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Oral contraceptives and cancer.

The use of combined oral contraceptives has been shown in a number of studies to alter a women's risk of developing some kinds of cancer. Specifically, a 50% reduction in the risk of both ovarian and endometrial cancer has been demonstrated. This protective effect appears to persist for some time after oral contraceptives are stopped. Combined oral contraceptives do not appear to effect substantially the overall risk of developing breast cancer, although some data suggest that selected subgroups of women may be at a greater risk of developing breast cancer if oral contraceptives are used at specific times in a woman's reproductive life, especially if used for long periods of time. However, the data are not entirely consistent on this issue. The effect of oral contraceptives on the risk of developing cervical cancer is also not entirely clear, although the data available suggest a slightly increased risk of intraepithelial cervical cancer with prolonged use of oral contraceptives.

Adolescent↗

Noncontraceptive benefits of oral contraceptives.

The noncontraceptive health benefits of oral contraceptives were initially summarized a decade ago. Studies conducted in the last decade confirmed the findings of earlier studies with high-dose oral contraceptives and extended them to low-dose formulations. Among the noncontraceptive health benefits first cited were reductions in menorrhagia, irregular menses, endometrial cancer, ovarian cancer, functional ovarian cysts, benign breast disease, dysmenorrhea, premenstrual tension and iron-deficiency anemia. In addition, women who used oral contraceptives were less likely to develop rheumatoid arthritis or acute salpingitis, particularly moderate or severe forms, than were women using no method of contraception. Despite the fact that such benefits were identified more than 10 years ago and despite their inclusion in oral contraceptive labeling, women today are largely unaware of the noncontraceptive health benefits associated with oral contraceptive use.

Adult↗

Hepatobiliary complications of oral contraceptives.

Complications secondary to the use of oral contraceptive agents are rare. Hepatobiliary complications, while often dramatic in presentation, occur infrequently. In a patient without predisposing conditions to complications, the benefits achieved with estrogen/progesterone products outweigh the risks. Those conditions that would absolutely and relatively contraindicate the use of oral contraceptives are listed in Table 4. Patients with a past history of liver disease in whom liver function tests have returned to normal may tolerate the introduction of oral contraceptives. They need to be monitored closely for adverse reactions. Patients who have experienced cholestatic jaundice of pregnancy should avoid all contraceptives because of a high risk of disease recurrence. Women whose first-degree relatives have experienced cholestasis of pregnancy or oral contraceptive-induced cholestasis may be at increased risk and should be closely monitored while taking birth-control pills. Women with current or previous benign or malignant hepatic tumors should not take oral contraceptives. Active hepatitis is an absolute contraindication to using birth control pills, although patients with a past history of hepatitis and no evidence of active disease can have a trial of these drugs with close follow-up. A final group of women who should avoid oral contraceptives is those with familial defects of biliary excretion, including the Dubin-Johnson syndrome, Rotor's syndrome, and benign intrahepatic recurrent cholestasis. Dubin-Johnson syndrome is often asymptomatic and may manifest only during pregnancy or during the use of oral contraceptives. The reduction in hepatic excretory function induced by the sex steroids can transform the mild hyperbilirubinemia into frank jaundice. Oral contraceptive agents are the most widely used reversible means of birth control currently available. Fortunately, the complications associated with these drugs are infrequent and may be decreasing due to lower-dose products. Complications still occur, however, and need to be recognized by the general internist as medication-induced problems so the offending drugs can be discontinued and appropriate treatment and follow-up initiated. In addition, patients at risk for the development of complications need to be recognized and advised prior to the introduction of oral contraceptives.

Adolescent↗

Contraceptive practice before and after therapeutic abortion. II. Use-effectiveness of oral contraceptives and intrauterine devices.

Of 180 women who underwent therapeutic abortion in a certain period in 1977, 71.7% were unmarried and 63.9% were unmarried primigravidas. At the first follow-up visit 3 to 6 weeks postabortion 55.0% of the unmarried primigravidas chose oral contraceptives and 43.2% chose intrauterine devices (IUDs). Of the unmarried women, 25.7% chose oral contraceptives and 65.7% chose IUDs. For unmarried primigravidas the 1-year continuation rates for oral contraceptives and IUDs were 83.6% and 93.8%, respectively. For married women the figures were 55.6% for oral contraceptives and 91.3% for IUDs. The differences between use of oral contraceptives and use of IUDs in the two groups of women was not statistically significant. We recorded no contraceptive failure, but three episodes of pelvic inflammatory disease occurred among unmarried primigravidas. The results indicate a high motivation for reliable methods and a high continuation rate following therapeutic abortion. The results may also indicate that oral contraceptives and IUDs represent equivalent methods for both parous and nulliparous women.

