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Biomedical subjects

Clarisa R Gracia

Publications and source records attributed to Clarisa R Gracia.

18 recordsLinked to original sources

Association of anti-mullerian hormone levels with obesity in late reproductive-age women.

OBJECTIVE: To describe anti-mullerian hormone (AMH) levels in healthy late reproductive age women and test the hypothesis that AMH levels are lower in obese compared to non-obese women. DESIGN: Cross-sectional study of AMH levels. Longitudinal analysis of a subgroup with 10 AMH measures over 8 years to support the cross-sectional results. SETTING: A population-based cohort of healthy late reproductive-age women. PARTICIPANTS: Selected from the cohort to provide comparisons of body mass index (BMI), menopausal status, age and race (n = 122). INTERVENTIONS: AMH levels were determined from blood samples collected in the parent study. MAIN OUTCOME MEASURE: Serum levels of AMH. RESULTS: AMH levels were 65% lower in obese women compared to non-obese women (0.016 ng/mL and 0.046 ng/mL, respectively). The geometric mean ratio was 0.35; 95% CI 0.13, 0.92, P=.034. AMH levels were significantly lower in the menopausal transition compared to premenopausal women and were significantly lower in all age groups > or =40 years compared to the 35-39 year-old women. BMI remained significantly associated with AMH levels in multivariable models that included adjustments for menopausal status, age, race and cycle day. In the longitudinal analysis of a subgroup, obese women had significantly lower mean AMH levels over the 8-year interval compared to the non-obese women (0.459 ng/mL; CI 0.28, 0.75 and 0.566 ng/mL; CI 0.34, 0.94, respectively; P=.016), corroborating the cross-sectional study results. CONCLUSIONS: Obese women have lower AMH levels compared to non-obese women in the late reproductive years. The findings offer further evidence of the complex relationships between obesity and reproductive hormone levels in women.

Age Factors↗

Risk factors for ectopic pregnancy in women with symptomatic first-trimester pregnancies.

OBJECTIVE: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among women presenting with pain and/or bleeding in early pregnancy. DESIGN: Nested case-control study. SETTING: University medical center. PATIENT(S): Women with symptomatic early pregnancies of unknown location presenting for care between January 1, 1990 and July 31, 1999. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and historical risk factors were compared between women with EP and women with ongoing intrauterine pregnancies or spontaneous abortions. RESULT(S): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95% confidence interval, 1.88-4.73] for one prior EP and 16.04 [5.39-47.72] for 2 or more), pelvic inflammatory disease history (1.5 [1.11-2.05]), pain at presentation (1.42 [1.06-1.92]), vaginal bleeding at presentation (1.42 [1.04-1.93]), and hCG of 501-2,000 mIU/mL (1.73 [1.24-2.42]). Age younger than 25 years (0.59 [0.41-0.85]) and a history of abortion were protective from EP (0.58 [0.38-0.90]). Prior nontubal pelvic surgery, past intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association with EP. CONCLUSION(S): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of historical and clinical factors associated with EP may aid in early diagnosis.

Adult↗

The relationship between obesity and race on inhibin B during the menopause transition.

OBJECTIVE: Data are lacking on the effects of obesity and race on inhibin B levels during the menopause transition. The purpose of this study was to determine the relationship among inhibin B levels, body mass index (BMI), and race during the menopause transition. DESIGN: In the Penn Ovarian Aging Study, a prospective cohort study of reproductive aging, 436 women aged 35 to 47 years were followed up with serial hormones, anthropometric measures, and questionnaires for 6 years. Univariate and multivariable analyses were performed comparing mean log transformed inhibin B levels among menopause stages, age groups, BMI categories, races, and smoking groups. RESULTS: In the univariate analyses, mean inhibin B levels were negatively associated with menopause stage, age, and BMI, but not significantly with race or smoking. Interactions of menopause status and BMI were significant (P < 0.001). Premenopausal women with a BMI of 25 or higher had significantly lower inhibin B levels compared with women with a BMI of less than 25 (41.8 pg/mL vs 58.4 pg/mL, P < 0.001), whereas postmenopausal women with a BMI of 30 or higher had significantly higher inhibin B levels compared with the postmenopausal women with a BMI of less than 25 (29.1 pg/mL vs 26.7 pg/mL, P < 0.001). CONCLUSIONS: Although BMI is a significant independent predictor of inhibin B levels, the relationship between BMI and inhibin B changes with advancing menopause stage. These data provide additional evidence that obesity influences hormones during the menopause transition.

Adult↗

Occupational exposures and male infertility.

