Adverse ocular reactions to oral contraceptive use

Many types of adverse ocular reactions to oral contraceptives (OCs) have been reported, but the role of OCs has not always been confirmed. Neuroophthalmologic complications may result from cerebral vascular accidents responsible for visual field deficits, accidents affecting the cerebral trunk, ischemic accidents resulting from obstruction of the internal carotid artery. The role of OCs in cerebral vascular accidents is controversial. Most reports concern older formulations containing high doses of estrogen. In the current state of knowledge it is generally agreed that OCs may induce an increased thromboembolic risk in women over 35, those who smoke, and those with risk factors for atherosclerosis. It is agreed that occurrence of a transient ischemic cerebral vascular accident requires immediate termination of OC use. OCs have been implicated occasionally in retrobulbar optic neuropathy, but the condition in young women appears more likely to be the 1st manifestation of a sclerosis. OCs appear to increase the incidence of benign intracranial hypertension, manifested by headaches, papillary edema endangering the optic nerve, and the absence of visible anomalies on the scanner. It is also recognized that migraines are induced or aggravated by OCs. Migraines are known to be linked to hormonal factors. Ophthalmic migraines belong to the subgroup of vascular migraines. Retinal vascular diseases such as occlusion of the central retinal artery, intraocular hemorrhage, and more rarely macular edema have been reported retrospectively but their documentation has been insufficient to permit determination of causality. The prognosis for retinal emboli is mediocre. Problems in color vision initially affecting blue have been described in OC users and may be a function of the duration of use. The condition is especially prevalent in diabetes. Pregnancy appears to accelerate the loss of visual field in some women with pigmentary retinopathy. For that reason some ophthalmologists recommend that they avoid OCs. Other ocular problems have been observed in OC users but no link has been proven and the only evidence is anecdotal. It has been suggested that OCs decrease tolerance for contact lenses, but prospective studies have not demonstrated a link. All contraindications to OC use should be scrupulously respected. Use should be terminated immediately in case of transient ischemic accident, appearance of sudden severe headaches, vertigo, or vision problems such as papillary edema or retinal hemorrhage.     

Evaluation of emotional reactions to oral contraceptive use

A review of available clinical studies indicates that 10 to 40 per cent of oral contraceptive users may suffer mild to moderate depression syndromes. Clinical and animal data indicate that a variety of mechanisms may be involved, including alterations in folate, pyridoxine, and vitamin B₁₂ metabolism, as well as related effects on biogenic amine metabolism. Interactive effects may result, such as impairment of usual coping mechanisms and psychological defenses by altered central nervous system function.     

Venous thromboembolism in relation to oral contraceptive use

The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contraceptive users relative to nonusers, even if women use oral contraceptives containing low doses of estrogen. Confidence intervals were wide, however, so that a reduction in the risk for users of lower dose formulations relative to users of higher dose formulations cannot be ruled out. Selection bias, if present, would have resulted in overestimation of the relative risk, but should not have distorted the comparisons according to dosage.     

Accuracy of self-screening for contraindications to combined oral contraceptive use

OBJECTIVE: To estimate how well a convenience sample of women from the general population could self-screen for contraindications to combined oral contraceptives using a medical checklist. METHODS: Women 18-49 years old (N=1,271) were recruited at two shopping malls and a flea market in El Paso, Texas, and asked first whether they thought birth control pills were medically safe for them. They then used a checklist to determine the presence of level 3 or 4 contraindications to combined oral contraceptives according to the World Health Organization Medical Eligibility Criteria. The women then were interviewed by a blinded nurse practitioner, who also measured blood pressure. RESULTS: The sensitivity of the unaided self-screen to detect true contraindications was 56.2% (95% confidence interval [CI] 51.7-60.6%), and specificity was 57.6% (95% CI 54.0-61.1%). The sensitivity of the checklist to detect true contraindications was 83.2% (95% CI 79.5-86.3%), and specificity was 88.8% (95% CI 86.3-90.9%). Using the checklist, 6.6% (95% CI 5.2-8.0%) of women incorrectly thought they were eligible for use when, in fact, they were contraindicated, largely because of unrecognized hypertension. Seven percent (95% CI 5.4-8.2%) of women incorrectly thought they were contraindicated when they truly were not, primarily because of misclassification of migraine headaches. In regression analysis, younger women, more educated women, and Spanish speakers were significantly more likely to correctly self-screen (P<.05). CONCLUSION: Self-screening for contraindications to oral contraceptives using a medical checklist is relatively accurate. Unaided screening is inaccurate and reflects common misperceptions about the safety of oral contraceptives. Over-the-counter provision of this method likely would be safe, especially for younger women and if independent blood pressure screening were encouraged.     