Abortion, Therapeutic↗

Increased incidence of postoperative localized osteitis in mandibular third molar surgery associated with patients using oral contraceptives.

Current literature has noted the various side effects of oral contraceptives. Oral surgeons have recently encountered an increased incidence of postoperative localized osteitis occurring with removal of manidibular third molars. This article documents the occurrence of this phenomenon among 105 women participating in a recent study at the Clinical Center of the National Institutes of Health.

Contraceptives, Oral↗

Compliance, counseling and satisfaction with oral contraceptives: a prospective evaluation.

CONTEXT: Oral contraceptive users' risk of accidental pregnancy may be higher than it should be, because of inconsistent pill-taking. However, few reliable data are available on pill users' everyday experiences with their method, especially characteristics that may affect consistency of use. METHODS: Two months after initiating or resuming oral contraceptive use, a nationwide sample of 943 women completed questionnaires examining their compliance with instructions for proper use, the quality of their interactions with their provider, their satisfaction with the method, and the frequency and costs of visits or calls to their providers because of pill-related side effects. Regression analyses were used to determine the factors associated with compliance difficulties and method dissatisfaction. RESULTS: In all, 47% of users missed one or more pills per cycle, and 22% missed two or more. Women who lacked an established pill-taking routine, who did not read and understand all of the informational material accompanying the pill package, or who experienced spotting or heavy bleeding had increased odds of missing two or more pills per cycle. Method satisfaction was most likely among women who were aware of the pill's noncontraceptive benefits, were satisfied with their relationship with their provider, had used the pill in the past and experienced few side effects. Some 22% of users called their provider at least once about pill-related side effects, and 9% made at least one visit for this reason; these women spent $25 and $62, respectively, to treat side effects. CONCLUSIONS: Improving pill use is a shared responsibility of the provider, the patient and, to a lesser degree, pill manufacturers. Awareness of potential difficulties such as inadequate counseling is a key step in helping women use oral contraceptives effectively.

Adult↗

[Metabolic studies under administration of oral contraceptives. A review].

The use of oral contraceptives can produce changes in the metabolism of carbohydrates, lipids, proteins, vitamins, and minerals. Responsible for the alterations seems to be the used oestrogen- and gestagen derivative and not so much the type of the contraceptive. The most frequent findings are raised serum-glucose-, insulin-, and triglyceride levels; disturbances in protein-metabolism increase the risk of developing thrombosis and hypertonia. Little is known about the significance of oral contraceptives on the vitamin- and mineral metabolism--yet extreme deficiencies have not been observed so far. Oral contraceptives can become an extra risk factor when given to women with metabolic disturbances.

Amino Acids↗

Pharmacogenetic aspects of the use of oral contraceptives and the risk of thrombosis.

Oral contraceptives are currently used by more than 100 million women in developed countries and are a highly efficacious method to prevent undesired pregnancies. However, oral contraceptives are associated with an increased risk of venous and arterial thrombosis, through changes in blood coagulation and fibrinolysis. In order to reduce such complications, the composition of oral contraceptives has changed over the past decades, both for the dose of oestrogen and the type of progestagen. However, the risk for venous thromboembolism remains, particularly for women who are carriers of inherited thrombophilia. In these women, prescription of oral contraceptives should be carried out on an individual basis. This review illustrates the risk of thrombosis, particularly venous thromboembolism, associated with the use of oral contraceptives, underlines the crucial role of the interaction of these drugs with other risk factors for the disease, and gives suggestions on the utility of thrombophilia screening before prescription.

Contraceptives, Oral↗

Insulin resistance, secretion, and metabolism in users of oral contraceptives.

Studies of insulin employing the oral glucose tolerance test demonstrate marked differences between the effects of different oral contraceptives, but provide little insight into the underlying disturbances. We investigated the metabolic basis of these disturbances by computer modelling of iv glucose tolerance test glucose, insulin, and C-peptide concentration profiles. Insulin resistance, secretion, and metabolism were evaluated in 296 oral contraceptive users and 95 nonusers. Four estrogen/progestin combinations, with similar estrogen but differing progestin contents, and 1 progestin-only formulation were studied. Effects on iv glucose tolerance test glucose, insulin, and C-peptide concentrations varied according to progestin content, with levonorgestrel-containing combinations having the greatest effect, followed by desogestrel and norethindrone. However, these formulations increased insulin resistance to a similar extent. The progestin-only formulation did not affect insulin resistance. Levonorgestrel combinations increased second phase pancreatic insulin secretion by 60-90%, but did not affect the insulin half-life. The desogestrel combination increased the insulin half-life by 28%, but did not affect insulin secretion. The effects of different combined oral contraceptives on glucose tolerance test glucose, insulin, and C-peptide concentration profiles appears to be due to a combination of estrogen-induced insulin resistance and progestin-associated changes in insulin half-life.

