Biomedical subjects

E W Freeman

Publications and source records attributed to E W Freeman.

At least 37 records · Page 2Linked to original sources

PubMed1999

Characteristics of placebo responses in medical treatment of premenstrual syndrome.

OBJECTIVE: This study characterizes the responses to placebo medication of patients with premenstrual syndrome (PMS) who were randomly assigned in controlled treatment trials. Possible predictors of placebo response were also examined. METHOD: Subjects from two randomized controlled trials were pooled. The 101 subjects met defined criteria for severe PMS, remained eligible after 1 month of single-blind placebo lead-in treatment, and were randomly assigned to 3 months of double-blind placebo treatment. Improvement in the current study was defined as a decrease of at least 50% in premenstrual symptom score from the pretreatment baseline. RESULTS: At endpoint, 20 (20%) of the placebo-treated subjects showed sustained improvement, 18 of these in at least 3 of the 4 months of placebo medication. Another 42% of subjects partially improved, and 39% were clearly unimproved throughout the study period. CONCLUSIONS: Some patients with severe PMS experience significant and sustained improvement with placebo medication, but the majority report only partial or no improvement. Patients who sustain improvement for at least 2 consecutive months are likely to remain improved, indicating the importance of nondrug factors in clinical care.

Adolescent↗

PubMed1998

Premenstrual syndromes.

Premenstrual syndromes (PMS) are a group of menstrually related, chronic, cyclical disorders manifested by emotional and physical symptoms in the second half of the menstrual cycle. A diagnosis of PMS is based on the timing and symptom pattern observed in daily symptom reports maintained by the patient. The etiology is unknown but is believed to involve genetic and dynamically evolving vulnerability, reproductive hormones, and neurotransmitters, as well as other brain processes. Effective medications have been identified for acute hormonal and symptomatic treatment of the disorder, but the time course and frequency of relapse and recurrence remain poorly understood. Further studies of PMS in all areas--etiology, pathobiology, diagnosis, course of illness, and treatment efficacy--are needed to increase the body of information about the menstrual cycle's effects on women's health and mood disorders.

Female↗

PubMed1997

Ovarian aging and hormone replacement therapy. Hormonal levels, symptoms, and attitudes of African-American and white women.

OBJECTIVES: To characterize reproductive hormone levels, symptoms, and attitudes related to menopause among healthy, menstruating white and African-American women aged 44 to 49 years. DESIGN: Pilot study; cross-sectional survey. SETTING: Community-based convenience sample of women in the Philadelphia metropolitan area. PARTICIPANTS: Thirty-three African-American and 35 white women. MEASUREMENTS: The survey instrument collected demographic data, medical and reproductive history, health practices and behaviors. It included previously validated function, depression, and quality-of-life instruments, and a Menopause Attitude Scale that included two factors, attitudes toward the menopause and attitudes toward medical therapy. Anthropometric measurements were taken at enrollment, and reproductive hormones and daily symptom logs were followed over two menstrual cycles. MAIN RESULTS: The two groups were comparable in mean age (African-American 46.2 years, white 46.9 years). Serum levels of estradiol, follicle-stimulating hormone, dihydroepiandrosterone-sulfate, and progesterone were comparable. Symptoms were similar in type and frequency. However, the African-American women had significantly more positive attitudes toward menopause, were more likely to rely on family for information about menopause, and were less likely to have been recommended hormone replacement therapy by their physicians. A majority of women in each group expressed satisfaction with the care they had received. CONCLUSIONS: Perimenopausal African-American and white women have different expectations of menopause and the role of medical care in menopause. This bears directly on women's acceptance of hormone replacement therapy. Conclusions are limited by the small sample size and convenience nature of the study population: further work with larger samples is needed to confirm these apparent differences.

Black or African American↗

PubMed1997

Gonadotropin-releasing hormone agonist in the treatment of premenstrual symptoms with and without ongoing dysphoria: a controlled study.

