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D W Cramer

Publications and source records attributed to D W Cramer.

At least 55 records · Page 3Linked to original sources
PubMed1997

Fragile X premutations are not a major cause of early menopause.

Fragile X syndrome is an X-linked mental retardation condition that usually is due to a trinucleotide-repeat expansion in the FMR1 gene. Whereas full-mutation alleles (> 230 repeats) lead to fragile X syndrome, premutation alleles (approximately 60-200 repeats) are apparently non-penetrant. However, previous studies have suggested that female premutation carriers may have an increased incidence of premature menopause. To test this possible association, we screened for premutation alleles among 216 women with early menopause (at age < 47 years), 33 of whom had premature menopause (at age < 40 years), as well as among 107 control women, all of whom were ascertained solely on the basis of age at menopause. No full-mutation alleles were found; and only one premutation allele was found, but, it was in a member of the control group. These results are consistent with what would be expected on the basis of chance only. Our sample size was sufficient to rule out a > or = 3-fold increased risk of early menopause and a > or = 9-fold increased risk of premature menopause due to an FMR1 premutation, under a model considering the risk of both sporadic and familial early menopause. Likewise, our results rule out a > or = 4-fold increased risk of familial early menopause and a > or = 26-fold increased risk of familial premature menopause, under a less probable model in which only familial early menopause is considered. These results indicate that the fragile X premutation is not a major risk factor for early menopause and suggest that the risk of premature menopause to fragile X-premutation carriers may not be as great as that reported elsewhere.

Adult↗
PubMed1996

Frequency of the BRCA1 185delAG mutation among Jewish women with ovarian cancer and matched population controls.

Among women of Ashkenazi Jewish origin, a frameshift mutation of the BRCA1 gene, designated 185delAG, occurs with a carrier frequency of approximately 1% and is estimated to account for about 39% of ovarian cancer cases occurring prior to age 50 years. To determine the actual frequency of this mutation among Jewish women with ovarian cancer, we tested DNA collected as part of an ongoing population-based case-control study of genetic and environmental factors for epithelial ovarian cancer in eastern Massachusetts. Using single-stranded conformational polymorphism analysis followed by direct sequencing, we found that 6 (19.4%) of 31 Jewish patients were carriers for a 185delAG mutation compared to 0 of 23 Jewish controls (P=0.03) Using empiric logic [correction of logits], the estimated relative risk for ovarian cancer associated with a 185delAG mutation is 12.0. The average age of the 6 patients with mutations was 48.3 years, significantly younger than the average of 57.4 years observed for the 25 patients without the mutation (P-0.05). For ovarian cancer diagnosed prior to age 50 years, three (37.5%) of eight patients carried the mutation. None of the six patients with the mutation had a history consistent with hereditary breast ovarian cancer syndrome, although two had a personal history of prior cancer. Our results provide empiric conformation of the estimated prevalence of 185delAG mutations among Jewish women with ovarian cancer.

BRCA1 Protein↗
PubMed1996

Predicting age at menopause.

This article reviews methodologic and clinical aspects of predicting age at menopause. Lifetable methods or logistic models applied to a perimenopausal population represent the most feasible and the least biased methods for estimating the probability of menopause by age. Information is emerging about risk factors besides age which influence risk for an earlier menopause and include a variety of medical, demographic, environmental, and genetic factors. The concept of menopause as a consequence of depleted oocytes suggests that the estimated number of ovulatory cycles might also be a useful predictor. Using these variables in a logistic model yields estimated probabilities of menopause for various risk profiles. Smokers who have accumulated more than 10 pack-years, women estimated to have had more than 300 ovulatory cycles, women with a history of depression, women who have lost one ovary at an early age, and women who have a family history of early menopause have earlier menopause and the greatest shift in the cumulative probability of menopause occurs in women with multiple risk factors.

Adult↗
PubMed1996

Determinants of preterm delivery in low-risk pregnancies. The RADIUS Study Group.

