Current Oral Contraceptives Research Articles

A pooled analysis of case-control studies of thyroid cancer. III. Oral contraceptives, menopausal replacement therapy and other female hormones.

The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe. Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity. Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR = 1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR = 1.1 for > 10 years since stopping). The association was stronger for papillary cancers (OR = 1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR = 0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment. The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.

Monocyte Tissue Factor Expression Is Enhanced in Women who Smoke and Use Oral Contraceptives

The association between use of oral contraceptives (OCs) and increased risk of thromboembolic disease has been firmly established. This risk increases when use of OCs is combined with cigarette smoking. The cellular mechanism favoring an hypercoagulable state under these behaviours is not known. Circulating monocytes are potent activators of the coagulation cascade through their ability to synthesize procoagulant tissue factor (TF). In the present study we report that monocyte TF expression is increased in women who use OCs and smoke. We studied monocyte TF expression in 4 groups of healthy pre-menopausal women (n = 15 each): (1) non-smoking OC non-users, (2) nonsmoking current OC users, (3) smoking OC non-users and (4) smoking OC users. TF expression was assessed on both mRNA and protein levels in unstimulated and LPS-stimulated cells. Transcriptional activation of the TF gene was assessed by analysis of the transcription factor NF-kappaB and its inhibitor molecule IkappaBalpha. Monocyte TF generation was significantly higher in OC users than in women who did not use OCs. Enhanced monocyte TF generation was also observed in smoking women when compared to non-smokers. Strongest monocyte TF expression occurred in women with combined smoking and use of OCs. The enhanced TF expression in monocytes from women using OCs or smoking was based on an increased TF gene transcription following activation of NF-kappaB. Experiments on cultured monocytes/macrophages demonstrated enhanced IkappaBalpha degradation in the presence of estradiol, suggesting that a direct hormone effect is responsible for the observed increase in monocyte TF expression. This study demonstrates that use of OCs and smoking is associated with an increase in monocyte TF expression in pre-menopausal women. Aberrant TF expression by blood monocytes may favour intravascular clotting activation in women with OC therapy. The further enhancement of TF activity observed in women who smoke and use OCs may explain the synergistic effect of smoking on risk of thromboembolic events associated with contraceptive use.

Breast cancer risk: perception versus reality

Evidence that breast cancer is hormonally mediated has fueled women’s concern that use of oral contraceptives (OC) will increase their risk of developing the disease. A recent reanalysis of combined worldwide epidemiologic evidence regarding the relationship between breast cancer risk and use of combination OC provides reassurance that there is little or no association between OC use and breast cancer. Ten or more years after discontinuation of OC use, there is no difference in cumulative risk of breast cancer among OC ever-users and never-users. The risk of breast cancer diagnosis is slightly elevated in current OC users and remains slightly elevated until about 10 years after OC discontinuation. Once recency of use is taken into account, other characteristics have little additional effect. There is no increase in breast cancer risk with increasing dose or duration of OC use and no difference in risk related to type of estrogen or progestin used. Moreover, those breast cancers diagnosed in OC ever-users were found to be significantly more likely to be localized than those diagnosed in same-age never-users.

Myocardial infarction and use of low-dose oral contraceptives: a pooled analysis of 2 US studies.

Population-based case-control studies to assess the relationship of low-dose oral contraceptive (OC) use with myocardial infarction (MI) were performed at 2 sites in the United States (California and Washington state). The purpose of the present study was to estimate risk of MI in relation to use of low-dose OCs in a pooled analysis combining results from the 2 sites. The study included as cases women aged 18 to 44 years with incident MI who had no prior history of ischemic heart disease or cerebrovascular disease. Women in the case and control groups were interviewed in person regarding OC use and cardiovascular risk factors. The analysis included 271 MI cases and 993 controls. Compared with noncurrent users, the adjusted pooled odds ratio for MI in current OC users was 0.94 (95% CI, 0.44, 2.20) after adjustment for major risk factors and sociodemographic factors. Compared with never users, the adjusted pooled odds ratio for MI was 0.56 (0.21, 1.49) in current OC users and 0.54 (0.31, 0.95) in past OC users. Among past OC users, duration and recency of use were unrelated to MI risk as was current hormone replacement therapy. There was no evidence of interaction between OC use and age, presence of cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes), obesity, or smoking. We conclude that low-dose OCs as used in these populations are safe with respect to risk of MI in women.

Epidemiology of oral contraceptives and cardiovascular disease.

