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Biomedical subjects

Ellen W Freeman

Publications and source records attributed to Ellen W Freeman.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

Associations of hormones and menopausal status with depressed mood in women with no history of depression.

CONTEXT: Whether depressed mood reported in the transition to menopause by women with no history of depression is associated with menopausal status and changes in reproductive hormones is controversial and lacks scientific information. OBJECTIVES: To identify new onset of depressive symptoms and diagnosed depressive disorders in the menopausal transition and to determine the associations of menopausal status, reproductive hormones, and other risk factors with these cases. DESIGN: A within-woman, longitudinal (8-year) study to identify risk factors of depressed mood. SETTING: A subset of a randomly identified, population-based cohort. PARTICIPANTS: Premenopausal women with no history of depression at cohort enrollment. MAIN OUTCOME MEASURES: The Center for Epidemiological Studies of Depression scale (CES-D) was used to assess depressive symptoms, and the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to identify clinical diagnoses of depressive disorders. RESULTS: High CES-D scores (> or=16) were more than 4 times more likely to occur during a woman's menopausal transition compared with when she was premenopausal (odds ratio, 4.29; 95% confidence interval, 2.39-7.72; P<.001). Within-woman change in menopausal status, increased levels of follicle-stimulating hormone and luteinizing hormone, and increased variability of estradiol, follicle-stimulating hormone, and luteinizing hormone around the woman's own mean levels were each significantly associated with high CES-D scores after adjusting for smoking, body mass index, premenstrual syndrome, hot flashes, poor sleep, health status, employment, and marital status. A diagnosis of depressive disorder was 2(1/2) times more likely to occur in the menopausal transition compared with when the woman was premenopausal (odds ratio, 2.50; 95% confidence interval, 1.25-5.02; P=.01); the hormone measures were also significantly associated with this outcome. CONCLUSION: Transition to menopause and its changing hormonal milieu are strongly associated with new onset of depressed mood among women with no history of depression.

Adult↗
PubMed2006

Premenstrual syndrome (PMS) in adolescents: severity and impairment.

OBJECTIVES: Identify the presence of patients with premenstrual syndrome (PMS) in an adolescent gynecology practice, and evaluate the reported severity, impairment and timing of the symptoms in the menstrual cycle. METHODS: Adolescents ages 13-18 years completed a symptom questionnaire, functional impairment ratings, and a brief medical history questionnaire during an office visit. Teens who responded that they had PMS and reported a premenstrual symptom score at least 50% greater than the postmenstrual score and rated moderate to severe impairment in one or more domains comprised the "PMS" group. Teens who responded that they had PMS but did not meet the symptom and impairment criteria were termed "PMS not supported." Teens who responded that they did not have PMS and did not meet the PMS symptom and impairment criteria were termed "No PMS." RESULTS: Study participants (n = 94) had a mean age of 16.5 years (+/-1.3 SD); 31% met the criteria for the PMS group, 54% said they had PMS but did not meet criteria, and 15% clearly had no PMS. In the PMS group, the most severe symptoms were mood swings, anxiety, and irritability, with the greatest impairment in the home/family domain. Dysmenorrhea and the duration of PMS were significantly associated (P < 0.01) with PMS in univariate and multivariate analyses. CONCLUSIONS: The reports of premenstrual symptoms, their severity, timing and impairment suggest that PMS is common in adolescents. Further study is warranted to confirm these results with prospective assessment of PMS and to evaluate treatments for adolescents who have clinically significant PMS.

Adolescent↗
PubMed2006

Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?

Current evidence suggests that the accepted treatments for premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While these treatments are more effective than placebo, response rates associated with them are far from satisfactory (<60%), such that, irrespective of treatment modality, there remain a significant number of women who are unresponsive to current conventional pharmacological therapy. The available data on response rates of specific types of premenstrual symptoms to, or symptom profiles that are most amenable to, each treatment modality are limited and not well defined because most studies were not designed to assess specific symptom profiles. Those studies that have attempted to evaluate which symptom profiles respond to specific therapies have revealed variations within the individual modalities, as well as between the different modalities. It appears that suppression of ovulation ameliorates a broad range of behavioural as well as physical premenstrual symptoms. SSRIs are most effective for irritability and anxiety symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic compounds are most efficacious for anxiety and anxious/depressive symptoms, while dopamine agonists, particularly bromocriptine, are perhaps most efficacious for mastalgia. Overall treatment response rates may improve if treatments are targeted at well-defined subgroups of patients. Re-analysis of available datasets from randomised clinical trials may shed more light on the notion that targeting women with specific premenstrual symptom profiles for specific treatment modalities would improve response rates beyond the current ceiling of approximately 60%. Such information would also improve understanding of the putative pathophysiological mechanisms underlying PMS and PMDD, and may point to a more specific diagnosis of these conditions.

Central Nervous System↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

Effects of antidepressants on quality of life in women with premenstrual dysphoric disorder.