From 14,948 low-risk singleton pregnancies, we calculated incidence, risk ratios, and attributable risks for characteristics associated with spontaneous and medically induced preterm delivery. There were 754 women who gave birth prior to 37 weeks of gestation (50.4/1000 deliveries). The greatest fraction of the incidence of prematurity among low-risk pregnancies was due to unknown factors associated with carrying a first live birth, regardless of preterm delivery mechanism (i.e., spontaneous labor, PROM, medical intervention), with population-attributable risk percents (PAR%) ranging from 16.0 to 30.5%. Other than nulliparity, male sex of the fetus accounted for the greatest fraction of spontaneous labor-induced prematurity incidence (PAR% = 13.6%), and maternal age greater than 30 years or a positive urine culture accounted for the greatest fraction of PROM-induced prematurity incidence (PAR% = 7.9 and 6.7, respectively). All other risk factors for either preterm labor or PROM accounted for less than 5% of the incidence. Three characteristics explained a large fraction of medically induced prematurity: women over 150 pounds at the onset of pregnancy (PAR% = 23.8), a > or = 2+ prenatal urine protein (PAR% = 18.7%), and cigarette smoking during the first trimester (PAR% = 8.6). Our results suggest known risk factors may explain only a small fraction of spontaneous preterm delivery incidence in low-risk pregnancies.

Adolescent↗
PubMed1996

Vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).

To follow-up our previous observation that vaginal agenesis might be associated with decreased activity of galactose-1-phosphate uridyl transferase (GALT), we studied activity and genotype of GALT in 13 daughters with vaginal agenesis and their mothers. For comparison, GALT measurements were available from 113 pre-menopausal women with no known Müllerian anomalies selected from the general population. Red cell GALT activity was significantly lower in both the daughters and their mothers in comparison with general population controls. Six out of thirteen (46%) daughters and two mothers of the remaining seven daughters (29%) were carriers for the N314D mutation of GALT associated with the Duarte variant of galactosaemia as compared to 16 out of 113 general population controls (14%) who possessed at least one N314D allele. Pigmentary skin changes and scoliosis were associated phenotypic findings in daughters with vaginal agenesis. We conclude that fetal or maternal GALT mutations that decrease GALT activity may be associated with vaginal agenesis and have, as their possible biological basis, increased intrauterine exposure to galactose which has been demonstrated in rodents to cause decreased oocyte survival and delayed vaginal opening in offspring.

Female↗
PubMed1996

Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).

To explore a possible connection between endometriosis, Müllerian anomalies, and possession of the N314D allele of the gene for galactose-1-phosphate uridyl transferase (GALT), we studied 33 women with endometriosis attending a fertility clinic. Patients completed questionnaires and had DNA tested for the N314D mutation of GALT. A previously completed general population survey of 111 women which obtained the same information was available for comparison. Women with endometriosis were more likely to carry at least one N314D allele (30% compared with 14%) and more likely to report a medical history of scoliosis (21% compared with 2%) compared to general population controls: two features we have described in women with vaginal agenesis. Compared with endometriosis cases without the N314D allele, those cases with the allele tended to have more advanced disease and a family history of endometriosis. We speculate that endometriosis may arise due to defects of canalization of the cervix leading to cervical stenosis and retrograde menstruation. The relevance of the N314D mutation, via this model, may derive from an association between abnormalities of galactose metabolism and vaginal agenesis which represents a canalization defect of the vaginal plate of the Müllerian tubercle, the same structure which gives rise to the cervix.

Contraceptives, Postcoital, Synthetic↗
PubMed1995

Association of medically treated depression and age at natural menopause.

Between October 1989 and November 1992, the authors surveyed approximately 10,000 women between 45 and 54 years of age residing in western metropolitan Boston and selected as cases all women naturally menopausal before age 40 and a sample of women naturally menopausal between ages 40 and 46. Controls were a random sample of women who were premenopausal or naturally menopausal after age 47. Based on the results of an in-person interview to assess past reproductive and medical history, 14% of 344 cases compared with 6% of 344 controls reported a history of medically treated depression at least 1 year prior to menopause or comparable reference age in controls (adjusted odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.3). The association of medically treated depression and early menopause was greatest in women naturally menopausal before age 40 compared with their age-and residence-matched controls (OR = 6.6, 95% CI 0.7-58.9) and in women who reported a history of medically treated depression that required more than 3 years of treatment (OR = 4.0, 95% CI = 1.3-12.0). This is the first study to suggest a link between a self-reported history of medically treated depression and early menopause. Additional studies are necessary to clarify the basis for this association.