Recent oral contraceptive use and adverse birth outcomes

Objective

To examine the possible association between oral contraceptive use and adverse birth outcomes.

Study design

We conducted a population-based cohort study of pregnant women who used oral contraceptives within 3 months before their last menstrual period. Subjects were divided into three groups, according to the interval (0–30, 31–60, and 61–90 days) between the dispensing date and their last menstrual period. For each exposed subject, 4 subjects without exposure to oral contraceptives were individually matched by infant's year of birth and plurality and by mother's age and parity.

Results

Oral contraceptive use within 30 days prior to the last menstrual period was associated with increased risks of very low birth weight (OR: 3.24, 95% CI: 1.18, 8.92), low birth weight (OR: 1.93, 95% CI: 1.17, 3.20), and preterm birth (OR: 1.61, 95% CI: 1.01, 2.55); however, oral contraceptive use 31–90 days prior to the last menstrual period did not increase the risk of low birth weight or preterm birth.

Conclusion

Our results indicate the use of oral contraceptives near the time of conception may be associated with an increased risk of low birth weight and preterm birth.     

Breast cancer risk in relation to early oral contraceptive use

It has been suggested that the risk of breast cancer is increased by oral contraceptive use before the first birth, or by use before age 25, particularly if certain formulations are used. These hypotheses were evaluated in a hospital-based case-control study. A total of 521 patients under age 45 with breast cancer were compared with 521 controls matched for age, time of interview, and geographic area. Oral contraceptive use before the first birth was reported by 155 patients and 137 controls. With allowance for confounding by multivariate analysis, the estimated relative risk was 1.0 (95% confidence interval, 0.6-1.5). The estimate was 1.0 (0.2-3.9) for any use among nulliparous women and 0.6 (0.3-1.3) for use before the first birth among parous women. Use before age 25 was reported by 145 patients and 141 controls, and the multivariate relative risk estimate was 1.0 (0.7-1.6); the results were similar when use of specific formulations was examined. For oral contraceptive use before either the first birth or age 25, the relative risk estimates were compatible with 1.0 for use of five or more years' duration or an interval since first use of at least 15 years. There was also no evidence of an increased risk in any subgroup including those at increased underlying risk because of factors such as a family history of breast cancer or a history of cystic breast disease. The findings suggest that, up to age 45, the risk of breast cancer is not influenced by the use of oral contraceptives before the first birth or before age 25 even if the use lasted for five or more years.     

Epidemiological studies of oral contraceptive use and breast cancer

Most epidemiological studies of a possible association between oral contraceptives (OCs) and breast cancer have given reassuring results. But some recent studies appear to suggest that OC use in young women may increase the risk of breast cancer. The possibility of a latent effect produces some uncertainty in the interpretation of epidemiological data. Different terminology has been suggested to describe the induction period, latency period, or incubation period before breast cancer is diagnosed. None of the transitions in development of breast cancer is usually observed directly, and the entire period before diagnosis may for convenience be called the latency period. 3 pertinent risk factors which shed light on the latency period are the age at 1st menstruation and at the 1st pregnancy, which typically have a latency period of 30 years or more; the effect of ionizing radiation at Hiroshima and Nagasaki, which had an apparent latency period of 20 years or more, and the effects of diethylstilbestrol administered to women in 1940-50 to prevent miscarriage, which had a latency period of 20 years or more. It is possible that OCs are associated with a later influence on the development of breast cancer, in which case contemporary epidemiological studies would not provide correct estimates of the final risk. Conventional epidemiological analyses assume that any potential influence of OCs on breast cancer risk will be immediately apparent. It is possible that the influence of OCs on breast cancer risk is less for women using OCs even for prolonged periods after a term pregnancy than for women using OCs before any pregnancy. A simulation of OC use in the United Kingdom by cohorts of women born between 1930-65 with different exposure times and latency periods demonstrated that the actual risk of O use may be elevated without becoming apparent for several decades.     

Long-term health risks and benefits of oral contraceptive use

The contraceptive effect of oral contraceptive use provides an important health benefit, particularly in developing countries, where the risks of pregnancy and childbearing are increased. Several important noncontraceptive health benefits of oral contraceptive use include the prevention of endometrial and ovarian cancers. Data are generally reassuring concerning the risks of oral contraceptive use, which include cardiovascular disease and breast and cervical cancer.     