To review the association between combined oral contraceptives and cardiovascular disease, with emphasis on oral contraceptives containing low doses of estrogen (low-dose oral contraceptives). A systematic search of the MEDLINE database was done for all relevant articles published between 1967 (when low-dose oral contraceptives were introduced in the United States) and June 1997. Textbooks, meeting proceedings, and reference lists were also searched. All English-language human epidemiology studies of oral contraceptives that used cardiovascular disease as an end point were reviewed. Animal and metabolic studies were reviewed only if they were especially relevant to the mechanism of action of oral contraceptives. Descriptive and analytic data from each study were collected. Data were organized by cardiovascular end point, study design, estrogen dose, and type of progestogen. Data on relative and absolute risk are presented to address current prescription guidelines. The risk for cardiovascular disease is lower with current preparations of oral contraceptives, including those that contain the new progestogens, than with older oral contraceptives containing high doses of estrogen. Among users of low-dose oral contraceptives, cardiovascular diseases occur mainly in smokers and women with predisposing factors. Every effort should be made to encourage smoking cessation among potential users of oral contraceptives.

Pill Use Makes Minimal Contribution to the Risk Of Myocardial Infarction

A case-control study conducted by the World Health Organization in 21 centers in 17 countries in Africa Asia Europe and Latin America and the Caribbean confirmed that acute myocardial infarction is a rare event in users of combined oral contraceptives (OCs) with no other risk factors for cardiovascular disease. A total of 368 women who had survived an acute myocardial infarction were compared with 941 age-matched controls. In Europe 87% of cases and 48% of controls had at least 1 risk factor for cardiovascular disease (i.e. family history of myocardial infarction or stroke smoking hypertension diabetes rheumatic heart disease or abnormal blood lipids); in developing countries these rates were 72% and 35% respectively. 31% of European women with myocardial infarction and 16% of controls were current combined OC users; in developing countries these rates were 23% and 9% respectively. Compared with past users and never users of combined OCs current OC users had approximately 5 times the risk of acute myocardial infarction (odds ratios of 5.0 in Europe and 4.8 in developing countries). Women who reported that their blood pressure had not been checked before initiating OC use had a higher risk of acute myocardial infarction (9.5 in Europe and 6.0 in developing countries) than those whose pressure had been checked (2.6 and 3.5 respectively). For women with blood pressure problems independent of pregnancy the odds ratios of myocardial infarction were 68.1 in Europe and 15.3 in developing countries. The elevated risk of acute myocardial infarction in OC users recorded in this study appears due to the influence of other risk factors for cardiovascular disease and a lack of screening for hypertension. A high body mass index and a history of hypertension were the largest contributors to the risk among OC users in Europe while smoking and a history of hypertension were most salient in developing countries.

Blood pressure in women using oral contraceptives: results from the Health Survey for England 1994.

To assess whether the blood pressure is higher among women who take oral contraceptives than it is among those who do not. A cross-sectional survey of a stratified random sample of English adults (aged > or = 16 years). Non-institutionalized households in England during 1994. From this sociodemographically representative sample of English adults, 3545 premenopausal women, of whom 892 were current users of oral contraceptives, were evaluated. An interviewer-administered questionnaire determined details of menopausal status, use of oral contraceptives and antihypertensive agents and other sociodemographic variables. Measurements of the weight, height and blood pressure (the mean of the last two of three readings taken with a Dinamap 8100 device) were recorded. Systolic and diastolic blood pressures adjusted for potential confounders by oral-contraceptive-user status. Mean blood pressures adjusted for age were significantly higher among oral contraceptive users (125/70 mmHg) than they were among non-users (123/68 mmHg, P < 0.001 both for systolic and for diastolic blood pressures). These results remained unchanged after further adjustment for the body mass index, alcohol intake, physical activity and hypertension treatment. Blood pressure differences tended to be larger among older oral contraceptive users. Oral contraceptives containing progestogen only were not associated with higher blood pressures. Despite the fact that most combined oral contraceptives in current use in England contain low doses of oestrogen, slightly but significantly higher blood pressures were observed among oral contraceptive users. Blood pressures should be screened before oral contraceptives are supplied and should be monitored regularly during oral contraceptive use.

