Long and irregular menstrual cycles, polycystic ovary syndrome, and ovarian cancer risk in a population-based case-control study.

Long and irregular menstrual cycles, a hallmark of polycystic ovary syndrome (PCOS), have been associated with higher androgen and lower sex hormone binding globulin levels and this altered hormonal environment may increase the risk of specific histologic subtypes of ovarian cancer. We investigated whether menstrual cycle characteristics and self-reported PCOS were associated with ovarian cancer risk among 2,041 women with epithelial ovarian cancer and 2,100 controls in the New England Case-Control Study (1992-2008). Menstrual cycle irregularity, menstrual cycle length, and PCOS were collected through in-person interview. Unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for ovarian cancer risk overall, and polytomous logistic regression to evaluate whether risk differed between histologic subtypes. Overall, we observed no elevation in ovarian cancer risk for women who reported periods that were never regular or for those reporting a menstrual cycle length of >35 days with ORs of 0.87 (95% CI = 0.69-1.10) and 0.83 (95% CI = 0.44-1.54), respectively. We observed no overall association between self-reported PCOS and ovarian cancer (OR = 0.97; 95% CI = 0.61-1.56). However, we observed significant differences in the association with menstrual cycle irregularity and risk of ovarian cancer subtypes (pheterogeneity = 0.03) as well as by BMI and OC use (pinteraction < 0.01). Most notable, menstrual cycle irregularity was associated with a decreased risk of high grade serous tumors but an increased risk of serous borderline tumors among women who had never used OCs and those who were overweight. Future research in a large collaborative consortium may help clarify these associations.

Temporal trends in healthcare utilization following primary melanoma diagnosis among Medicare beneficiaries.

BACKGROUND: Little is known about the impact of primary melanoma diagnosis on healthcare utilization and changes in utilization over time. OBJECTIVES: To evaluate population-based temporal trends in healthcare utilization following primary melanoma diagnosis. METHODS: We conducted a before-and-after multiple time series study of Medicare beneficiaries aged ≥ 66 years with primary melanoma diagnoses between 2000 and 2009 using the Surveillance, Epidemiology, and End Results Medicare database. Primary exposure was time from primary melanoma diagnosis at 3-6 months and 6-24 months postdiagnosis. Covariates included tumour-, patient- and geographical-level characteristics and healthcare utilization in the 6 months before diagnosis. Poisson regression was used to estimate population-based risk-adjusted utilization rates for skin biopsies, benign skin excisions, internal medicine office visits and dermatology office visits. RESULTS: The study population included 56 254 patients with first diagnoses of primary melanoma. Most patients were ≥ 75 years old (56·8%), male (62·1%), and had in situ melanoma (42·4%) or localized invasive melanoma (45·9%). From 2000 to 2009, risk-adjusted skin biopsy rates 24 months postdiagnosis increased from 358·3 to 541·3 per 1000 person-years (P < 0·001), and dermatology visits increased from 989·0 to 1535·6 per 1000 person-years (P < 0·001). Benign excisions and internal medicine visits remained stable. In 2000, risk-adjusted skin biopsy rates 6 months postdiagnosis increased by 208·5 relative to the 6 months before diagnosis (148·7 vs. 357·2) compared with an observed absolute increase of 272·5 (290·9 vs. 563·1) in 2009. Trends in dermatology visits were similar. CONCLUSIONS: Utilization of skin biopsies and dermatology office visits following primary melanoma diagnosis has increased substantially over time. These results may inform optimization of care delivery for melanoma within the Medicare population.

Skin biopsy utilization and melanoma incidence among Medicare beneficiaries.