The purpose of this study was to determine the association between male occupational exposures and infertility. A retrospective case-control study was performed using data collected between 1991 and 1997 at nine US clinical sites as part of a previously conducted large multicenter trial. Cases were defined as infertile males whose partner had an infertility evaluation with normal results, and controls were defined as fertile males whose partner became pregnant within 2 years. Exposures were assessed by means of self-report questionnaires. Bivariate, stratified, and multivariable analyses were performed. A total of 650 infertile cases and 698 fertile controls were compared. In the final model, a protective association with infertility was observed for occupational exposures to radiation (odds ratio=0.21, 95% confidence interval: 0.06, 0.77) and video display terminals (odds ratio=0.30, 95% confidence interval: 0.13, 0.68). No significant associations were noted between infertility and exposure to shift work, metal fumes, electromagnetic fields, solvents, lead, paint, pesticides, work-related stress, or vibration. Overall, no clear, clinically important associations between occupational exposures and male infertility could be identified in this study.

Adult↗

Tubal ligation does not affect hormonal changes during the early menopausal transition.

BACKGROUND: To determine if women with a bilateral tubal ligation (BTL) were more likely to experience hormonal changes indicative of the transition to menopause or an increase in menopausal symptoms compared to women without a BTL. METHODS: Menopausal symptoms and hormone profiles of 134 women reporting a BTL were compared throughout the course of a 4-year follow-up study to 172 women without a BTL. Generalized linear regression models for repeated measures were used to estimate the independent effect of BTL on menopausal symptoms and hormonal levels adjusted for covariates. RESULTS: Forty-four percent of women reported a BTL and over one-half of women with a BTL experienced hot flashes. Women with a BTL had similar hormonal levels over the study period compared to women without a BTL. In addition, no relationship was found between BTL and any of the menopausal symptoms, including hot flashes, decreased libido or increased anxiety adjusting for age, race, body mass index (BMI), education, menopausal status and parity. CONCLUSION: These findings document that women with a BTL have similar changes in sex hormone levels over the perimenopausal period compared to women without a BTL independent of other covariates. In addition, the reporting of menopausal symptoms was similar between the groups.

Adult↗

Defining menopause status: creation of a new definition to identify the early changes of the menopausal transition.

OBJECTIVE: Several menopausal staging definitions are currently being used in ongoing studies designed to identify changes occurring during menopause. The objective of this study was to determine which definition captures the earliest hormonal changes in the menopausal transition. DESIGN: In this prospective cohort study, women aged 35 to 47 years were followed for 5 years. Women were classified as premenopausal, early transition, late transition, and postmenopausal by 2 different menopausal staging systems defined by bleeding patterns. Definitions from the Study of Women Health Across the Nation (SWAN) and Stages of Reproductive Aging Workshop (STRAW) were compared. A new menopausal staging system (PENN-5) was also developed with five groups rather than four to distinguish among women with more subtle changes in cycle length. For each staging system, a linear regression model was created comparing mean hormone values (inhibin B, FSH, LH, E2) and menopausal stages at each assessment. Race, body mass index, cycle day, smoking, and follow-up time were included in the model. RESULTS: Statistically significant differences in mean inhibin B and FSH levels, but not estradiol levels, were detected between the earliest menopausal stages of each definition. Significant differences in LH values were detected among the earliest stages of the SWAN and STRAW definitions, but not the PENN-5 definition. CONCLUSIONS: Subtle changes in menstrual cycle length reflect significant changes in inhibin B and FSH levels during the menopausal transition. Therefore, it appears that subtle changes in bleeding pattern may be helpful in identifying the earliest hormonal changes during menopausal transition.

Adult↗

Risk factors for spontaneous abortion in early symptomatic first-trimester pregnancies.

OBJECTIVE: To evaluate the association of an ultimate diagnosis of miscarriage with various clinical symptoms and historical factors in a cohort of women presenting with pain, bleeding, or both in the first trimester of pregnancy. METHODS: This was a case-control study from a population of women presenting for care with pelvic pain or vaginal bleeding in the first trimester of pregnancy whose diagnoses were not definite upon initial evaluation. Analyses were performed in 2 ways. In one instance cases were defined as women ultimately definitively diagnosed with a miscarriage and controls were defined as women with a pregnancy that did not result in miscarriage (ectopic pregnancy or ongoing intrauterine pregnancy). The second analysis compared women with a miscarriage only to women who had an ongoing intrauterine pregnancy. RESULTS: A total of 2,026 women were evaluated, with 1,192 ultimately diagnosed with a spontaneous abortion, 367 with ectopic pregnancy, and 467 with a viable intrauterine pregnancy. Although many risk factors were individually associated with miscarriage in preliminary analysis, in the final analysis only extremes in age (< 25 and > 35) and the complaint of bleeding (odds ratio [OR] 7.35, 95% confidence interval[CI] 5.74-9.41) were associated with miscarriage. The complaint of pain (OR 0.72, 95% CI 0.57-0.92), human chorionic gonadotropin (hCG) value greater than 500 (hCG < or = 500 IU/mL compared with hCG 501-2000: OR 0.52, 95% CI 0.39-0.69) and concurrent cervical infection (OR 0.69, 95% CI 0.55-0.88) were negatively associated with miscarriage. CONCLUSION: Few factors predict miscarriage in women who present with a symptomatic first trimester pregnancy of unknown location. Heavy bleeding was most strongly associated with miscarriage. Concurrent cervical infections should not be overlooked as a cause of bleeding in early pregnancy and were not associated with miscarriage. LEVEL OF EVIDENCE: II-2.

