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Biomedical subjects

E W Freeman

Publications and source records attributed to E W Freeman.

At least 19 recordsLinked to original sources
PubMed2005

Follicular phase hormone levels and menstrual bleeding status in the approach to menopause.

OBJECTIVE: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels. DESIGN: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years. SETTING: Women in Philadelphia County, PA, identified by random-digit telephone dialing. PARTICIPANT(S): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436). DATA COLLECTION: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period. MAIN OUTCOME MEASURE(S): Serum levels of follicular E(2), FSH, inhibin B, and LH. RESULT(S): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30. CONCLUSION(S): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.

Adult↗
PubMed2004

Premenstrual syndrome as a predictor of menopausal symptoms.

OBJECTIVE: To estimate whether premenstrual syndrome (PMS) predicts common menopausal symptoms assessed longitudinally for 5 years among women in the transition to menopause. METHODS: Data were obtained from a structured interview questionnaire, daily symptom ratings, and standard measures of depressive symptoms and sleep quality at 7 assessment periods in a population-based cohort of 436 women. Menstrual status was determined by menstrual bleeding dates. Hormones were measured in the early follicular phase, with a maximum of 14 measures per subject. Multivariate logistic regression models for repeated measures were used to estimate the effects of study variables. RESULTS: Premenstrual syndrome significantly decreased with age (P <.001) and with changes in menstrual bleeding status (P =.003). Women with PMS at enrollment were more likely over the 5-year period to report menopausal hot flushes (odds ratio [OR] 2.09; confidence interval [CI] 1.42, 3.08; P <.001); depressed mood (OR 2.34; CI 1.60. 3.43; P <.001); poor sleep (OR 1.72; CI 1.16, 2.53; P =.007), and decreased libido (OR 1.54; CI 1.06, 2.24; P =.024) after adjusting for age, race, diagnosis of major depression, and estradiol. Subjects' fluctuations in estradiol were significantly associated with hot flushes, depressive symptoms, and poor sleep. CONCLUSION: Premenstrual syndrome decreased in the transition to menopause. Women who reported PMS at baseline were at greater risk of menopausal hot flushes, depressed mood, poor sleep, and decreased libido. Further studies of the associations of symptoms and changes in ovarian function are needed to elucidate the underlying symptom physiology and aid in the development of effective treatments for women during the menopausal transition.

Adult↗
PubMed2003

Premenstrual dysphoric disorder and psychiatric co-morbidity.

Premenstrual dysphoric disorder (PMDD) can occur co-morbidly with other axis I disorders, particularly mood and anxiety disorders. The data supporting this diagnostic dilemma are reviewed in terms of methodological comparisons between studies. The point prevalence of the co-occurrence of PMDD and other psychiatric disorders is discussed as well as implications for treatment and further study.

Anxiety Disorders↗
PubMed2002

Evaluation of a unique oral contraceptive (Yasmin) in the management of premenstrual dysphoric disorder.

Over three-quarters of women experience some physical and emotional changes associated with the menstrual cycle. Irritability, tension, fatigue, depression, breast tenderness and bloating are among the most common premenstrual symptoms. Approximately 5-10% of women of childbearing age experience premenstrual symptoms to a degree that disrupts their functioning in the home or workplace and that meet criteria for premenstrual dysphoric disorder (PMDD). Serotonergic antidepressants are clearly effective for PMDD, with about 60% of subjects responding to this treatment in controlled studies. Oral contraceptives are commonly used to treat premenstrual symptoms but are an understudied intervention with no information on their efficacy for PMDD). The recent introduction of an oral contraceptive (Yasmin, Schering AG, Berlin, Germany), containing low-dose ethinylestradiol (EE) combined with a new progestogen, drospirenone (DRSP), may offer clinical efficacy for PMDD as a result of the unique pharmacological profile of this progestogen, which is a spirolactone derivative with antimineralocorticoid and antiandrogenic activity. A randomized, placebo-controlled study of DRSP/EE in women with PMDD found a consistently greater reduction of symptoms-from baseline for all 22 premenstrual symptoms assessed (using the Calendar of Premenstrual Experiences, COPE) and for the four statistically derived symptom factors in the group taking DRSP/EE compared to the placebo group. For appetite, acne and food craving (factor 3), the difference between the DRSP/EE group and the placebo group was statistically significant (p = 0.027). These preliminary results suggest the beneficial effect of DRSP/EE on PMDD and offer an alternative class of medication that also provides the range of benefits of oral contraception for women with PMDD.