BACKGROUND: Melanoma incidence has increased in recent decades in the U.S.A. Uncertainty remains regarding how much of this increase is attributable to greater melanoma screening activities, potential detection bias and overdiagnosis. OBJECTIVES: To use a cross-sectional ecological analysis to evaluate the relationship between skin biopsy and melanoma incidence rates over a more recent time period than prior reports. METHODS: Examination of the association of biopsy rates and melanoma incidence (invasive and in situ) in SEER-Medicare data (including 10 states) for 2002-2009. RESULTS: The skin biopsy rate increased by approximately 50% (6% per year) throughout this 8-year period, from 7012 biopsies per 100 000 persons in 2002 to 10 528 biopsies per 100 000 persons in 2009. The overall melanoma incidence rate increased approximately 4% (< 1% per year) over the same time period. The incidence of melanoma in situ increased approximately 10% (1% per year), while the incidence of invasive melanoma increased from 2002 to 2005 then decreased from 2006 to 2009. Regression models estimated that, on average, for every 1000 skin biopsies performed, an additional 5·2 (95% confidence interval 4·1-6·3) cases of melanoma in situ were diagnosed and 8·1 (95% confidence interval 6·7-9·5) cases of invasive melanoma were diagnosed. When considering individual states, some demonstrated a positive association between biopsy rate and invasive melanoma incidence, others an inverse association, and still others a more complex pattern. CONCLUSIONS: Increased skin biopsies over time are associated with increased diagnosis of in situ melanoma, but the association with invasive melanoma is more complex.

Is There a Need for Including Spiritual Care in Interdisciplinary Rehabilitation of Chronic Pain Patients? Investigating an Innovative Strategy.

OBJECTIVE: Chronic noncancer pain influences patient's quality of life and their ability to cope. Pain relieving medication and other specific treatments commonly integrated in biopsychosocial rehabilitation demonstrate modest benefits in pain relief and improved functioning of individuals. Spiritual care, covering the fourth dimension provides insight, inspires hope and purpose, and is thought to mediate mental and physical health for patients. This study explores the need for its inclusion in interdisciplinary pain rehabilitation and describes the requirements and test environment for evaluation. METHODS: Outcomes of spiritual care and interdisciplinary pain rehabilitation in follow-up studies of randomized controlled trials contained in systematic reviews were summarized. Pubmed, Cochrane, and PsycINFO were searched, citation tracking was applied, articles of follow-up studies therein were located. Literature was searched for insights pertaining to requirements for an assessment of including this fourth dimension. RESULTS: No systematic reviews for spiritual care were identified. Five systematic reviews of biopsychosocial rehabilitation containing 14 studies describing long-term outcomes were retrieved. The importance of coping in maintaining long-term outcomes was empirically illustrated. The required test environment is provided by a structured multidimensional care pathway separating spirituality from well-being and mental health, with measures of treatment outcome installed enabling a comparison with benchmarks. CONCLUSIONS: Active coping seems beneficial for maintaining positive long-term outcomes of interdisciplinary pain rehabilitation Spiritual care may be conducive to active coping. Further research is warranted to explore the additive value of this spiritual care in the context of a multidimensional care pathway.

Dietary fat intake and risk of epithelial ovarian cancer by tumour histology.

BACKGROUND: Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype. METHODS: We evaluated fat intake in a New England case-control study including 1872 cases and 1978 population-based controls (1992-2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between fat intake and EOC risk and polytomous logistic regression was used to test whether associations varied by histologic subtype. RESULTS: We observed a decreased risk of EOC when comparing the highest vs lowest quartiles of intake of omega-3 (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.66-0.96, P-trend=0.01) and omega-6 (OR=0.77, 95% CI 0.64-0.94, P-trend=0.02) and an increased risk with high consumption of trans fat (OR=1.30, 95% CI 1.08-1.57, P-trend=0.002). There was no significant heterogeneity by tumour histologic subtype; however, we observed a strong decreased risk for endometrioid invasive tumours with high intake of omega-3 (quartile (Q) 4 vs Q1, OR=0.58, 95% CI 0.41-0.82, P-trend=0.003). CONCLUSIONS: These findings suggest that higher intake of omega-3 may be protective for EOC overall and endometrioid tumours in particular, whereas greater consumption of trans fat may increase risk of EOC overall.

Infection control and prevention considerations.