This review examines the effects of antidepressant medications on premenstrual dysphoric disorder (PMDD) and the diminished quality of life (QOL) that accompanies the disorder. PMDD is a chronic condition in women that emerges in the second half of the menstrual cycle and remits during the menstrual period. The affective and behavioural symptoms of PMDD adversely affect functioning and QOL to a disabling degree, particularly in the domains of family and personal relationships, work productivity and social activities. The serotonergic antidepressants, specifically the selective serotonin reuptake inhibitors (SSRIs), are effective for PMDD. Continuous and luteal-phase dosing regimens with SSRIs are similarly effective and well tolerated. Treatment of PMDD with a serotonergic antidepressant significantly improves functioning and QOL in all studies that have systematically examined QOL issues in this disorder. Although the data show that PMDD is effectively treated with serotonergic antidepressants and that functional impairment that accompanies the disorder is also improved with treatment, the social and economic burden of PMDD continues to be widely unrecognised. Greater awareness of the effectiveness of treatments and reliable measures of the direct and indirect healthcare costs of the disorder when it remains untreated are needed.

Adult↗
PubMed2005

A preliminary study of luteal phase versus symptom-onset dosing with escitalopram for premenstrual dysphoric disorder.

OBJECTIVE: This preliminary study compared the efficacy and tolerability of escitalopram administered at symptom onset or throughout the luteal phase in premenstrual dysphoric disorder (PMDD). METHOD: Twenty-seven women meeting DSM-IV criteria for PMDD were randomly assigned in a double-blind manner to luteal phase (N = 13) or symptom-onset (N = 14) dosing of escitalopram (10-20 mg/day) for 3 consecutive menstrual cycles. Participants were enrolled from November 2002 to July 2003, and data collection was completed in December 2003. Symptoms were assessed using the 17-item Penn Daily Symptom Report (DSR), the Clinical Global Impressions-Improvement scale, the Hamilton Rating Scale for Depression, and the Sheehan Disability Scale. Scores were compared using repeated measures analysis of covariance and t statistics. RESULTS: Luteal phase and symptom-onset groups received escitalopram for a mean of 13.5 and 6.0 days, respectively (mean +/- SD dose = 15.2 +/- 5.1 mg/day at the third treatment cycle). Total premenstrual DSR scores significantly improved from baseline (p = .003), with a 57% decrease in the luteal phase group and a 51% decrease in the symptom-onset group. Clinical improvement (DSR score decrease > or = 50% from baseline) was reported by 11 of 13 patients in the luteal phase group and 9 of 14 patients in the symptom-onset group. Symptom severity differentiated the response in the symptom-onset group, with those having more severe symptoms less likely to respond. Symptom severity did not differentiate treatment response to luteal phase dosing. Escitalopram was well tolerated. Adverse events were mild and transient, with only 2 patients discontinuing due to adverse events related to the medication. CONCLUSION: Premenstrual dysphoric disorder improved significantly with either luteal phase or symptom-onset dosing of escitalopram. Women with more severe PMDD may respond better to luteal phase dosing than symptom-onset dosing.

Adult↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

Continuous or intermittent dosing with sertraline for patients with severe premenstrual syndrome or premenstrual dysphoric disorder.

OBJECTIVE: The authors compared the efficacy and acceptability of continuous versus intermittent treatment with a selective serotonin reuptake inhibitor in women with severe premenstrual syndrome and determined the effects of postmenstrual symptom severity and depression history as covariates of the treatment response. METHOD: Patients who met symptom criteria and reported impaired functioning after three screening cycles were randomly assigned to three cycles of double-blind, placebo-controlled treatment with continuous (full-cycle dosing) or intermittent (luteal-phase dosing) sertraline. The design was stratified for severity of postmenstrual symptoms and history of major depression. Flexible sertraline dose was 50-100 mg/day. Outcome measures were the Daily Symptom Rating Form score and patient global ratings of functioning. RESULTS: Both sertraline groups improved significantly more than the placebo group as assessed by total premenstrual Daily Symptom Rating Form scores for 3 treatment months. Daily Symptom Rating Form factors that were significantly more improved in the sertraline groups were mood and physical symptoms. Sertraline improvement occurred swiftly in the first month of treatment. Gradual placebo improvement was similar to sertraline in the third month. Subjects with higher postmenstrual symptoms before treatment remained more symptomatic regardless of the dosing regimen. A history of major depression was not associated with treatment response. More sertraline-treated subjects reported improved functioning in the domains of family relationships, social activities, and sexual activity. CONCLUSIONS: Premenstrual dosing does not differ from continuous dosing with sertraline in premenstrual syndrome treatment. Higher levels of postmenstrual symptoms limit treatment response and are important to define in treatment of premenstrual syndrome.

Adolescent↗
PubMed2004

Luteal phase administration of agents for the treatment of premenstrual dysphoric disorder.