Abortion, Spontaneous↗

Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis.

BACKGROUND: Recurrent pregnancy loss (RPL) is a significant clinical problem. Recently, thrombophilias have been implicated as a possible cause. Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are the most common types of hereditary thrombophilias, but are usually undiagnosed because most carriers are asymptomatic. The relationship between FVL, G20210A, and RPL has been investigated with conflicting results. This study analyzed existing data to determine whether an association exists. METHODS: A systematic review of the literature was performed. Only case-control studies that defined RPL as 2 or more pregnancy losses in the first or second trimester and that confirmed mutations by DNA analysis were included. Sixteen studies were selected for the FVL meta-analysis and 7 for the G20210A analysis. Stratified and multivariate logistic regression analyses were performed with the use of aggregate data. Results were confirmed by means of fixed- and random-effects meta-analyses models. RESULTS: The combined odds ratios for the association between RPL and FVL and between RPL and G20210A were 2.0 (95% confidence interval, 1.5-2.7; P<.001) and 2.0 (95% confidence interval, 1.0-4.0; P =.03), respectively. Similar results were produced by the logistic regression and both fixed- and random-effects meta-analysis models. CONCLUSIONS: Carriers of FVL or prothrombin gene mutations have double the risk of experiencing 2 or more miscarriages compared with women without thrombophilias. Hereditary thrombophilias may be an unrecognized cause of RPL. We recommend testing for these mutations in women with RPL.

Abortion, Habitual↗

Hormones and menopausal status as predictors of depression in women in transition to menopause.

BACKGROUND: Associations between depressed mood and hormonal changes during transition to menopause are controversial. To our knowledge, there has been no prospective study of these associations in women commencing when they are premenopausal. OBJECTIVE: To longitudinally study the associations among reproductive hormones, menopausal status, and other predictors of depressed mood in midlife women. DESIGN: Cohort study with 6 assessment periods during a 4-year interval. Blood samples were collected 12 times during the follicular phase (days 2-6). SETTING: Philadelphia County, Pennsylvania. PARTICIPANTS: A randomly identified, population-based, stratified sample of African American (n = 218) and white (n = 218) women aged 35 to 47 years with regular menstrual cycles, no hormonal or psychotropic medication use, and no serious physical or mental health problems at enrollment. MAIN OUTCOME MEASURES: Center for Epidemiologic Studies Depression Scale score and history of depression via the Primary Care Evaluation of Mental Disorders. RESULTS: There was an increased likelihood of depressive symptoms during transition to menopause and a decreased likelihood after menopause after adjustment for other predictors of depression, including history of depression, severe premenstrual syndrome, poor sleep, age, race, and employment status (P =.03). The likelihood of depressive symptoms decreased for individuals with a rapidly increasing follicle-stimulating hormone profile (P< or =.001) and also decreased with age compared with premenopausal women (P =.02). Participant aggregate profiles with increasing estradiol levels were significantly associated with depressive symptoms in bivariate analysis (P =.053). CONCLUSIONS: Depressive symptoms as assessed herein increased during transition to menopause and decreased in postmenopausal women. Hormone associations provided corroborating evidence that the changing hormonal milieu contributes to dysphoric mood during transition to menopause.

Adult↗

Acute consequences of the menopausal transition: the rise of common menopausal symptoms.

More than 80% of women experience psychologic or physical symptoms in the late reproductive years, with varying degrees of severity and disruption in their lives. Patients and clinicians have misconceptions about what changes are considered "normal" or"abnormal" during this period. Of importance to clinicians, large-scale longitudinal studies recently have been conducted to better characterize and explore changes during this period. This article re-views the current evidence regarding the acute symptoms of the menopausal transition, including vasomotor symptoms, mood changes, sleep problems, and changes in sexual functioning.

