Oral Contraceptive Agents Research Articles

Meta-analysis of the role of oral contraceptive agents in inflammatory bowel disease.

Numerous epidemiological studies have been performed to determine factors that might contribute to the development of inflammatory bowel disease. Although the role of oral contraceptive agents in Crohn's disease (CD) and ulcerative colitis (UC) have been assessed, most studies were of small sample size and characterised by low statistical precision. A meta-analysis was performed to increase the statistical power and to investigate the association between the use of oral contraceptives and the development of CD and UC. The study was based on a search of a Medline database from 1975 to October 1993 and a review of reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. All studies specifically designed to evaluate this association were selected. The combined results of nine studies--two cohort studies (30,379 unexposed and 30,673 exposed patients) and seven case-control studies (482 CD, 237 UC, and 3198 controls)--which satisfied our selection criteria were evaluated. The pooled relative risk (adjusted for smoking) associated with oral contraceptive use was 1.44 (1.12, 1.86) for CD and 1.29 (0.94, 1.77) for UC. These results suggest modest associations between the use of oral contraceptives and the development of CD and UC. As these associations are weak, non-causal explanations for the findings cannot be eliminated.

Intrahepatic Cholestasis of Pregnancy

Cholestasis of pregnancy may be relatively benign causing little more than maternal pruritus, or it may cause significant fetal mortality. It is likely under-diagnosed as it is not always considered, and the most appropriate testing is often unavailable. Subsequent pregnancies may or may not be affected. There appear to be both genetic and environmental factors at play.The biochemistry of bile metabolism is altered during pregnancy. This may be due to an inherited hypersensitivity to estrogens at a genetic level. This increase in bile may affect the fetus by decreasing placental blood flow through a number of mechanisms, with the most severe outcome being fetal demise. Non-stress testing does not appear to be predictive of fetal demise. No studies have assessed the role of the biophysical profile in managing this disease.Treatment of the disease only alters maternal morbidity. There is little information on future long-term effects on the mothers. While it is known that they do not tolerate oral contraceptive agents, there have been no studies regarding susceptible women’s responses to post-menopausal hormone replacement.

Reversible ischemic colitis in young women. Association with oral contraceptive use.

Ischemic colitis, a condition of middle-aged to elderly patients, occurs uncommonly in younger persons. In this study, we describe the clinical and pathological features of 18 young adults (mean age, 29 years; age range, 17-39 years) with spontaneous ischemic colitis, 17 of whom were women. All presented with abrupt onset of severe, cramping abdominal pain followed by hematochezia. Colonoscopic visualization of the mucosa showed segmental hyperemia, friability, and erosion affecting the distal transverse colon (three cases), splenic flexure (three cases), descending colon (five cases), and sigmoid (seven cases). Mucosal biopsy documented superficial ischemic necrosis in seven patients; 11 patients had full-thickness mucosal necrosis with regeneration. Colonic mucosa proximal and distal to the ischemic segment was endoscopically normal in all patients and histologically normal in the eight patients in whom biopsies were obtained. All patients recovered with supportive care. Median duration of illness was 2.1 days (range, 1-4 days). Ten women (59%) were using low-dose estrogenic oral contraceptive agents, compared with the 1988 national average of 18.5% oral contraceptive users among females aged 15 to 44 years. The calculated odds ratio yielded a greater than sixfold relative risk for the occurrence of ischemic colitis among oral contraceptive users. In addition, four women not currently on hormonal contraceptive therapy had a past history of oral contraceptive use; the three remaining women were taking estrogen as replacement therapy after oophorectomy. In one patient, documented reversible ischemic colitis recurred on resumption of oral contraceptive use; four women reported symptoms and signs of recurrent ischemia but did not seek further medical evaluation. Our data indicate that transient colonic ischemia represents a form of acute segmental colitis in young adults; before the 5th decade of life, spontaneous ischemic colitis is a disorder found almost exclusively in women and is associated with the clinical use of exogenous estrogenic agents.

