Effect Of Oral Contraceptive Use Research Articles

P103 Oral contraceptive use does not affect CF disease severity

Several studies using a variety of in vitro models indicate that sex hormones such as oestrogen can alter ion transport across epithelial cells by either directly affecting CFTR or altering...

Intrinsic Coagulation Activation and the Risk of Arterial Thrombosis in Young Women

Background— Classically, intrinsic coagulation proteins are thought to have a minor role in hemostasis. Recently, these proteins, especially FXII, were implicated as possible key players in the pathogenesis of arterial thrombosis. This study aims to determine the risks of arterial thrombosis conferred by increased activation of intrinsic coagulation proteins in young women and the effect of oral contraceptive use on this association. Methods and Results— The Risk of Arterial Thrombosis In relation to Oral contraceptives (RATIO) study is a population-based case-control study including young women (age 18 to 50 years) with myocardial infarction (n=205) and ischemic stroke (n=175) and 638 healthy controls. Intrinsic coagulation protein activation was determined by measuring activated protein-inhibitor complexes. This complex is with C1 esterase inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH). Odds ratios (ORs) and corresponding confidence intervals (95% CIs) were calculated with logistic regression. High levels of protein activation (>90th percentile of controls) showed an increased risk of ischemic stroke: FXIIa-C1-INH (OR, 2.1; 95% CI, 1.3 to 3.5), FXIa-C1-INH (OR, 2.8; 95% CI, 1.6 to 4.7), FXIa-AT-INH (OR, 2.3; 95% CI, 1.4 to 4.0), and Kallikrein-C1 (OR, 4.3; 95% CI, 2.6 to 7.2). If anything, myocardial infarction risk was only increased by Kallikrein-C1-INH (OR, 1.5; 95% CI, 0.9 to 2.5). Oral contraceptive use further increased the risks. Conclusions— High levels of activated proteins of the intrinsic coagulation system are associated with arterial thrombosis, whereas the strength of these associations differs for myocardial infarction and ischemic stroke. This contradicts similar analyses among men in the Northwick Park Heart Study. Together with the finding that oral contraceptive use further increases the risks, the question of whether the role of intrinsic coagulation proteins in the pathogenesis of arterial thrombosis is sex-specific is raised.

Genetic epidemiology of epithelial ovarian cancer.

Aside from age, family history is the strongest predictor of ovarian cancer risk. Genetic components of risk for ovarian cancer have been evaluated by a number of designs, including case-control studies of family history and other risk factors, segregation and genetic linkage studies, and studies of biomarkers and tumor-specific cytogenetic abnormalities. Data were extracted from all available case-control studies that included family history. Cytogenetic, biomarker, segregation, analytic, and genetic linkage studies were reviewed. Family history of ovarian cancer confers a 3.6-fold increased risk for this disease. Segregation studies of breast and ovarian cancer in five large families were consistent with dominant inheritance. Low levels of alpha-L-fucosidase confer mildly increased risk for ovarian cancer. Low galactose-1-phosphate uridyl transferase and type A blood group may increase risk for ovarian cancer. Cytogenetic and oncogene studies have identified regions that may be important in tumorigenesis and metastasis, but discriminating between early and late changes is difficult from these studies. Presence of a genetic susceptibility locus for breast and ovarian cancer has been confirmed on chromosome 17q21. Family history is an important predictor of ovarian cancer risk. In rare families, a specific dominantly acting gene can be identified, but in the vast majority of familial ovarian cancers the underlying mechanism remains unclear. Specific studies are needed for women with a family history of ovarian cancer because evidence suggests modification of the effects of oral contraceptive use and reproductive patterns in this population of women.