Gonadotropin-releasing hormone (GnRH) agonists have been shown to reduce symptoms of premenstrual syndrome (PMS). This randomized, placebo-controlled study examined the efficacy of the GnRH agonist, leuprolide acetate depot, in a clearly defined PMS sample versus women with premenstrual symptoms in combination with dysphoric symptoms throughout the cycle, termed the premenstrual exacerbation (PME) group. Evaluation included the Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and the subject Penn Dally Symptoms Report (DSR) maintained throughout the study. Thirty-three eligible women were randomized to double-blind treatment and administered 3.75 mg of depot leuprolide or a placebo once a month for 3 months. The subjects were seen for efficacy evaluations at the end of each cycle. Outcome measures were the DSRs and the 17-item Hamilton Depression Rating Scale (HAM-D17). The PMS leuprolide subjects improved significantly compared with the PMS placebo and PME leuprolide groups. The PME leuprolide group, who had dysphoric symptoms throughout the cycle, did not improve. Depression symptoms were at clinical levels premenstrually in the PMS and PME groups; following treatment they remitted in the PMS group but not in the PME leuprolide subjects. Efficacy did not occur until after several months of leuprolide treatment, but there was no evidence that PMS symptoms worsened with the onset of treatment. These results replicate the findings in our preliminary open-label study. Leuprolide reduced PMS symptoms to minimal levels where symptoms were limited to the luteal phase. Leuprolide was not effective for women with ongoing dysphoric symptoms, suggesting that premenstrual depression may have mechanisms different from those of other dysphoric mood disorders.

Adult↗

PubMed1997

Premenstrual syndrome: current perspectives on treatment and etiology.

In the past year, randomized controlled clinical trials of treatments for clearly diagnosed premenstrual syndrome reported efficacy for serotonergic antidepressants and a gonadotropin-releasing hormone agonist. Preliminary data suggested efficacy for spironolactone and a carbohydraterich beverage. Several neuroendocrine studies have contributed to a growing list of findings that suggest an underlying neurobiological vulnerability in premenstrual syndrome.

Animals↗

PubMed1996

Reliability and validity of a daily diary for premenstrual syndrome.

Daily ratings of symptoms are essential to confirm a diagnosis of premenstrual syndrome (PMS). The 17-item Daily Symptom Report (DSR) is relatively brief and appropriate for clinical and primary care settings. We report the reliability, factor structure and relationships with other standard mood measures of the DSR as a measure of PMS. The sample includes 170 women who sought medical treatment for severe PMS and a non-clinical comparison group of 54 healthy women in the same age range. Cronbach's coefficient alpha was 0.92 for the premenstrual DSR scores, indicating very high internal consistency for the 17 symptoms. Factor analysis yielded four factors describing mood, behavioral items, pain, and physical symptoms. In the PMS sample, there were moderate correlations between the DSR and the Hamilton Rating Scale for Depression, the Profile of Mood States, and the Premenstrual Assessment Form. The moderate correlations of the DSR with other standard symptom measures add to the evidence that PMS overlaps with other mood disorders at the premenstrual time but is not simply a brief depression or a truncated anxiety disorder.

Adolescent↗

PubMed1996

Sertraline versus desipramine in the treatment of premenstrual syndrome: an open-label trial.

BACKGROUND: Antidepressant medications have appeared to be effective treatments for premenstrual syndrome (PMS) in several small trials. This open-label study examined the efficacy of and tolerance for a new serotonergic antidepressant compared with a traditional tricyclic antidepressant in PMS treatment. METHOD: For two menstrual cycles in women meeting well-defined criteria for PMS, an open-label comparison of the serotonin selective sertraline (N = 17) and the noradrenergic desipramine (N = 15) was performed. Dose was flexible, with a mean dose in the second cycle of 87 mg/day for sertraline and 110 mg/day for desipramine. Outcome measures were the premenstrual daily symptom report (DSR) scores and the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Sertraline and desipramine reduced depressive symptoms as assessed by the HAM-D, both achieving similar reductions in the HAM-D scores. Reduction of total premenstrual symptoms as assessed by the DSR score was observably greater with sertraline, but the difference compared with desipramine was not statistically significant in this small sample. Subjects were more likely to perceive desipramine side effects as intolerable; 4 of the 15 desipramine-treated subjects discontinued compared with none in the sertraline group. Subjects who were previously treated in a PMS program without good therapeutic response were less likely to respond to either medication, suggesting a treatment-resistant group. CONCLUSION: Sertraline and possibly desipramine appear to be effective treatments for PMS. Sertraline was better tolerated, resulting in greater patient acceptance. A placebo-controlled trial in which subjects are randomly assigned to the medication is clearly needed to support or refute these preliminary findings.

1-Naphthylamine↗

PubMed1996

Fluvoxamine for premenstrual dysphoric disorder: a pilot study.