Adolescent↗

Oral contraception: trends over time.

Since their introduction in 1960, oral contraceptives have undergone an evolution in content and dosage. The doses of the steroid components of combination oral contraceptives have been dramatically decreased since the first formulations. Ethinyl estradiol is now used as the estrogenic component of most combination oral contraceptives. The majority of progestins currently used in combination oral contraceptives are derivatives of 19-nortestosterone. However, drospirenone, which is combined with ethinyl estradiol in a new combination oral contraceptive, is a novel progestin that is derived from 17 alpha-spirolactone and is an analogue of spironolactone. The extremely low failure rate with ideal use of combination oral contraceptives is seldom duplicated in actual usage. Women often discontinue combination oral contraceptives within the first 2 months due to side effects that would likely have decreased over time. Although there are some areas of increased health risk with combination oral contraceptives, the benefits far outweigh the potential risks. In addition to providing effective contraception, combination oral contraceptives are sometimes used for their many noncontraceptive health benefits--e.g., treatment of menstrual irregularities and management of premenstrual symptoms. The most practical solution to the problem of poor compliance appears to lie in providing adequate education and counseling to women using combination oral contraceptives so that they know how to use them properly and what side effects they might expect. Patients also need to be given the facts about potential increases in the risk of certain conditions to help correct any misperceptions.

Adult↗

Use of dydrogesterone as a progestogen for oral contraception.

Dydrogesterone is a potent orally active progestogen that has been used in clinical practice for over 40 years. Chemically, it belongs to the class of retrosteroids. Dydrogesterone is closely related to endogenous progesterone. It differs from most other synthetic progestogens in that it has no estrogenic, androgenic, glucocorticoid, or anabolic effects. The use of progestogens such as dydrogesterone is indicated in all cases of relative or absolute endogenous progesterone deficiency. Nowadays, dydrogesterone is mainly used in hormone replacement therapy (HRT). The present pilot study explored whether dydrogesterone could also be used as a progestogen for oral contraception. Given its highly favorable safety and tolerability profile, it would provide improvement over existing progestogens currently used in oral contraceptives (OCs). The results of this study indicate that dydrogesterone might indeed be a suitable candidate for use in oral contraception. This concept is currently being investigated further in two open-label phase II trials.

Adolescent↗

[Risk of thrombosis with oral contraceptives: value of a thrombophilia screening test].

Oral contraceptives increase the natural incidence of venous thrombosis of 1-2/10,000 women per year 3- to 4-fold. Recent studies have shown that desogestrel or gestodene containing formulations bear twice the risk of older low-dose ovulation inhibitors. During pregnancy, the incidence of thrombosis rises to 10/10,000 women-years and post partum up to 40/ 10,000. For 60% of thromboses no causal explanation can be found. In approximately 40% of the patients an inherited thrombophilia can be presumed. Among the hereditary types of thrombophilia, a resistance to activated protein C (APC-resistance) represents nearly 50%, while in 15 to 20% a deficiency of antithrombin III, protein C or protein S is found. APC-resistance, with a prevalence of 3-5% in the general population, increases the risk of thrombosis 8-fold and in users of oral contraceptives 35-fold. Antithrombin III-deficiency carries a comparable risk. Protein C-deficiency increases the risk of thrombosis 9-fold and in users of oral contraceptives 15-fold. Ovulation inhibitors do not influence the risk of thrombosis in women with protein S-deficiency. Anti-phospholipid-antibodies increase during treatment with oral contraceptives and represent a considerably enhanced risk of thrombosis. Inherent thrombophilia is suspected in a patient with a positive history or family history of thrombosis, especially with thrombosis before the age of 40 or with atypical localisation. Even in these risk groups, the cost-benefit ratio of selective screening is unfavorable, as today at most 70% of the hereditary thrombophilias can be diagnosed by laboratory analysis, and only very few of the patients will actually experience a thrombotic event: only 3 of 1000 carriers of APC-resistance will suffer from thrombosis during oral contraception. On the other hand, a negative result of laboratory tests does not exclude a hereditary thrombophilic disorder. At present, it is unclear whether a selective screening process is superior to a careful assessment of individual and family history. A general screening, however, cannot be justified because of the unfavorable cost/benefit ratio. If the individual or family history or pathological laboratory parameters indicate an increased risk of thrombosis, this risk has to be carefully weighed against the consequences of discontinuation of pill use. Those few individuals with risk factors who will experience a thrombo-embolic event, cannot be identified in advance. If oral contraceptives represent a particularly high risk in patients with thrombophilic disorders and/or other risk factors, other contraceptive methods should be considered. If a patient with risk factors decides on the use of oral contraceptives, she must be informed that in the case of symptoms indicating a thrombosis, a physician should be consulted immediately. The earlier an appropriate therapy is initiated, the more effectively pulmonary thrombo-embolism and permanent damage, such as the post-phlebitic syndrome, can be prevented.