Oral Contraceptive Use and Estrogen/Progesterone Receptor–Negative Breast Cancer among African American Women

Oral contraceptive formulations have changed over time, making it relevant to assess the effect of more recent formulations on breast cancer risk. In addition, some studies have found stronger positive associations of oral contraceptive use with estrogen receptor-negative (ER(-)) than with ER-positive (ER(+)) breast cancer. We carried out the first assessment of the effect of oral contraceptive use on the incidence of breast cancer classified by receptor status among African American women, a group disproportionately affected by ER(-) cancer. We followed 53,848 Black Women's Health Study participants from 1995 to 2007 through biennial health questionnaires, in which participants reported information about incident breast cancer, oral contraceptive use, and breast cancer risk factors. Pathology information was obtained on receptor status for 789 incident cases. Incidence rate ratios (IRR) with 95% confidence intervals (95% CI) were derived from Cox regression models with control for confounding factors. Ever use of oral contraceptives was more strongly associated with ER(-)PR(-) breast cancer (279 cases; IRR, 1.65; 95% CI, 1.19-2.30) than with ER(+)PR(+) cancer (386 cases; IRR, 1.11; 95% CI, 0.86-1.42). The risk of ER(-)PR(-) breast cancer increased with increasing duration of use among recent users. These results indicate that the oral contraceptive formulations used in recent decades increase breast cancer risk in African American women, with a greater effect for ER(-) than ER(+) cancer. Mechanisms to explain the adverse influence of oral contraceptive use on ER(-) breast cancer need to be elucidated.

The Effect of Initiating Oral Contraceptive Use on Voice: A Case Study

To examine the effects of initiating oral contraceptive (OC) use on spectrally based acoustic measures. Case history. A 23-year-old female volunteered to participate in the study. Voice recordings were obtained during eight consecutive menstrual cycles: two cycles before the onset of OC use and six cycles after the initiation of OC use. Recordings consisted of three trials of the sustained vowel /æ/ and were obtained during the follicular phase (preovulation, days 9-11) and luteal phase (premenstruation, days 20-22) of each cycle. Measurements obtained included the following: (1) H1-H2, the ratio of the amplitude of the first harmonic to the amplitude of the second harmonic, which correlates to closed quotient duration; (2) H1-A1, the ratio of the amplitude of the first harmonic to the amplitude of the first formant, which correlates to glottal width; and (3) H1-A3, the ratio of the first harmonic to the amplitude of the third formant, which correlates to the abruptness of vocal fold closure. In addition, acoustic measures of voice perturbation, jitter, shimmer, and noise-to-harmonic ratio were measured. The participant exhibited changes in glottal characteristics in conjunction with initiation of OC use. Both the H1-H2 and H1-A1 differences changed with OC use relative to menstrual cycle phase. These two measures have been correlated with the glottal measures of closed quotient and glottal width, respectively. However, there was no significant change in the H1-A3 difference, indicating no effect of OC use on the speed of vocal fold closure. The results of this study indicate that the onset of OC use can result in vocal changes as noted by different patterns of glottal adjustment across menstrual cycle phases.

Oral contraceptives and breast cancer risk in BRCA1 and BRCA2 mutation carriers

Estrogen and progestin in oral contraceptives may be carcinogenic to the breast, and their use has been associated with a modest increase in the risk of breast cancer in the general female population. Women who carry deleterious mutations in breast cancer susceptibility genes, BRCA1 and BRCA2, have a significantly higher risk of breast and ovarian cancer. The literature on the role of oral contraceptives in carriers is sparse and the results are inconclusive. Findings from some case-control studies and the International BRCA1/2 Carrier Cohort Study suggest that oral contraceptive use may be associated with an increased risk of breast cancer in BRCA1 and BRCA2 carriers. Understanding the potential effects of oral contraceptive use among carriers has important implications for preventive strategies and clinical management. Both the possible protective effect for ovarian cancer risk and the increased potential risk of breast cancer must be considered.

Oral contraceptives and the risk of multiple sclerosis: A review of the epidemiologic evidence

Multiple sclerosis (MS) is more frequent in women than in men, suggesting that sex hormones could play a role in the development of MS. For this reason, several studies have assessed whether use of oral contraceptives modifies the risk of MS. In this article, we review the methodology and results of published epidemiologic studies addressing this issue. On the whole, the existing epidemiologic evidence does not support an important effect of oral contraceptive use on the risk of MS, though it does suggest that oral contraceptives might delay the onset of the disease.

