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Oral contraceptives: effect of folate and vitamin B12 metabolism.

Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant.

Anemia, Megaloblastic↗

Oral contraceptives: effects on plasma insulin response to glucose and on the response to insulin and 2-deoxyglucose uptake by peripheral tissue.

Oral contraceptive steroids, norethynodrel and mestranol, were fed to 11-wk-old female Sprague-Dawley rats, in combination and in quantities proportional to those used by women for contraceptive purposes. Three experiments were performed. The first experiment, demonstrated that 10 wk of treatment, impaired the animal's glucose tolerance, but not its insulin response to glucose. The second experiment demonstrated that 6 wk of steroid feeding, decreased the in vivo conversion of blood U-14C-labeled glucose into adipose tissue fatty acids and into diaphragm glycogen, although the effect on the diaphragm was not statistically significant. In the third experiment, it was found that the uptake of 2-deoxyglucose-1-14C by the adipose tissue removed from rats after 6 wk of treatment, was not different from that of control tissue, but the uptake by the hemidiaphragms was slightly lower.

Adipose Tissue↗

Oral contraceptive effects on methylprednisolone pharmacokinetics and pharmacodynamics.

OBJECTIVE: Oral contraceptive (OC) steroids alter the disposition of numerous drugs, including corticosteroids. We investigated the pharmacokinetics and pharmacodynamics of methylprednisolone. METHODS: Twelve women (six women used OC steroids and six women did not) received intravenous methylprednisolone (0.6 mg/kg ideal body weight). Methylprednisolone disposition was assessed from plasma concentrations. Pharmacodynamic parameters measured were plasma cortisol, whole blood histamine (reflecting basophils), and blood helper T lymphocytes. RESULTS: Methylprednisolone clearance was significantly decreased in the women who used OC steroids (0.298 versus 0.447 L/hr/kg), resulting in a longer elimination half-life (2.20 versus 1.72 hours). With use of indirect response models, significant differences were observed with the cortisol and basophil responses. A larger value for the concentration that inhibits the zero-order production rate by 50% (0.37 versus 0.11 ng/ml) was observed in the women who used OC steroids for suppression of cortisol secretion, indicating less sensitivity to the suppressive effects of methylprednisolone. Greater net suppression of basophils was observed in the users of OC steroids (area under the response curve, 694 versus 401 ng x hr/ml). No differences were observed for helper T-cell responses. CONCLUSION: OC steroids appear to inhibit methylprednisolone metabolism. However, mixed changes in several responses occur, indicating that women can probably receive similar doses of methylprednisolone irrespective of OC steroid use.

Adult↗

Understanding risk: a randomized controlled trial of communicating contraceptive effectiveness.

OBJECTIVE: To determine which of three different approaches increased women's understanding of risk of pregnancy associated with different contraceptive methods. METHODS: We randomly assigned 461 reproductive-age women to one of three tables presenting pregnancy risk (Food and Drug Administration table with numbers, World Health Organization table with numbers and categories, or table with categories). We evaluated participant knowledge before and after being shown the assigned table. RESULTS: The most important reason for choosing a contraceptive was how well it works (53%), followed by ease of use (13%), and protection against sexually transmitted disease or human immunodeficiency virus (11%). Before looking at the tables, about half the participants knew that hormone shots are more effective than pills (48%) and that pills are more effective than condoms (57%). For these two key comparisons, the category table compared to the Food and Drug Administration table with numbers improved knowledge significantly more (37% versus 20% and 27% versus 14%; both P <.05). Compared with those assigned to the Food and Drug Administration table with numbers, significantly fewer participants assigned to the category table said the table was difficult to read (6% versus 19%; P <.01). Most participants in all three groups said their assigned table provided enough information to choose a contraceptive method. CONCLUSION: The table with categories communicated relative contraceptive effectiveness better than the tables with numbers. However, without being presented with numbers, participants grossly overestimated the absolute risk of pregnancy using contraceptives. A combination of categories and a general range of risk for each category may provide the most accurate understanding of both relative and absolute pregnancy risk.

Adolescent↗

Women's knowledge of taking oral contraceptive pills correctly and of emergency contraception: effect of providing information leaflets in general practice.