Adult↗
PubMed1995

Fertility therapy in the setting of a history of invasive epithelial ovarian cancer.

A link between fertility drugs and epithelial ovarian cancer has been suggested by at least one case-control study, and by multiple case reports of such tumors developing following fertility drug therapy. We report the case of a woman with stage IC grade 1 mucinous epithelial ovarian cancer who died of recurrent disease shortly after receiving gonadotropin therapy for ovulation induction. The patient was initially treated with a staging procedure, unilateral salpingo-oophorectomy, and 3 courses of cytoxan and carboplatinum. Over the next 3 years she underwent 2 cycles of ovulation induction with exogenous gonadotropins. Five months after the second cycle, the patient presented with a bowel obstruction and extensive recurrence of disease. Two months later she died despite extensive surgical debulking, and cis-platinum and Taxol chemotherapy. Although a causal relationship between fertility therapy and ovarian cancer has not been established, this case report suggests ovulation induction may be inadvisable in a woman with a prior diagnosis of invasive epithelial ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed1995

Self-reported use of antidepressants or benzodiazepine tranquilizers and risk of epithelial ovarian cancer: evidence from two combined case-control studies (Massachusetts, United States).

Data from two population-based case-control studies in the greater metropolitan Boston, MA (USA) were used to assess the association of self-reported use of antidepressants or benzodiazepine tranquilizers and epithelial ovarian cancer. Cases were women between 18 and 80 years of age diagnosed with epithelial ovarian cancer during two time periods: November 1978 through September 1981, and July 1984 through September 1987. Female controls were identified from Massachusetts town books and were frequency-matched to cases by age, race, and precinct of residence. In-person interviews assessed reproductive and medical histories as well as prescription medication use. Prior use of antidepressants or benzodiazepine tranquilizers exceeding one to six months was associated with an increased risk of ovarian cancer (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 0.9-4.8, and adjusted OR = 1.8, CI = 1.0-3.1, respectively). The association was confined primarily to women whose first use occurred before age 50 years (adjusted OR = 3.5, CI = 1.3-9.2, and adjusted OR = 2.7, CI = 1.3-5.6, respectively). No association was observed with respect to other non-hormonal medications reported.

Adolescent↗
PubMed1995

Epidemiologic predictors of cesarean section in nulliparous patients at low risk. RADIUS Study Group. Routine Antenatal Diagnostic Imaging with Ultrasound Study.

OBJECTIVES: We sought to determine whether certain maternal and fetal characteristics influenced the risk of maternal- and fetal-indicated cesarean sections in pregnant women at low risk for adverse perinatal outcomes. STUDY DESIGN: From a cohort of 6393 low-risk nulliparous patients maternal and fetal indicated cesarean section rates with 95% confidence intervals were calculated and stratified by demographic, anthropometric, and clinical tests and measurements. The strongest risk factors were modeled by means of multiple logistic regression. RESULTS: Few risk factors distinguished maternal from fetal characteristics preceding cesarean delivery. Maternal age was associated with increased cesarean section risk in the tallest group of women only, and cesarean section rates decreased with increasing height, increased with higher prepregnancy weights, and was highest in women carrying male fetuses. Higher first prenatal visit diastolic blood pressure, increasing numbers of nonstress tests, > or = 2+ prenatal urine protein, late sonograms, geographic region, and practice type were statistically significant risk factors as well. Interestingly, results of prenatal visit tests and measurements contributed less to the prevalence of cesarean section than did age, fetal sex, and anthropometric parameters. However, the generalizability of these results is limited to low-risk (predominantly white) populations. CONCLUSIONS: Of the risk factors we were able to assess, a large proportion of the incidence of cesarean section in this population of nulliparous patients at low risk was attributable to age, sex of fetus, and anthropometric patient profiles.

Adolescent↗
PubMed1995

Case-control study of risk factors for partial molar pregnancy.