This review focuses on current information about luteal phase administration (i.e. typically for the last 2 weeks of the menstrual cycle) of pharmacological agents for the treatment of premenstrual dysphoric disorder (PMDD). Compared with continuous administration, a luteal phase administration regimen reduces the exposure to medication and lowers the costs of treatment. Based on evidence from randomised clinical trials, SSRIs are the first-line treatment for PMDD at this time. Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration. Clinical trials of these agents and citalopram have demonstrated that symptom reduction is similar with both administration regimens. When used to treat PMDD, SSRI doses are consistent with those used for major depressive disorder. The medications are well tolerated; discontinuation symptoms with this intermittent administration regimen have not been reported. Other medications that have been examined in clinical trials for PMDD or severe premenstrual syndrome (PMS) using luteal phase administration include buspirone, alprazolam, tryptophan and progesterone. Buspirone and alprazolam show only modest efficacy in PMS (in some but not all studies), but there may be a lower incidence of sexual adverse effects with these medications than with SSRIs. Symptom reduction with tryptophan was significantly greater than with placebo, but the availability of this medication is strictly limited because of safety concerns. Progesterone has consistently failed to show efficacy for severe PMS/PMDD in large, randomised, placebo-controlled trials.

Animals↗
PubMed2003

Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis.

Because of the prevalence, chronicity and distress caused by premenstrual symptoms (PMS), diagnosis and effective treatments are important information for clinicians. The DSM-IV requires at least five specified symptoms for premenstrual dysphoric disorder (PMDD), a severe dysphoric form of PMS, while the ICD-10 requires only one distressing symptom for a diagnosis of PMS. Many women who seek treatment fall between these two diagnostic approaches, and standard diagnostic criteria for clinically significant PMS are needed. A diagnosis of PMS consists of determining the timing of the symptoms in relation to menses, meaningful change between post- and premenstrual symptom severity and a clinically significant severity of the symptoms. A differential diagnosis to distinguish PMS from other medical and psychiatric conditions is important for appropriate treatment. No hormone or laboratory test indicates a PMS diagnosis. The current diagnostic standard requires confirmation of subjective symptom reports by prospective daily diaries. Diagnostic criteria for PMS must recognize the broad range of symptoms, the temporal pattern of the symptoms and the critical issue of symptom severity, which differentiates clinically significant PMS from normal menstrual cycle changes.

Cost of Illness↗
PubMed2003

Weight gain among women in the late reproductive years.

BACKGROUND: Given the impact of obesity on mortality and morbidity in women, we evaluated correlates of weight gain in women ages 35-47 years. METHODS: Three hundred and thirty-six African American and Caucasian American women, randomly selected from among urban residents aged 35-47 years and pre-menopausal at baseline, were included in the prospective cohort study. Participants were followed over a 4-year period. Baseline measures included anthropometric variables, socio-demographic factors, measures of anxiety, depressed mood, quality of life, and self-reported measures of diet, vigorous physical activity, alcohol consumption and cigarette smoking. Hormone measurements were obtained during the follicular phase of the menstrual cycle. Weight gain was assessed by comparing the baseline weight with weight measured at the end of the 4-year period. RESULTS: Over 25% of the cohort gained > or =10 lb during follow-up. Five of the 14 women (36%) who were considered menopausal gained weight. Women aged 45-47 were 61% less likely to gain > or =10 lb compared with women aged 35-39 [odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.18-0.87]. Depressed mood was a major correlate of weight gain (OR = 1.9, 95% CI 1.09-3.31). Other psychological measures, including anxiety and quality of life, were similarly correlated with weight gain. No association was detected for levels of sex hormones or self-reported measures of physical activity. Most recalled dietary factors were not predictive of subsequent weight gain in our population. CONCLUSIONS: In this population-based sample of women aged 35-47 years, psychological factors were the major predictors of gaining > or =10 lb during a 4-year follow-up period. Few of the other measures, including baseline hormone values, were correlated with subsequent weight gain. These findings suggest that screening for depression and anxiety may be important clinical assessments to identify women at increased risk of substantial weight gain.

Adult↗
PubMed2002

Current update of hormonal and psychotropic drug treatment of premenstrual dysphoric disorder.

This review discusses the current status of diagnosis and treatment of premenstrual dysphoric disorder (PMDD), with an emphasis on studies that have been published in the medical literature during the 2001 to 2002 interval. Serotonergic antidepressants are effective for PMDD, and are currently considered the first-line treatment. Recent clinical trials have shown that selective serotonin reuptake inhibitors, taken only during the symptomatic luteal phase, are also effective for PMDD. One study reported efficacy for a slow-release formulation of fluoxetine that was taken two times during the menstrual cycle. Oral contraceptives still lack definitive evidence of efficacy as a treatment for PMDD, although a new contraceptive formulation has appeared promising for the mood and behavioral symptoms of the disorder. The results of a meta-analysis of the published trials of progesterone and progestins further indicate that these hormones are not effective in the management of PMDD.

Adult↗