BACKGROUND: About one third of all pregnancies are unplanned and 20% of all pregnancies end in abortion. More than 170,000 legal abortions are performed in the United Kingdom annually. Nearly all general practitioners provide contraceptive advice; the most commonly used form of reversible contraception is the oral contraceptive pill. AIM: The aim of this study was to determine factors associated with women's knowledge of taking the contraceptive pill correctly and of emergency contraception, and to investigate if their knowledge could be improved in general practice by providing women with Family Planning Association information leaflets. METHOD: An uncontrolled intervention study was performed in one rural and one urban English general practice, using a self-completion questionnaire that was initially administered to women attending their general practitioner for oral contraception over six months from 1 October 1992. The questionnaire asked for: sociodemographic information; knowledge of how late women can be taking an oral contraceptive pill and still be protected against unplanned pregnancy; for how many days after being late with a pill they need to use other precautions; sources and methods of emergency contraception; and for how long the methods are effective after the primary contraceptive failure. After completing the questionnaire women were given two leaflets: one about how to take their prescribed contraceptive pill correctly and one about emergency contraception. Three to 12 months later the same questionnaire was administered in the same manner. RESULTS: Of 449 women completing the first questionnaire, 233 (52%) completed the second questionnaire. Initially 71% of 406 women taking an oestrogen/progestogen combined pill knew about the '12-hour rule' and 17% knew about the 'seven-day rule'; giving women information about the pill they were taking increased the extent of knowledge about these rules among 212 respondents to 82% (P < 0.01) and to 25% (P < 0.05), respectively. The proportion of respondents who knew that they could obtain emergency contraception from their own general practitioner, from any general practitioner and from family planning clinics all increased after they had received the leaflets (from 84% to 92%, from 34% to 47% and from 82% to 90%, respectively, all P < 0.01). There were significant improvements in the proportion of women knowing the duration of effectiveness of emergency contraception. However, after receiving the leaflet on emergency contraception the majority of women still did not know for how long after unprotected intercourse the high-dose combined pill and the intrauterine contraceptive device were effective (80% and 93% of 233 women, respectively). Improvements in knowledge depended upon women's social class, previous use of emergency contraception and with which practice they were registered. CONCLUSION: Providing women with leaflets about taking the contraceptive pill correctly and about emergency contraception appears to improve significantly their extent of such knowledge. If such practice was adopted elsewhere this increased knowledge might reduce the number of unplanned pregnancies in the UK. The effect of general practitioners personally providing such leaflets, with or without verbal instruction, warrants further study.

Adolescent↗

Contraceptive effects of intravaginal application of acrosin and hyaluronidase inhibitors in rabbit.

Eight single-drug and combinations of two-drug treatments were used to study the contraceptive efficacy of the intravaginal application of acrosin inhibitors (TLCK; NPGB) and hyaluronidase inhibitors (Compound 53D/k; Phosphorylated hesperidin) in the rabbit. Drug concentrations were selected so that they did not inhibit rabbit sperm motility upon incubation at 37 degrees C for 30 minutes. In the first series, the drugs were added to semen before artificial insemination; in the second series, the drugs were administered intravaginally before artificial insemination with untreated rabbit semen. The data show that these drugs are highly effective intravaginal contraceptives in the rabbit. The data suggest that this is a specific inhibitory effect on fertilization since the drug concentrations used did not affect sperm motility.

Amino Acid Chloromethyl Ketones↗

Contraceptive effect of proligestone on spotted seals and crossbreeds of spotted seals and harbor seals.

Spotted seals (Phoca largha) and related crossbreeds maintained at Kamogawa Sea World breed seasonally from the end of January to middle of March. For contraception in these animals, the effect of a single administration of a contraceptive synthetic luteal hormone for dogs, proligestone (PRG), was investigated. The animals tested were 10 seals aged 4-24 years old, and a total of 35 trials were performed over five years. PRG was administered in 23 trials during January, which was one month before the estimated estrus, and in 12 trials during December of the previous year, which was two months before the estimated estrus. The dose of PRG was 5 mg/kg in 32 trials and 10 mg/kg in 3 trials. The effect of the contraception was judged by the presence or absence of delivery. Among 23 animals treated in January, 2 animals treated with 5 mg/kg PRG became pregnant, but the contraception was successful in the other 21 animals. Contraception was successful in all 12 trials treated with 5 mg/kg PRG in December. Overall, contraception was successful in 94.3% (33/35). Therefore, a single administration of 5 mg/kg PRG in December may be an effective method of contraception for seals.

Animals↗

Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety.

Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a decade, and worldwide for 40 years. Benefits and risks of hormonal therapy are often under scrutiny; however, long-term clinical experience has established the safety of this long-acting contraceptive. This article reviews the contraceptive efficacy, potential noncontraceptive health benefits and long-term safety of with regard to risk of cardiovascular events, breast and gynecologic malignancy and osteopenia. Comparisons with other hormonal contraceptives are made as clinically appropriate. Common patient management issues, including effects on menstrual cycle, body weight and mood, are also addressed. Finally, this review provides recommendations for appropriate patient selection.

Contraceptive Agents, Female↗

[Clinical study on the contraceptive effectiveness of trisiston from the Jenapharm firm].

Now triphasic contraceptive preparations are used widely. Some news low dose formulations are available on the market, among them Trisiston. The study was conducted to confirm clinically acceptance and effectiveness of Trisiston. There were 437 volunteers mostly multiparous, with a mean age of +/- 25 years who participated in a multi center study. They were taking pills for a 3 to 12 cycles. Cumulatively 4026 cycles were observed. The investigation was conducted according special protocol. At the admission a complete medical history was obtained and a general physical and gynecological examination was performed. All subject were controlled every 3rd month included laboratory tests (blood levels of Hb, WBC, RBC, ESR, carbohydrate metabolism, clotting factors, bilirubin, creatinine, protein, glucose, albumin, LDL, HDL). There was no case of pregnancy. Pearl index = 0. The Trisiston was well tolerated by most of women (80%). Some effects like headache, vertigo, mastalgia, spotting and breakthrough bleeding, loss of libido, premenstrual syndrome were observed in 20% patients, soma of our patients (20%) discontinued contraceptive.