BACKGROUND: Serotonergic agents appear to be effective treatments for premenstrual symptoms in a number of small trials. The purpose of this open-label treatment study was to collect pilot information on the efficacy of fluvoxamine for premenstrual dysphoric disorder (PDD). METHOD: Twelve women who sought medical treatment for premenstrual symptoms were evaluated. The main outcome measure was the premenstrual score from daily symptom reports (DSRs) maintained by the subjects. After a 2-month screening period, 10 subjects who met DSM-IV criteria for PDD were treated with fluvoxamine taken daily for two menstrual cycles. The mean dose at 4 weeks was 85 mg/day; at 8 weeks, all subjects took 100 mg/day. RESULTS: The mean premenstrual DSR scores improved at 4 weeks from the pretreatment baseline (paired t test, p < .0008) and remained improved at 8 weeks at approximately the same level (p < .003). Symptoms with the greatest improvement (p < .003, significant with the Bonferroni adjustment) were irritability, anxiety, feeling out of control, and decreased interest in usual activity. Sixty percent (6/10) of the subjects reported at least a 50% reduction in the DSR scores, a conservative clinical definition of improvement. The mean premenstrual Hamilton Rating Scale for Depression scores decreased from 19 at the pretreatment baseline to 9 at the 4-week evaluation. The main side effects were insomnia (N = 6), fatigue (N = 4), dry mouth (N = 4), and nausea (N = 3) and were generally mild and transient. CONCLUSION: These promising pilot data show the importance of a controlled trial over a longer time period to provide definitive information on the efficacy of fluvoxamine for premenstrual dysphoric disorder.

Adolescent↗

PubMed1995

A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome.

OBJECTIVE: To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. DESIGN: Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. SETTING: University hospital PMS medical treatment outpatient program in obstetrics/gynecology department. SUBJECTS: Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events. INTERVENTION: A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. MAIN OUTCOME MEASURES: Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. RESULTS: Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. CONCLUSIONS: Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS.

Administration, Oral↗

PubMed1995

Daily plasma estradiol and progesterone levels over the menstrual cycle and their relation to premenstrual symptoms.

The present study extends a previous report of lower plasma ACTH levels in women with premenstrual syndrome (PMS) compared with asymptomatic controls. Plasma levels of estradiol and progesterone were measured daily in 10 women with confirmed PMS and 8 asymptomatic women. Daily symptom reports were maintained during the same menstrual cycle. Both estradiol and progesterone levels were consistently, but not significantly, higher throughout the cycle in PMS subjects compared with controls. From the follicular to the early luteal phase, estradiol levels were significantly higher in a previously defined PMS subgroup 2 with more severe symptoms throughout the cycle compared with both the less severe PMS subgroup 1 and controls. Progesterone levels were significantly and positively correlated with PMS symptoms along the entire menstrual cycle, preceding the symptoms by 5-7 days. These preliminary results provide support for the hypothesis that the presence of progesterone at early luteal phase levels is required for PMS symptoms to occur.

Adult↗

PubMed1995

A clinician's guide to the premenstrual syndrome.

Many women have menstrual symptoms, but relatively few have severe PMS. PMS is a well-defined premenstrual cluster of predominantly affective symptoms that disrupt a woman's daily functioning. PMS is diagnosed with prospective charting of symptoms and should be differentiated from nondisruptive menstrual symptoms, major affective disorders, and other common medical and gynecologic conditions. Most women with PMS can be helped. The serotonin reuptake inhibitors are becoming the first line of therapy for PMS because they are effective, easily tolerated, and free of major side effects. There is also evidence supporting the role of other antidepressants, anxiolytics, and GnRH agonists in the treatment of PMS. Although increasing control of one's life, promoting a healthy diet, the avoidance of salt and caffeine, vitamin supplementation, and exercise have not been proved as effective treatment for PMS, they should be promoted for their obvious general health benefits. No one treatment fits the heterogeneous PMS population. A trial of medication should be continued for two or three menstrual cycles with appropriate dose adjustments. If relief is not sufficient, other agents or other treatments should be initiated.

Diagnosis, Differential↗

PubMed1995

Relationships between age and symptom severity among women seeking medical treatment for premenstrual symptoms.