Total Laparoscopic Radical Hysterectomy in the Treatment of Early Cervical Cancer

Total laparoscopic radical hysterectomy (TLRH) has been reported since the early 1990 s. Although the acceptance of TLRH had been slow over the past 15 years, several teams throughout the world have recently reported promising results in the treatment of early cervical cancer with this procedure. Several modifications of the originally described technique have also been reported. From the currently existing data, these is no doubt that TLRH is technically feasible. Its operative safety profile is comparable to that of radical abdominal hysterectomy (RAH), and there exist sufficient data to suggest that the histopathologic outcome is also similar in terms of local radicality and lymph node yield. The duration of the procedure has become acceptable but remains still longer in comparison to RAH, in most series. It is now evident that with increasing experience, repetition, standardization, and incorporation of technological advances, duration can be reduced considerably and become similar to that of RAH. Total laparoscopic radical hysterectomy is associated with less blood loss, faster recovery and return of bowel function, reduced febrile morbidity, and a better cosmetic result. Nevertheless, shorter hospitalization in comparison to that observed after RAH is not consistently reported, and return of normal bladder activity is similar to that observed after RAH. It is also true that the currently existing recurrence and survival data are still immature to draw safe conclusions on its long-term oncological safety. Probably, the time has come for a multicenter randomized study between TLRH and RAH with participation of the institutions with significant experience in this procedure.

Last Word on Point:Counterpoint: Estrogen and sex do/do not significantly influence post-exercise indexes of muscle damage, inflammation, and repair

POINT-COUNTERPOINTLast Word on Point:Counterpoint: Estrogen and sex do/do not significantly influence post-exercise indexes of muscle damage, inflammation, and repairMonica J. Hubal and Priscilla M. ClarksonMonica J. Hubal and Priscilla M. ClarksonPublished Online:01 Mar 2009https://doi.org/10.1152/japplphysiol.00030.2009MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor:We thank those who contributed interesting and insightful ideas. We have consistently found in relatively large samples (over 100 subjects, where we were sufficiently powered to detect small differences between groups) that there was no difference between men and women in soreness response to muscle damaging exercise and that women had either an equal or greater strength loss postexercise (2, 5). Strength loss is considered a valid and reliable assessment of muscle damage. If estrogen protects women from exertional muscle damage, we would have found differences in these measures, given our sample size. In addition, we have tested several of these large cohorts for effects of oral contraceptive use and found little difference between users and non-users. Although studies of pre- versus post-menopausal women could provide insight into estrogenic effects in humans, we agree with several of the respondents that these studies would be confounded either by interindividual variability (cross-sectional design) or by age-related changes in muscle (longitudinal design). We have also not detected consistent sex differences in the frequency of men and women as “high responders” to eccentric exercise, likely due to the low frequency of high responders in the population. Moreover, a high response to eccentric exercise may be driven, at least in part, by genetic predisposition (1).The compelling data that Dr. Tiidus presents showing that estrogen is protective against exercise-induced muscle damage in rats is intriguing because of estrogen's protective effect in lowering heart disease risk in women. From these results, it might be suggested that estrogen could also protect skeletal muscle in women. However, women tend to show greater prevalence/risk of some disease-associated myopathies, such as statin-induced myopathy (albeit this could be due to body size) (4) and poly- and dermato-myositis (3). We agree that a good test to conclusively show that estrogen does not protect skeletal muscle of women when exposed to damaging exercise is to test a group of ovariectomized women in a longitudinal design. However, if estrogen served as a significant protector against skeletal muscle damage, we would have observed differences in muscle damage indicators between men and women in our research studies. If estrogenic effects were so minimal as not to be observed in our studies, we question their relevance.REFERENCES1 Clarkson PM, Hoffman EP, Zambraski E, Gordish-Dressman H, Kearns A, Hubal M, Harmon B, Devaney JM. ACTN3 and MLCK genotype associations with exertional muscle damage. J Appl Physiol 99: 564–569, 2005.Link | ISI | Google Scholar2 Hubal MJ, Rubinstein SR, Clarkson PM. Muscle function in men and women during maximal eccentric exercise. J Strength Cond Res 22: 1332–1338, 2008.Crossref | ISI | Google Scholar3 Mastaglia FL, Phillips BA. Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic criteria. Rheum Dis Clin North Am 28: 723–741, 2002.Crossref | ISI | Google Scholar4 Rosenson RS. Current overview of statin-induced myopathy. Am J Med 116: 408–416, 2004.Crossref | ISI | Google Scholar5 Sewright KA, Hubal MJ, Kearns A, Holbrook MT, Clarkson PM. Sex differences in response to maximal eccentric exercise. Med Sci Sports Exerc 40: 242–251, 2008.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: M. J. Hubal, Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010 (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited BySex Differences in Exercise-Induced Muscle Pain and Muscle DamageThe Journal of Pain, Vol. 13, No. 12 More from this issue > Volume 106Issue 3March 2009Pages 1022-1022 Copyright & PermissionsCopyright © 2009 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00030.2009History Published online 1 March 2009 Published in print 1 March 2009 Metrics

