PubMed Health⌕ Search

Biomedical subjects

D W Cramer

Publications and source records attributed to D W Cramer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome.

Leptin is an adipocyte-derived hormone which plays a central role in the regulation of body weight and energy homeostasis and in signalling to the brain that adequate energy stores are available for reproduction. Although leptin may affect reproduction by regulating the hypothalamic-pituitary-gonadal axis, recent in-vitro observations indicate that leptin may also have direct intra-ovarian actions. Leptin concentrations were measured in women who succeeded in becoming pregnant within three cycles of in-vitro fertilization (IVF) or gamete intra-fallopian transfer (n = 53), in women who failed to become pregnant within three cycles (n = 50), and in women with polycystic ovarian syndrome (PCOS) (n = 22). It was found that lower follicular fluid leptin concentrations were a marker of assisted reproduction treatment success in normal women. Women with PCOS had higher leptin concentrations than women without such a diagnosis, but this was due to their higher body mass index (BMI). After adjustment for age and BMI, women with PCOS who became pregnant tended to have lower mean follicular fluid leptin concentrations than women with PCOS who did not succeed at becoming pregnant. Further studies exploiting the strengths of the IVF model are needed to assess whether the prognostic role for follicular fluid leptin in human reproduction is independent of other factors, and to elucidate the underlying mechanisms.

Adult↗
PubMed2000

Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy.

PURPOSE: To review the findings at prophylactic oophorectomy of a series of women who presented to a familial breast and ovarian cancer clinic. MATERIALS AND METHODS: Data from medical charts, operative notes, and pathology reports were collected on women who had undergone prophylactic oophorectomies because of the elevated risk of ovarian cancer. Because only a subset of patients underwent BRCA1 and BRCA2 testing, each patient's risk of hereditary predisposition was calculated using the Berry-Parmigiani model and family history data. RESULTS: From June 1989 to December 1998, 50 women seen at our clinic underwent prophylactic oophorectomy, 33 of whom had a calculated risk of carrying a germline BRCA1 or BRCA2 mutation greater than 25%. Among this group, four incidental tumors were found (four of 33, or 12%); one tumor was noted at the time of surgery and three were noted only in the final pathology. Two patients had microscopic, poorly differentiated serous adenocarcinomas in multiple sites on both ovaries. A third patient had a bilateral serous borderline tumor with micropapillary features. The fourth patient had a microscopic serous borderline ovarian tumor. All four patients had germline BRCA1 or BRCA2 mutations, and three had unremarkable transvaginal ultrasonography examinations within 6 months before prophylactic surgery. CONCLUSION: Foci of malignant tumor are not uncommon in prophylactic oophorectomies performed in women at very high risk for ovarian cancer and may not be detected on ultrasonograms. Surgeons should have a high suspicion of finding cancer in these women at the time of prophylactic surgery, and careful pathologic assessment of the specimens should be conducted.

Adult↗
PubMed2000

A case-control study of galactose consumption and metabolism in relation to ovarian cancer.

Consumption or metabolism of dairy sugar and ovarian cancer have been linked based on evidence that galactose may be toxic to ovarian germ cells and that ovarian cancer is induced in animals by depletion of oocytes. We assessed consumption of dairy products and obtained blood for biochemical and molecular genetic assessment of galactose metabolism in 563 women with newly diagnosed epithelial ovarian cancer and 523 control women selected either by random digit dialing or through lists of residents in eastern Massachusetts and New Hampshire. We observed no significant differences between cases and controls in usual consumption of various types of dairy products or total daily lactose (the principal source of galactose in the diet); nor did we find that RBC activity of either galactose-1-phosphate uridyl transferase (GALT) or galactokinase differed. The mean (and SE) activity of uridine diphospho-galactose 4'-epimerase (in micromoles per hour per gram of hemoglobin) was, however, significantly lower (P < 0.005) in cases compared with controls, 20.32 (0.31) versus 21.64 (0.36). Ovarian cancer cases were also more likely to carry the N314D polymorphism of the GALT gene, generally predisposing to lower GALT activity. The difference was most evident for endometrioid and clear cell types of ovarian cancer, in which 3.9% of cases were found to be homozygous for N314D compared with 0.4% of controls, yielding an odds ratio and 95% confidence interval of 14.17 (2.62-76.60). We conclude that, whereas adult consumption of lactose carries no clear risk for the disease, certain genetic or biochemical features of galactose metabolism may influence disease risk for particular types of ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed1999

Evaluation of a population roster as a source of population controls: the Massachusetts Resident Lists.