Adolescent↗

Molecular basis of pubertal abnormalities.

The causes of abnormal pubertal development are numerous. Recent molecular investigation has increased our understanding of the genetic basis of pubertal disorders. Investigators have identified some of the genes that are critical for normal puberty and have begun to elucidate the genes and pathogenesis of genetic disorders associated with abnormal pubertal development. Identification of specific chromosomal abnormalities and gene mutations allows for diagnostic testing and enables the clinician to provide accurate counseling of the recurrence risk for relatives. In the future, knowledge of the genetic basis of these disorders will facilitate the development of novel therapies and approaches to the fertility assessment and treatment of individuals with pubertal disorders. Although great strides have been made in identifying these genes, questions remain. Why do some genetic mutations affect puberty differentially in males and females? What is the long-term impact in terms of future fertility, and what is the risk to the offspring of such patients? Further research is needed to address these issues and to identify additional genetic loci involved in pubertal development.

Adolescent↗

Usefulness of pipelle endometrial biopsy in the diagnosis of women at risk for ectopic pregnancy.

OBJECTIVE: The purpose of this study was to determine the accuracy of endometrial Pipelle (Unimar) biopsy to detect chorionic villi in suspected ectopic pregnancy. STUDY DESIGN: This was a blinded prospective trial that involved 32 women who were in stable condition with suspected ectopic pregnancy. Endometrial pipelle sampling was performed before uterine dilation and curettage. Pipelle and frozen section results were compared with final disease. RESULTS: Ten of 32 patients (31%) had chorionic villi that was consistent with a miscarriage; 22 of 32 patients (69%) had none detected. Pipelle biopsy had a sensitivity of 30% (95% CI, 6.7-65.2), a specificity of 100% (95% CI, 84.5-100), a positive predictive value of 100% (95% CI, 29.2-100), and a negative predictive value of 76% (95% CI, 56.5-87). Frozen section had a sensitivity of 87.5% (95% CI, 47.3-99.7), a specificity of 100% (95% CI, 83.1-100), a positive predictive value of 100% (95% CI, 59-100), and a negative predictive value of 95.3% (95% CI, 76.1-99.8). CONCLUSION: In patients with suspected ectopic pregnancy, Pipelle sampling is not a substitute for curettage because the sensitivity and predictive values are unacceptable.

Abortion, Spontaneous↗

Presumed diagnosis of ectopic pregnancy.

OBJECTIVE: To evaluate the accuracy of the diagnosis of presumed ectopic pregnancy. METHODS: This was a retrospective cohort analysis at a tertiary care medical center. The patient population was composed of 1) clinically stable pregnant women with human chorionic gonadotropin (hCG) above 2000 mIU/mL and no evidence of an intrauterine pregnancy by ultrasound, or 2) women with an abnormal rise or fall of serial hCG below 2000 mIU/mL. Outcome was determined by pathologic evidence of chorionic villi in the endometrial curettings (or fallopian tube), or complete resolution of hCG. RESULTS: Overall, 38.4% (43/112) of the women were diagnosed with a miscarriage and 61.6% (69/112) were found to have an ectopic pregnancy. No significant difference was found in race, age, gravity, parity, hCG trends, or time to diagnosis between women with ectopic pregnancies and those with miscarriages. Patients were more likely to be diagnosed with an ectopic pregnancy if the initial hCG value was below the discriminatory zone (relative risk 2.44; 95% confidence interval 1.07, 5.52). Ultrasound correlated well with the final diagnosis (P =.001) but was not definitive. CONCLUSION: In an effort to save time, avoid dilation and curettage (D&C), and treat with methotrexate, the presence of an ectopic pregnancy is often presumed. The presumed diagnosis of ectopic pregnancy is inaccurate in almost 40% of cases. A D&C is necessary to differentiate an ectopic pregnancy from a miscarriage before a woman is presumptively treated with methotrexate.

Abortion, Spontaneous↗

Predictors of decreased libido in women during the late reproductive years.

