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PubMed1987

Oral contraceptives in the United States: trends in content and potency.

Data from the National Prescription Audit, a nationwide pharmaceutical marketing research data base, were reviewed to study changes in the type of oral contraceptives marketed in the US, their content and their relative oestrogen and progestin potency over the 21-year time period of 1964-84. Three major types and 42 brands of oral contraceptives were marketed in the US during this time period. All oral contraceptives dispensed in the US have contained one of nine different progestins and one of two oestrogens or, in the case of the progestin-only pills, no oestrogen at all. A comprehensive classification listing all 42 brands of oral contraceptives by content and strength is presented. Secular changes in oral contraceptive potency are described in terms of a categorization scheme which simultaneously ranks both the oestrogen and progestin potencies of each oral contraceptive. Over the time period studied, oral contraceptives have evolved from high strength, high potency drugs to much lower strength, lower potency drugs. The epidemiological implications of these shifts in oral contraceptive content and potency are discussed.

Contraceptives, Oral↗
PubMed1975

Oral contraceptives as related to cancer and benign lesions of the breast.

We conducted a case-control study to search for any relationship between use of oral contraceptives and development of breast cancer or benign breast disease. Women less than 50 years old with these diseases were matched with 2 controls by age, race, religion, and hospital. Home interviews elicited information on oral contraceptive use and other host and environmental factors. The study population comprised 1,770 women, including 452 with breast cancer and 446 with benign breast disease. The relative risk of developing cancer or benign disease was measured by matched set and summary chi-square analyses. Although the relative risk of developing breast cancer among "ever-users" of oral contraceptives was 1.1, the risk among women using oral contraceptives for 2-4 years was 1.9 (significantly increased). This risk estimate reached 2.5 for the 2- to 4-year users if they were still taking oral contraceptives when entered into study. Moreover, prior biopsy for benign breast disease increased the cancer risk among long-term users by as much as 11-fold. The relative risk of breast cancer did not vary by age, interval since first use, earliest year of use, or interval since last use. These results could be interpreted to indicate that oral contraceptives did not induce breast cancer but may have accelerated the growth rate of preexisting breast cancer. The relative risk of developing benign breast disease among ever-users of oral contraceptives was 0.8 (significantly reduced); it decreased with longer duration of use until it reached 0.2 for women who took these hormones 8 years or more. The relative risk of benign breast was not affected by earliest year of use or interval since last use. We concluded that oral contraceptives reduced the incidence of benign breast disease, but that use of steroid hormones is ill-advised for women with already established benign breast disease.

Adolescent↗
PubMed1989

Oral contraceptive use and liver cancer.

The risk of liver cancer in relation to use of oral contraceptives was evaluated in a hospital-based case-control study conducted in five US cities from 1977 to 1985. Twelve new cases of liver cancer were identified in women aged 19-54 years; five controls selected from among patients hospitalized for acute conditions unrelated to oral contraceptive use were matched to each case on age (five-year categories), date of interview (three-year categories), and geographic location of the hospital. Among nine cases classified as having hepatocellular carcinoma, eight (89%) had used oral contraceptives; only 16 (36%) of 45 matched controls had used oral contraceptives. Among three other cases (two with cholangiocarcinomas and one with liver cancer of undetermined type), all had used oral contraceptives, compared with four of 15 matched controls. The results confirm the strong positive association between oral contraceptive use and hepatocellular carcinoma observed in earlier studies. Such an association is consistent with evidence that oral contraceptive use is associated with benign hepatic tumors in young women. However, the number of cases of liver cancer in the United States that are attributable to oral contraceptive use is probably small, because liver cancer is extremely rare in the United States.

Adenoma, Bile Duct↗
PubMed2000

The potential role of contraception in reducing abortion.