Venous Thromboembolism And `Third-Generation' Pills May Not Be Related

A recently published case-control study conducted in the UK suggests that the association between venous thromboembolism risk and use of third-generation oral contraceptives (OCs) identified in an earlier cohort analysis may be an artifact of age confounding. The investigators used computerized records from 143 general practitioners in the UK to compare the incidence of venous thromboembolism among users of the most common OCs and they performed a case-control study to calculate the odds ratio associated with different types of pills. The final sample included 491908 women born during 1941-81 who contributed 234899 woman-years of exposure to steroidal contraception including 108824 woman-years of exposure to third-generation progestogens. In all 85 women had a history of venous thromboembolism (29 users of second-generation OCs 54 users of third-generation products and 2 users of progestin-only pills). After adjustment for 5-year age groups users of third-generation pills were 1.7 times more likely than users of second-generation OCs to have experienced venous thromboembolism a finding consistent with the results of previous studies. The case-control portion of the study compared the 83 women who had a venous thromboembolism with 313 controls matched by physicians practice current OC use and exact year of birth. Regression analyses adjusted for potentially confounding variables revealed no significant differences in venous thromboembolism risk between users of second- versus first-generation OCs. The investigators contend that matching by exact age not 5-year age bands is essential to ensure that controls are representative of the population from which cases are drawn.

Slightly Increased Risk of Breast Cancer Among Pill Users Disappears 10 Years after Discontinuation

A collaborative analysis of 90% of the data collected worldwide on the association between oral contraceptive (OC) use and breast cancer indicated that this risk is transitory and does not persist beyond 10 years after OC discontinuation. The analysis pooled data on 53297 women with breast cancer and 100239 hospital or population controls from 54 prospective and case-control studies with a minimum of 100 women with invasive breast cancer conducted in 25 countries. Overall 41% of breast cancer cases and 40% of controls were ever-users of combined OCs. The median duration of use was 16 years. Current OC users were 24% more likely than never-users to develop breast cancer while women who had discontinued OC use 1-4 years earlier were 16% more likely. However any increased risk disappeared when analysis included women who discontinued OC use 10 or more years before the study. Moreover tumors detected in OC ever-users were 10% less likely than those in never-users to have spread to the lymph nodes and 30% less likely to have metastasized elsewhere.

Clinical overview of hormonal contraception with special emphasis on long-term effects

The impact of oral contraceptive (OC) use on cardiovascular diseases and carcinogenesis is a major issue in clinical practice and research in developing countries. Overall the most recent research suggests that OCs lower the risk of endometrial and ovarian cancer and this protection is long-lasting. There is no association with skin melanoma and breast cancer risk although there is a moderately increased risk of breast cancer among current OC users. The relative risk of both cardiovascular and cerebrovascular disease is increased about 2-fold in current OC users but no such association has been found in ex-users. Despite these generally favorable findings OC prescribing literature focuses heavily on contraindications and adverse side effects. This distortion may result in the unnecessary avoidance or termination of OCs by many women in need of an effective reversible contraceptive method.

Reliability of data from proxy respondents in an international case-control study of cardiovascular disease and oral contraceptives. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.

To evaluate the reliability of data supplied in a case-control study by proxy respondents for cases who were too ill to do so themselves. A hospital based, case-control study of the current use of oral contraceptives (OC) and cardiovascular diseases. Data from "true" controls matched to a subset of cases were compared with those supplied by proxy respondents about the true controls. Hospitals in 21 centres from Africa, Asia, Europe, and Latin America. For a subset of cases, 403 pairs of controls-one "true" and one proxy-were interviewed. "True" controls were matched by age, place, and time of admission and were admitted with 1 of 27 permissible diagnoses not associated with OC use. Proxy controls were either relatives or friends of true controls. Levels of concordance between data from proxy and true controls were high for most variables regarding recent events, including current OC use, but were greatly diminished when detailed information, particularly from the past, was required. Husbands were usually the best proxy, although this was question-specific. The sensitivity and specificity of proxy responses were 93% (95% confidence intervals: 77%, 99%) and 100% (98%, 100%) respectively, for current use of OC. Assuming the misclassification of current OC use by proxy cases is similar to that produced by proxy controls, the estimated impact of using proxy data on risk estimates associated with current OC use was to bias the overall estimate of risk of stroke by less than 3% and the risks of both acute myocardial infarction and venous thromboembolism by less than 1%. Friends or relatives, and particularly husbands, provided reliable information when used as proxy respondents for young women. The estimated impact of misclassification by proxy respondents on overall risk estimates in the WHO collaborative study was less than that which would have arisen if information from proxy respondents had not been used.