Adult↗
PubMed2001

DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years.

BACKGROUND: The objective of this study was to elucidate the associations of dehydroepiandrosterone sulfate (DHEA-S) levels and depressive symptoms in African American and Caucasian women in the late reproductive years, a transitional age zone preceding the perimenopause, in which ovarian aging and associated endocrine changes begin. We had hypothesized that lower levels of DHEA-S would be associated with depressive symptoms and that, because DHEA-S levels decline with increasing age, older women would have an increased prevalence of depressive symptoms. METHODS: This cross-sectional study used a population-based urban sample recruited through random digit telephone dialing. The sample was 338 women between the ages of 35 and 47 years with regular menses. Half the sample was African American and half was Caucasian. RESULTS: Higher DHEA-S levels were associated with depressive symptoms in women in the younger half of this cohort. Lower DHEA-S levels were associated with depressive symptoms in the women in the older half of this cohort. The direction of the relationship of DHEA-S and depressive symptoms changes with age, being a positive relationship in younger women and an inverse relationship in the older women in this cohort. This change in the direction of the relationship appears to occur at a younger age in African American women. CONCLUSIONS: Our hypothesis of a relationship between low DHEA-S levels and elevated depressive symptoms was supported only in the older women in this cohort. Unexpectedly, younger women in this cohort demonstrated a positive association between DHEA-S levels and depressive symptoms. Changes in DHEA-S levels, depressive symptoms, and the relationship of other hormones in the hypothalamic-pituitary-adrenal axis need to be better understood in premenopausal women approaching perimenopause.

Adult↗
PubMed2001

Racial differences in sex hormone levels in women approaching the transition to menopause.

OBJECTIVE: Evaluate racial differences in reproducibility of hormone levels over time (estradiol, DHEAS, FSH, and testosterone) while adjusting for covariates previously identified as relevant in the study population. DESIGN: Longitudinal cohort study. SETTING: Healthy, late-reproductive-age women in a community-based sample. PATIENT(S): African American and Caucasian women identified by random digit dialing. INTERVENTION(S): Hormone levels measured in the early follicular phase of the menstrual cycle four times over 9 months. A multivariate, linear mixed model estimated effects on hormone levels of race, age at enrollment, age at menarche, number of pregnancies, current smoking, alcohol consumption, body mass index (BMI), waist/hip ratio (WHR), and menstrual cycle length. MAIN OUTCOME MEASURE(S): Follicular plasma levels of estradiol, FSH, DHEAS, and testosterone. RESULT(S): African American but not Caucasian women had significantly lower levels of estradiol and DHEAS with increasing age. African American but not Caucasian women had significantly decreased levels of estradiol and significantly increased levels of DHEAS with increasing BMI. No racial differences in reproducibility of hormone measures were found. CONCLUSION(S): There are racial differences in associations of hormone levels with age and BMI in late reproductive age women. Further study is needed to replicate these findings and to determine the relationships of these hormonal associations with menopausal symptoms.

Adult↗
PubMed2001

Sleep quality, estradiol levels, and behavioral factors in late reproductive age women.

OBJECTIVE: To estimate the prevalence of perceived poor sleep in women aged 35-49 years and to correlate sleep quality with levels of gonadal steroids and predictors of poor sleep. METHODS: A cohort of 218 black and 218 white women aged 35-47 years at enrollment (aged 37-49 at final follow-up) with regular menstrual cycles was identified through random digit dialing for a longitudinal study of ovarian aging correlates. Data obtained at four assessment periods, including enrollment, over a 2-year interval were collected between days 1 and 6 (mean = 3.9) of the menstrual cycle. The primary outcome measure was subjects' rating of sleep quality at each assessment period. Associations of sleep quality with hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral, and demographic variables were examined in bivariable and multivariable analyses. RESULTS: Approximately 17% of subjects reported poor sleep at each assessment period. Significant independent associations with poor sleep included greater incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.08, 2.12, P =.02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P =.04), higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P <.001), greater caffeine consumption (OR 1.25; 95% CI 1.04, 1.49, P =.02), and lower estradiol levels in women aged 45-49 (OR 0.53; 95% CI 0.34, 0.84, P =.006), after adjustment for current use of sleep medications. CONCLUSION: Both hormonal and behavioral factors were associated with sleep quality. Estradiol levels are an important factor in poor sleep reported by women in the 45-49 age group. Further evaluation of estrogen treatment for poor sleep of women 45 years and older is warranted.