Adult↗

A prospective study of pregravid oral contraceptive use in relation to fetal growth.

OBJECTIVE: Because oral contraceptives are so widely used, any health consequences may have substantial public health implications. Whether pregravid oral contraceptives could affect subsequent pregnancies has not been adequately studied. The study objectives were to examine whether pregravid oral contraceptive use affects fetal growth and pregnancy hormone levels. DESIGN: A prospective study of pregnant women followed through pregnancy. SETTING: A major teaching hospital in Boston, USA. POPULATION: Two hundred and sixty Caucasian pregnant women, with a mean age of 31, and a parity of no more than two. Seventy-nine percent of the women were pregravid oral contraceptive users. METHODS: Exposure and covariate data were collected through structured questionnaires. Blood was drawn for hormonal analysis during the 16th and 27th gestational week. Information on pregravid oral contraceptive use included duration and recency of use, and oral contraceptive formulation. Multivariate regression models were used to examine the effect of pregravid oral contraceptive use on birth outcomes and the studied pregnancy hormones. MAIN OUTCOME MEASURES: Birthweight, placental weight, gestational age, pregnancy hormone levels of oestriol and progesterone at 16th and 27th gestational week. RESULTS: Adjusting for confounders, pregravid oral contraceptive use increased birthweight (mean difference =+207.3 g, 95% CI =+77.6 to +337.1) and placental weight (mean difference =+64.9 g, 95% CI =+13.0 to +116.9) compared with never use. Women with prior oral contraceptive use had higher levels of serum progesterone (P= 0.002) and oestriol (P= 0.12) at the 27th gestational week measurement. The effect on birthweight, placental weight and hormones was stronger among those using oral contraceptives in the previous year and those using a high progestin/high oestrogen potency preparation. CONCLUSIONS: Pregravid oral contraceptive use is positively associated with fetal growth, and this effect may be mediated through oestriol and progesterone.

Adolescent↗

Effect of oral alanine loads on the serum triglycerides of oral contraceptive users and normal subjects.

The effect of orally administered L-alanine loads on serum triglycerides, and plasma insulin and glucose, was studied in 23 women using an estrogen-containing oral contraceptive and 13 healthy female controls. Oral contraceptive users had significantly higher fasting serum triglycerides than the controls. Serum triglycerides concentrations udnerwent little changes in the controls after alanine ingestion, whereas the oral contraceptive users showed increases which were maintained throughout the 3-hr sampling period. The two groups had similar elevations in plasma insulin after alanine loading; the glucose concentrations were unchanged. The changes in serum triglycerides may have resulted from increased metabolism of alanine to pyruvate, and its incorporation into lipids under the stimulus of elevated insulin levels.

Adult↗

Effect of various oral contraceptive combinations on dysmenorrhea.

The influence of different oral contraceptives on the prevalence and severity of dysmenorrhea was investigated in a representative sample of 19-year-old women from an urban Swedish population. The prevalence and severity of dysmenorrhea were significantly (p less than 0.01) reduced amongst users of progestogen-dominated oral contraceptives compared to a control group of women who used neither oral contraceptives nor an intrauterine device. However, there was no significant difference in the prevalence and severity of dysmenorrhea between users of oral contraceptives with low progestogen activity and the same control group. Thus, the relative progestogen activity of the oral contraceptive used appears to be of importance for the effective treatment of dysmenorrhea. Possible reasons for the superior therapeutic efficacy of progestogen-dominated oral contraceptives are discussed. Further studies are, however, necessary to evaluate the importance of the progestogen activity of oral contraceptives in the treatment of dysmenorrhea.

Absenteeism↗

Quantitative analysis of ethynodiol diacetate and ethinyl estradiol/mestranol in oral contraceptive tablets by high-performance liquid chromatography.

A procedure is described for the assay of ethynodiol diacetate and ethinyl estradiol/mestranol by HPLC using two UV detectors at 210 and 280 nm. The system was acetonitrile 38% (v/v) in water as mobile phase on a 250 x 3.2-mm i.d. RP-2 column, with butylated hydroxytoluene as the internal standard. There was greater than 99% recovery from synthetic preparations and the coefficient of variation was greater than 2.0% for formulations.

Chromatography, High Pressure Liquid↗