This study examines the potential role of further increases in contraceptive prevalence and effectiveness in reducing abortion rates. The model used in this analysis links the abortion rate to its direct determinants, including couples' reproductive preferences, the prevalence and effectiveness of contraceptive practice to implement these preferences, and the probability of undergoing an abortion to avoid an unintended birth when a contraceptive fails or is not used. An assessment of the tradeoff between contraception and abortion yields estimates of the decline in the total abortion rate that would result from an illustrative increase of 10 percentage points in prevalence. This effect varies among societies, primarily because the tendency to obtain an abortion after an unintended pregnancy varies. For example, in a population with an abortion probability of 0.5, a 10 percentage-point increase in prevalence would avert approximately 0.45 abortions per woman, assuming contraception is 95 percent effective. If all unintended pregnancies were aborted, this effect would be three times larger. Eliminating all unintended pregnancies and subsequent abortions would require a rise in contraceptive prevalence to the level at which all fecund women who do not wish to become pregnant practice contraception that is 100 percent effective. A procedure is provided for estimating this "perfect" level of contraceptive prevalence.

Abortion, Induced↗
PubMed1994

Oral contraceptive use and mortality during 12 years of follow-up: the Nurses' Health Study.

OBJECTIVE: To examine prospectively the risk for mortality among women who had ever used oral contraceptives compared with those who had never used oral contraceptives. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 166,755 women aged 30 to 55 years in 1976, followed through 1988 (1.3 million person-years of follow-up). RESULTS: On the basis of 2879 deaths, we found no overall difference in mortality among women who had ever used oral contraceptives compared with women who had never used oral contraceptives; the relative risk for ever-users, adjusted for age, body mass index, and cigarette smoking was 0.93 (95% CI, 0.85 to 1.01). We observed no trend in risk for total mortality with increasing duration of past use of oral contraceptives. After adjusting for age, body mass index, and cigarette smoking, women who had used oral contraceptives for 10 or more years had a relative risk of 1.06 (CI, 0.83 to 1.35). CONCLUSION: Use of oral contraceptives is safe; no evidence from this study indicates that long durations of oral contraceptive use adversely affect long-term risk for mortality.

Adult↗
PubMed1976

[Does oral contraception cause cancer? (author's transl)].

A complete answer to the question of the relationship between malignant tumors in man and the administration of contraceptive steroids is at present not possible. Difficulties of the investigation are caused by the multiplicity of compounds used for contraception, the generally slow development of malignant tumors and the difficulty of the epidemiologic and statistical investigations on the multi-factorial etiology of cancer. Nevertheless, it can be stated with a high degree of certainty that "cancer due to the pill" does not exist in man and that a direct hormonal induction of malignant tumors in man cannot be proved. The question whether oral contraceptives may favor the development of cancer indirectly is explored in this paper regarding cancer of the female genital tract and the breast. No correlation between oral contraception and squamous cell carcinomas of the vulva and vagina and tumors of the ovary is known. As yet no statistics are available on the incidence of carcinoma of the endometrium in women who took oral contraceptives during their reproductive life span. Because of the direct hormonal suppression of the endometrial growth by oral contraception, a protective effect against endometrial hyperplasia and endometrial cancer must be expected. For cancer of the female breast no protective and no enhancing cancer risk due to progestational agents can be postulated. The known fragmentary data suggest a more protective value. Regarding dysplasia and carcinoma in situ of the uterine cervix large investigations in high numbers of patients are available. An increase of the risk to develop cancer of the cervix by using oral contraception cannot be shown with sufficient accuracy at our present state of knowledge by statistical means. Some observations suggest that oral contraception increases the relevant exogenous factors for carcinogenesis of the uterine cervix such as sexual behavior and hygiene.

Breast Neoplasms↗
PubMed1990

Effects of steroidal contraceptives on gallbladder: a review.