Adult↗
PubMed2001

Venlafaxine in the treatment of premenstrual dysphoric disorder.

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine, a new-generation antidepressant that selectively inhibits serotonin and norepinephrine reuptake, in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: We conducted a randomized, double-blind, placebo-controlled, parallel-group, flexible-dose trial. After three screening cycles, including a single-blind placebo cycle, 164 women were randomly assigned to double-blind treatment with venlafaxine (50-200 mg/day) or placebo for four menstrual cycles. Primary outcome measures were the total premenstrual symptom scores as assessed by a daily symptom report (DSR) and the Hamilton Rating Scale for Depression. RESULTS: Venlafaxine was significantly more effective than placebo in reducing PMDD symptoms as assessed by DSR scores (P <.001 for last observation carried forward and observed analyses). Sixty percent of venlafaxine versus 35% of placebo subjects improved >50% (P =.003). Forty-three percent of venlafaxine subjects versus 25% of placebo subjects experienced symptom remission, defined as reduction of DSR scores to the postmenstrual level (P =.034). Venlafaxine treatment was significantly better than placebo for all statistically derived DSR factors (mood, function, pain, and physical symptoms). Improvement was relatively swift, with approximately 80% symptom reduction in the first treatment cycle. Mean venlafaxine doses ranged from 50 mg/day in the first treatment cycle to 130 mg/day in the fourth treatment cycle. Adverse events such as nausea, insomnia, and dizziness were mild and transient. CONCLUSIONS: Venlafaxine is significantly more efficacious than placebo for PMDD treatment. Response to treatment can occur in the first treatment cycle, and venlafaxine is well tolerated. Further studies are needed to evaluate the potential of intermittent (luteal phase) dosing for this cyclic disorder and the efficacy of long-term maintenance treatment with venlafaxine.

Adult↗
PubMed2000

Psychosocial functioning in women with premenstrual dysphoric disorder before and after treatment with sertraline or placebo.

BACKGROUND: The objective of this study was to evaluate the pretreatment psychosocial functioning of women with premenstrual dysphoric disorder (PMDD) and the effect of sertraline treatment on psychosocial functioning in these patients. METHOD: Two hundred forty-three women recruited from 12 university-affiliated sites and meeting DSM-IV criteria for PMDD completed 1 cycle of single-blind placebo and were randomly assigned to flexible dose sertraline or placebo for 3 cycles. Psychosocial functioning was assessed by the Daily Record of Severity of Problems (DRSP), the Social Adjustment Scale (SAS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). RESULTS: SAS scores during the follicular phase were similar to SAS scores of community norms, whereas the pretreatment SAS and Q-LES-Q scores during the luteal phase were similar to scores of women with depressive disorders. Sertraline was significantly more effective than placebo in improving psychosocial functioning as measured by the SAS, the Q-LES-Q, and the 3 DRSP items of impaired productivity, interference with social activities, and interference with relationships with others. Improvement in psychosocial functioning assessed by SAS and Q-LES-Q correlated with improvement in symptomatology assessed by the Clinical Global Impressions-Improvement (CGI-I) scale and the Hamilton Rating Scale for Depression (HAM-D). Remitters (CGI-I score of 1) were more likely to function better at baseline and showed larger improvements in functioning and quality of life with treatment compared with nonremitters. CONCLUSION: Sertraline was superior to placebo in improving psychosocial functioning in women with PMDD as reflected by SAS, Q-LES-Q, and DRSP measures. Functional improvement correlated with improvement in premenstrual symptomatology and was apparent by the second cycle of treatment. Comparison of pretreatment SAS scores in women with PMDD with the scores of other populations of women documents the degree of luteal phase functional impairment in women with PMDD and a relative absence of follicular phase impairment.

Adaptation, Psychological↗
PubMed2000

Prior benzodiazepine exposure and benzodiazepine treatment outcome.