Reproductive and Hormonal Factors, and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Results from the International BRCA1/2 Carrier Cohort Study

Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies. We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework. There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had ever used OC were at a significantly reduced risk of developing ovarian cancer (hazard ratio, 0.52; 95% confidence intervals, 0.37-0.73; P = 0.0002) and increasing duration of OC use was associated with a reduced ovarian cancer risk (P trend = 0.0004). The protective effect of OC use for BRCA1 mutation carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive conclusions. The results provide further confirmation that OC use, number of full-term pregnancies, and tubal ligation are associated with ovarian cancer risk in BRCA1 carriers to a similar relative extent as in the general population.

Interaction Between Oral Contraceptive Use and Coagulation Factor Levels in Deep Vein Thrombosis

Background: Since not all women using oral contraceptives (OC) develop deep vein thrombosis (DVT), the presence of additional risk factors in women with DVT and OC use is likely. High levels of coagulation factor activities are established risk factors of DVT. There are, however, limited data on the combined effect of OC use and high levels of procoagulant coagulation factors, a shortened aPTT or markers of inflammation like erythrocyte sedimentation rate (ESR) or CRP.Materials and Methods: 246 women with a first DVT (123 associated with OC use) and 246 normal women matched for age and date of birth were evaluated. Cut-off values for continuous variables were the 90% percentile determined in normal women. OC use influences the levels of many coagulation factors. Using the mean effect of OC use on coagulation factor levels (measured in the control subjects), we estimated the coagulation factor levels in patients prior to the index date, i.e. the time of the thrombosis.Results: Use of OC was associated with an increase in risk of 3.0. This risk increased due to interaction with factor I (FI) (Odds Ratio (OR) 14.2, p=0.0001), FVIII (OR 5.1, p=0.0001), FIX (OR 5.5, p=0.0001), FXI (OR 12.0, p=0.0001), vWF:Ag (OR 7.7, p=0.0001) and aPTT (OR 20.2, p=0.004). In contrast, no significant increase in risk was found when OC use was associated with high levels of ESR or CRP.Conclusion: The results of this study indicate that the joint effects of OC use and high coagulation factor levels increase the risk of DVT. This risk increase appears to be of clinical relevance particularly in individuals with shortened aPTT values or high levels of fibrinogen.