Age at the time of seeking treatment for premenstrual symptoms (PMS) was examined in a sample of 332 women who reported severe distress and met criteria for Late Luteal Phase Dysphoric Disorder (LLPDD). The mean age of the sample was 33.1 (+/- 5.3) years. Severity of symptoms decreased with age and was not associated with the duration of symptoms. Depression-related factors were associated with the severity of PMS, and together with the duration of symptoms, were the best discriminators between the younger (ages 20-35) and older (ages 36-44) women in this sample. These data suggest that the years of the late twenties through mid-thirties are the most vulnerable time for distressing PMS and fail to support the clinical premise that PMS worsens with age until menopause. Further longitudinal study should be conducted to confirm and extend these findings.

Adult↗

PubMed1994

Nefazodone in the treatment of premenstrual syndrome: a preliminary study.

Nefazodone, a new phenylpiperazine antidepressant agent with serotonin type 2 antagonism and serotonin reuptake inhibition, was evaluated in two patient groups to determine its effectiveness in reducing the symptoms of premenstrual syndrome (PMS). The two studied groups were PMS patients with no coexisting major depression or dysthymia (N = 23) and PMS patients with current major depression or dysthymia, termed the premenstrual exacerbation group (N = 24). The two patient groups received open-label nefazodone for 8 weeks, with optional maintenance at the same dose for up to 1 year. The initial dose was 100 mg, titrated to 600 mg/day, on a twice-daily dosing schedule. Symptoms were assessed by the Hamilton Rating Scale for Depression and by Daily Symptom Ratings. Premenstrual symptoms improved significantly from pretreatment baseline values, with similar improvement for the PMS and premenstrual exacerbation groups. Significantly improvement occurred by the end of the first treated cycle (4 weeks of therapy), at an average dose of 245 (range, 100 to 400) mg, and was maintained thereafter. Nefazodone was well tolerated, side effects were often transient, and the most common were nausea and headache. Forty-seven of 54 patients completed 2 months of therapy, with a mean daily nefazodone dose of 319 mg at the 2-month point. A placebo-controlled study should be conducted to confirm and extend these promising preliminary findings.

Adolescent↗

PubMed1993

Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers.

Progesterone is readily reduced in humans to its A-ring metabolites, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one). The latter have been reported to have anxiolytic, hypnotic and anesthetic actions when administered to laboratory animals and (or) humans. Consequently, we measured allopregnanolone and pregnanolone in 18 healthy females, ages 18-25, at the time of peak plasma progesterone following an oral dose of micronized progesterone (1,200 mg) in a double-blind, placebo-controlled study. The plasma levels of the parent steroid and metabolites were compared with changes in mood, cognition, and motor performance following progesterone administration. We observed good correlations between plasma progesterone and plasma allopregnanolone (r = 0.85), plasma pregnanolone (r = 0.81) and the combined metabolites (r = 0.92). Plasma allopregnanolone was significantly correlated with measures of fatigue, confusion and immediate recall, and these correlation coefficients were somewhat greater than those for plasma progesterone and these same behavioral measures. Significant changes in fatigue, delayed verbal recall and symbol copying were experienced by subjects who achieved high levels (> or = 95.55 nmol/l) of these anxiolytic metabolites, while those with lower metabolite levels reported no negative effects. These data suggest that allopregnanolone and pregnanolone may contribute to or mediate the observed behavioral effects of progesterone.

Administration, Oral↗

PubMed1993

Preliminary evidence for plasma adrenocorticotropin levels as biological correlates of premenstrual symptoms.

Premenstrual syndrome (PMS) is a menstrual cycle-related disorder of mood and behavior with unknown etiology and lack of evidence of endocrine imbalances. The absence of menstrual cyclicity eliminates PMS symptoms, and cyclic gonadal changes appear necessary but not sufficient cause for behavioral symptoms in predisposed women. As there are many depressive symptoms in PMS, we focused on the neuroendocrine characteristics of depression, primarily hypothalamic-pituitary-adrenal hyperactivity, and investigated plasma adrenocorticotropin (ACTH) and cortisol levels in the menstrual cycle. Blood samples were drawn daily from ten patients with PMS and eight asymptomatic control subjects who also reported symptoms daily throughout one menstrual cycle. The ACTH levels were significantly lower in patients with PMS compared to control subjects in the luteal phase. Two PMS subgroups were identified by cluster analysis applied to symptom scores. Plasma ACTH levels of PMS Cluster 1 subjects were significantly lower compared to controls. The ACTH levels of PMS Cluster 2 subjects were nearly identical to controls. These preliminary results suggest distinct hormonal subgroups in the heterogeneous PMS population and support further study of ACTH as a biological correlate of PMS.

