Past Oral Contraceptive Use Research Articles

The Effect of Oral Contraceptive: Different Patterns of Use on Circulating IGF-1 and Bone Mineral Density in Healthy Premenopausal Women.

Both insulin-like growth factor-1(IGF-1) and oral contraceptive (OC) use have been linked to premenopausal breast and colorectal cancers, osteoporosis and cardiovascular disease. Understanding the effects of different patterns of use of OC on IGF-1 levels and bone mineral density (BMD) may offer insight into its influence on osteoporosis. We conducted a cross-sectional study, which included 135 women, who were then divided into three groups: Group A who were OC current users, 41 women; Group B who never use OC, 51 women; and Group C who were past users of OC, 41 women. Each patient completed a questionnaire on demographic parameters, marital state history and contraception history including duration of use and type of contraceptive pills or used method. Lower-end radius, proximal femur and lumbar spine BMD were measured by dual-energy X-ray absorptiometry. IGF-1 was assessed with chemiluminescent immunometric assay. The three groups were similar in total body T value of BMD (with slight better results in past users than the other two groups but it was statistically insignificant difference), and past users showed significantly higher BMD values compared to current users at spine, femur and forearm. Nonusers also had better BMD values compared to current users (spine and forearm BMD). Among past users, the mean level of circulating IGF-1 was higher than the other two groups and that difference was statistically significant. Past OC use and/or nonuse has a more favorable impact on BMD compared to current use and that this relationship is in part mediated by IGF-1. Hence, it appears that OC use is beneficial to BMD if used in the past and then discontinued or if never used at all compared to current use.

Physical activity, body mass index and bone mineral density—associations in a prospective population-based cohort of women and men: The Canadian Multicentre Osteoporosis Study (CaMos)

Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor. The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant. The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex. Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.

Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis

The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE). This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression. Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52). Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.

Interstitial Cystitis is Associated with Vulvodynia and Sexual Dysfunction—A Case-Control Study

Dyspareunia and sexual dysfunction are common in women with urological disorders. The study of comorbidity between interstitial cystitis (IC) and vulvodynia seems to be relevant to understand the mechanism generating pain in these conditions. To conduct a case-control study for evaluating vulvodynia and sexual dysfunction in women with IC. Forty-seven women with new diagnosis (National Institutes of Health [NIH]/National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] Criteria) of IC were compared with 188 age-matched, negative controls. Each woman completed a semi-structured interview and the Female Sexual Function Index (FSFI). A gynecological examination to assess vulvodynia (cotton swab testing) and genital health (vulvoscopy, Pap smear, culture, and vaginal health index score [VHIS]) was performed. Prevalence of vulvodynia, sexual function, and sociodemographic/gynecological variables significantly associated with IC. Spontaneous or provoked vulvodynia was reported by 23.4% and 74.5% of IC cases, respectively. Sexual function was significantly impaired (median total FSFI score: IC cases 16.85 ± 8.73 vs. controls 27.34 ± 6.41; P<0.0001) in sexually active women, and 23.4% of IC cases as compared to 9% of controls reported no sexual activity in the year preceding the study (χ(2) for trend=38.2, P<0.0001). VHIS was highly impaired in women with IC in comparison with controls (P<0.0001). Variables significantly associated with IC were a diagnosis of menopause (odds ratio [OR]=31.2, 95% confidence interval [CI]=8.1-120.5), past (OR=4.6, 95% CI=1.74-12.1) or current (OR=6.9, 95% CI=2.1-22.1) oral contraceptive use, and a histologically confirmed diagnosis of endometriosis (OR=3.7, 95% CI=1.1-12.7). We found an increased prevalence of vulvodynia among women with recently diagnosed IC; both conditions seem to have profound consequences on women's sexual function. A potential role for sex hormone-dependent mechanisms into the comorbidity of vulvar and bladder pain is proposed, but further research is warranted.