In regard to gallbladder disease and oral contraceptive use, more than ten controlled epidemiologic studies have been reported and reviewed in this paper. The findings presented concerning the association of oral contraceptive use with the development of a gallbladder disease are contradictory. Oral contraceptive use and use of estrogens in postmenopausal women have been reported to be associated with increased attack-rates of a gallbladder disease, but the increased risk is found higher in those using estrogens than progestin based oral contraceptives. Other studies, however, have reported little overall effect of oral contraceptive use on the risk of the gallbladder disease. Where increased risk has been documented, this has been more related to duration than overall. The increased risk of oral contraceptive use to gallbladder disease has been observed higher in the 6-12 months of usage. Only one study has reported increased risk of gallbladder disease in long-term users. The increased gallbladder disease in oral contraceptive users may be greater in multiparae than in nulliparae; pregnancy and obesity may also pose an increased risk to the disease in oral contraceptive users. However, these findings are not widely accepted.

Adult↗
PubMedDate not supplied

Religious affiliation and contraceptive usage: changing American patterns, 1955-82.

This paper presents national estimates of contraceptive usage patterns among white women from 1955-82 for the major religious populations in the United States. Drawing on several surveys, the data show that in 1955 differences in contraceptive use between white Protestants and Catholics were very large and corresponded to the higher fertility levels among Catholics. By 1982, all the major religious groups had experienced downward changes in expected family size and all used effective contraceptive methods, including sterilization, the pill, and the IUD. Despite some convergence in the patterns of contraceptive usage over time, significant differences in contraceptive use styles remain among Catholics, Protestants, Jews, and those of no religious affiliation after multivariate controls eliminated socioeconomic and sociodemographic differences among these subpopulations. The evidence points to the multiple contraceptive paths to similar levels of low fertility. A series of hypotheses are proposed to account for these different contraceptive use styles that relate to religious communities, peer pressure and social norms, differential sex roles, male-female communication patterns, and the differential use of physician-based versus other sources of contraceptives.

Adolescent↗
PubMed1990

Long-term experience with a low-dose oral contraceptive.

Oral contraception has proved to be the most efficient reversible method of fertility control for over 25 years. During this period, various investigations and epidemiological studies have suggested that some risks may be involved, but, on the other hand, a number of non-contraceptive benefits have become obvious. The results of these investigations were taken into account when new formulations had to be developed, with an aim to improving hormonal fertility control with regard to its tolerance, cycle control, and impact on metabolism. Since then, the objective of research has been to contrive new hormonal contraceptives which ensure safety to the largest possible extent, from a medical point of view, for the sake of the patient, without affecting contraceptive effectiveness. The aim to reduce side-effects connected with the use of oral contraception, as well as to lower the risks possibly involved, has obviously been achieved by extensive research. Both by devising a new substance and reducing doses, the criteria of modern low-dose oral contraception have been met, as has become evident in the course of the clinical experience gathered with Femovan.

Acne Vulgaris↗
PubMed1980

Effects of oral contraceptive agents on copper and zinc balance in young women.

Young adult women were selected from a group of volunteers on the basis of present and past use of oral contraceptive agents. Subjects were either those who had never used oral contraceptives or those who had used an agent for a minimum of two menstrual cycles. All subjects were fed diets that provided 2.02 to 2.11 mg of copper and 9.15 to 9.10 mg of zinc daily in an 18-day controlled metabolic study. Both oral contraceptive users and nonusers were in negative zinc balance and zinc excretion as not different (P > 0.05) for the groups. Oral contraceptives did not alter (P > 0.05) the metabolic balance of copper; the mean copper retention values were -0.16 mg/day for the nonusers and -0.13 mg/day for the users of oral contraceptives. As anticipated from reports in the literature, the plasma copper levels were higher (P < 0.01) in the oral contraceptive group, but the levels of zinc were not different. Although blood levels of zinc and copper are usually changed with the use of oral contraceptives, the retention of the two nutrients appears not to be affected.

Adult↗
PubMed1987

The role of contraceptive use in cervical cancer: the Maryland Cervical Cancer Case-Control Study.