The Effect of the Phase of the Menstrual Cycle and the Birth Control Pill on Athletic Performance

Investigators are not in agreement on the effects of either the phase of the menstrual cycle, or the administration of OCAs on athletic performance. It appears, however, that apart from subtle changes in some variables, for most women there is no significant effect. Medals have been won and world records set in any phase of the menstrual cycle, and also by women taking OCAs. In terms of documentation of cycle phase, newer hormonal measurement techniques such as the levels of urinary luteinizing hormone (LH) to detect ovulation or salivary progesterone, should make it easier in the future to obviate the methodologic difficulties encountered in earlier studies. Further studies should also focus on the midcycle estradiol surge as well, in order to determine the relative contributions of estrogen and progesterone to any observed performance changes. Given the possibility that some cardiovascular, respiratory, and metabolic variables may change slightly during the course of a regular ovulatory menstrual cycle, it behooves researchers who are using women as subjects in other types of studies to standardize the menstrual cycle phase in which they are tested, in order to eliminate any possible confounding effects due to hormonal variation. Regarding the effects of oral contraceptives on performance, any conclusions from the studies to date are complicated by the proliferation of preparations currently on the market. Further studies are needed on monophasic, biphasic and triphasic formulations, including OCAs with the newer progestins (desogestrel, gestodene and norgestimate), as well as the progesterone-only agents (both oral and injectable). Prospective double blind randomized studies must be done, using a proper control group. The difficulty with this technique, however, is that women in the control group will inevitably be in various phases of the cycle, so accurate hormonal documentation is also essential in order to correctly interpret the findings. Just as the past few decades have seen a significant advancement in the participation of women in sports, future years should bring an enhanced scientific knowledge base about the interactions of the special hormonal considerations of the exercising woman throughout her reproductive life cycle.

Unwanted pregnancies: Understanding contraceptive use and benefits in adolescents and older women

The highest percentages of unintended pregnancies and the largest increases in births reported in the United States in recent years were in adolescents and in women more than 35 years of age. Increasing numbers of these women will require contraception to avoid unintended pregnancy. In adolescents the combined oral contraceptive agents protect fertility indirectly and exert favorable actions on menstrual dysfunction and certain hormone-related disorders such as acne and hirsutism. To avoid sexually transmitted disease, barrier protection should be used along with oral contraceptives until mutually monogamous, stable relationships are established. Healthy older women who are nonsmokers may also safely use currently available contraceptives. These agents have little impact on metabolic parameters linked to the development of cardiovascular disease. In addition to providing reliable contraception, oral contraceptives offer noncontraceptive benefits to older reproductive-age women, including control of abnormal bleeding and a reduction in the incidence of ovarian and endometrial cancers and other gynecologic pathology. Intrauterine devices and progestin implants are safe, effective, and underused in the United States. Progestin implants may have an additional role in patients for whom estrogen preparations are contraindicated. Counseling is very important before insertion because of the high rate of nuisance side effects. The contraception selection process must consider the efficacy and acceptability of the specific method to avoid the probability of unintended pregnancy and the risk of sexually transmitted diseases.

Unwanted pregnancies: Understanding contraceptive use and benefits in adolescents and older women

The highest percentages of unintended pregnancies and the largest increases in births reported in the United States in recent years were in adolescents and in women more than 35 years of age. Increasing numbers of these women will require contraception to avoid unintended pregnancy. In adolescents the combined oral contraceptive agents protect fertility indirectly and exert favorable actions on menstrual dysfunction and certain hormone-related disorders such as acne and hirsutism. To avoid sexually transmitted disease, barrier protection should be used along with oral contraceptives until mutually monogamous, stable relationships are established. Healthy older women who are nonsmokers may also safely use currently available contraceptives. These agents have little impact on metabolic parameters linked to the development of cardiovascular disease. In addition to providing reliable contraception, oral contraceptives offer noncontraceptive benefits to older reproductive-age women, including control of abnormal bleeding and a reduction in the incidence of ovarian and endometrial cancers and other gynecologic pathology. Intrauterine devices and progestin implants are safe, effective, and underused in the United States. Progestin implants may have an additional role in patients for whom estrogen preparations are contraindicated. Counseling is very important before insertion because of the high rate of nuisance side effects. The contraception selection process must consider the efficacy and acceptability of the specific,method to avoid the probability of unintended pregnancy and the risk of sexually transmitted diseases. (Ann J OBSTEr GYNECOL 1993;168:2042-8.)

Do oral contraceptive agents affect the risk of breast cancer? A meta-analysis of the case-control reports.