Due to the nature of their underlying illness and treatment regimens, cancer patients are at increased risk of infection. Though the advent and widespread use of anti-infective agents has allowed for the application of ever-greater immune-suppressing therapies with successful treatment of infectious complications, prevention of infection remains the primary goal. The evolutionary changes of microorganisms, whereby resistance to anti-infective therapy is increasingly common, have facilitated a paradigm shift in the field of healthcare epidemiology. No longer is the focus on "control" of infection once established in a healthcare environment. Rather, the emphasis is on prevention of infection before it occurs. The most basic tenet of infection prevention, and the cornerstone of all well-designed infection prevention and control programs, is hand hygiene. The hands of healthcare workers provide a common potential source for transmission of infectious agents, and effective decontamination of the hands reduces the risk of transmission of infectious material to other patients. Once infection is suspected or established; however, implementation of effective control strategies is important to limit the spread of infection within a healthcare environment. This chapter outlines the basic tenets of infection prevention, principles of isolation precautions and control measures, and elements for a successful infection control and prevention program.

Reproductive characteristics in relation to ovarian cancer risk by histologic pathways.

STUDY QUESTION: Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification? SUMMARY ANSWER: Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer. WHAT IS KNOWN ALREADY: Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways. DESIGN: This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center. MAIN RESULTS AND THE ROLE OF CHANCE: We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥ 3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥ 3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility. LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study. WIDER IMPLICATIONS OF THE FINDINGS: This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types. STUDY FUNDING/COMPETING INTEREST(S): This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Recent skin self-examination and doctor visits in relation to melanoma risk and tumour depth.

BACKGROUND: Little is known about the potential benefit of skin self-examination for melanoma prevention and early detection. OBJECTIVES: To determine whether skin self-examination is associated with reduced melanoma risk, self-detection of tumours, and reduced risk of deeper melanomas. METHODS: We used data from a population-based case-control study (423 cases, 678 controls) to assess recent skin self-examination in relation to self-detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest. RESULTS: Skin self-examination conducted 1-11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54-1·02). Melanoma risk was decreased for those who conducted skin self-examination and saw a doctor (OR 0·52; 95% CI 0·30-0·90). Among cases, those who examined their skin were twice as likely to self-detect the melanoma (OR 2·23; 95% CI 1·47-3·38), but self-detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self-examination 1-11 times during a recent year (OR 0·39; 95% CI 0·18-0·81), but was not influenced by seeing a doctor, or by conducting skin self-examination and seeing a doctor. CONCLUSIONS: Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self-examination 1-11 times annually. Melanoma risk was markedly reduced by skin self-examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self-examination for melanoma prevention and early detection.

Variation in access to sugar-sweetened beverages in vending machines across rural, town and urban high schools.

OBJECTIVES: The 2010 Dietary Guidelines for Americans include reducing consumption of sugar-sweetened beverages. Among the many possible routes of access for youth, school vending machines provide ready availability of sugar-sweetened beverages. The purpose of this study was to determine variation in high school student access to sugar-sweetened beverages through vending machines by geographic location - urban, town or rural - and to offer an approach for analysing school vending machine content. STUDY DESIGN: Cross-sectional observational study. METHODS: Between October 2007 and May 2008, trained coders recorded beverage vending machine content and machine-front advertising in 113 machines across 26 schools in New Hampshire and Vermont, USA. RESULTS: Compared with town schools, urban schools were significantly less likely to offer sugar-sweetened beverages (P = 0.002). Rural schools also offered more sugar-sweetened beverages than urban schools, but this difference was not significant. Advertisements for sugar-sweetened beverages were highly prevalent in town schools. CONCLUSIONS: High school students have ready access to sugar-sweetened beverages through their school vending machines. Town schools offer the highest risk of exposure; school vending machines located in towns offer up to twice as much access to sugar-sweetened beverages in both content and advertising compared with urban locations. Variation by geographic region suggests that healthier environments are possible and some schools can lead as inspirational role models.

