian malignancy. Protective factors include conditions that suspend ovulation, such as pregnancy, lactation and oral contraceptive use. Hereditary syndromes account for 10% of ovarian cancer cases. The breast ovarian cancer syndrome is caused by mutations in the BRCA1 and BRCA2 genes and is associated with an 11-40% risk of developing ovarian cancer. The hereditary nonpolyposis colorectal cancer syndrome (HNPCC, or Lynch II) is caused by mutations in DNA mismatch repair genes and carries a 12% risk of ovarian cancer. Due to a lack of adequate screening techniques, women with BRCA1, BRCA2 or HNPCC mutations should consider prophylactic removal of the ovaries and fallopian tubes when childbearing is complete. Genetic polymorphisms are hereditary genetic variations that may act in concert with other genetic, hormonal or environmental factors to potentiate the risk of ovarian cancer. Finally, ovarian cancer risk is altered by environmental and behavioral factors. Further study of the risk factors for ovarian cancer is needed to develop effective preventive strategies.

Female↗

Unintended and unwanted pregnancy in Halifax: the rate and associated factors.

We present the results of a study designed to assess the incidence of unintended and unwanted pregnancies in Halifax, Nova Scotia, and to characterize the socioeconomic and demographic factors associated with women at high risk. Of 200 pregnancies, 32.5% were unintended and 16.5% unwanted. This, together with the rate of therapeutic abortions among Halifax area women, suggests that approximately 45% and 32% of conceptions leading to viable pregnancies are unintended and unwanted, respectively. Contrary to data collected in 1971, the majority of these women were single. Marital status and parity were significant determinants of both pregnancy intention and wantedness. According to these results, unintended and unwanted pregnancies continue to occur at high rates among certain groups of women living in the Halifax region, despite improvements in the efficacy and availability of contraceptives.

Contraception Behavior↗

Effects of iron supplementation and discontinuation on serum copper, zinc, calcium, and magnesium levels in women.

The purpose of this study was: 1) to establish the prevalence of depleted iron stores, iron deficiency, and low serum levels for copper, zinc, calcium, and magnesium in a healthy female population; and 2) to examine the effects of iron supplementation and discontinuation on the serum levels of the above minerals. One hundred eleven healthy women between the ages of 18 and 40 yr reported for fasted morning blood sampling for iron, copper, zinc, calcium, and magnesium status. Forty-five subjects were either iron-deficient as defined by a hemoglobin level below 120 g.l-1 (four subjects) or iron deplete as defined by a serum ferritin value below 20 micrograms.l-1 (43 subjects). Two subjects fit both criteria. This subgroup continued with the study and were prescribed a normal therapeutic iron dose (320 mg elemental iron per day, taken as two Slow-Fe tablets.d-1 for a period of 12 wk). The subjects then discontinued the iron supplementation for a further 12 wk. The response of the various blood minerals was monitored at 6-wk intervals. Twenty-five subjects completed the full 24-wk treatment. The main conclusions to be made from this study were that: 1) For this sample population of women, iron depletion was quite common (39%), although low hemoglobin values (< 120 g.l-1) were only seen in 3.6%. No subjects fell below the criteria for low serum copper levels (< 13.3 mumol.l-1) nor low serum magnesium levels (< 0.6 mmol.l-1). Seven subjects (6.5%) fell below the criteria for low serum zinc levels (< 11.5 mumol.l-1) while two subjects (1.8%) were below the criteria for low serum calcium levels (< 2.20 mmol.l-1). 2) Therapeutic oral iron supplementation was successful in raising mean serum ferritin values from 15.9 micrograms.l-1 to 36.5 micrograms.l-1 but was not associated with decrements in serum copper or calcium levels. 3) The treatment did not significantly effect serum zinc and magnesium levels during the supplementation period, but a downward trend continued through the discontinuation phase so that at 18 and 24 wk serum zinc and magnesium levels were significantly lower than baseline. 4) Oral contraceptive use was associated with elevated serum copper and ferritin values and lowered serum magnesium levels.