Clinical chemistry alterations in pregnancy and oral contraceptive use

In this study the effects of pregnancy and oral contraceptive use on plasma glucose concentrations, hepatic, renal, and thyroid function tests, and their relationships to plasma lipoprotein lipids after an overnight fast are compared. Observations were made in 546 pregnant women at 36 weeks' gestation, 56 women using oral contraceptive hormones, and 77 women not using sex hormones. All subjects were randomly selected from defined populations. Compared with nonpregnant women not using hormones, median plasma glucose concentrations are 3% lower with oral contraceptive use and 17% lower in pregnancy. Plasma total bilirubin concentrations are lowered by similar amounts in oral contraceptive users (29%) and in pregnancy (32%). Serum glutamic oxaloacetic transaminase is slightly lower among hormone users (9%) but is significantly higher (27%) in pregnancy. Alkaline phosphatase is significantly lower in oral contraceptive users (23%) but is higher in pregnancy (86%). Serum globulin concentrations are unaffected by pregnancy or oral contraceptive use. Compared with nonusers, thyroxine is 30% higher in oral contraceptive users and 100% higher during pregnancy. Serum creatinine is unaffected by sex steroid use but is 28% lower in pregnancy. Associations of these test results with plasma hormone concentrations corroborate hormonal mechanisms and suggest that some alkaline phosphatase and serum glutamic oxaloacetic transaminase come from the placenta. Relationships of these clinical measurements to lipoprotein lipids in pregnancy are generally weak and do not point to important controlling relationships, but effects similar to those seen in nonpregnant subjects are seen with hyperglycemia (associated with elevated triglyceride) and elevated thyroxine levels (associated with lower cholesterol and triglyceride).(ABSTRACT TRUNCATED AT 250 WORDS)     

New concepts in oral contraceptive pill use.

Over 30 years have elapsed since the introduction of the combination oral contraceptive pill. During this time, the estrogen and progestogen components of the pill have been reduced 80% and 90%, respectively. An improved understanding of the mechanisms involved in the metabolism of the oral contraceptive pill steroids now exists that allows us to better understand interactions of the pill with other drugs and medications. In an effort to reduce adverse reactions to the oral contraceptive pill, new progestogens have been developed for contraceptive pills soon to become commercially available. These issues as well as the concept of the pill-free interval are discussed in this review.     

The emerging use of the 20-microg oral contraceptive

OBJECTIVE: To highlight studies that investigated the efficacy, safety, and tolerability of low-dose oral contraceptives (OCs) containing 20 microg of ethinyl estradiol (EE) and to discuss the use of these low-dose contraceptives in women from adolescence to menopause and the noncontraceptive health benefits likely to be afforded by low-dose contraceptives. DESIGN: Relevant literature was identified by searching MEDLINE and EMBASE. Other sources were located by consulting the bibliographies of the material collected from Medline and EMBASE. Sources for additional information included documents from the United States Food and Drug Administration and the Physicians' Desk Reference (54th ed.). CONCLUSION(S): The current lowest available dose of EE used for OCs in the United States is 20 microg. Formulations with 20 microg of EE are efficacious and have a low incidence of estrogen-related side effects. Since this lowest effective EE dose inhibits ovarian activity, 20 microg of EE should also provide the noncontraceptive health benefits of OCs. Both contraceptive and noncontraceptive benefits of OCs are available to most women from adolescence to menopause without complications.     

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.     

Neuroendocrine dysfunction in galactorrhea-amenorrhea after oral contraceptive use.

Nonpuerperal alactorrhea and amenorrhea have been reported following the use of oral contraceptives. Treatment of this condition with ergot alkaloids has proved to be of great therapeutic value. Pretreatment plasma hLH and hFSH concentrations in 13 women with postqill galactorrhea-amenorrhea (PPGA) were 6.6 plus or minus 0.6 (SE.) and 5.0 plus or minus 0.8 mlU/ml, respectively. The mean prolactin concentration was 80.7 plus or minus 13.2 ng/ml. After complete evaluation in which diagnostic evidence of pituitary tumor was absent, the patients were treated with ergocryptine (CB-154). The mean hPRL concentration at 14 days of therapy was 7.8 p;us or minus 1.9 ng/ml. Cyclic gonadotropin secretion resumed in all but one instance; ovulation was confirmed on the basis of a biphasic temperature chart and in 5 cases, endometrial biopsy. Measurement of serum dopamine-beta-hydroxylase (DBH) activity indicated a significant decline at the end of 8 weeks of CB-154 therapy. The fall in hPRL was not necessarily associated with a fall in DBH. The majority of women in this study exhibited a consistent personality suggesting varying degrees of anxiety unrelated to the PPGA and usually antedating the use of oral contraceptives. PPGA was found in women without hyperprolactinemia, but altered hPRL secretion was evident in all instances. The data suggest that the disorder of cyclic gonadotropin secretion is related to altered hPRL secretion, but the mechanism is possibly related to a catecholamine abnormality. The data support the presence of an inherent cyclic mechanism for the secretion of gonadotropins. CB-154 therapy does not affect conception, and no teratogenic effects were observed in 2 infants born to women who had received CB-154 during the first 40 days of gestation.