Recent evidence on the importance of sexual history and sexually transmissible agents in cervical cancer has been reported. Case-control studies have frequently demonstrated increased risk of cervical cancer for women using oral contraceptives, while laboratory results have shown that vaginal spermicides inactivate various sexually transmissible agents. To determine the role of contraceptive use in cervical cancer, 153 cases of Maryland women with invasive cervical cancer and age, race, and residence-matched controls were interviewed in 1985, focusing on sexual history, health care utilization patterns, screening history, contraceptive use, and smoking. Overall, lifetime use of contraceptives was protective of cervical cancer (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.2-0.7). Use of oral contraceptives (OR = 0.48), diaphragm (OR = 0.29), and vaginal spermicides (OR = 0.28) were more frequent in controls than cases. After adjustment for behavioral factors (age at first intercourse, smoking, gaps in Papanicolaou smear testing, and obstetrician-gynecologist visits), use of vaginal spermicides remained significant (OR = 0.30), although use of oral contraceptives and barrier methods of contraception failed to remain significant. The effectiveness of vaginal spermicides in preventing cervical cancer may be due to their antiviral action.

Adult↗
PubMed1995

Hormonal male contraception: progress and prospects for the 21st century.

During the second half of the 20th century, progress in developing novel, practical contraceptive methods for men has lagged significantly behind developments for women. Despite the lack of reliable, reversible methods, men throughout the world continue to be strongly involved in family planning but a greater involvement will require more attractive and reliable contraceptive options for men. The closest to fruition are hormonal methods the features of which are reviewed. Landmark WHO contraceptive efficacy studies have established that hormonally-induced azoospermia provides highly effective and reversible contraception for at least 12 months with minimal short-term side effects. Even among the small subgroup of men who remain oligozoospermic during hormonal suppression, good contraceptive efficacy is achieved. The present goals are to develop improved second generation hormonal regimens which provide more uniform azoospermia to obviate the need for monitoring of sperm output and to develop long-acting depot testosterone formulations used alone or with additional gonadotrophin suppressive agents such as progestins or GnRH antagonists. Significant obstacles to progress are the flight of industry from contraceptive R&D dur to the financial deterrent posed by the product liability crisis as well as the low priority accorded male reproductive health. Together those will determine whether the range of contraceptive options available to our children in the 21st century will improve, or whether the historically recent unbalanced increase in reliance on women for family planning will continue.

Animals↗
PubMedDate not supplied

Teenagers' perceptions of unplanned adolescent pregnancies and oral contraceptive use.

Adolescent women who are sexually active often do not use contraceptives consistently and correctly. Adolescents are sexually active for an average of 15 months before initiating regular contraceptive use and the majority of young women who initiate use discontinue within the first year after initiation. This study enrolled 50 young women who initiated oral contraceptive use and was designed to provide more understanding of their perceptions about the possibility of an unplanned pregnancy and about contraceptive use. They were again contacted 6 weeks after initiation of oral contraceptives to assess continuation. Findings revealed that 90% of the subjects were sexually active at the time of the first visit; the mean period of sexual activity was 15 months. Only 30% had used a nonprescription birth control method during this period. While perceiving themselves to be highly susceptible to pregnancy, many young women continue to have psychosocial barriers to contraceptive use. Follow-up contact revealed more than 10% of the subjects were not using oral contraceptives.

Adolescent↗
PubMed1997

Emergency contraception: preventing unintended pregnancy.

Approximately 60% of all pregnancies are unintended at the time of conception, either unwanted or mistimed. Emergency contraception (i.e., use of a birth control method after intercourse has occurred) is a preventive treatment that has been underutilized. Six brands of oral contraceptives have recently been found by the U.S. Food and Drug Administration to be safe and effective as emergency contraceptive pills. These pills have been shown to reduce the likelihood of pregnancy occurring by at least 74%. Treatment with emergency contraceptive pills should be initiated within 72 hours of unprotected intercourse. Adverse effects include nausea, vomiting headache, and a change in menstrual bleeding patterns. Postcoital insertion of an intrauterine device is also highly effective as a postcoital contraceptive, but only in a select group of patients at low risk for sexually transmitted diseases. Promotion of access to emergency contraception includes educating both patients and providers about the method and making emergency contraceptive pills available to patients even before the need arises.

