Benefits and risk of oral contraceptives. A reassessment.
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Biomedical subjects
Publications and source records attributed to R T Burkman.
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The major risk factors for coronary heart disease in women are much the same as in men. They include elevated cholesterol, hypertension, diabetes, cigarette smoking, severe obesity, a history of stroke and/or thromboembolic disease, and a family history of premature coronary heart disease. Diabetes appears to confer a greater risk and hypertension to have a lesser effect in women than in men. The obstetrician-gynecologist's role as primary care physician is important in terms of risk reduction counseling in areas that are amenable to change: diet, exercise and cigarette smoking. A fourth area, prescribing hormonal therapy, including oral contraceptives and hormone replacement, is the one risk reduction modality that is within the physician's control.
Substantial improvements have been made in oral contraceptives, a new injectable contraceptive (Norplant), and the intrauterine device (IUD). Major risks with oral contraceptives have declined substantially, and a number of noncontraceptive health benefits have been discovered. Norplant is probably the first new contraceptive in recent years, and offers long-term contraception with high efficacy and modest risks. The IUD, by carefully selecting users, is a safe and efficacious contraceptive method. The major risk, pelvic inflammatory disease (PID), is far less common if one avoids use in the presence of risk factors for PID.
The effectiveness of a low-dose oral contraceptive (OC) in suppressing plasma levels of gonadotropins, ovarian, and adrenal androgens and stimulating sex hormone-binding globulin (SHBG) was evaluated prospectively in nonhirsute women. Thirty-three women ingested 35 micrograms of ethinyl estradiol and 1 mg of norethindrone beginning within day 1 to 5 of the menstrual cycle. Baseline levels of luteinizing hormone, follicle-stimulating hormone, total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), and SHBG were obtained before ingestion of the OC and repeated after 3, 6 and, 9 months of OC use on day 1 to 5 of the OC "cycle". A significant suppression of gonadotropin levels is seen in nonhirsute women. Sex hormone binding globulin is consistently stimulated by the low-dose OC. A significant suppression of T and DHEAS is observed. No change was seen in levels of A. The demonstrated effects become evident at 3 months and are maintained at 6 and 9 months.
A randomized clinical trial of oral contraceptives evaluated 67 women on 50 ug ethinyl estradiol (EE) and 1.0 mg norethindrone (NE), 61 women on 35 ug EE and 1.0 mg NE, and 64 women on 35 ug EE and 0.5 mg NE. At baseline, three, six and nine months, lipids and lipoproteins were measured as well as selected plasma determinations of the contraceptive steroids. Data was related to change in outlier status for lipids/lipoproteins (less than 10th percentile for high-density lipoprotein cholesterol and apolipoprotein A-1, greater than 90th percentile for all others). Women on the lowest dose preparation had the smallest trend towards outlier status for high-density lipoprotein cholesterol and apolipoprotein A-1. An increase over the time period of the study in the initial slope (one hour level minus zero hour level over time) of NE and a decrease in the initial slope of EE was associated with a shift to outlier status for low-density lipoprotein cholesterol. A number of other relationships were also shown. Use of the techniques described might assist in identifying sub-groups of women at risk for adverse cardiovascular sequelae associated with oral contraceptive use.
A randomized clinical trial of oral contraceptives evaluated 67 women on 50 micrograms ethinyl estradiol (EE) and 1.0 mg norethindrone (NE), 61 women on 35 micrograms EE and 1.0 mg NE, and 64 women on 35 micrograms EE and 0.5 mg NE. Fasting lipids and lipoproteins were measured at baseline, three, six and nine months. All groups showed an increase in plasma total cholesterol, triglycerides, low-density lipoprotein/apolipoprotein B and apolipoprotein A-1. The group taking the preparation with 0.5 mg of NE was the only one to result in an elevation of high-density lipoprotein cholesterol; the other two groups showed declines in the mean levels of this lipoprotein over the study time period. Mean changes in lipid/lipoprotein levels associated with oral contraceptive use appear to be at least partially related to the doses of the contraceptive steroids.