We designed a study to assess the association of oral contraceptive use and the development of breast cancer for women in the following groups: (1) ever oral contraceptive users, (2) long-term oral contraceptive users, and (3) oral contraceptive users before a first full-term pregnancy. A MEDLINE search of studies published in English from 1966 to 1990 was conducted using the following key words: "oral contraceptive and breast carcinoma." Eligible studies included all published case-control reports of nonduplicated data on a population (hospital or community-based). The following data were extracted from each report: country, age of subjects, number of cases and controls, whether it was a hospital or community-based study, and results. Two evaluators using a quality-assessment instrument independently and blindly reviewed the methods and data analysis section from each eligible study. In the category of "ever oral contraceptive users," an estimate of the pooled relative risk with 95 percent confidence intervals (CIs) was calculated. In the categories of "duration of oral contraceptive use" and "duration of oral contraceptive use before a first full-term pregnancy," Spearman's rank correlation coefficient (rs) was calculated. For the categories of "ever oral contraceptive users" and "long-term oral contraceptive users," no association between the use of oral contraceptives and the development of breast cancer could be detected (pooled relative risk "ever oral contraceptive users" = 1.07, 95 percent CI 0.78 to 1.36, rs "duration of use" -0.153, P = 0.189). For the category of "oral contraceptive use before a first full-term pregnancy," a significant correlation was found (rs = +0.497, P = 0.011). Many reports failed to demonstrate adequate protection against the biases most relevant to case-control methods (namely, recall bias, interviewer bias, surveillance bias, and nonresponse bias) and therefore received low-quality scores. This meta-analysis suggests a possible increased risk for breast cancer in women who use oral contraceptives before a first full-term pregnancy. The data, however, are confounded by studies that are generally of low quality. Further studies addressing the risk for breast cancer in oral contraceptive users need to be designed with methods that limit the biases inherent in case-control studies.

Noncontraceptive benefits of oral contraceptive agents. Patients should know the positive effects.

Physicians' role as teachers and counselors includes the responsibility to provide detailed and accurate information on the risks and benefits of therapy whenever a prescription is written. Inaccurate or overly negative communication, particularly from the mass media, may confuse patients trying to make an informed decision regarding use of oral contraceptives. Patients have the right to be informed of possible prevention of life-threatening disease and improvement of quality of life as a result of oral contraceptive therapy.

Influence of oral contraceptive agents on kidney function and protein metabolism

The present study was an investigation of the effect of oral contraceptives on kidney function as well as a brief examination of protein metabolism, since glomerular filtration rate depends to a large extent on daily protein intake. 28 healthy women not taking contraceptives and 46 healthy women (aged 20-28 y) on one of three different types of oral contraceptive (combination preparations) were investigated [Minulet/Femovan, Marvelon, Diane]. In all groups on oral contraceptives the endogenous creatinine clearance was significantly increased. The potassium excretion rate was significantly elevated in the groups taking Marvelon and Diane, and the sodium excretion rate was significantly increased in those on Minulet/Femovan and Diane. In all groups on contraceptives the albumin excretion rate was numerically but not significantly elevated. No significant differences were found in the daily oral protein intake or the nitrogen excretion rate on comparing the groups taking contraceptives with the control group. However, the ratio nitrogen excretion rate/daily protein intake was significantly increased in those on Minulet/Femovan and Diane. The study has shown that besides their various effects on renal tubular function, oral contraceptives are able to increase the glomerular filtration rate, and certain types have a protein catabolic effect.

Lipid and carbohydrate effects of a new triphasic oral contraceptive containing norgestimate.

Data are reported from the combined results of two studies assessing the lipid and carbohydrate effects of a triphasic preparation of norgestimate and ethinyl estradiol (Ortho TriCyclen, Tri-Cilest) over a 2-year period in 1,783 healthy women. Mean values for serum levels of high-density lipoprotein cholesterol (HDL-C) were increased significantly, with a percent change at 24 months of 13.2. Values for the ratio of low-density lipoprotein cholesterol to HDL-C were reduced throughout the study period (mean change of -6.4% at cycle 24). There were no clinically significant changes in fasting blood glucose levels or insulin levels or in values for glycosylated hemoglobin. These results are consistent with those of previous studies and indicate that the triphasic preparation of norgestimate and etinyl estradiol is a selective and minimally androgenic oral contraceptive agent. Long-term therapeutic benefit may accrue from the favorable influences on the lipid profile.

Oral contraceptive use may protect against low bone mass. Henry Ford Hospital Osteoporosis Cooperative Research Group

This cross-sectional retrospective epidemiologic study investigated risk factors for low bone mineral density (BMD) in a group of 2297 women, 76% of whom were postmenopausal. Reproductive information, history of oral contraceptive use, BMD measurements, and other data were available from women presenting to 12 osteoporosis screening centers in 1986 and 1987. Each woman was classified into a BMD category based on the range of BMD measurements at her respective center. Menopause, increasing age and years since menopause, and decreasing body mass index were associated with low BMD. A history of oral contraceptive use was protective against low BMD (odds ratio = 0.35, 95% confidence interval = 0.23 to 0.53). Multivariate analyses confirmed this result and further demonstrated that increasing duration of use was protective. These data suggest that prior use of oral contraceptive agents is associated with higher levels of BMD and that the degree of protection from lower BMD is related to duration of exposure.