Adolescent↗

Selection and performance of the levonorgestrel-releasing intrauterine system.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNg IUS) is a hormonal contraceptive that is used in the uterine cavity. To determine whether the reasons for choosing LNg IUS vs. copperreleasing intrauterine devices (Cu IUDs) differ and whether their performances are comparable, we carried out a retrospective study in Finland during the first years of LNg IUS use. METHODS: Gynecological and contraceptive histories of 626 LNg IUS and 626 Cu IUD users and the performance of the device were reviewed from patient records. RESULTS: Women who accepted the LNg IUS were more likely than Cu IUD acceptors to have a history of menstrual bleeding of 6 days or more (44.4% vs. 28.4%), heavy bleeding (44.8% vs. 8.4%) and moderate or severe dysmenorrhea (15.9% vs. 7.5%). In both groups, 70% of the women had used Cu IUDs earlier. However, the LNg IUS acceptors had had more side effects during previous use of CU IUDs (58.2% vs. 28.8%). They also reported more side effects that resulted in discontinuation of a previous Cu IUD (39.4% vs. 10.1%). However, the 12-month life-table continuation rates of 80.6 (SE 1.9)% vs. 83.4 (SE 1.8)% were alike. Cu IUD users discontinued the current method more often because of problems of bleeding and unwanted pregnancy. Among those women who had previously discontinued a hormonal method because of hormonal side effects, there were no differences in the continuation rates of the two groups. CONCLUSIONS: LNg IUS can be successfully used by women who cannot use a CU IUD or who have experienced hormonal side effects with oral contraceptives.

Adult↗

Actinomyces in the vaginas of women with and without intrauterine contraceptive devices.

Either Actinomyces israeli, A. naeslundii, or Arachnia propionica was found, by immunofluorescence studies, in cervicovaginal mucus from 36% of 50 women. One or more of these organisms were found in a surprising 27% of those with neither intrauterine contraceptive devices (IUDs) nor intravaginal foreign bodies. The only common finding was abundant vaginal mucus, and no clinical features were more serious than vaginal itching, odor, or vague discomfort. Among those women who harbored actinomycetes, the average duration of continuous IUD use was 5.3 years; the comparable figure for those with no infection was 2.1 years.

Actinomyces↗

The present and future of immunologic approaches to contraception.

A vaccine capable of causing active immunity against one or more key elements of conception would have several advantages over currently available methods of fertility regulation. It would be amenable to mass use, would require only periodic follow-up, and would not require continuous user motivation. Although natural infertility attributable to immunologic factors has been amply documented, the natural mechanism has been only partially delineated. Consequently, researchers trying to develop a workable vaccine are taking various approaches. This report includes a discussion of autoimmune aspermatogenesis, anti-zona pellucida, anti-nonhormonal placenta-specific protein vaccines, and immunization against female and/or early embryonic antigens, including current approaches to the development of an anti-human chorionic gonadotrophin (HCG) vaccine. The potential advantages and disadvantages of the various immunologic methods are discussed, and the author concludes that although the problems associated with present methods of immunologic contraception are substantial they can be resolved.

Animals↗

Use of contraception and abortion in Greece: a review.

Greece has one of the highest rates of abortions in Europe and a very low prevalence of contraceptive use apart from withdrawal and condoms. Based on limited data from the past 30 years, this paper describes the context in which Greek women make reproductive decisions, and the history of family planning and abortion policies and services in Greece. It shows that in spite of the persistence of the traditional importance placed on marriage and motherhood, the fertility rate in Greece is very low. Sex education is still not included in the school curriculum, and the lack of accurate information on contraception and the prevention of unwanted pregnancy, especially in adolescence, still have critical repercussions for women's life choices. Although the public sector has been required to provide family planning services since 1980, only 2% of women of reproductive age were accessing these services in 1990, based mainly in urban centres. In 2001, one in four women of reproductive age had had at least one unwanted pregnancy ending in abortion; the rate was one in ten in the 16-24 age group and one in three in the 35-45 age group. With an almost complete lack of preventive policies in Greece, women continue to have to rely on abortion to control births.

Abortion, Induced↗

Social and behavioural influences on the uptake of hormone replacement therapy among younger women.