Published population rosters can serve as a convenient source of population controls. The authors evaluated one such roster, the Massachusetts Resident Lists, by estimating the completeness of the Lists and by describing the differences between persons included and not included on the Lists. The subjects were cases from three case-control studies of ovarian cancer conducted in eastern Massachusetts between 1978 and 1996. For each of the three case series, more than 90% of the cases were located on the Resident Lists. Age was one of the primary differences to emerge between cases included and not included; in the most recent case series, cases younger than age 40 years were less likely than older cases to be included on the Lists.

Adult↗
PubMed1999

Genital talc exposure and risk of ovarian cancer.

Epidemiologic studies have suggested an increased risk for ovarian cancer associated with the use of talcum powder in genital hygiene, but the biologic credibility of the association has been questioned. We conducted a population-based case-control study in eastern Massachusetts and New Hampshire involving 563 women with newly diagnosed epithelial ovarian cancer and 523 control women selected either by random digit dialing or through lists of residents. Use of body powders was assessed through personal interview and the exposure odds ratio (OR) for the use of talc in genital hygiene was calculated. Cases were more likely than controls (45% vs. 36%) to have used talc as a body powder in some manner, and the excess was confined to patients who used talc on the perineum directly or as a dusting powder to underwear or sanitary napkins. Relative to women who never used body powder or used it only in non-genital areas, the OR (and 95% confidence interval) associated with genital exposure to talc was 1.60 (1.18 and 2. 15) after adjustment for age, study location, parity, oral contraceptive use, body mass index and family history of breast or ovarian cancer. Exposure prior to rather than after a first livebirth appeared to be more harmful, and the association was most apparent for women with invasive serous cancers and least apparent for those with mucinous tumors. We conclude that there is a significant association between the use of talc in genital hygiene and risk of epithelial ovarian cancer that, when viewed in perspective of published data on this association, warrants more formal public health warnings.

Adult↗
PubMed1999

Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls.

Leptin reflects the amount of energy stores, regulates energy balance and is associated with circulating levels of reproductive hormones and insulin-like growth factor-I (IGF-I). Breast cancer has also been associated with obesity, reproductive hormones and circulating IGF-I levels. To determine whether leptin is involved in the etiology of breast cancer, we compared serum leptin levels in 83 cases of pre-menopausal carcinoma in situ of the breast and 69 healthy controls recruited in Massachusetts. Serum leptin levels were 13.69 + 1.3 ng/ml in cases and 16.03 + 1.7 ng/ml in controls. Data were also analyzed using multiple logistic regression with adjustment for known risk factors for the development of breast cancer as well as anthropometric, demographic and hormonal variables, including estradiol, prolactin, IGF-I and IGF-binding protein-3. Odds ratios were 1.75 (95% CI, 0.73-4.21) for the second control-defined tertile and 1.54 (0.46-5.16) for the third control-defined tertile relative to the first. Thus, leptin does not appear to increase the risk of pre-menopausal breast cancer in situ substantially.

Adult↗
PubMed1999

Prevalence and predictors of depressive symptoms in older premenopausal women: the Harvard Study of Moods and Cycles.