Ovarian hormones and reproductive risk factors for breast cancer in premenopausal women: the Norwegian EBBA-I study

BACKGROUNDOvarian hormones, parity and length of ‘menarche-to-first birth’ time interval are known risk factors for breast cancer, yet the associations between 17β-estradiol, progesterone and these reproductive factors remain unclear.METHODSA total of 204 women (25–35 years) who participated in the Norwegian EBBA-I study collected daily saliva samples for one complete menstrual cycle, and filled in a reproductive history questionnaire. Anthropometry was measured and saliva samples were analyzed for ovarian hormones. Associations between parity, the interval and ovarian hormones, and effects of hormone-related lifestyle factors were studied in linear regression models.RESULTSMean age was 30.7 years, and age of menarche 13.1 years. Parous women had on average 1.9 births, and age at first birth was 24.5 years. No association was observed between parity and ovarian steroids. In nulliparous women, higher waist circumference (≥77.75 cm) and longer oral contraceptive (OC) use (≥3 years) were associated with higher levels of 17β-estradiol. Short (<10 years) versus long (>13.5 years) ‘menarche-to-first birth’ interval was associated with higher overall mean (Ptrend = 0.029), 47% higher maximum peak and 30% higher mid-cycle levels of 17β-estradiol. We observed a 2.6% decrease in overall mean salivary 17β-estradiol with each 1-year increase in the interval.CONCLUSIONSNulliparous women may be more susceptible to lifestyle factors, abdominal overweight and past OC use, influencing metabolic and hormonal profiles and thus breast cancer risk. Short time between ‘menarche-to-first birth’ is linked to higher ovarian hormone levels among regularly cycling women, suggesting that timing of first birth is related to fecundity.

Effect of hormone replacement therapy (HRT) on periodontal status of postmenopausal women

SummaryBackgroundThe risks/benefits balance of hormone replacement therapy (HRT) is controversial. The aim of this study was to assess the periodontal status of a postmenopausal women group receiving HRT and to determine the effects of HRT on clinical measures of periodontal disease.Material/MethodsNinety-one postmenopausal women, 52 taking HRT (HRT+) and 39 not taking HRT (HRT−), completed the study. Clinical parameters measured included visible supragingival plaque, probing pocket depth (PD) and clinical attachment level (CAL). Gingival status was recorded as gingival bleeding on probing (BOP). Previous oral contraceptive use and current and past smoking status were also assessed.ResultsData indicated that PD and CAL were not significantly different between HRT+ patients and HRT− patients (P=0.8067 and P=0.1627, respectively). The HRT+ group exhibited significantly lower visible plaque levels compared to the control group (P<0.0001). The percentage of gingival sites with positive BOP was significantly lower in the HRT+ group compared to the HRT− group (34.85% vs. 65.15%; P=0.0007). Plaque accumulation was also tested in ANCOVA as a possible explanatory variable for the differences observed in gingival bleeding. The ANCOVA showed no significant differences in gingival bleeding between HRT+ and HRT− women (P=0.4677). No significant differences in past smoking status and oral contraceptive use were detected between HRT+ and HRT− women (P=0.9999 and P=0.0845, respectively).ConclusionsThese findings indicated that long-term HRT was not associated with relevant effects on periodontal status and clinical measures of periodontal disease, thus suggesting that HRT may not confer protection against periodontitis in postmenopausal women.

Prevalence of cholelithiasis in a Turkish population sample of postmenopausal women.

Gallstone disease is a global health problem worldwide. Potential risk factors for gallstone disease have not been well established except for age and gender. We aimed to investigate the prevalence and potential risk factors for gallstone disease in a population of postmenopausal women. A detailed Turkish questionnaire was prepared, and 474 of 502 postmenopausal women seen at the menopause clinic of Dr. Zekai Tahir Burak Hospital were included in the study. Sociodemographic, medical and reproductive characteristics were analyzed. Subjects were divided into two groups. The gallstone disease group (Group 1, n=73) was defined by both prior histories of gallstones diagnosis or cholecystectomy in the postmenopausal period and the presence of current sonographically diagnosed gallstones; Group 2 (n=401) included women with no gallstone disease. The present study found a 15.4% prevalence rate of cholelithiasis in a Turkish population sample of postmenopausal women. The demographic characteristics were similar between the two groups. The mean gravidity was 5.25 in Group 1 and 4.9 in Group 2. The number of subjects with past oral contraceptive use was 17 (23.3%) in Group 1 and 56 (13.9%) in Group 2. The number of women who took hormone replacement therapy was 40 (54.8%) in Group 1 and 222 (55.3%) in Group 2. There was no significant difference related to mean total cholesterol levels (216.5±44.9 mg/dl versus 215.9±44.3 mg/dl; p=0.915) and mean triglycerides (134.5±54.8 mg/dl versus 143.2±77 mg/dl; p=0.202) between the two groups. No risk factors for developing gallstones were determined among the evaluated parameters in postmenopausal women.