Borderline ovarian tumors in Sweden 1960–2005: Trends in incidence and age at diagnosis compared to ovarian cancer

The aim of the study was to investigate long-term trends in the incidence of borderline tumors and ovarian cancer in Sweden during 1960-2005, based on data from the population-based Swedish Cancer Register. We identified 6,288 patients with borderline ovarian tumors and a total of 34,977 cases of ovarian cancer during the study period. The age-standardized incidence of borderline ovarian tumors increased from 1.0 to 5.3 per 100,000 women-years from 1960-1964 to 2000-2005 and the incidence of ovarian cancer increased from 16.4 to 19.7 per 100,000 women-years from 1960-1964 to 1980-1989 and then declined to 16.6 per 100,000 women-years to the period 2000-2005. Borderline ovarian tumors comprised 15% of all primary ovarian neoplasms and the proportion increased from 8.3 to 23.6% during the study period. The median age at diagnosis for patients with borderline ovarian tumors and ovarian cancer was 55.2 and 61.6 years, respectively. In women younger than 40 years, 34% of all primary ovarian malignancies consisted of borderline ovarian tumors. For the 5 birth cohorts evaluated, the peaks of incidence occurred in stepwise younger age for each younger birth cohort for both borderline tumors and ovarian cancer. The increasing incidence of borderline ovarian tumors could be explained by an increase in diagnostic activity and by a lack of protective effect of oral contraceptive use. The decline in invasive tumors could be explained by a combination of factors, where the contribution of each is uncertain: shifting exposure to risk factors, a protective effect of oral contraceptive use, and increased detection of and removal of precancerous lesions.

Premenstrual Asthma: Prevalence, Cycle-to-Cycle Variability and Relationship to Oral Contraceptive Use and Menstrual Symptoms

The prevalence of asthma is higher in women than men of reproductive age and almost half of all hospitalisations for asthma in women occur during the perimenstrual phase of the cycle. The mechanisms of premenstrual asthma (PMA) are unknown and a definition of PMA has not been clearly presented in the literature. The objective of this study was to determine the prevalence of PMA using a variety of definitions, to investigate the cycle-to-cycle variation in PMA, the effects of oral contraceptive use and the relationship between PMA and premenstrual symptoms. Premenopausal women with asthma (n = 28) were prospectively followed for at least 12 weeks over 2–4 consecutive menstrual cycles. Asthma symptoms, β2-agonist and inhaled corticosteroid use and morning and evening peak expiratory flow were recorded daily. The following types of PMA definitions were investigated: self-reported PMA, increased symptoms, increased medication use, decreased peak flow or a combination of changes in symptoms, medication and peak flow. Changes of more than 20%, for at least 2 consecutive days of the luteal phase (last 14 days of the cycle prior to menstruation) compared to the early follicular phase average (first 7 days after menstruation) were considered PMA. Using a composite definition where subjects experienced increased symptoms and medication use with or without a change in peak flow, 16 subjects were classified as having PMA (57%), while 12 did not have PMA. Only 4 subjects (25%) had PMA in every cycle examined. Fifty-five percent of subjects who used oral contraceptives had PMA, while 59% of subjects who did not use oral contraceptives had PMA. Women who were defined PMA using the composite definition were more likely than those without PMA to experience a 20% decrease in peak flow during the luteal phase. There was no relationship between asthma symptoms and premenstrual symptoms on day 1 of the menstrual cycle in women with PMA. PMA resulting in increased symptoms and medication use occurred in 57% of subjects studied for 2–4 menstrual cycles. The use of oral contraceptives is not protective and further work is required to elucidate the mechanisms of PMA.

Oral contraceptives and clinical recurrence of human papillomavirus lesions and cervical intraepithelial neoplasia following treatment

Objective To evaluate the effect of oral contraceptive use on the recurrence rate of human papillomavirus (HPV) lesions and cervical intraepithelial neoplasia (CIN) following ablative or excisional procedures in a long-term follow-up. Method The study was conducted with 650 oral contraceptive users presenting with HPV lesions and/or CIN, and 670 women who had these lesions but did not use oral contraceptives acted as controls. The participants underwent cytologic evaluations, colposcopy, and direct biopsy, followed by either ablative treatment by laser carbon dioxide vaporization or excision by a loop electrosurgical excision procedure or cold knife conization. They were then followed up for a minimum of 5 years. Results The recurrence rates did not differ statistically between the case and control groups. Conclusion Oral contraceptive use was not found to increase the recurrence rate of HPV lesions and/or CIN after ablative or surgical treatment.