BACKGROUND: The Harvard Study of Moods and Cycles is a community-based cohort study designed to evaluate the relationship between major depression and changes in menstrual and ovarian function. METHODS: All women aged 36 to 44 years with a verifiable address from 7 Boston, Mass, metropolitan communities were selected from the Massachusetts Town Books. A self-administered questionnaire assessed demographic characteristics and menstrual history, depression history, and current depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) in 4161 women. RESULTS: We observed a score of 16 or more on the CES-D in 22.4% of women surveyed, and 8.6% scored 25 or more. Widowed, divorced, or separated women were twice as likely as married women to have depression scores greater than 16 (95% confidence interval, 1.6-2.8), and smokers in the upper tertile of pack-years were 1.9 times more likely to have CES-D scores of 16 or more (95% confidence interval, 1.5-2.3). Relative to nulliparous women, those with 1 or 2 children had a 30% lower risk of historic mood disorder, and those with 3 or more children had an even greater reduction in risk (odds ratio, 0.4; 95% confidence interval, 0.3-0.6). Menstrual cycle irregularities were largely unassociated with current or past depression. However, 5 of 8 premenstrual symptoms were significantly associated with CES-D scores of 16 or more. CONCLUSIONS: These findings corroborate the prevalence of depression reported by other community-based studies, and also support a relationship between depressive symptoms and marital status, cigarette smoking, nulliparity, and premenstrual symptoms.

Adult↗
PubMed1999

Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates.

OBJECTIVE: To compare the efficacy of GnRH agonists used in either the flare (short) or down-regulation (long) regimen as part of IVF or GIFT treatment cycles. DESIGN: Observational study. SETTING: Three IVF clinics. PATIENT(S): One thousand two hundred forty-four couples accepted for IVF or GIFT treatment at participating clinics. INTERVENTION(S): In vitro fertilization or GIFT protocols standard to each clinic were recorded. MAIN OUTCOME MEASURE(S): Treatment cycle characteristics and outcomes, including E2 level, number of oocytes retrieved, and clinical pregnancy rate. RESULT(S): At site 1, there were 146 clinical pregnancies in 980 flare cycles, for a pregnancy rate of 14.9%, compared with 148 clinical pregnancies in 650 down-regulation cycles, for a pregnancy rate of 22.8%. This difference persisted after adjustment for age, primary infertility diagnosis, GIFT or IVF therapy, and year of treatment, and appeared to be mediated largely by the number of oocytes retrieved (mean, 9.8 for downregulation and 8.7 for flare in the first cycle). Despite having fewer oocytes retrieved, women who received flare regimens had higher E2 levels before hCG administration. CONCLUSION(S): Women who received GnRH agonists in a flare regimen had 11% fewer oocytes retrieved and a 35% reduction in the clinical pregnancy rate compared with those who received them in a down-regulation regimen; this difference was not explained by patient selection factors.

Adult↗
PubMed1999

A population-based study of BRCA1 and BRCA2 mutations in Jewish women with epithelial ovarian cancer.

OBJECTIVE: To determine the frequency of BRCA1 mutations 185delAG and 5382insC and BRCA2 mutation 6174delT in Jewish women with ovarian cancer and in matched controls in a population-based study. METHODS: Forty-eight Jewish women with epithelial ovarian cancer (32 invasive and 16 borderline) and 33 Jewish control subjects were obtained from a population-based, case-control study of ovarian cancer in eastern Massachusetts and New Hampshire. Mutational analysis on exons 2 and 20 of BRCA1 and exon 11 of BRCA2 was conducted on blood samples from patients and controls. RESULTS: Fourteen (44%) of 32 Jewish patients with invasive epithelial ovarian cancer carried either a 185delAG mutation of BRCA1 (n = 8) or a 6174delT mutation on BRCA2 (n = 6). Neither of these mutations was identified in 16 women with borderline ovarian tumors or in 33 controls. No 5382insC mutation of BRCA1 was identified in any of the patients or control subjects in the series. Family history did not predict mutation status. CONCLUSION: BRCA1 185delAG and BRCA2 6174delT mutations are frequent in Jewish women with invasive epithelial ovarian cancer, irrespective of family history. Genetic counseling might be warranted in women with invasive epithelial ovarian cancer based on Jewish ethnicity alone.

BRCA2 Protein↗
PubMed1999

Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome.