The contraceptive benefits of oral contraceptives have become well known since the introduction of this birth control method in the 1960s. Since that time, a more sophisticated understanding of the hormonal components of the medication has developed, along with reduction in the dosages of these hormones. During the past decade in particular, the medical literature has documented a number of noncontraceptive benefits delineated by studies conducted in Europe and the United States. Users of oral contraceptives have reduced rates of both endometrial and ovarian cancer, and this protection persists even when oral contraceptive use is discontinued. The risk of ectopic pregnancy is reduced up to tenfold among oral contraceptive users and the risk of pelvic inflammatory disease (salpingitis), two- to fourfold. The necessity for performing surgical excision of benign breast cysts or functional ovarian cysts is substantially reduced in women who take oral contraceptives. There also is evidence that the risk of rheumatoid arthritis is reduced in oral contraceptive users. Finally, women who take oral contraceptives have less menstrual dysfunction, such as menorrhagia and dysmenorrhea, than do nonusers. In the United States, it has been estimated that as many as 50,000 hospital admissions are prevented annually because of the noncontraceptive benefits of these drugs. Accordingly, these benefits should be taken into account when discussing contraceptive methods with patients.
A cervical pregnancy was diagnosed by ultrasonography and managed with methotrexate. In view of the substantial morbidity associated with this form of ectopic pregnancy, medical management is an option for treatment.
Obesity, defined as an increase of 20% or more above desired weight, has been found to be an independent, albeit weak, risk factor for coronary heart disease in women and may increase the relative risk of other factors such as hypertension, diabetes mellitus, and elevated total serum cholesterol and low-density lipoprotein-cholesterol. Type A personality and stress, on the other hand, appear to be moderate risk factors for coronary heart disease in women as well as in men. Approximately twice as many cardiovascular events occurred in type A women 35 to 64 years old as in type B women of the same age group. As expected, cigarette smoking is a major risk factor, primarily in young women. Women with smoking patterns similar to those of men experience similar rates of cardiovascular morbidity and mortality. In addition, smoking apparently acts synergistically with oral contraceptives and elevated total serum cholesterol to further increase risk.
As part of the Women's Health Study, a case-control study conducted in nine cities in the United States, women hospitalized with an ectopic pregnancy and women hospitalized with non-gynecologic, medical or surgical diagnoses were interviewed concerning past reproductive history. There were 462 women meeting eligibility criteria in the ectopic pregnancy case group and 2326 women meeting the criteria for the control group. After adjustment for a number of possible confounders, the relative risk of ectopic pregnancy for women with a history of one induced abortion was 1.0 (95% confidence limits: 0.5 to 1.8) and was 0.9 (95% confidence limits: 0.8 to 1.1) for women with a history of two or more prior induced abortions. These results suggest that prior induced abortion does not significantly increase the risk of subsequent ectopic pregnancy.
Oral contraceptive (OC) use and alcohol consumption have been shown to alter the levels of lipids and lipoproteins in the blood. The effect of alcohol consumption on levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, LDL-B, Apo-A1, the ratio of HDL cholesterol/total cholesterol, HDL cholesterol/LDL cholesterol, and the ratio of LDL cholesterol/LDL-B among normal healthy young women before initiation of oral contraceptives and after six months of oral contraceptive use are both described. Of primary interest is the mediating effect of alcohol consumption on the association between steroid usage and blood lipid values. At baseline, ethanol consumption was found to be positively associated with triglycerides, HDL-C, and Apo-A1 and negatively associated with LDL-C/LDL-B. After adjustment for several covariables, alcohol consumption was found to be positively associated with the increases in triglycerides and in Apo-A1 observed at 3 and 6 months after initiation of OCs. Since these two parameters are believed to have opposite relationships to cardiovascular disease, the effect of alcohol consumption remains uncertain.
Cervical rupture and subsequent development of a cervicovaginal fistula is a relatively uncommon but well-documented complication of midtrimester abortion. Patients with cervicovaginal fistula may be at increased risk of subsequent infertility and obstetric complications.
To determine the effects of oral contraceptives on lipids and lipoproteins over a six-month period, we randomized 266 women into four oral contraceptive groups: ethinyl estradiol 35 micrograms plus ethynodiol diacetate 1 mg, ethinyl estradiol 30 micrograms plus levonorgestrel 0.15 mg, ethinyl estradiol 35 micrograms plus norethindrone 1 mg, and ethinyl estradiol 35 micrograms plus norethindrone 0.5 and 1 mg (biphasic). For all groups, total cholesterol increased 5.9-9.1% from baseline values over the six months. Triglycerides increased with all preparations, with the ethynodiol diacetate group (37.6%) and the biphasic norethindrone group (45.3%) showing the greatest increase. Low-density lipoprotein cholesterol increased 10-15.6% among the groups; low-density lipoprotein-apolipoprotein B changed proportional to the low-density lipoprotein cholesterol increases. All groups except the ethynodiol diacetate group showed a decrease of high-density lipoprotein cholesterol, with the levonorgestrel group (8.7%) and biphasic norethindrone group (4.5%) showing the largest declines. Apolipoprotein A-1 increased in all groups, with the ethynodiol diacetate preparation (19.3%) showing the greatest increase and the levonorgestrel preparation (3.2%) showing the smallest increase from baseline values. The changes in apolipoprotein A-1 were out of proportion to the changes in high-density lipoprotein cholesterol, suggesting that the high-density lipoprotein particle may be undergoing some type of metabolic alteration.