Endometriosis and estroprogestins: the chicken or the egg causality dilemma

Dysmenorrhea as a reason to initiate estroprogestins is significantly more common in women with endometriosis than in women without the disease. This might explain the previously reported mild association between endometriosis and past use of oral contraceptives.

Reproductive Factors, Hormone Use, and Risk for Lung Cancer in Postmenopausal Women, the Nurses' Health Study

There is increasing evidence suggesting that female hormones may play a significant role in lung cancer development. We evaluated the associations between reproductive factors, exogenous hormone use, and lung cancer incidence in the Nurses' Health Study. We assessed age at menopause, age at menarche, type of menopause, parity, age at first birth, postmenopausal hormone (PMH) use, and past oral contraceptive use in 107,171 postmenopausal women. Cox models were used to estimate the hazard ratios for each exposure, adjusting for smoking and other covariates. We identified 1,729 lung cancer cases during follow-up from 1984 to 2006. Menopause onset before 44 years of age (hazard ratio, 1.39; 95% confidence interval, 1.14-1.70) and past oral contraceptive use for >5 years (hazard ratio, 1.22; 95% confidence interval, 1.05-1.42) were associated with increased lung cancer risk. These associations were strongest in current smokers and small cell histology. In never smokers, increased parity was associated with decreased risk among parous women (P trend = 0.03), whereas in current smokers, older age at first birth was associated with increased risk (P trend = 0.02). PMH use was not associated with overall lung cancer incidence. However, nonsignificant results of increased risk in adenocarcinoma were seen with current PMH use. Our findings suggest female hormones may influence lung carcinogenesis, although the effect is likely modest, varied by histologic subtype, and altered by smoking. Further investigation of the pathophysiology of female hormones in lung cancer subtypes and their interaction with smoking will lead to better understanding of lung carcinogenesis.

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

Microcirculatory function in postmenopausal women: Role of aging, hormonal exposure and metabolic syndrome

Menopausal hormone therapy (HT) has shown conflicting cardiovascular endpoints, depending on the women studied. The endothelium is the main site for sex steroids cardiovascular action. To assess the influence of age, previous hormonal exposure and of metabolic syndrome (MS) on microcirculatory function, we studied 68 normotensive non-diabetic postmenopausal women, 34–70 years old, by dynamic nailfold videocapillaroscopy evaluating red blood cell velocity (RBCV) at baseline and during the reactive hyperemia response after 1 min ischemia (RBCV max) and time taken to reach it (TRBCV max). There was an inverse correlation between RBCV and RBCV max, versus age ( p = 0.02 for both) and time since menopause (TSM, p = 0.01 and p = 0.03, respectively). Women who used oral contraceptives in the past showed higher RBCV (1.51 ± 0.10 vs. 1.43 ± 0.09 mm/s, p = 0.01) and RBCV max (1.70 ± 0.11 vs. 1.63 ± 0.07 mm/s, p = 0.03) compared to never user ones. A longer time after menopause without HT was associated to lower RBCV max ( p = 0.05). Women with MS had longer TRBCV max (9.85 ± 1.77 vs. 8.47 ± 1.71 s, p = 0.02), as well as those with higher hematocrit, hemoglobin and leukocyte counts ( p = 0.03, p = 0.01 and p = 0.03, respectively) and lower HDL ( p = 0.03). In conclusion, in postmenopausal women of low cardiovascular risk, advanced age, longer TSM, longer time after menopause without HT and MS were associated to microcirculatory function impairment, whereas past use of oral contraceptives seemed to have a protective effect.

A prospective study of reproductive factors, hormone use, and risk of lung cancer in postmenopausal women