BACKGROUND: We examined discontinuation symptoms following brief benzodiazepine therapy (8 weeks) and intermittent benzodiazepine therapy (2 weeks with at least 2 weeks without drug) and associations with prior benzodiazepine use. The hypothesis was that prior benzodiazepine use would predispose patients to more severe discontinuation symptoms. METHOD: Data were drawn from 3 double-blind, randomized, placebo-controlled, published treatment trials: alprazolam for patients with premenstrual syndrome (PMS) and diazepam and lorazepam for patients with generalized anxiety disorder (GAD). The PMS group provided prospective daily symptom ratings, which allowed ongoing investigation of effects of prior treatment. In the GAD groups, taper outcome was examined after 8 weeks of benzodiazepine therapy as a function of prior benzodiazepine use and as a function of time since last prior benzodiazepine use. Symptom scores were analyzed using t statistics in the PMS group and analysis of covariance with 8-week scores as the covariate in the GAD groups. RESULTS: The PMS subjects reported no increase in symptom scores and no significant difference from placebo-treated subjects during taper and discontinuation of alprazolam in the follicular phase of each treatment cycle. In the GAD trials, the results of treatment discontinuation did not differ significantly as a function of presence or absence of prior benzodiazepine use or as a function of time since last benzodiazepine use. CONCLUSION: These preliminary data fail to support the hypothesis that prior benzodiazepine use predisposes patients to more severe discontinuation symptoms when treatment is brief and doses are low.

Alprazolam↗
PubMed2000

Predictors of response to sertraline treatment of severe premenstrual syndromes.

BACKGROUND: Serotonergic antidepressant medications have demonstrated efficacy in the treatment of severe premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Over 60% of subjects responded well to sertraline treatment for PMS and PMDD in double-blind controlled studies. However, no studies have evaluated the predictors of treatment response for this disorder. The current study examined pretreatment demographic, medical history, and clinical symptom predictors of sertraline response in PMS and PMDD treatment. METHOD: Sixty-two subjects diagnosed with severe PMS (according to the Daily Symptom Report and global ratings of functional impairment) or PMDD (DSM-IV) received sertraline treatment as part of a randomized, double-blind, placebo-controlled treatment efficacy study. All subjects completed 3 screening cycles, including a single-blind placebo washout cycle, prior to 3 cycles of double-blind treatment. Outcome was assessed across the domains of PMS symptoms and quality of life. Demographic, medical history, and symptom variables were used to predict sertraline response. RESULTS: Baseline postmenstrual symptom ratings were significantly and independently associated with posttreatment PMS symptoms in multivariate analysis. Premenstrual and postmenstrual ratings of depression, medical history variables, and demographic variables were not significantly predictive of response to sertraline. CONCLUSION: Baseline postmenstrual symptom ratings controlled for baseline premenstrual symptoms were associated with PMS symptoms at sertraline treatment endpoint. The findings suggest that nonmenstrual-related baseline characteristics other than depression may influence sertraline treatment outcome in patients with higher postmenstrual symptom levels.

Adolescent↗
PubMed1999

Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder: a randomized controlled trial.

BACKGROUND: Studies show that selective serotonin reuptake inhibitors are effective for severe premenstrual syndrome and premenstrual dysphoric disorder. This study compares the efficacy of a selective serotonin reuptake inhibitor with that of a tricyclic antidepressant to determine whether efficacy for premenstrual syndrome/premenstrual dysphoric disorder is a general or more serotonergic effect of antidepressants. METHODS: After 3 screening months, 189 subjects were randomized to sertraline hydrochloride, desipramine hydrochloride, or placebo for 3 months of double-blind treatment. The flexible dosage range was 50 to 150 mg/d. The outcome measures included the Penn Daily Symptom Report (DSR), the Hamilton Depression Rating Scale, the Clinical Global Impressions-Severity Scale, the Quality of Life Scale, and Patient Global Ratings of Functioning and Improvement. Analyses included all subjects with treatment data, with the last observation carried forward. RESULTS: Sertraline was significantly more effective than placebo or desipramine; desipramine was not better than placebo (F2,163 = 12.47, P<.001). All DSR factors were more improved with sertraline compared with desipramine and placebo; the factors for mood (P<.001) and pain (P = .05) were significant, and the results of all outcome measures were consistent. A history of depression, postmenstrual symptom levels, and other diagnostic variables added individually as covariates did not alter the treatment results. At end point analysis, DSR symptoms had decreased by more than 50% in 40 subjects (65%) in the sertraline group, 18 subjects (36%) in the desipramine group, and 16 subjects (29%) in the placebo group (P<.001). CONCLUSIONS: The comparison of 2 classes of antidepressants strongly favored the serotonergic drug, which effectively reduced symptoms and improved functioning and was well tolerated by women with severe premenstrual syndrome. A history of depression did not alter the treatment results.