Myocardial infarction in users of low-dose oral contraceptives

To determine the relationship between the use of low-dose (less than 50 micrograms estrogen) oral contraceptives (OC) and myocardial infarction. In this population-based case-control study, all incident myocardial infarctions in women, ages 15-44 years who were members of the Kaiser Permanente Medical Care Program, Northern and Southern California regions were ascertained during a 39-month period from 1991 through 1994. For each woman with myocardial infarction, up to three age- and facility-matched controls were chosen at random from female members. Information about OC use (predominantly low-dose preparations) was obtained in face-to-face interviews. There were 187 incident cases of myocardial infarction during 3.6 million woman-years of observation (incidence rate, 5.2 per 100,000 woman-years). The prevalence of several risk factors for myocardial infarction was lower in controls who were current users of OCs than in controls who were noncurrent (past and never) users. The odds ratio for myocardial infarction in current OC users compared with noncurrent users was 1.65 (95% confidence interval 0.45, 6.06) after adjustment for major risk factors and for race and ethnicity, corresponding to an excess risk of less than one case per 100,000 woman-years. The study had 80% power to detect a relative risk of 2.3 (one-sided test, alpha = .05). The odds ratio of myocardial infarction in past OC users was not elevated. With respect to myocardial infarction, low-dose oral contraceptives can be used safely by women who lack risk factors for coronary heart disease.

Prospective study of exogenous hormones and risk of pulmonary embolism in women

Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.

Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study

Background The association between use of oral contraceptives (OCs) and cerebral infarction was established in studies from northern Europe and the USA during the 1960s and 1970s. Since then, the constituents of hormonal OCs have changed and now contain lower doses of oestrogen and progestagen. Current recommendations restrict OC use to younger women who do not have other risk factors for cardiovascular disease, in this international study we assessed the risk of CC-associated first stroke in women from Europe and other countries throughout Vie world.Methods In this hospital-based, case-control study, we assessed the risk of ischaemic stroke in association with current use of combined OCs in 697 cases, aged 20-44 years, and 1962 age-matched hospital controls in 21 centres in Africa, Asia, Europe, and Latin America. The diagnosis of ischaemic stroke was almost exclusively based on computed tomography (CT), magnetic resonance imaging (MRI), or cerebral angiography carried out within 3 weeks of the clinical event. Ail cases and controls were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, details of lifetime contraceptive use, and blood-pressure measurements before the most recent episode of OC use.Findings The overall odds ratio of ischaemic stroke was 2 . 99 (95% CI 1 . 65-5 . 40) in Europe and 2 . 93 (2 . 15-4 . 00) in the non-European (developing) countries, Odds ratios were lower in younger women and those who did not smoke, and less than 2 in women who did not have hypertension and who reported that their blood pressure had been checked before the current episode of OC use. By contrast, among current OC users with a history of hypertension, the odds ratio was 10 . 7 (2 . 04-56 . 6) in Europe and 14 . 5 (5 . 36-39 . 0) in the developing countries. In Europe, the odds ratio associated with current use of low-dose OCs (<50 mu g oestrogen) was 1 . 53 (0 . 71-3 . 31), whereas for higher-dose preparations it was 5 . 30 (2 . 56-11 . 0). In the developing countries, there was no significant difference between overall estimates of risk associated with use of low-dose or higher-dose OCs (3 . 26 [2 . 19-4 . 86] vs 2 . 71 [1 . 75-4 . 19]), This differential effect of dose in Europe and the developing countries is likely to be due to different levels of other risk factors among users of low-dose and higher-dose OCs in the two groups of countries. There was no significant increase in odds ratios with increasing duration of OC use among current users; odds ratios were not significantly increased after cessation of OC use.Interpretation The incidence of ischaemic stroke is low in women of reproductive age and any risk attributable to OC use is small. The risk can be further reduced if users are younger than 35 years, do not smoke, do not have a history of hypertension, and have blood pressure measured before the start of QC use. In such women OC preparations with low oestrogen doses may be associated with even lower risk.

Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study

<h2>Summary</h2><h3>Background</h3> The risk of haemorrhagic stroke associated with use of oral contraceptives (OCs) is less well-established than that for ischaemic stroke. We assessed the risk of haemorrhagic stroke associated with current use of modern OCs as now used throughout the world. <h3>Methods</h3> In this WHO collaborative, case-control study, we assessed the association between risk of haemorrhagic stroke and use of combined OCs in 1068 cases, aged 20·44 years, and 2910 age-matched controls. We also assessed risks for all strokes combined (haemorrhagic, ischaemic, and unclassified) based on 2198 cases and 6086 controls. <h3>Findings</h3> Overall, current use of combined OCs was associated with slightly increased risk of haemorrhagic stroke; the increase was significant in the developing countries (odds ratio 1·76 [95% CI 1·34–2·30]) but not in Europe (1·38 [0·84–2·25]). Use of OCs in women younger than 35 years did not affect risk of haemorrhagic stroke in either group of countries, whereas in women aged older than 35 years, odds ratios were greater than 2. Women who were current users of OCs and had a history of hypertension (detected before current episode of OC use, but not during pregnancy) had a substantially increased risk (ten-fold to 15-fold) of haemorrhagic stroke compared with women who did not use OCs and had no history of hypertension. Odds ratios among current OC users who were also current cigarette smokers were greater than 3. In both groups of countries, past use of OCs, dose of oestrogen, and dose and type of progestagen had no effect on risk, and risks were similar for subarachnoid and intracerebral haemorrhage. The odds ratios for any type of stroke associated with current use of low-dose (<50 ug oestrogen) and higher-dose OCs were 1·41 (0·90–2·20) and 2 71 (1·70–4·32), respectively, in Europe and 1·86 (1·49–2·33) and 1·92 (1·48–2·50) in the developing countries. From these data we estimated that about 13% and 8% of all strokes in women aged 20·44 in Europe and the developing countries, respectively, are attributable to the use of OCs. <h3>Interpretation</h3> The risk of haemorrhagic stroke attributable to OC use is not increased in younger women and is only slightly increased in older women. The estimated excess risk of all stroke types associated with use of low-oestrogen and higher-oestrogen dose OCs in Europe was about two and eight, respectively, per 100 000 woman-years of OC use. However, findings need to be considered in the context of other risks and benefits associated with OC use, as well as those associated with the use of other forms of contraception.

Oral contraceptives and breast cancer

A review of data pooled from 54 case-control studies concluded that both current users of oral contraceptives (OCs) and recent discontinuers have a slightly elevated risk of breast cancer (odds ratios, 1.24 for current users and 1.16 for women who discontinued OC use 1-4 years earlier). It should be noted, however, that the pooling of data involved in this analysis cannot overcome methodological problems inherent in the individual studies, particularly selection bias. The risk of breast cancer in the fertile, sexually active women who use OCs may differ from that in sexually inactive or infertile nonusers. Moreover, women who consider themselves to be at personal risk of breast cancer may opt not to use the pill. The relationship of sensitivity to exogenous hormones, which leads many women to discontinue OC use, to hormone production and breast cancer risk is unknown. Other factors that may have an impact on breast cancer risk include age at starting and stopping OC use, continuity and duration of use, and reproductive history variables such as pregnancies, childbearing, and breast feeding. For example, both OC use before 20 years of age and long-term use before first pregnancy are increasingly common. The impact of current OC use patterns on breast cancer risk should be the focus of future methodologically sound case-control studies.

The Economics of Contraceptives R&amp;D

A recent report by an Institute of Medicine (IOM) committee on contraceptive research and development (RD not one seems to sell contraceptive drugs or devices. The pharmaceutical market, which has changed dramatically during the past decade, has spoken. It now focuses on blockbuster drugs dealing with diseases of aging or deterioration in the increasingly geriatric populations of affluent Japan, North America, and Europe, not the needs of the poor pediatric societies of Latin America, Asia, and Africa. An item in the same issue (Random Samples, 31 May, p. 1269) features the ominous trends for infectious diseases, listing the four biggest global killers: acute respiratory infections, diarrheal diseases, tuberculosis, and malaria. If we again consider the minute fraction of the huge R&D budgets of the top eight pharmaceutical companies dedicated to these fields, we see that unmet burning societal needs do not necessarily equal financial returns. The most important point missed by the IOM committee is that the features of a truly novel contraceptive (say, a contraceptive vaccine or a once-a-month anti-implantation or menses-inducer pill) associated with major societal advantages (for example, low cost and long duration for a vaccine; short action and minimal pill consumption involving 13 pills per year for a menses-inducer versus 250 or more pills per year for current oral contraceptives) are precisely the economic disincentives keeping companies, which search for billion-dollar drugs used daily, from reentering the contraceptive field. The proposal “that commitments [by international aid agencies] to buy large volumes of contraceptives would induce companies to develop low-cost products” is a pipe dream. The only reason why some of the current oral contraceptive manufacturers will sell monthly pill regimens at 20 cents a package in lots of multimillion units to the Agency for International Development is the fact that an affluent American woman buying the same product in a drugstore pays more than 100 times that price. Absent that latter market, a pharmaceutical company would go broke if it focused on the low-cost public-sector market for a new contraceptive. More realistic, though politically unpopular, incentives for industrial involvement have been suggested earlier ([1][2]). 1. 1.[↵][3]1. C. Djerassi , Science 245 356 1989); ibid . 166, 468 (1969); ibid . 169, 941 (1970). [OpenUrl][4][Abstract/FREE Full Text][5] [1]: /lookup/doi/10.1126/science.272.5266.1258a [2]: #ref-1 [3]: #xref-ref-1-1 View reference 1. in text [4]: {openurl}?query=rft.jtitle%253DScience%26rft.stitle%253DScience%26rft.aulast%253DDjerassi%26rft.auinit1%253DC%26rft.volume%253D245%26rft.issue%253D4916%26rft.spage%253D356%26rft.epage%253D361%26rft.atitle%253DThe%2Bbitter%2Bpill%26rft_id%253Dinfo%253Adoi%252F10.1126%252Fscience.2667135%26rft_id%253Dinfo%253Apmid%252F2667135%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIyNDUvNDkxNi8zNTYiO3M6NDoiYXRvbSI7czoyNToiL3NjaS8yNzIvNTI3MC8xODU3LjQuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9