OBJECTIVE: To identify risk factors for decreased libido among women in the late reproductive years. DESIGN: Prospective cohort. Women aged 35 to 47 years identified through random digit dialing were prospectively followed for 4 years with serial hormone assays and standardized questionnaires. Mean hormone values, hormone trends over 4 years, and fluctuation in hormone levels were compared among women with and without a decrease in libido at the last assessment period. Total testosterone, dihydroepiandrosterone sulfate, estradiol, follicle-stimulating hormone, luteinizing hormone, body mass index, psychosocial, and socioeconomic variables were evaluated using multivariable logistic regression. RESULTS: Of 326 women, 87 (27%) reported a decreased libido, whereas 239 (73%) did not. Participant-specific means for all hormone levels over the study period were similar among both groups. However, total testosterone fluctuation over the study was significantly different between groups. Women whose testosterone levels fluctuated from 3.8 to 21.5 ng/dL around a mean value of 9 ng/dL were four times more likely to report decreased libido compared with women with little fluctuation in testosterone [odds ratio (OR) 4.0; 95% CI, 1.6-10.0]. Depression (OR 3.4; 95%CI, 1.9-6.1), vaginal dryness (OR 3.5; 95%CI, 1.8-6.6), and children living at home (OR 1.4; 95%CI, 1.1-1.7) were also independently associated with decreased libido. CONCLUSIONS: Decreased libido in the late reproductive years is associated with a pronounced fluctuation in total testosterone over time. Other independent risk factors for decreased libido include vaginal dryness, depression, and living with children. Sexual dysfunction is a complex disorder, related to physiological and psychosocial factors, requiring further investigation.

Adult↗

Predicting participation in prospective studies of ovarian aging.

OBJECTIVE: Identifying clinical markers and characteristics of the transition to menopause is an important woman's health issue, and recent long-term, prospective, cohort studies are just beginning to offer insight into methods of predicting the transition to menopause. One of the major challenges of conducting prospective cohort studies is the problem of attrition-both the retention of study participants and the influence of dropouts on the final study results. We conducted this systematic analysis to: 1) identify baseline predictors of subsequent long-term participation, and 2) determine the demographic, psychosocial, and hormonal differences between participants and dropouts among a group of premenopausal women enrolled in a longitudinal study of ovarian aging. DESIGN: Using data from the Penn Ovarian Aging study, premenopausal women aged 35 to 47 enrolled in the study were classified as either Active (full participants), Skipped, or Dropped participants based on their visit pattern during a 4-year study interval. RESULTS: Most of the demographic and psychosocial variables did not significantly differ between the Active, Skipped, or Dropped groups. There was no racial difference in study participation. The Dropouts were more likely to have a high school education and were less likely to report menopause symptoms compared with the Actives (P < 0.01). The Skipped group reported more anxiety (P < 0.05), and members were more likely to have less than a high school education compared with the Actives (P < 0.03). Hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, dehydroepiandrosterone, testosterone) at enrollment were within the premenopausal range and did not significantly differ among the three study groups. These findings remained after adjustment for covariates and hormone levels in multivariate analyses. CONCLUSIONS: Education, anxiety levels and menopause symptoms at baseline differed marginally between the women participating fully and those who dropped out or skipped multiple assessments. These findings are important and indicate that long-term study participation rates do not differ substantially by racial group or any of the other demographic or hormonal characteristics examined.

Adult↗

The role of anxiety and hormonal changes in menopausal hot flashes.

OBJECTIVE: To estimate the association of anxiety with menopausal hot flashes in the early transition to menopause. DESIGN: A randomly identified, population-based cohort of midlife women followed up for 6 years to assess reproductive hormones and other physical, emotional, and behavioral factors. At enrollment, the women were premenopausal, aged 35 to 47 years, and had regular menstrual cycles in the normal range. Enrollment was stratified to obtain equal numbers of African American (n = 219) and white (n = 217) women. RESULTS: At the 6-year endpoint, 32% of the women were in the early transition stage and 20% reached the late menopausal transition or were postmenopausal. Reports of hot flashes increased with the transition stages, which were determined by bleeding patterns. At endpoint, hot flashes were reported by 37% of the premenopausal women, 48% of those in the early transition, 63% of women in the late transition, and 79% of the postmenopausal women. Anxiety scores were significantly associated with the occurrence of hot flashes and were also significantly associated with the severity and frequency of hot flashes (each outcome at P < 0.001). Compared with women in the normal anxiety range, women with moderate anxiety were nearly three times more likely to report hot flashes and women with high anxiety were nearly five times more likely to report hot flashes. Anxiety remained strongly associated with hot flashes after adjusting for menopause stage, depressive symptoms, smoking, body mass index, estradiol, race, age, and time. In a predictive model, anxiety levels at the previous assessment period and the change in anxiety from the previous assessment period significantly predicted hot flashes (P < 0.001). CONCLUSIONS: Anxiety is strongly associated with menopausal hot flashes after adjusting for other variables including menopause stage, smoking, and estradiol levels. Anxiety preceded hot flashes in this cohort. Additional studies are needed to examine the duration of menopausal hot flashes and to determine whether treatments that target anxiety effectively reduce menopausal hot flashes.

Adult↗