OBJECTIVE: The purpose of our study was to identify risk factors for partial molar pregnancy from a woman's general, reproductive, and dietary history. STUDY DESIGN: Sixty-five women with pathologically confirmed partial molar pregnancy were interviewed, and their experiences were compared with those of 130 age-matched control women who had successfully completed a pregnancy with delivery of a live infant at the same hospital during the same calendar period. RESULTS: Multivariate analysis revealed that exposures which independently and significantly predicted increased risk for partial molar pregnancy included irregular cycles, pregnancy histories including only male infants among prior live births, and oral contraceptive use for > 4 years. Dietary factors previously postulated for complete molar pregnancy including protein, fat, vitamin A, or carotene were found not to be related to risk for partial molar pregnancy. CONCLUSION: Epidemiologic patterns for complete and partial molar pregnancies appear to differ somewhat; risk for partial mole is associated with reproductive history but not dietary factors.

Adult↗
PubMed1995

Does "incessant" ovulation increase risk for early menopause?

OBJECTIVE: We attempted to determine whether gynecologic histories differ in women who have and have not experienced an early menopause. STUDY DESIGN: A group of 344 "case" women whose average age at menopause was 42.2 years and an age-matched group of 344 "control" women still menstruating or menopausal after age 46 were selected from a survey of 10,606 women aged 45 to 54 years for interviews about their reproductive history. RESULTS: Case women were more likely to have had menarche at or before age 11, had shorter cycle lengths, had fewer pregnancies with live births, and had more frequent pelvic operations including unilateral oophorectomy and multiple cesarean sections. Case women had a greater number of presumed ovulatory cycles, as estimated from age at menarche, average cycle length, and years of anovulation associated with pregnancies or oral contraceptive use. In a multivariate model including smoking status and body mass index, ovulatory cycles were a significant predictor of early menopause, especially after an estimated 300 ovulations. CONCLUSION: The reproductive histories of women who experienced an early menopause suggest a pattern of more rapid oocyte loss ("incessant" ovulation).

Case-Control Studies↗
PubMed1995

Cross-sectional and case-controlled analyses of the association between smoking and early menopause.

To examine potential confounders and dose-response data for the association between smoking and menopause, we used both a cross-sectional and case-controlled approach. In total, 10,606 middle-aged women residing in eastern Massachusetts were surveyed about their age at menopause and smoking history; 344 women (cases) with natural menopause prior to age 47 and 344 age-matched women (controls) who were still menstruating or who had a menopause after age 46 were selected for further study. Risk for menopause was assessed by Kaplan-Meier, Cox proportional hazards, or logistic regression models. From cross-sectional data on 8657 women aged 45-54, the hazards odds ratio for a natural menopause among women who ever smoked compared to non-smokers was 1.31 (95% C.L. 1.21-1.42) and among women who had accumulated 30 or more pack-years was 1.87 (95% C.L. 1.67-2.04) after adjustment for parity and weight. An additional potential confounder from the case-controlled study was lower educational attainment, and after adjustment for this variable, significant trends persisted for risk of early menopause associated with age began smoking (P = 0.03), years of smoking (P = 0.01) and pack-years of smoking (P = 0.03). This study demonstrates an association between smoking and early menopause in both cross-sectional and case-controlled data that is not confounded by parity, weight, socio-economic status, or nutritional variables.

Adult↗
PubMed1995

Epidemiologic evidence for uterine growth factors in the pathogenesis of ovarian cancer.

To examine the association between ovarian cancer and prior hysterectomy or tubal ligation in light of various interpretations, we combined data from two previously conducted case-control studies of ovarian cancer. This included 450 women with histologically verified epithelial ovarian cancer and 454 age-matched women from the general population for whom data on prior pelvic surgery were available to estimate exposure odds ratios. Overall there was a nonsignificant deficit of case patients who had had a hysterectomy or tubal ligation (odds ratio (OR) = 0.9; 95% confidence interval (CI), 0.6 to 1.3). A protective effect of prior hysterectomy or tubal ligation was more apparent among women who had the surgery 20 or more years previously (OR = 0.6; 95% Ci, 0.3 to 1.1), women who had not used talc in their hygiene (OR = 0.6; 95% CI, 0.4 to 1.0), and women with mucinous tumors of the ovary (OR = 0.3; 95% CI, 0.1 to 1.0). Although these data do not clearly establish the validity of or mechanisms for an association between prior pelvic surgery and ovarian cancer, we speculate that such an association exists and may be mediated through absent or reduced uterine growth factors that reach the ovaries through the uteroovarian circulation, with mucinous tumors most dependent on such factors.