To test the hypothesis that dimeric inhibin A and/or inhibin B concentrations represent improved markers of in-vitro fertilization (IVF) outcome over follicle stimulating hormone (FSH), 78 women who achieved pregnancy within three assisted reproduction treatment cycles were matched to 78 women who underwent at least three assisted reproductive treatment cycles and failed to achieve pregnancy. Baseline serum inhibin B and FSH were obtained between days 1 and 4 in a cycle prior to ovarian stimulation, and inhibin A and B were measured immediately before the ovulatory stimulus and in follicular fluid from the lead follicle. Comparing pregnant and non-pregnant subjects at baseline, younger age (34.0 +/- 0.5 versus 36.0 +/- 0.5 years; P < 0.003) and a combination of FSH lower than the median value (11.2 IU/l) and inhibin B higher than the median value (76.5 pg/ml) were associated with pregnancy (P < 0.03), but FSH (11.7 +/- 0.5 versus 12.9 +/- 0.9 IU/ml) and inhibin B (89.0 +/- 10.2 versus 79.7 +/- 7.7 pg/ml) were not independently associated. At the time of the ovulatory stimulus, serum inhibin A (52.8 +/- 3.8 versus 40.0 +/- 2.7 IU/ml; P < 0.004), inhibin B (1623.8 +/- 165.1 versus 859.2 +/- 94.8 pg/ml; P < 0.0009) and the number of oocytes retrieved (14.6 +/- 0.8 versus 10.1 +/- 0.6; P < 0.0001) were predictive of pregnancy when controlled for age. Inhibin A was correlated with the number of embryos (r = 0.4; P < 0.0001). However, neither inhibin A nor inhibin B provided additional information in predicting successful outcome over age and number of oocytes. We conclude that: (i) in patients undergoing assisted reproductive technology, age and number of oocytes retrieved are the strongest predictors of success; (ii) of the parameters available prior to cycle initiation, a combination of lower FSH and higher inhibin B was associated with a greater chance for a successful outcome but an absolute cut-off could not be defined; and (iii) during ovarian stimulation, higher concentrations of inhibin A and inhibin B in serum are associated with successful IVF and mark ovarian reserve as a measure of oocyte number and quality.

Adult↗
PubMed1998

Over-the-counter analgesics and risk of ovarian cancer.

BACKGROUND: Evidence that aspirin and other non-steroidal anti-inflammatory drugs reduce risk for colorectal cancer has prompted interest in their ability to prevent other cancers. We aimed to find out what effect over-the-counter analgesics have on risk of ovarian cancer. METHODS: In a case-control study we compared use of over-the-counter analgesics by 563 women from eastern Massachusetts and New Hampshire, USA, who had epithelial ovarian cancer with 523 women from the general population. We calculated exposure odds ratios to estimate the effect of over-the-counter analgesics on ovarian cancer risk. Use of over-the-counter analgesics was assessed through interviews and defined as use at least once a week continuously for at least 6 months. FINDINGS: The odds ratio for risk of ovarian cancer for aspirin use was 0.75 (95% CI 0.52-1.10), that for ibuprofen was 1.03 (0.64-1.64), and that for paracetamol was 0.52 (0.31-0.86), after adjusting for age, study centre, education, religion, parity, oral contraceptive use, and menstrual, arthritic, or headache pain. Relative to no use, the lower risk of ovarian cancer associated with paracetamol was more apparent for use on a daily basis, 0.39 (0.21-0.74), for more than 10 years of use, 0.40 (0.19-0.88), or for more than 20 tablet years defined as (tablets per day x years of use), 0.45 (0.20-0.99). INTERPRETATION: In our data, there was a statistically significant inverse association between paracetamol use and ovarian cancer risk. There was a modest but non-significant inverse association with aspirin use and ovarian cancer and no association with ibuprofen use. Experimental studies in rodents demonstrating uterine and ovarian atrophy at high doses of paracetamol and decreased ovarian-cyst formation at lower doses suggest a biological basis for our observations.

Acetaminophen↗
PubMed1998

Relation of luteinizing hormone levels to body mass index in premenopausal women.