1501 Background: There has been increased interest in understanding the role of hormonal factors in lung cancer (LC) in women with the observation that it exhibits different epidemiologic patterns and treatment response when compared to men. However, results of published studies have been inconsistent, possibly due to inadequate smoking adjustment. Methods: We prospectively examined the associations between reproductive factors, exogenous hormone use, and LC incidence in 106,574 postmenopausal women in the Nurses’ Health Study. Participants completed biennial questionnaires which included updated smoking history. We assessed age at menopause, age at menarche, type of menopause, parity, postmenopausal hormone (PMH), and oral contraceptive use. Cox proportional hazards modeling was used to estimate the relative risks (RR) of each exposure, adjusted for smoking status, number of cigarettes, time since quitting, age of initiating smoking, fruit/vegetable intake, body mass index, and environmental smoking exposure. Results: We identified 1,565 LC cases during follow up from 1984 to 2004. Parity was associated with decreased LC risk in never smokers (RR = 0.54, 95% CI 0.31–0.96) but increased risk in current smokers (RR = 1.44, 95% CI 1.03–2.02). No association was seen in former smokers. Also, younger age at menopause was associated with higher LC risk in women with natural menopause (p-trend = 0.016). PMH use was not associated with LC incidence. The RR for current PMH users was 1.01 (95% CI 0.87–1.17) and for past users was 0.95 (95% CI 0.82–1.1). No significant association was seen when assessed by duration of PMH use, time since last use, or type of PMH. However, past use of oral contraceptives for greater than 5 years was associated with increased LC risk (RR = 1.2, 95% CI 1.03–1.41). Conclusions: These results suggest that there may be an association between hormonal factors and LC development, and further suggest that the mechanism may differ in smokers versus lifelong never smokers. No significant financial relationships to disclose.

Abstract 3002: Long Term Oral Contraceptive Use is an Independent Risk Factor for Arterial Stiffening

Oral contraceptives (OC) are among the most frequently used drugs in the world with approximately 100 million women worldwide taking OC. In contrast to the active controversy surrounding hormone replacement therapy, little attention has been focused on OC, a drug therapy taken by far more women for far longer time periods. We describe the population effects of current and long-term OC exposure on a prognostically well validated marker of arterial stiffness: carotid-femoral pulse wave velocity (PWV). The Asklepios study is a representative sample (2524 apparently healthy M/F volunteers, aged 35–55 years, 1301 women) from the Belgian general population, free from overt cardiovascular disease. The subjects were extensively screened (biochemistry, lifestyle, cardiac and vascular echography, arterial tonometry). PWV was measured from flow patterns registered by Doppler echography in the femoral and carotid arteries. Of 1301 women (median age 45.7 y), 27.4% were actively taking OC. In contrast past use of OC is far more prevalent with 81% of women having taken OC for at least 1 year. The median duration of exposition in these women was 13 years. Age-adjusted PWV was higher in women currently taking OC: 6.75 versus 6.55 m/s (difference 0.19 ± 0.09 m/s; p = 0.034). However, current OC users also had higher blood pressures (BP): systolic BP (+4.4 ± 0.9 mmHg; p &lt; 0.001), diastolic BP (+2.3 ± 0.6 mmHg; p &lt; 0.001). After adjustement for BP, the difference in PWV between current OC users and non-users became non-significant: 6.60 versus 6.62 m/s (difference 0.02 ± 0.09 m/s; p = 0.814). In contrast, duration of OC use is a significant determinant of PWV, even after adjustement for age, BP, lipid levels, body size, heart rate, drug therapy (lipid-lowering, antihypertensive), glycemic status and smoking: F = 6.1; p = 0.013. Per 10 years of OC exposure PWV increased by 0.1 m/s (0.02– 0.18; p = 0.013). Use of OC is associated with increased vascular stiffness in women. Current use is associated with increased PWV because OC’s increase blood pressure, long-term use (probably through structural remodelling of the vessels) is an independent determinant of PWV, increasing PWV by 0.10 m/s per 10 years exposure.

Menopausal and Reproductive Factors and Risk of Age-Related Macular Degeneration

To investigate whether estrogen exposures are associated with lower risks of age-related macular degeneration (AMD). Postmenopausal hormone (PMH) use, past use of oral contraceptives (OCs), ages at menarche and menopause, and parity were assessed among 74,996 postmenopausal women. Over 22 years, cases of early (n = 554) and neovascular (n = 334) AMD with a visual acuity of 20/30 or worse were identified. Cox models were used to calculate the relative risk for each exposure, adjusted for smoking and other factors. Current PMH users had a notable 48% lower risk of neovascular AMD compared with those who had never used PMH, although risk did not decline linearly with longer durations of use. Risk was lowest for PMH users who had used OCs in the past (P value for interaction, .03). In contrast, risk of early AMD was a notable 34% higher among current PMH users and OC use was unassociated with risk. The only remarkable finding for the endogenous estrogenic factors was a 26% lower risk of early AMD for parous women. Although PMH and OC use were associated with a lower risk of neovascular AMD, no benefit was observed for early AMD. Factors influencing lifetime exposure to estrogens were not consistently associated with the disease.