Contraceptives, Postcoital↗
PubMed2000

Modern combined oral contraceptives for pain associated with endometriosis.

BACKGROUND: Endometriosis is a major women's health-care problem. It causes pain and/or infertility, and affects millions of women worldwide. Endometriosis is defined according to histological criteria by the presence of tissue resembling endometrium in sites outside the uterus, most commonly the ovaries and peritoneum. The aim of treatment has been to remove the deposits of ectopic endometrium that are thought to be responsible for the symptoms of endometriosis. This can be achieved surgically by destroying or removing the implants; medical therapies induce atrophy within the hormonally-dependent ectopic endometrium. The duration of hormonal treatment may be limited by unwanted side effects. There is some evidence, however, from epidemiological research that current use of the combined oral contraceptive pill (OCP) is associated with a reduced incidence of endometriosis. The combined pill has the great advantage over other hormonal treatments that it can be taken indefinitely. OBJECTIVES: The aim of this review was to establish the role of modern oral contraceptives in the management of painful symptoms ascribed to endometriosis. SEARCH STRATEGY: The search strategy of the Menstrual Disorders Group was utilised to identify all randomised trials of the use of oral contraceptives in the treatment of symptomatic endometriosis. In addition a search of the Cochrane Controlled Trials Register was undertaken together with approaches to pharmaceutical companies. SELECTION CRITERIA: All truly randomised controlled trials of the use of oral contraceptive pills in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis made visually at a surgical procedure, were included. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction was carried out independently by two reviewers. One of the assessors was an expert in the content matter. MAIN RESULTS: Only one study was identified which satisfied the inclusion criteria. The oral contraceptive used in a conventional manner was less effective than a GnRH analogue in the relief of dysmenorrhoea. No significant difference was noted between the effectiveness of the oral contraceptive pill and a GnRH analogue in the relief of dyspareunia or non-menstrual pain. Headaches and weight gain were more commonly associated with oral contraceptive usage than with GnRH analogue usage whereas hot flushes, insomnia and vaginal dryness were less common. REVIEWER'S CONCLUSIONS: There is a paucity of data relating to the use of oral contraceptive preparations in the treatment of symptomtic endometriosis. The data such as it is supports the common practice of the use of the oral contraceptive pill as a first line therapy but further research is required to fully evaluate its role in the management of endometriosis.

Contraceptives, Oral↗
PubMed1995

[13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose oral contraceptives.

The [13C]aminopyrine breath test measures hepatic mixed function oxidase activity. The cumulative percent dose recovered over 2 hr is a sensitive indicator of hepatic dysfunction; values < or = 7.0% have been shown to indicate severe liver disease. Previous studies have suggested that the test results may be influenced by the use of oral contraceptives steroids. We compared the results from five non-oral contraceptive-using women with those from 31 women whose duration of oral contraceptive steroid usage ranged from 4 to 204 months. The women were taking one of four oral contraceptive formulations that differed in the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5, 0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and 28 of the menstrual cycle. Cumulative percent dose recovery values among the normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/- 1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid users showed a marked reduction in cumulative percent dose recovery at 21 days, averaging 6.1 +/- 2.3% (P < 0.001), and returned to normal values (10.2 +/- 3.5%) at 28 days in most women(seven days after oral contraceptive steroid usage was paused). The adverse impact on hepatic mixed function oxidase by oral contraceptive formulations did not differ on the basis of estrogen or progesterone content. The adverse impact of oral contraceptive usage on the mixed function oxidase activity measured by the [13C]aminopyrine breath test must be considered for women of childbearing potential.

Adult↗
PubMed1975

Oral contraceptives and thromboembolism: a reassessment.