Antidepressive Agents, Second-Generation↗
PubMed1999

Racial differences in menopause information and the experience of hot flashes.

OBJECTIVE: To compare the prevalence of hot flashes and health education regarding menopause in African-American and white American women in the late reproductive years. DESIGN: Cross-sectional study. SETTING: Population-based sample recruited through random digit dialing. PARTICIPANTS: The sample was 436 women between the ages of 35 and 48 years with regular menses. Half the sample was African American and half was white American. MAIN RESULTS: African-American women (53%) were more likely than white American women (29%) to have experienced hot flashes (p < .001). The difference remained after adjustment for body-mass index, education, menstrual cycle characteristics, and gynecologic and medical history. Despite the high prevalence of symptoms, few women had discussed menopausal management with their physicians. For white women the media were the primary source of menopause-related information, whereas African-American women reported that their family was the primary source of information. CONCLUSIONS: These results indicate that hot flashes occur commonly among women in their thirties and forties who have regular menstrual cycles and that the prevalence of hot flashes appears to differ by race. Studies should be designed to evaluate the hormonal and physiologic implications of these symptoms among women in their late reproductive years. Few of these women had discussed menopause with their physicians. Given the differences in sources of information about menopause, development of culture-specific health education programs should be considered.

Adult↗
PubMed1999

Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant.

Evidence that serotonergic antidepressants are effective for treating premenstrual syndrome (PMS) raises the question of whether dosing only in the symptomatic premenstrual phase is effective for this disorder. This preliminary randomized, double-blind study compared the responses to half-cycle or full-cycle dosing of sertraline in 31 patients who completed a preceding double-blind, short-term treatment trial. The subjects fulfilled criteria for severe PMS when they entered the preceding controlled trial. At the end of the short-term treatment trial, the double-blind was not broken; both improved and unimproved subjects were randomized in a double-blind fashion to receive either full-cycle or half-cycle sertraline in the 3-month extension study. Results showed that the total premenstrual scores from the Penn Daily Symptom Report (DSR) were lower in the half-cycle dosing group in each of the 3 treatment months but did not differ with statistical significance from the full-cycle dosing group. Further analysis of the 17 DSR items showed that mood swings, nervous tension, feeling out of control, and confusion were significantly lower (p < 0.05) at endpoint in the half-cycle dosing group. Overall, subjects who improved in prior treatment remained improved; approximately half the subjects who were unimproved at entry into the extension study improved, regardless of the dosing regimen. The results add support to other preliminary reports of efficacy of serotonergic antidepressants administered premenstrually and indicate the clinical importance of determining an optimal dose/benefit ratio of serotonergic antidepressants for PMS patients.

Adolescent↗
PubMed1999

Differences in urinary excretion patterns of the hLH beta core fragment in premenopausal, perimenopausal, and postmenopausal women.

OBJECTIVE: The heterodimeric luteinizing hormone beta core fragment (hLH beta cf) is a highly stable urinary analyte reflective of circulating hLH. It is measured easily because of its high molar content and has none of the multiple isoforms and subunit dissociation problems of LH urinary measurements. As part of a long-term effort to develop new biochemical assays to stage women during the perimenopausal transition, we have examined the patterns of urinary excretion of this metabolite of hLH in premenopausal, perimenopausal, and postmenopausal women. DESIGN: We measured the concentration of the hLH beta cf in 10 consecutive first morning void urine specimens from premenopausal, perimenopausal, and postmenopausal women. Day 1 of collection was the first day of menses in the cycling women. RESULTS: Postmenopausal women exhibited a widely fluctuating pattern of LH beta core fragment excretion, which is not correlated with hLH measured by immunofluorometric assay or with follicle-stimulating hormone measured by immunofluorometric assay. The postmenopausal group was easily distinguished from premenopausal women on the basis of an area-under-the-curve concentration function. Perimenopausal women displayed intermediate hLH beta cf concentrations; some clearly were in postmenopausal ranges, and others were in the premenopausal ranges. CONCLUSIONS: The pattern of excretion and concentrations of the hLH beta cf is significantly different between premenopausal and postmenopausal women. Perimenopausal women exhibited intermediate changes. The capability to measure this type of stable urinary metabolite as a reflection of changes in dynamics of its parent circulating hormone offers new possibilities in the development and application of large-scale testing that does not require blood sampling.

Adult↗