OBJECTIVE: To describe the social and behavioural influences on the uptake of hormone replacement therapy before the age of 50. DESIGN: Nationally representative birth cohort study with detailed hormone replacement therapy histories and prospective data on health, social and behavioural factors collected throughout life. SETTING: England, Scotland and Wales. POPULATION: General population sample of 1,572 women followed to the age of 50 years. MAIN OUTCOME MEASURE: Age at first hormone replacement therapy use RESULTS: By the age of 50 years, 45% of women had tried hormone replacement therapy and one third were current users. Over two-fifths of users had tried more than one preparation and over one quarter had episodic use. For the vast majority, prescribing conformed to current guidelines. More educated women took hormone replacement therapy for long term prevention compared with their less educated peers. Hysterectomy increased the chances of taking hormone replacement therapy, particularly where an oophorectomy had also been performed, and was associated with longer and more continuous use. Results of a Cox's proportional hazards model showed that the age at which first hormone replacement therapy is used by women who have not had a hysterectomy was influenced by previous contact with health services for menstrual disorders, previous use of oral contraception and cigarettes, past reporting of health problems and low social class. The relation between smoking and low social class with early use of hormone replacement therapy may be due to their association with early menopause. CONCLUSIONS: The trend over the last two decades towards greater use of hormone replacement therapy has continued unabated for younger women. So far, hormone replacement therapy users in this generation have had less healthy lifestyles and social advantages than nonusers, in contrast to many older mainly American studies based on earlier generations. This may have long term implications for health and health care as the postwar baby boom generation ages.

Adult↗

Modern oral contraceptives and dysmenorrhoea.

Women with primary dysmenorrhoea not sufficiently helped by triphasic oral contraceptives (OCs) were offered a modern, low-dose monophasic OC containing 30 micrograms of ethinylestradiol and 150 micrograms of desogestrel. The study shows that for these women, the monophasic pill was the better alternative. The fact that 19 of 23 women who continue treatment on the monophasic OC indicates that this type of pill may be chosen as the first alternative for women with primary dysmenorrhoea.

Adolescent↗

Early patterns of sexual activity: age cohort differences in Australia.

Patterns of first sexual activity among Australians born between the 1940s and 1980s were analysed using data from a national telephone survey of 1784 adults (876 males; 908 females). Sixty-one percent of those randomly selected from the Australian electoral roll and contactable by telephone responded. Many trends, including earlier first intercourse--from 20 to 18 years (females) and 18.8 to 17.8 years (males)--were established with the 40-49 year cohort, whose sexual debut was in the late 1960s-70s. Significant age-cohort effects saw women in the contemporary (18-29 year) cohort draw level with males for age at first intercourse and first sex before age 16 and before leaving school. First intercourse contraceptive use climbed from 30% to 80%. Condom use quadrupled to 70%. Australian age-cohort effects are remarkably consistent with those in similar western cultures: gender convergence in sexual experience and increasing avoidance of sexually transmitted disease and pregnancy. If such trends continue, positive long-term outcomes for health and social wellbeing should result.

Adolescent↗

Efficacy and safety of a low-dose 24-day combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone.

The aim of this open-label, multicenter, noncomparative study was to determine the efficacy, safety and bleeding profile of a new low-dose, monophasic combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone administered daily for 24 days followed by a 4-day hormone-free interval. Contraceptive efficacy was analyzed for 1018 women completing 11,140 treatment cycles. Eleven pregnancies occurred, giving a Pearl Index (PI) of 1.29 (upper limit of the 95% confidence interval [CI], 2.30); of these pregnancies, five were considered due to method failure, giving an adjusted PI of 0.72 (upper limit of the 95% CI, 1.69). A total of 7 (0.7%) women discontinued study medication because of irregular bleeding, suggesting a favorable bleeding profile. Overall, the treatment was well tolerated with an excellent safety profile. The majority of women (86%) stated that they were satisfied or very satisfied with the treatment and over 70% of women would have continued with the study medication.

Adolescent↗

A qualitative study of perceptions, attitudes, and experiences of long-term levonorgestrel implant users.