The relationship between oral contraceptive usage and thromboembolism is controversial. Since thromboembolism is often undiagnosed, both clinically and at routine autopsy, most epidemiologic analyses rest or a very uncertain factual base. There are increases in blood coagulation factors in oral contraceptive users similar to, but less than, those seen in pregnancy, which is not associated with increased thromboembolism. Hematologists emphasize that these changes do not define a "hypercoagulable" state, and they do not define or predict the occurrence of thrombosis. Intrinsic vascular wall changes, unrelated to drug use, may play a role in sporadic cases of thromboembolism. When the incidence of thromboembolism in very large Phase III trials of conventional oral contraceptives is compared to that in other populations (patients admitted to the hospital, women who visit a physician, pregnant women, or users of nonestrogenic oral contraceptives), no difference is seen. Epidemiologic studies by the "case-control" ("trohoc") method consistently show an increase "relative risk" associated with oral contraceptive use in subjects with "idiopathic" thromboembolism but no increased risk in thromboembolism patients as a whole or in those with predisposing factors. This retrospective epidemiologic technique, its particular applications, and the inferences drawn are open to serious criticism, as are studies claiming a relationship between estrogen dose and thromboembolism incidence. An Australian prospective survey found no increased risk among users, and a large British study which initially reported an increased risk is currently undergoing recalculation. The only controlled clinical experiment (with random assignment of subjects to vaginal versus high-estrogen contraceptives) showed no increased incidence in the drug-treated group. Statistical associations derived from "trohoc" studies do not establish causal relationships; moreover, their risk estimates are in conflict with the findings of large Phase III clinical surveys including subjects using estrogen-free contraceptives, with at least one prospective clinical survey, and with a randomized, controlled clinical trial. The data relating estrogen dosage to thromboembolism incidence are ambiguous, at best. Thus, the claim of a causal relationship between oral contraceptive steroids and thromboembolism does not appear to be firmly founded, and the belief that predisposing factors increase the risk to contraceptive users is equally insubstantial.

Adolescent↗
PubMed2006

Female sex and oral contraceptive use accelerate nicotine metabolism.

BACKGROUND: Several studies have reported that female smokers have a higher risk of lung cancer than male smokers. This could be related to sex differences in nicotine metabolism and related smoking behavior. This study tested the hypothesis that women metabolize nicotine more rapidly than men and that, among women, oral contraceptive users metabolize nicotine more rapidly than nonusers of oral contraceptives. METHODS: Two hundred seventy-eight healthy volunteers who were twins and 16 who were siblings of twins, recruited from the Northern California Twin Registry, received an infusion of deuterium-labeled nicotine and cotinine with frequent blood sampling. The plasma clearances of nicotine and cotinine, the clearance of nicotine to cotinine (an index of cytochrome P450 [CYP] 2A6 activity), and the ratio of trans-3'-hydroxycotinine to cotinine (another indicator of CYP2A6 activity) were measured. RESULTS: The clearances of nicotine and cotinine, the clearance of nicotine to cotinine, and the trans-3'-hydroxycotinine/cotinine ratio were significantly higher in women than in men (nicotine clearance, 15.6 +/- 4.3 mL.min(-1).kg(-1) in men versus 18.8 +/- 6.6 mL.min(-1).kg(-1) in women; P < .001); they were also higher among women taking oral contraceptives than in those who were not taking oral contraceptives (nicotine clearance, 22.5 +/- 6.6 mL.min(-1).kg(-1) in women taking oral contraceptives versus 17.6 +/- 6.1 mL.min(-1).kg(-1) in those who were not; P < .05). Women who were menopausal or postmenopausal were not different from men. Among oral contraceptive users, nicotine metabolism was accelerated among those taking combined and estrogen-only contraceptives but not progesterone-only contraceptives. CONCLUSIONS: Sex hormones influence nicotine metabolism. Nicotine and cotinine metabolism is faster in women than in men and is faster in women taking oral contraceptives compared with those who are not. Accelerated nicotine metabolism appears to be a result of estrogen. Sex-related differences in nicotine clearance could affect smoking behaviors, as well as response to nicotine medications, and could be a marker for altered metabolism of nicotine-derived carcinogens.

Adolescent↗