The impact of right ventricular hemodynamics on the performance of a left ventricular assist device in a numerical simulation model.

OBJECTIVES: Left ventricular assist devices (LVADs) have been established as alternative to heart transplantation for patients with end-stage heart failure refractory to medical therapy. Right heart failure (RHF) after LVAD implantation is associated with inferior outcome. Its preoperative anticipation may influence the selection between a pure left ventricular and a biventricular device type and, thus, improve outcomes. Reliable algorithms to predict RHF are missing. METHODS: A numerical model was used for simulation of a cardiovascular circulation. The LVAD was placed as parallel circuit between left ventricle and aorta. In contrast to other studies, the dynamic hydraulic behavior of a pulsatile LVAD was replaced by that of a continuous LVAD. A variety of hemodynamic states was tested mimicking different right heart conditions. Adjustable parameters included heart rate (HR), pulmonary vascular resistance (PVR), tricuspid regurgitation (TR), right ventricular contractility (RVC) and pump speed. Outcome parameters comprised central venous pressure (CVP), mean pulmonary artery pressure (mPAP), cardiac output (CO) and occurrence of suction. RESULTS: Alteration of HR, PVR, TR, RVC and pump speed resulted in diverse effects on CO, CVP and mPAP, resulting in improvement, impairment or no change of the circulation, depending on the degree of alteration. CONCLUSIONS: The numerical simulation model allows prediction of circulatory changes and LVAD behaviour following variation of hemodynamic parameters. Such a prediction may be of particular advantage to anticipate RHF after LVAD implantation. It may help preoperatively to choose the appropriate strategy of only left ventricular or both left and right ventricular support.

Treatment outcomes in patients with third-generation cephalosporin-resistant Enterobacter bacteremia.

BACKGROUND: Infections with resistant Enterobacter spp. are increasingly described, yet data on outcomes associated with these infections are limited. METHODS: A retrospective cohort study was conducted to investigate outcomes of hospitalized patients with third-generation cephalosporin-resistant (CR) Enterobacter bacteremia. Cephalosporin resistance was detected using cefotaxime and cefpodoxime. Patients with Enterobacter spp. bacteremia from January 2006 through February 2008 defined the population. We defined cases as those with CR isolates; controls were patients with bacteremia due to non-CR isolates. Treatment failure was defined as persistence of the presenting signs of infection 72 h after initial culture collection. RESULTS: Of the 95 Enterobacter cases identified, 31 (33%) were CR. CR cases were significantly associated with treatment failure (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.14-6.94). This association was not seen after adjustment for age, simplified acute physiology score (SAPS II), and inappropriate empiric antibiotic therapy. Inappropriate empiric therapy (adjusted OR 3.86, 95% CI 1.32-11.31) and SAPS II score (adjusted OR 1.09, 95% CI 1.02-1.16) were significantly associated with treatment failure in the multivariate analysis. CONCLUSIONS: Third-generation cephalosporin-resistant Enterobacter bacteremia is associated with treatment failure due to receipt of inappropriate empiric antibiotic therapy and severity of illness.

A case series of drotrecogin alfa (activated) in lung transplant recipients.

Severe sepsis in lung transplant recipients is a challenging problem and carries a high mortality. Recombinant human activated protein C (drotrecogin alfa [activated]) has been approved for use in patients with severe sepsis. Its use has been shown to be safe and impart a survival advantage. However, the safety of drotrecogin alfa activated has not been evaluated in lung transplant recipients. We report for the first time on the use of drotrecogin alfa activated in six lung transplant recipients. Clinical trials are warranted to further evaluate the use of drotrecogin alfa activated in transplant recipients.

Prostaglandin E2 induction of monoblastic differentiation utilizes both cAMP and non-cAMP dependent signalling systems.