The present study examined the perceptions, attitudes, and experiences of long-term contraceptive implant users. Group interviews were conducted to obtain qualitative in-depth attitude and opinion data from 31 women who had used the implant for a minimum of four years. Results indicated that many women had experienced side effects with implant use, in particular during the first year. The primary motivations for continuing the use of implant were: women's strong desire for a long-term, reversible, and convenient method that offered effective protection from pregnancy, a strong need for control over one's life, and general dissatisfaction with alternative methods. Exposure to negative media reports, and peer commentaries did not influence implant's continued use. However, intensive educational counseling prior to insertion played a significant role in the long-term use of implant. Findings from this study indicate that women are willing to accept side effects as the price to be paid for an effective and convenient contraceptive method, and for gaining control over their lives. Furthermore, women appear to be less influenced by opposing social climate, in the absence of negative personal experiences. Our findings underscore the importance of educational counseling prior to implant insertion.

Adult↗

Effect of ethynodiol diacetate and a combination-type oral contraceptive compound on carbohydrate metabolism. II. One year intravenous glucose tolerance study.

Blood glucose and plasma insulin levels were measured in two groups of women, following one year of oral contraceptive therapy of different types. There were no significant differences from pretreatment glucose and insulin values in the first group of women (on ethynodiol diacetate). In the second group (on norethynodrel and mestranol), there was a significant elevation of mean blood glucose levels in the fasting state and at all times of an i.v. glucose tolerance test. Furthermore, a statistically significant alteration in plasma insulin was observed at all times of the test (except at 120 min). Patients participating in this study will continue this treatment, and results of carbohydrate metabolism monitoring will be reported after 2 years of therapy.

Adult↗

Cyproterone acetate versus levonorgestrel combined with ethinyl estradiol in the treatment of acne. Results of a multicenter study.

In spite of an abundant literature on antiandrogen treatment with cyproterone acetate (CA) there have been no objectively measured results to prove statistically the possible superiority of CA over combined oral contraceptive pills in the treatment of acne vulgaris. A multicenter study was therefore done, in which two preparations containing CA in combination with ethinylestradiol (EE) were compared with a marketed combined oral contraceptive pill. The preparations studied were: CA 2 mg + EE 50 micrograms (Diane), CA 2 mg + EE 35 micrograms (Diane mite), Levonorgestrel 150 micrograms + EE 30 micrograms (Neovletta). A woman was eligible for the study if she was found by a dermatologist to have at least eight acne lesions (sum of papules, pustules, cysts and nodules) on her face, was otherwise healthy and without medication. After a primary assessment of the number of acne lesions by the dermatologist the woman was referred to a gynecologist and given one of the three test preparations double-blind and at random. The treatment was to continue for 6 months. 133 women were recruited at eight different centers. The groups thus constituted were of similar size and comparable with regard to age, degree of acne, and menstrual and contraceptive histories. As the number of acne lesions varied considerably between patients all data were converted into percentage change during treatment before they were processed in a computer. After only 4 months of treatment the patients on Diane and Diane mite had a significantly greater reduction in the number of acne lesions compared with those on Neovletta.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

Is hormonal treatment efficacious in the management of ovarian cysts in women with histories of endometriosis?

In a controlled, randomized study, we evaluated the effectiveness of various hormonal regimens in treating 70 women (mean age 34.7 +/- 5.7 years) who had unilateral of bilateral ovarian cysts presumed to be physiological (functional) and a history of endometriosis. The patients were assigned randomly to one of the following groups: group I (control), no treatment; group II, oral contraceptives (35 micrograms ethinyl oestradiol and 1 mg norethindrone); group III, oral contraceptives (50 micrograms ethinyl oestradiol and 1 mg norethindrone); group IV, danazol 800 mg/day. Serum CA-125 concentrations were measured in 32 women. All medications were taken continuously for 6 weeks. Subjects were re-evaluated by pelvic examination and transvaginal ultrasound. Those with persistent cysts were offered diagnostic and possible operative laparoscopy. As 11 patients did not complete the study and five did not follow-up, the final study population comprised 54 women. At 6 weeks follow-up, complete resolution of cysts was found in: group I, 12 out of 18 (66.7%); group II, five out of none (55.6%); group III, eight out of 14 (57.1%); and group IV, seven out of 13 (53.9%). Two of the 22 women with persistent cysts opted for 6 weeks further medical therapy and achieved complete resolution; 19 underwent laparoscopy, and one was lost to follow-up. All laparoscopic findings revealed benign masses. We found no statistically significant effect when hormonal treatment was compared with expectant management. There was no correlation between serum CA-125 concentrations and the persistence of resolution of cysts.

Adult↗