Adrenocorticotropic Hormone↗

PubMed1993

Premenstrual symptoms and dysmenorrhea in relation to emotional distress factors in adolescents.

The extent to which premenstrual symptoms occur when they are distinguished from primary dysmenorrhea and the relationship of premenstrual symptoms to other emotional distress in adolescents is not well understood. This pilot investigation examined relationships between premenstrual symptoms, dysmenorrhea and emotional distress factors in a sample of 165 females, ages 15-19 years. Premenstrual symptoms were correlated with dysmenorrhea (r = 0.54, p < 0.0001). Subjects with premenstrual symptoms had significantly more emotional distress than the normal group as assessed by the Symptom Checklist (SCL-90), an objective self-report questionnaire. In contrast, dysmenorrhea had no relationship with the SCL factors and no interaction with premenstrual symptoms in relation to emotional distress. The SCL scores significantly decreased from baseline (2 years earlier) in the normal group but not in the premenstrual symptom group. The data show that premenstrual symptoms were associated with other emotional distress factors in adolescents while dysmenorrhea was not. A further prospective, longitudinal study of menstrually-related symptoms in adolescents is needed to learn about the development of these premenstrual symptoms that may be related to the premenstrual syndrome seen clinically in the later reproductive years.

Adolescent↗

PubMed1993

Gonadotropin-releasing hormone agonist in treatment of premenstrual symptoms with and without comorbidity of depression: a pilot study.

BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa) in depot form for once-a-month rather than daily injection was examined in a small open trial to determine the extent of reduction of premenstrual symptoms, particularly premenstrual "depression." METHOD: Women who met criteria for premenstrual syndrome (PMS) or for PMS with comorbidity of major depression (MD), based on DSM-III-R criteria, were evaluated for the study. Evaluation included Structured Clinical Interview for DSM-III-R, administered in the follicular phase, and Daily Symptom Report (DSR), maintained throughout the study. Seven PMS subjects and two subjects who met the severity and change criteria for PMS but had concurrent MD were administered 3.75 mg of depot leuprolide monthly. Symptom change as reported on the DSR was compared with the untreated baseline scores. RESULTS: Six of seven PMS subjects had cessation of menses and significant decreases in premenstrual symptoms (p < .0001), which were reduced to their follicular phase levels. Physical symptoms of swelling and breast tenderness were among the most improved symptoms. Despite cessation of menses, the two MD subjects showed little improvement in premenstrual symptoms and no improvement in depressive symptoms. The premenstrual depression scores decreased almost completely in the PMS subjects, but increased slightly in the MD subjects. CONCLUSION: This small open trial suggests that GnRH agonist therapy reduces premenstrual symptoms including "depression" in women who meet criteria for PMS but not in women with PMS and MD. Further controlled study of the role of ovarian function in mood disorders is needed.

Adult↗

PubMed1992

Perceptions of infertility and treatment stress in females as compared with males entering in vitro fertilization treatment.

OBJECTIVE: To determine gender similarities and differences in perceptions of infertility and anticipated treatment stress in couples enrolling for in vitro fertilization (IVF) treatment. DESIGN: Both partners were evaluated at enrollment of IVF treatment. The evaluation was part of the screening procedure. SETTING: The Department of Obstetrics and Gynecology at a teaching hospital. PATIENTS, PARTICIPANTS: Two hundred consecutive couples who entered an IVF treatment program. MAIN OUTCOME MEASURES: Self-report questionnaire included items on the duration of infertility, degree of social support, effect of infertility on sexual relationship, expected likelihood of achieving pregnancy, anticipation of stress during treatment, and a self-rating scale of emotional reactions to infertility. RESULTS: The women anticipated more stress in IVF treatment but also rated greater degree of social support than the men. Both partners overestimated their chances of a successful treatment outcome. Factor analysis of the Infertility Scale produced three factors that were similar for both sexes. The first factor represented the desire to have a child as a major focus of life with inadequacy of the male role, social functioning and work efficiency, and pressure to have a child following. CONCLUSIONS: Women reported more stress, but the factors affecting stress of infertility were very similar for both partners. The intense focus on having a child was the predominant factor in anticipated stress of IVF treatment for both males and females.

Adult↗