Adult↗

Long-term use of an injectable contraceptive: effect of depot-norethisterone oenanthate on carbohydrate metabolism.

In order to determine the metabolic effects of long-term use of the injectable contraceptive norethisterone oenanthate, plasma glucose and serum insulin concentrations were studied in two groups of women who had used the method continuously for at least five years. Group 1 comprised 24 subjects, from whom only fasting blood samples were taken. Despite similar plasma glucose concentrations to those of the controls, the subjects had significantly increased serum insulin concentrations (164.5 (39.9) v 120.3 (34.3) pmol/l, p less than 0.01). In addition the insulin:glucose ratios were also significantly increased (34.3 (8.5) v 24.6 (6.7), p less than 0.01), consistent with decreased insulin sensitivity. Group 2 comprised 13 of the original 24 subjects who also had an oral glucose tolerance test. Basal plasma glucose concentrations were similar in the subjects and their controls, whilst the significantly increased insulin:glucose ratios (35.0 (7.7) v 28.7 (5.6), p less than 0.05) were consistent with the results of the larger group. Following oral glucose challenge, plasma glucose concentrations, serum insulin concentrations and insulin:glucose ratios were similar in the subjects and their controls throughout the test. Thus, long-term use of norethisterone oenanthate injections is associated with a decrease in peripheral insulin sensitivity. However, these changes are not associated with any evidence of oral glucose intolerance.

Adult↗

Oral contraceptives: effects on carbohydrate metabolism, insulin like activity and histology of the pancreas.

The effect of the combination type oral contraceptive and its estrogen (mestranol) and progesterone (ethynodiol diacetate) components on the intravenous glucose tolerance test (IVGTT), intravenous tolbutamide test (IVTT), serum insulin like activity (ILA) and morphology of beta cells of the pancreas was investigated in female rabbits. The combination produced impairment of glucose tolerance in all animals after 24 weeks treatment. Fifty percent of animals in the estrogen treated group and 33.3 percent of animals in the progesterone treated group developed impairment of glucose tolerance after 24 weeks. A reduction in the glucose response to IVTT was observed in all the animals following 24 weeks treatment with the combination, estrogen or progesterone. A significant decline in fasting serum ILA and post glucose ILA was observed in animals treated with the combination and estrogen. A small but consistent decline in the serum ILA was observed in animals treated with ethynodiol diacetate. A rise in serum FFA paralleled the abnormality of glucose tolerance. Morphological changes in the cytostructure of pancreatic islets in the form of degranulation and degeneration of cells were observed in the pancreas of animals treated with the combination, and to lesser extent in animals treated with estrogen and progesterone. These observations indicate that the disturbances in carbohydrate and lipid metabolism produced by oral contraceptives may be associated with damage to beta cells and low circulating insulin in rabbits.

Animals↗

Biochemical aspects of hormonal contraception: effects on bone metabolism.

Both trabecular and cortical bone mineral content reduction physiologically occur during the premenopausal period and, overall, at the time of menopause. It is related to plasma estrogen fall. Several studies have examined the relationship between bone density and oral contraceptives (OCs), but their results disagree. The different results may be due to the small number of patients investigated, the different OC formulations, and to the multifactorial nature of the bone loss phenomenon. Furthermore, the use of different techniques and different sites for measuring the bone density may limit the interpretation and reproducibility of the reported findings. Our previous studies evidenced that: (1) in premenopausal (40-45 years) women (n = 26), OCs, over a period of 2 years, do not induce any change either in bone mineral density or in bone metabolism biochemical markers (osteocalcin, alkaline phosphatase, urinary hydroxyproline/creatinine ratio; and (2) independent from the therapy length, the premenopausal use of OCs does not modify the bone mineral loss in postmenopausal patients (n = 40). The present study compared, over a period of 36 months, in perimenopausal (46-53 years; follicle stimulating hormone < or = 35 mU/ml; estradiol < 50 pg/ml) women, the effect of OCs (n = 8) on bone metabolism. The results were compared with those of a matched control group (n = 9). In the treated group, a slight, though not significant, bone mass improvement was observed during the entire therapy period, whereas, in the control group, a continued and progressive bone mass loss was observed and a significant decrease was shown at the end of the observational period. Our data suggest that OCs have no significant effects on bone metabolism in women during their childbearing years. However, OCs may be beneficial in inhibiting bone reabsorption in pre- and postmenopause. Furthermore, the pill, also in virtue of its contraceptive effect, would be the first presidium in hormone therapy in the premenopause.

Alkaline Phosphatase↗