Changes in androgens during treatment with four low-dose contractptives

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest ®, Femodeen ®, Marvelon ®, or Mercilon ®. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5α-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17α-hydroxy-progesterone (17OHP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon ® group when compared to Cilest ® and Marvelon ® (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon ® (−75%) as compared to the others (−100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.

New Generation of Progestins May Raise Oral Contraceptive Users' Risk of Blood Clots

Three recent studies indicate that oral contraceptives (OCs) containing the progestins gestodene or desogestrel may increase the risk of venous thromboembolism in users. A World Health Organization case-control study (1143 cases 3000 controls) found that current OC users were at consistently higher risk of venous thromboembolism than nonusers. The risk was exacerbated in European OC users who had a history of pregnancy-related hypertension. Risk was closely associated with type of progestin. European users of combination OCs with the older progestins had relative risks of 3.4-4.1 whereas the new low-dose combination OC was associated with a risk 7.4 times higher than in nonusers. In developing countries these figures were 2.8-3.8 and 12.2 respectively. In a more detailed analysis of 769 hospitalized cases and 1979 hospitalized (and 246 nonhospitalized) controls it was found that OC use had a 4.1 increased risk of thromboembolism and the risk in the newer OCs was 9.4 versus 3.4 in the older formulations. In this study the risk of thromboembolism in nonusers was estimated to be 3.9/100000 woman years compared to 10.3 among levonorgestrel users and 21.3 among gestodene or desogestrel users. A computer analysis of data on healthy women in the UK under age 40 revealed that 4.3 deaths/100000 occurred in women using levonorgestrel 4.8 in those who used gestodene and 1.5 among those who used desogestrel. After controls these differences were not significant. Further analysis of cases of nonfatal venous thromboembolism indicated that women using the newer formulations had twice the risk of those using the older formulations. A Dutch study found similar results. Since this increased risk would translate into one additional death per million users per year it is difficult to make a clinical decision about the new formulations which may decrease the risk of myocardial infarction and diabetes. Further research is indicated to determine the impact of the new progestins on stroke and myocardial infarction.

Many Pill Users in Egypt Lack Adequate Knowledge About How to Take the Pill

According to data from the 1988 Egypt Demographic and Health Survey incorrect use patterns are widespread among oral contraceptive (OC) acceptors. 1258 of the 8911 ever-married women ages 15-49 years included in the survey identified themselves current OC users. 90% did not start a new pill pack on the correct day 37% had missed one or more pill in the preceding cycle 24% failed to take all the pills in their proper sequence and 61% were unaware that they should take two pills the day after a dose was missed. Most disturbing was the finding that 22% took the pills on an as needed basis. Survey respondents had been using OCs for an average of two years. Logistic regression analysis found that proper OC use was significantly greater among women whose husbands purchased their pills than among women who obtained their supply themselves and among those who did not experience OC-related side effects. Rural women with no schooling who relied on government supply sources were seven times more likely to take the pills out of sequence than urban educated women with a private supply source. Recommended to improve compliance are training programs for providers such pharmacy clerks and package inserts that include clear simple pictorial instructions.