Ovarian cancer and oral contraceptives

Since the 1960s oral contraceptives have become a dominant form of female contraception in most developed countries. In the UK 25% of women aged 16-49 years and 62% of women aged 16-24 years rely on combined oestrogen-progestin or progestin-only (minipill) oral contraceptives. In the USA 19% of women aged 15-44 years (and 32% of 20-24-year-olds) take oral contraceptives. These drugs are the most effective reversible birth-control method and widespread use has been the cornerstone of family-planning initiatives worldwide. A causal role for oral contraceptives in various cancers was first suspected soon after their use became widespread but todays low-dose formulations are relatively safe drugs. Oral contraceptives have been linked with increased risks for some cancers (breast and cervix) and with protective effects for others (ovarian endometrial and colorectal). Calculation of the net effect on womens health is fraught with uncertainties. There are inherent difficulties associated with ascertaining the nature of exposure to oral contraceptives such as age at first use duration of use time since last use formulation of contraceptives (sequential combined or progestin-only) and dose. Furthermore epidemiological studies must include information about potential confounders such as sociodemographics family history of cancer comorbidity reproductive-health variables history of hormone-replacement therapy (HRT) and relevant lifestyle characteristics. For a woman in her 50s or 60s recalling past use of oral contraceptives is not easy. In case-control studies recall bias may further compound this problem because women with cancer might make a greater effort to recollect past exposures than their cancer-free counterparts. (excerpt)

Past use of oral contraceptives and hormone replacement therapy in women with angiographic coronary artery disease: a case-control study

To evaluate the relationship between past use of hormone replacement therapy (HRT)/ oral contraceptives (OC) and angiographic coronary artery disease (CAD). A case-control study. All women who were submitted to coronary angiography from January to December 2004 at the University Hospital, Ribeirão Preto School of Medicine (Brazil), were enrolled in this study and divided into two groups: with and without CAD. For the purposes of these analyses, coronary artery disease was defined as equal or greater than 70% luminal diameter stenosis in at least one epicardial coronary artery. The reproductive status was obtained from the medical records with a detailed questionnaire. We used unpaired t test, Fisher exact test or Qui-Square to compare the variables. Data were available for 203 of 383 patients who were submitted to angiocoronariography. Compared to patients without CAD (n = 119), patients with CAD (n = 84) were older (CAD: 62.8 ± 11.1 years vs. no-CAD 53.1 ± 12.1 years; P<0.0001), had a higher frequency of multiparity (CAD: 84% vs. no-CAD: 68%; P=0.03) and a higher proportion of them was menopausal (CAD:97% vs. no-CAD:79%; P=0.0009). The frequency of HRT use was higher among patients without CAD (CAD:28% vs. no-CAD:56%), with the use of HRT being associated with a lower risk for CAD [odds-ratio: 3.2 (1.2–8.3)]. The use of OC was not associated with a significant reduction of risk for CAD and the frequency of OC use did not differ between groups. There was no difference in the time of use of HRT or OC between CAD and no-CAD patients (HRT use: CAD = 4.9 ± 4.2 years vs. no-CAD = 2.7 ± 2.1 years; P=0.07; time of OC use: CAD = 8.8 ± 6.7 years vs. no-CAD = 6.1 ± 4.1 years; P=0.08). HRT but not OC use is associated with a reduced risk for CAD.

Past oral contraceptive and hormone therapy use and endogenous hormone concentrations in postmenopausal women

Exogenous sex hormone use is associated with many health effects. Current exogenous hormone use influences endogenous sex hormone levels, but little is known about longer term effects on endogenous hormones after cessation of use. The aim of this study was to examine the relationship between past hormone use and current endogenous hormone status. This was a cross-sectional study of 1,983 postmenopausal women aged 55 to 81 years from the general community. The women were not currently using exogenous hormones. Past use of oral contraceptives (OCs) and hormone therapy (HT) as well as circulating endogenous sex hormones and sex hormone-binding globulin concentrations were evaluated. Past OC users had significantly lower endogenous estradiol, estrone, androstenedione, testosterone, and sex hormone-binding globulin concentrations compared with never users independent of age, body mass index, smoking, physical activity, and reproductive factors. Past HT users had significantly lower testosterone and 17alpha-hydroxyprogesterone concentrations. Past OC use and HT use were both independently associated with lower testosterone concentrations: -9% (95% CI: -16% to -2%) for ever OC use compared with never OC use and -7% (95% CI: -17% to -2%) for ever HT use compared with never HT use. The magnitude of 5% to 10% differences in endogenous hormone concentrations was similar or greater for past OC use compared with past HT use, although OC use occurred earlier in the past. Past OC use and HT use seem to be related to long-term differences in endogenous sex hormones and sex hormone-binding globulin concentrations in postmenopausal women many years after cessation of use. These findings have implications for understanding the longer term effects of exogenous hormone exposures earlier in life with health and disease risk in later life.