Oral Contraceptive Use May Protect Against Low Bone Mass

This cross-sectional retrospective epidemiologic study investigated risk factors for low bone mineral density (BMD) in a group of 2297 women, 76% of whom were postmenopausal. Reproductive information, history of oral contraceptive use, BMD measurements, and other data were available from women presenting to 12 osteoporosis screening centers in 1986 and 1987. Each woman was classified into a BMD category based on the range of BMD measurements at her respective center. Menopause, increasing age and years since menopause, and decreasing body mass index were associated with low BMD. A history of oral contraceptive use was protective against low BMD (odds ratio = 0.35, 95% confidence interval = 0.23 to 0.53). Multivariate analyses confirmed this result and further demonstrated that increasing duration of use was protective. These data suggest that prior use of oral contraceptive agents is associated with higher levels of BMD and that the degree of protection from lower BMD is related to duration of exposure. (Arch Intern Med. 1991;151:1971-1976)

The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism

International Journal of Gynecology & ObstetricsVolume 36, Issue 1 p. 86-87 Citation from the literature Gynecological endocrinology The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism IF Godsland, IF GodslandSearch for more papers by this authorD Crook, D CrookSearch for more papers by this authorR Simpson, R SimpsonSearch for more papers by this authorT Proudler, T ProudlerSearch for more papers by this authorC Felton, C FeltonSearch for more papers by this authorB Lees, B LeesSearch for more papers by this authorV Anyaoku, V AnyaokuSearch for more papers by this authorM Devenport, M DevenportSearch for more papers by this authorV Wynn, V WynnSearch for more papers by this author IF Godsland, IF GodslandSearch for more papers by this authorD Crook, D CrookSearch for more papers by this authorR Simpson, R SimpsonSearch for more papers by this authorT Proudler, T ProudlerSearch for more papers by this authorC Felton, C FeltonSearch for more papers by this authorB Lees, B LeesSearch for more papers by this authorV Anyaoku, V AnyaokuSearch for more papers by this authorM Devenport, M DevenportSearch for more papers by this authorV Wynn, V WynnSearch for more papers by this author First published: September 1991 https://doi.org/10.1016/0020-7292(91)90218-TAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume36, Issue1September 1991Pages 86-87 RelatedInformation

Characteristics of the new progestogens in combination oral contraceptives

This review details the characteristic features of three new progestogens which soon will be available in low-combination oral contraceptive agents in the United States. Available data suggest that desogestrel, gestodene, and norgestimate are extremely potent progestogens with few androgenic side effects. The smaller changes in lipids induced by these progestogens seem to confer some advantage to the use of preparations containing one of these agents. Whether this advantage is also present clinically remains to be determined.

The Effects of Different Formulations of Oral Contraceptive Agents on Lipid and Carbohydrate Metabolism

Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.

Drug utilization in breast-feeding women. A survey in Oslo

In a retrospective questionnaire survey of 885 women who had given birth 3-5 months before, fewer of those who were still breast-feeding at 4 months (n = 645) were using drugs than those who had stopped breast-feeding before 4 months (n = 240), during the 2 week period preceding registration. The average number of doses (Defined Daily Doses/1000 women/day) was 166 and 307, respectively, in that period. The number of doses taken was significantly associated with the use of oral contraceptive agents (p less than 0.005) and young maternal age (p less than 0.05). Most of the variation in drug use between breast-feeding and not breast-feeding mothers was probably due to the greater use of contraception by the latter. The number of drugs used per mother in the 4 month period seemed to be best predicted by her and her infant's disorders. Long-term medication in breast-feeding women included many drugs for which there is incomplete or no data about milk transfer, e.g. salbutamol, clemastine, dexchlorpheniramine, phenylpropanolamine, cromoglycate and levomepromazine. The disorders most extensively treated with drugs in this period were dyspepsia, haemorrhoids and inflammation of the breast. The finding that smoking was associated with early weaning and consumption of alcohol with prolonged breast-feeding calls for further investigation. More information on these drug and health issues to the breast-feeding mother is highly desirable.