The association between oral contraceptive use and lobular and ductal breast cancer in young women

Recent reports indicate that the incidence of lobular breast cancer is increasing at a faster rate than ductal breast cancer, which may be due to the differential effects of exogenous hormones by histology. To address this issue, we examined whether the relationship between oral contraceptive use and incident breast cancer differs between lobular and ductal subtypes in young women. A population-based sample of in situ and invasive breast cancer cases between ages 20 and 44 were recruited from Atlanta, GA; Seattle-Puget Sound, WA and central New Jersey. Controls were sampled from the same areas by random-digit dialing, and were frequency matched to the expected case age distribution. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using polytomous logistic regression. Among the 100 lobular cancers, 1,164 ductal cancers, and 1,501 controls, the odds ratios for oral contraceptive ever use were 1.10 (95% CI = 0.68-1.78) for lobular cancers and 1.21 (95% CI = 1.01-1.45) for ductal cancers, adjusted for study site, age at diagnosis, and pap screening history. Our results suggest that the magnitude of the association between ever use of oral contraceptives and breast cancer in young women does not vary strongly by histologic subtype. These results are similar to previous studies that report little difference in the effect of oral contraceptive use on breast cancer by histology.

Oral contraceptive and IUD use and endometrial cancer: A population‐based case–control study in Shanghai, China

Oral contraceptive (OC) and intrauterine device (IUD) use have been shown to be protective factors for endometrial cancer in several epidemiological studies; however, few studies have been conducted in Chinese populations. We evaluated the association between OC and IUD use and endometrial cancer risk in a population-based case-control study among Chinese women in Shanghai, China. The study included 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched healthy controls. Logistic regression models were used to estimate adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). In our study population, 18.5% cases and 24.9% controls reported having ever used OCs with an OR of 0.75 (95% CI, 0.60-0.93), after adjusting for known risk or protective factors for endometrial cancer. The risk of endometrial cancer decreased with long-term use of OCs with the OR for more than 72 months of use being 0.50 (95% CI, 0.30-0.85). The effect of OC use remained 25 or more years after cessation of use; the associated OR was 0.57 (95% CI = 0.42-0.78) as compared to nonusers. Similarly, fewer cases than controls had ever used IUD, with the multivariable adjusted OR being 0.53 (95% CI = 0.43-0.65). A reduction in risk was observed regardless the duration of use or age at first and last use. These results suggest that OC and IUD use may confer long-term protection against endometrial cancer.

Extra‐tumoral breast tissue in breast cancer patients: Variations with steroid contraceptive use

The association between oral contraceptive (OC) use and benign breast changes in extra-tumoral breast tissue was studied histologically in 1,503 breast cancer patients from The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. The occurrence of ductal hyperplasia, ductal atypia, sclerosing adenosis, cysts, apocrine metaplasia, apocrine hyperplasia, apocrine atypia, adenosis, lobular atypia, duct ectasia, calcifications, inflammatory reaction, lactational metaplasia and a high epithelial-stromal ratio was graded semi-quantitatively. Prevalence odds ratio (POR) for each histologic variable was calculated by logistic regression analyses. Patients who had ever used OC had lower occurrence of ductal hyperplasia than never users (POR 0.72 (95% CI 0.52-0.99)). Current use and more than 8 years of use was also associated with a lower prevalence of ductal hyperplasia (POR 0.40 (0.20-0.81) and POR 0.33 (0.17-0.64), respectively). Age > 35 years at first use was associated with increased prevalence of ductal carcinoma in situ (POR 2.15 (1.05-4.40)), but not of atypical ductal hyperplasia. Our results show that the effects of OC use on ductal hyperplasia in non-neoplastic breast tissue of breast cancer patients are similar to what others have found in patients with benign breast disease only. The increased prevalence of extra-tumoral ductal carcinoma in situ in breast cancer patients who started OC use at high age may possibly be explained by a longer preinvasive phase in these patients.

Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing

Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged ⩽40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32–3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02–2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17–1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.

Oral Contraceptives, Angiotensin-Dependent Renal Vasoconstriction, and Risk of Diabetic Nephropathy

Diabetes, the leading cause of end-stage renal disease in the U.S., is believed to involve activation of the renin angiotensin system (RAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic kidney are unclear. Renal plasma flow (RPF) response to captopril, as an index of RAS activity, was investigated in 92 women (41 nondiabetic OC nonusers, 10 nondiabetic OC users, 29 diabetic OC nonusers, and 12 diabetic OC users). Based on the hemodynamic findings, we examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1-24). Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril (9 +/- 10 ml x min(-1) x 1.73 m(-2), P = 0.6). In comparison, nondiabetic OC users showed a significant increase (69 +/- 35 ml x min(-1) x 1.73 m(-2), P = 0.02) (P = 0.04 vs. nondiabetic OC nonusers). Diabetic OC nonusers demonstrated the anticipated vasodilator response (58 +/- 12 ml x min(-1) x 1.73 m(-2), P < 0.0001). Diabetic OC users showed the largest responses (84 +/- 12 ml x min(-1) x 1.73 m(-2), P = 0.002) (P = 0.04 vs. diabetic OC nonusers). Plasma renin activity did not vary with OC use (P = 0.3). The RPF responses to captopril and angiotensin receptor blocker were highly correlated (r = 0.72, P < 0.001), suggesting clear involvement of the RAS. In the observational study, 18% (6/33 [95% CI 4.3-32.1]) of OC users developed macroalbuminuria compared with 2% (2/81 [0-5.9]) of OC nonusers (P = 0.003, univariate analysis). After adjustment for known risk factors with a Cox regression model, OC use remained a predictor for the development of macroalbuminuria (relative risk 8.90 [95%CI 1.79-44.36], P = 0.008). The strong association of OC use with angiotensin-dependent control of the renal circulation and the development of macroalbuminuria suggest that OC use may be a risk factor for diabetic nephropathy. Large prospective studies are required to further investigate this relationship.

Examination of Effects of Oral Contraceptive Use on Electromyography and Mechanomyography Findings During Muscle Fatigue of the Rectus Femoris

Background: Female athletes are reported to be at an increased risk for anterior cruciate ligament (ACL) injuries compared to male athletes. Fatigue may play a role in the occurrence of ACL injuries due to changes in dynamic stability of the knee. Purpose: To determine changes in muscle function across the menstrual cycle for women not using oral contraceptive (NOC) and women using oral contraceptives (OC) during concentric (CON) and eccentric (ECC) isotonic muscle fatigue actions. Study Design: Prospective quasi-experimental cohort design. Methods: Fourteen healthy, physically active women (Mean ± SEM, 23 ± 1 yrs, 1.7 ± 1 m, 60 ± 2 kg) were recruited and tested 3 times throughout one complete menstrual cycle. The NOC group (N = 6) was not taking any form of hormonal treatment and all had normal menstrual cycles lasting between 26 and 32 days. The second group (N = 8) had been taking OC for at least 6 months. Each participant performed one maximal isotonic strength (1-RM) test of the leg extensors. For each of the 3 testing sessions, each participant performed a fatigue protocol at 50% of 1-RM. Bipolar surface EMG electrodes were placed mid-thigh over the rectus femoris with a piezoelectric MMG recording device placed between the two electrodes. Results: No significant 2-way interactions for number of repetitions performed on each day, CON EMG, ECC EMG, CON MMG, or ECC MMG during fatigue. Conclusions: Based on the results from our sample population, no evidence was found to support the hypotheses of differences in muscle function between NOC and OC females.