OBJECTIVE: To assess the relationship between body mass index (BMI) and basal LH and the LH-FSH ratio in normally menstruating women. DESIGN: Cross-sectional analysis. SETTING: A teaching hospital clinic. PATIENT(S): Premenopausal women without cancer, not currently using oral contraceptives, selected from a familial ovarian cancer clinic or the general population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Early follicular phase plasma LH and FSH. RESULT(S): Luteinizing hormone increased slightly and nonsignificantly (P = 0.44) from the first to the second quintile of BMI and decreased over all subsequent quintiles. Women in the highest quintile of BMI (> 27.1) had significantly lower LH levels than women in the lowest quintile of BMI (< or = 20.4; P = 0.003). Compared with women in the second quintile of BMI who had the highest LH levels, women in the highest quintile of BMI had LH levels that were 40% lower. The relationship between BMI and the LH-FSH ratio was similar, though not as strong. CONCLUSION(S): Over most of the range of BMIs observed in this study, BMI was inversely associated with LH. These results suggest that the upper limits of normal for LH may need to be shifted downward for heavier women.

Adult↗
PubMed1998

Basal hormone levels in women who use acetaminophen for menstrual pain.

OBJECTIVE: To compare basal gonadotropin and estradiol levels between women using acetaminophen versus those using no or other types of analgesics. DESIGN: Observational study. SETTING: Three IVF clinics in greater Boston. PATIENT(S): Three hundred eighty-six women accepted for their first IVF treatment who completed questionnaires recording medical history, including analgesic use for menstrual pain, and who had blood drawn during the menstrual phase of a cycle before treatment. MAIN OUTCOME MEASURE(S): Basal FSH, LH, and estradiol. RESULT(S): Basal hormone levels, especially LH, were lower for women who regularly used acetaminophen compared with women who used no medication or other types of analgesics. Lower hormone levels in acetaminophen users were consistently observed when women were subdivided by age, body mass index, smoking history, and degree of menstrual pain-features that might have influenced analgesic use or hormone levels. CONCLUSION(S): This study provides preliminary evidence that acetaminophen may lower gonadotropin and estradiol levels and offers a biologic basis for the epidemiologic observation that acetaminophen use may reduce the risk of ovarian cancer.

Acetaminophen↗
PubMed1998

Psychotropic medication use and risk of epithelial ovarian cancer.

Long-term use of psychotropic medication may increase the risk for epithelial ovarian cancer through increased gonadotropin secretion or direct ovarian stimulation of adrenergic receptors, effects which may affect ovarian cancer pathogenesis. An earlier case-control study found that prior use of antidepressants or benzodiazepine tranquilizers was associated with a 2-fold increase in risk of epithelial ovarian cancer. However, that study lacked details on all types of psychotropic medications, length of use, and the categorization of the specific action of these medications on the hypothalamic-pituitary-ovarian axis. In a new case-control study conducted in eastern Massachusetts (MA) and all of New Hampshire (NH), we identified all women with newly diagnosed ovarian cancer between May 1992 and March 1997. We interviewed 563 women diagnosed with malignant or borderline epithelial ovarian tumors and 523 controls identified through random digit dialing and the use of Town Books (residential listings by name, age, and precinct). Participants were asked to provide the name of medications used for 6 months or longer, the age at first use, and total months or years of use. Psychotropic medications included amphetamines, sedatives, barbiturates/anticonvulsants, antidepressants, and antipsychotics. Self-reported use of psychotropic medication for 6 months or longer was associated with a statistically significant increase in risk of invasive ovarian cancer [odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.3]. Relative to nonusers, risk was greatest in those whose first use occurred premenopausally for more than 2 years (OR, 2.9; CI, 1.3-6.6). The association was largely confined to use of medications that operate through dopaminergic mechanisms (OR, 2.9; CI, 1.3-6.4) or gabaergic pathways (OR, 1.5; CI, 0.9-2.5) as opposed to serotoninergic pathways (OR, 1.0; CI, 0.4-2.1). These results are consistent with the hypothesis that psychotropic medications induce gonadotropin secretion, which in turn may increase ovarian cancer risk. However, until other studies confirm our findings and determine whether they apply to medications with specific neuroendocrine actions, it is premature to advise a change in clinical practice and conclude that these medications indeed play a role in the etiology of ovarian cancer.