Assessing the Acceptability of NORPLANT Implants in Four Countries: Findings from Focus Group Research

In 1986-87, a qualitative research project was conducted in the Dominican Republic, Egypt, Indonesia, and Thailand to expand understanding of the acceptability of NORPLANT contraceptive implants beyond inferences made on the basis of continuation rates. In each of the four study sites, focus group discussions or in-depth interviews were held with potential acceptors, current NORPLANT users, discontinuers, husbands of women in these three groups, and service providers. Nonclinical participants generally had little formal education and lived primarily in urban or semi-urban areas where NORPLANT has been available for at least five years. The study focused on attitudes, perceptions, and experiences of each group regarding NORPLANT implants. Results suggest that factors having an impact on the acceptability of NORPLANT implants fall into three general categories: medical/technical, cultural/religious, and informational/educational. This article discusses each of these categories, including programmatic implications of the findings, and puts forward recommendations for enhancing NORPLANT introduction efforts on the basis of these findings.

Influence of steroid hormones on protein-platelet interaction at the blood-polymer interface

To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced thrombosis needs to be better understood. Steroidal hormones have a profound role in thrombosis and haemostasis, although adequate studies are not available to demonstrate their part in the thromboembolic phenomena that occur at the blood-foreign material interface. We studied the interfacial phenomena of five steroid hormonal drugs, Sustanon®, Menstrogen®, Mixogen®, Durabolin® and Ovral® and their interaction with proteins and platelets toward an artificial surface using contact angle, polyacrylamide gel electrophoresis, trace labelling methods etc. This study demonstrates the effect of these hormones to modulate platelet-surface attachment in the presence of platelet inducers. The addition of steroid hormones to the polymer-protein system can inhibit the level of surface-bound albumin where the fibrinogen binding to an artificial surface has been enhanced or unaltered. Steroids also increase platelet-surface attachment to variable degrees. Prolonged use of steroids or the oestrogen-containing oral contraceptive agents may not be advisable for patients having an artificial implant in contact with blood.

The Effect of Antibiotics on the Efficacy of Oral Contraceptives

What is currently known about the interaction of oral contraceptives and antibiotic drugs? This remains a pertinent question for all dermatologists. At our institution, a large number of women of child-bearing age are seen at the student infirmary. During eight typical half-day dermatology clinics, 53 women were seen with inflammatory papulopustular or cystic acne who were appropriate candidates for oral antibiotics. Of these women, 27 (51%) were receiving some form of oral contraceptive agent. After a brief discussion regarding the possibility of decreased efficacy, one patient refused oral therapy and two patients expressed enough concern so that topical therapy was minimized and oral therapy was deferred. This recent sample of patient communication with the physician points up the importance of understanding the current data available regarding the interaction of oral contraceptives with antibiotic therapy. Indeed, 10 million women in the United States are currently taking oral contraceptives. 1 The 1989

Etiologic factors in renovascular fibromuscular dysplasia. A case-control study.

The role of several factors that have been suggested as being of etiologic importance in renovascular fibromuscular dysplasia was examined in a case-control study of 33 patients with angiographically demonstrated fibromuscular dysplasia and 61 renal transplant donor control subjects with normal renal arteries. The factors studied included use of oral contraceptive agents or markers of sex hormone dysfunction, mechanical stress to the renal artery wall, human lymphocytic antigen (HLA) type, cigarette smoking, history of hypertension for more than 5 years, and family history of cardiovascular disease. The risk of fibromuscular dysplasia was significantly (p = 0.003) increased (odds ratio = 4.1, 95% confidence interval = 1.5-10.9) among cigarette smokers. A significant (p less than 0.001) dose-response relation was noted between cigarette use and the risk of fibromuscular dysplasia developing (odds ratio = 8.6 for those who had smoked more than 10 pack-years). Personal history of hypertension more than 5 years was also associated (odds ratio = 5.0, 95% confidence interval = 1.1-22.8) with a significantly (p = 0.036) increased risk for the development of fibromuscular dysplasia. HLA-DRw6 antigen was more common in the 33 fibromuscular dysplasia patients than in the 61 renal transplant donor control subjects (odds ratio = 3.00, p = 0.067) or a second group of 934 ambulatory control subjects (odds ratio = 2.51, p = 0.031). Adjustment for cigarette smoking increased the odds ratio to 5.0 (95% confidence interval = 1.3-19.6). There was a positive though not statistically significant (odds ratio = 1.7, p = 0.175) association noted between family history of cardiovascular disease and fibromuscular dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)