U937 cells can be induced to express receptor for complement 5a (C5aR) by sequential 2 day treatments of cells with dihydroxyvitamin D-3 (1,25(OH)2D3) followed by prostaglandin E2. We asked whether the action of prostaglandin E2 to cause maximal C5aR expression required only activation of the cAMP-dependent protein kinase (PKA). Prostaglandin E2 dose dependently activated PKA in control and 1,25(OH)2D3 treated cells; by 4 h the PKA did not respond to further prostaglandin E2 challenge. We hypothesized that prostaglandin E2 actions transduced via PKA should be complete by 4 h; i.e., C5aR induction should be equivalent in cells treated with prostaglandin E2 for 4 h and for 2 days. All cells were treated for the first 2 days with 1,25(OH)2D3 and the second 2 days with prostaglandin E2 or cAMP analogs. C5aR number was measured after 4 days total culture. 4 h pulse treatments with agents were given at the end of the 1,25(OH)2D3 treatment. Cells exposed to a 4 h pulse of prostaglandin E2 had only 68.2 +/- 4.4% the amount of C5aR seen in cells continuously exposed to prostaglandin E2. Continuous culture with a cAMP analog pair (50 microM each of 8-thiomethyl-cAMP + N6-benzoyl-cAMP), which caused a 41.7% +/- 10.8% increase PKA activation above basal, resulted in only 51% +/- 16% of the C5aR numbers seen in cells cultured for 2 days with prostaglandin E2, where PKA remained at basal activity. We therefore concluded that C5aR expression caused by prostaglandin E2 could not be ascribed entirely to duration or degree of activation of cAMP-dependent signalling pathways. We investigated the possibility that the calcium sensitive protein kinase C was involved. Cytoplasmic protein kinase C was increased 154% +/- 14% above control in cells treated with sequential 2 days treatments of 1,25(OH)2D3 and prostaglandin E2. A 147% +/- 2% increase in membrane associated protein kinase C was also seen 10 min after phorbol myristate acetate stimulation in the above treatment group. Finally, phorbol myristate acetate augmented the C5aR induction caused by cAMP analog. We propose that the mechanism of prostaglandin E2 synergism with 1,25(OH)2D3 in causing C5aR induction in U937 cells includes signal transduction not only by the cAMP cascade, but also via protein kinase C modulated pathways.

Regulation of complement 5a receptor expression in U937 cells by phorbol ester.

Receptors for the anaphylactic portion of complement, C5a, are not initially expressed in the monoblastic U937 cell line, but appear as the cell is induced to differentiate by the synergistic actions of 1,25(OH)2D and cyclic adenosine monophosphate (cAMP). Phorbol myristate acetate (PMA), which activates the protein kinase C pathway (PKC), does not cause C5a receptor (C5aR) expression when used as a single agent. The induction of C5aR by the synergistic actions of 1,25(OH)2D and cAMP, however, can be augmented as much as 180% by the addition of PMA. C5aR arising in cells exposed to 1,25(OH)2D and 8,4-chlorophenylthio-cAMP have an affinity constant of about 0.4 nM as assessed by cold competition analysis. We show here that when phorbol augmentation of receptor number occurs, the affinity constant is increased by 3.6-fold. In an effort to ascertain whether the change in C5aR Kd involved a PKC-dependent event we examined whether 5-60 min exposure of C5aR-positive cells to PMA would change C5aR Kd. Acutely, PMA caused a downregulation of receptor binding with decreases in apparent receptor number out of proportion to changes in Kd. One hundred nanomolar PMA, which effects nearly complete translocation of PKC to the membrane, consistently caused a 70-90% decrease in C5a surface binding. This downregulation was proportional to PMA dose and exposure time. Micromolar concentrations of the microtubule depolymerizing agents colchicine and vinblastine caused a less drastic downregulation, about 50% of the maximal phorbol effect. Our data suggest that activation of the PKC system might acutely limit the macrophage's ability to respond to C5a; chronically, phorbols upregulate receptor expression, most likely through positive effects on C5aR gene expression.

Prenatal diethylstilbestrol exposure and risk of obesity in adult women.

Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: -0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.

Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women.

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (ß), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (ß=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (ß=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (ß=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (ß=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml--indicators of low ovarian reserve--were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.