Body Size and Risk of Epithelial Ovarian Cancer (United States)

We conducted a population-based case-control study of epithelial ovarian cancer in relation to measures of body size and adult weight change. In particular, we sought to characterize the independent relation of body weight at particular ages with risk. In-person interviews were sought with 35-54 year-old female residents of metropolitan Atlanta, Seattle or Detroit diagnosed with ovarian cancer during 1994-1998, and with controls sampled from these populations. Information provided by 355 cases and 1,637 controls was analyzed using unconditional logistic regression. The risk among women in the top tenth, relative to women in the lowest fourth, of the distribution of body weight at age 18 years was 1.5 (95% confidence interval, 1.0-2.2); at age 30, 1.9 (1.2-2.9); and 5 years before the reference date, it was 2.1 (1.4-3.3). While our results did not substantiate risk elevations reported in previous studies among subsets of women (e.g., with particular histologic tumor subtypes or according to past oral contraceptive use), we noted a particularly increased risk among women who reported 10 or more pounds gained during their first year of oral contraceptive use. Our findings suggest that risk of epithelial ovarian cancer may be most closely linked with body weight in the relatively recent past (but before the time in which the disease may manifest as weight loss) among women who develop this disease during the years before or shortly after menopause.

Past oral contraceptive use and angiographic coronary artery disease in postmenopausal women: data from the National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation

To evaluate past oral contraceptive use and angiographic coronary artery disease in women. Academic medical centers. Six hundred seventy-two postmenopausal women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) with coronary risk factors undergoing coronary angiography for suspected myocardial ischemia. Past oral contraceptive use, assessed by reproductive questionnaire. Quantitative coronary artery disease, assessed by a core angiography laboratory. Past oral contraceptive use was associated with a lower mean coronary artery disease severity index score (mean +/- SD: 11.8 +/- 10.3 vs. 18.7 +/- 17.3) compared with non-prior users, despite age adjustment. Past oral contraceptive use remained a significant independent negative predictor of coronary artery disease severity when adjusting for coronary risk factors, including age, diabetes mellitus, triglycerides, low-density lipoprotein cholesterol, smoking, aspirin use, and lipid-lowering medication (model R2 = 0.19). The modeling indicated that past oral contraceptive use was associated with a 2.44 lower coronary artery disease severity score index. There was no apparent relationship between duration of past oral contraceptive use and the coronary artery disease severity index score. Past oral contraceptive use is associated with less coronary artery disease, measured by quantitative coronary angiography, among postmenopausal women with suspected myocardial ischemia. These findings suggest that a prospective study should address the hypothesis that past oral contraceptive use during the premenopausal years might offer women protection from atherosclerotic coronary disease later in life.

The Role of Intradermal Skin Testing and Patch Testing in the Diagnosis of Autoimmune Progesterone Dermatitis

Autoimmune progesterone dermatitis is a rare clinical condition in which patients display hypersensitivity to endogenous progesterone. It manifests as a cyclical cutaneous eruption that flares during the luteal phase of the menstrual cycle, when progesterone levels peak, and resolves partially or completely a few days after menses. Its cutaneous manifestations are variable and include urticaria, eczematous eruptions, vesiculopustular eruptions, fixed drug eruptions, stomatitis, erythema multiforme, and anaphylaxis. Autoimmune progesterone dermatitis has been diagnosed previously with intradermal skin testing or intramuscular progesterone challenge. Treatment of progesterone hypersensitivity generally consists of ovulation inhibition with pharmaceutical agents or oophorectomy; other therapies (eg, thalidomide) have also been used with success. We report a case of cyclical erythema multiforme (EM) induced by hypersensitivity to endogenous progesterone in a patient with a history of past oral contraceptive use. After herpes simplex virus was ruled out as an etiologic factor, a diagnosis of progesterone hypersensitivity was confirmed with intradermal skin testing. Results of subsequent patch testing with various progesterone derivatives were negative. The EM outbreaks were suppressed temporarily by continuous administration of Loestrin (ethinyl estradiol plus norethindrone), which also increased the responsiveness of the outbreaks to prednisone tapers.