Estrogens and progestins for contraception or hormonal replacement therapy are widely used by practitioners. These steroids have substantial effects on lipids and lipoproteins that appear to be primarily related to chemical structure of the compound, dosage, and a patient's hormonal status. Although the mechanisms by which alterations in lipid and lipoproteins affect atherogenesis are not fully understood, epidemiologic studies clearly associate alterations with risk of coronary heart disease. Attention to these alterations by progestins and estrogens, as well as further research on how these steroids may exert other cardiovascular effects, is important because atherosclerotic heart disease is a major cause of morbidity and mortality for women as they age.
We compared tissue culture with Papanicolaou-stained cervical smears, endocervical cytologic smears stained with immunofluorescent monoclonal antibody, and a direct immunofluorescent stain of cervical specimens (MicroTrak) for detection of Chlamydia trachomatis in cervical specimens. Fifty-one (21%) of 245 women had positive cultures for C. trachomatis, 14 (27%) of whom had clinical evidence of cervicitis. With the criteria of intracytoplasmic coccoid inclusion bodies within metaplastic cells, 45 (34%) of 130 Papanicolaou smears were read as suggestive for C. trachomatis. Seventeen of the 45 positive Papanicolaou smears were positive on culture and 28 were negative (sensitivity 54%, specificity 71%). In contrast, 48 of 51 women with positive cultures and one woman with a negative culture had positive immunofluorescent-stained cytologic smears (sensitivity 94%, specificity 99%, with positive predictive value of 98%). Similarly, 47 of 51 women with positive cultures also had positive results with MicroTrak direct immunofluorescent stain, with only one positive specimen in 196 women with negative cultures (sensitivity 92%, specificity 99%, with positive predictive value of 98%). This study demonstrates that immunofluorescent staining of cervical specimens or of cytologic smears is a more sensitive and specific method than routine Papanicolaou smear for detection of chlamydia infection in a high-prevalence population.
The Johns Hopkins Program for International Education in Gynecology and Obstetrics (JHPIEGO) began in June of 1973 with financial assistance from the Agency for International Development (AID). The purpose of the organization was to provide training and medical equipment to physicians in developing countries to update their education in reproductive health. JHPIEGO began by offering courses in the United States and shortly thereafter began training at centers in the developing countries themselves. Because of its important contributions to gynecological diagnosis in addition to its use in fertility management, laparoscopic equipment has been a major item in JHPIEGO reproductive health training. This paper details the development and role of laparoscopic training in JHPIEGO's program. Laparoscopic training begins with selection of trainees from appropriate institutions. Training itself begins with a didactic session at Baltimore or an in-country center. Trainees then receive clinical training and perform a minimum number of procedures, after which the practitioner, if he or she has successfully completed the clinical practice, can be named eligible to receive medical equipment to be donated to his or her institution. When equipment is installed, a field visit is made by a JHPIEGO consultant to insure the proper use and upkeep of equipment, and the understanding and implementation of standards and procedures. JHPIEGO has trained almost 3000 physicians in laparoscopy techniques between 1973 and 1984.
The steroid dosages of oral contraceptives have declined substantially since the 1960s. With the dosage reduction there is evidence that the major risks associated with oral contraceptive use have also been reduced. More research is needed to determine whether current preparations, such as the triphasics, offer further advantages.
An international program to determine the reversibility of female sterilization in Asia using microsurgical technique was established in 1980. One hundred eleven of 219 patients (51%) conceived following tubal anastomosis; of these, 79 delivered living children. The overall cumulative probability of conception at the end of follow-up, as determined by life-table analysis, was 63%. A decreased pregnancy rate was associated with anastomosis of tubes sterilized by electrocautery methods.