Adenocarcinoma, Mucinous↗
PubMed1995

Effects of previous use of oral contraceptives on early follicular phase follicle-stimulating hormone.

OBJECTIVE: To determine if previous oral contraceptive (OC) use is associated with changes in early follicular phase FSH, LH or E2. DESIGN: A cross-sectional study examining determinants of early follicular phase hormone levels. SUBJECTS: Subjects included 106 premenopausal women with a family history of ovarian cancer and 116 premenopausal women without this history who were not taking OCs currently. All subjects completed a structured interview and gave an early follicular phase blood sample. SETTING: Gynecologic Epidemiology Center and Familial Ovarian Cancer Research Center. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, LH, and E2 were measured in early follicular phase plasma samples. RESULTS: Recency or length of prior OC use did not affect early follicular phase LH or E2 levels. Length of OC use did not affect FSH levels in all subjects; but lower levels of FSH were observed in women over age 45 who had used OCs for > 5 years. Early follicular phase FSH is lower in women with OC use within the past 5 years compared with women with more remote use or who never used OCs, after adjustment for age, smoking, and family history status. CONCLUSIONS: Past use of OCs may have a residual effect on basal FSH levels in women not using them currently that depends on recency of use and to a lesser extent duration of prior use.

Adult↗
PubMed1995

Family history as a predictor of early menopause.

OBJECTIVE: To determine the relative importance of family history as a predictor of early menopause. DESIGN: Case-control study. From a population-based survey of 10,606 women between 45 and 54 years of age, we selected 344 cases with early menopause (average age 42.2 years) and 344 age-matched controls who were still menstruating or who had a menopause after age 46 years. Subjects were interviewed about their medical and family history and blood was drawn for identification of women who were carriers for the classic or Duarte variant of galactosemia, a potential hereditary factor for early menopause. Logistic regression analysis was used to estimate the risk of an early menopause in women with and without a family history of early menopause. RESULTS: Overall 129 (37.5%) of the early menopause cases reported a family history of menopause before age 46 years in a mother, sister, aunt, or grandmother compared to 31 (9.0%) of controls yielding an odds ratio (OR) of 6.1 (95% confidence interval [CI] of 3.9 to 9.4) after adjustment for smoking history, education, parity, and body mass index. Risk for early menopause associated with family history of same was greatest: for family history in a sister, OR = 9.1 (95% CI 3.1 to 26.5); multiple relatives, OR = 12.4 (95% CI 4.4 to 34.2); and cases menopausal before age 40 years, OR = 8.4 (95% CI 2.5 to 31.2). Cases with a family history of early menopause were not more likely to have errors of galactose metabolism compared with cases without a family history or to all controls, nor did they possess Turner's stigmata such as short stature, but they were less likely to have brothers in their sibships. CONCLUSIONS: Although preferential recall of family history by women with early menopause could contribute to the association between family history and early menopause observed in this study, a genetic factor is also plausible including partial deletions of the X chromosome compatible with the deficiency of male siblings in cases with family history of early menopause.

Adult↗
PubMed1994

Characteristics of women with a family history of ovarian cancer. I. Galactose consumption and metabolism.

BACKGROUND: Galactose metabolism may be a risk factor for ovarian cancer based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study examines galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian cancer has not yet developed. METHODS: The authors studied 106 premenopausal women (FOC patients) with one primary or two second-degree relatives with ovarian cancer compared with 116 age matched control subjects without a family history of ovarian cancer (FOC controls). All women completed questionnaires and had blood drawn to measure GALT activity and genotype. RESULTS: Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC patients, significantly lower than the mean of 23.1 observed in FOC control subjects, (P = 0.001). FOC patients more frequently displayed the Duarte variant of galactosemia as detected by electrophoresis. In a subset of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular genetic detection of the N314D mutation that is associated with the Duarte variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects. CONCLUSION: Galactose metabolism differs between women with and without a family history of ovarian cancer, suggesting that it may be a genetic risk factor for ovarian cancer, possibly mediated through oocyte toxicity from galactose.

Adult↗