Adult↗
PubMed1998

Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast.

We evaluated the association of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) with risk of breast cancer in a study of 94 cases of premenopausal ductal carcinoma in situ and 76 controls. Compared with women in the lowest tertile of IGF-I, women in the upper two tertiles of IGF-I had an elevated risk for ductal carcinoma in situ. Conversely, compared with women in the lowest tertile of IGFBP-3, women in the upper two tertiles of IGFBP-3 had a decreased risk for ductal carcinoma in situ. After grouping women on the basis of both IGF-I and IGFBP-3, women in the highest two tertiles of IGF-I and the lowest tertile of IGFBP-3 were at notably higher risk than women in the lowest tertile of IGF-I and the highest two tertiles of IGFBP-3 (odds ratio = 3.7; 95% confidence interval = 1.1-12.2). We conclude that the combination of high IGF-I and low IGFBP-3 may increase the risk of premenopausal ductal carcinoma in situ.

Adult↗
PubMed1997

Epidemiologic determinants of endometriosis: a hospital-based case-control study.

PURPOSE: Risk factors for endometriosis were identified through data obtained from a case-control study at Brigham and Women's Hospital in Boston, Massachusetts. METHODS: Cases were 50 women with infertility-associated endometriosis. The primary control group consisted of 89 fertile women without endometriosis, and an alternate control group consisted of 47 infertile women without endometriosis. RESULTS: The risk of endometriosis was positively associated with height (OR), 2.8 per 10 cam increase; 95% confidence interval (CI), 1.4-5.6) and inversely associated with weight (OR, 0.7 per 10 kg increase; 95% CI, 0.5-1.0) and body mass index (OR, 0.7 per 5 kg/m2 increase; 95% CI, 0.4-1.1). We observed an inverse association with exercise (OR, 0.6; 95% CI, 0.3-1.5), but the effect was limited to women who exercised > or = 4 hours per week (OR, 0.4; 95% CI, 0.2-1.2). Endometriosis was not associated with either smoking or alcohol consumption. CONCLUSIONS: Our findings suggest that the fertility status of controls can strongly influence associations seen with menstrual characteristics. This study is one of few to address the issue of control selection for a case-control study of endometriosis. Specifically, potential problems encountered using fertile and infertile control women are examined and discussed.

Adult↗
PubMed1997

Prevalence of endometriosis in adolescent girls with chronic pelvic pain not responding to conventional therapy.

STUDY OBJECTIVE: To evaluate adolescent girls with chronic pelvic pain not responding to conventional medical therapy, using advances in operative laparoscopy to determine endometriosis prevalence, clinical stage, and type of lesion. DESIGN: A descriptive retrospective study of subjects who (1) were referred for the evaluation of chronic pelvic pain, (2) did not respond to a nonsteroidal anti-inflammatory drug and an oral contraceptive pill, and (3) underwent a laparoscopy to determine the etiology of the pelvic pain. SETTING: Patients referred to a surgical gynecologist in a pediatric/adolescent gynecology and reproductive endocrine academic practice. PARTICIPANTS: All patients younger than 22 years of age with chronic pelvic pain. INTERVENTION: Operative laparoscopy to determine the etiology of the chronic pelvic pain. MAIN OUTCOME MEASURES: Operative laparoscopy results including stage and description of endometriosis. RESULTS: More than two thirds of the study population (69.6%) was found to have endometriosis. All subjects had either stage I or II as determined by the American Fertility Society's classification system. The nature of the pain in the 32 subjects with endometriosis was both acyclic and cyclic in 20 (62.5%), acyclic only in 9 (28.1%), and cyclic only in 3 (9.4%). Other presenting symptoms included gastrointestinal in 11 (34.3%), urinary in 4 (12.5%), and irregular menses in 3 (9.4%). CONCLUSIONS: Adolescents with chronic pelvic pain not responding to medical therapy have a high rate of endometriosis and should be referred to a gynecologist who is experienced with the subtle laparoscopic findings of atypical endometriosis to diagnose the etiology of the pelvic pain and initiate appropriate therapy.

Adolescent↗