Daily salivary cortisol patterns in midlife women with hot flashes.

OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.

Hormone variations associated with quantitative fat measures in the menopausal transition.

OBJECTIVE: Reproductive hormone levels are associated with body size, and the association between estradiol and body size varies over the menopausal transition. This study aims to delineate these relationships using quantitative measures of visceral and subcutaneous fat. METHODS: Early follicular hormones (follicle stimulating hormone (FSH), estradiol, luteinizing hormone, dehydroepiandrosterone sulfate, testosterone) and T-1 weighted abdominal MRI images were obtained in a cross-sectional assessment of 77 women in the Penn Ovarian Aging Study. Fat volume (cm(3)) was quantified using validated software (Amira) and divided into tertiles of visceral and subcutaneous fat volume for analysis. Multivariable linear regression models compared hormone values between tertiles adjusting for race, age, and menopausal status. RESULTS: In adjusted models, estradiol was positively associated with visceral fat tertiles (geometric mean (GM) estradiol (pg/ml): Low 13.0, Mid 17.5, High 26.7, p = 0.006) while FSH was inversely associated with visceral fat tertiles (GM FSH (mIU/ml): Low 42.8, Mid 43.2, High 30.8, p = 0.03). The association of estradiol with visceral and subcutaneous fat tertiles varied by menopausal status (p < 0.001). In the early transition, estradiol was similar across tertiles of fat; postmenopause, estradiol was positively associated with visceral fat. Other hormones were not associated with fat measures. CONCLUSIONS: Estradiol was associated with quantitative measures of visceral fat and varies by menopausal status. This finding suggests that visceral fat may be an important mediator in hormone changes over the menopausal transition.

Hormone changes associated with the menopausal transition.

The menopausal transition (MT) is the time in each woman's reproductive life that precedes the final menstrual period (FMP). MT is associated with changes in bleeding pattern and hormone profiles. In recent years, research efforts have characterized changes in reproductive hormones over MT in order to elucidate the process of late reproductive aging and potentially identify predictors of time to menopause. Follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B and estradiol represent the four primary hormone measures of these investigations. Current data show an increase in FSH and decreases in AMH, inhibin B and estradiol over MT. AMH appears to be the first marker to change, followed by FSH and inhibin B. Estradiol declines in late MT. To date, there are no validated hormone cutpoints that predict the length of MT or FMP. There are very preliminary data on AMH as a predictor of menopause. Until further evidence identifies clinically useful hormone levels for predicting MT or FMP, diagnosis of MT and FMP should be based on clinical signs and symptoms only.

Does AMH relate to timing of menopause? Results of an Individual Patient Data meta- analysis.

CONTEXT: Anti-Müllerian hormone based (AMH) age at menopause predictions remain cumbersome due to predictive inaccuracy. OBJECTIVE: To perform an Individual Patient Data (IPD) meta-analysis, regarding AMH based menopause prediction. DATA SOURCES: A systematic literature search was performed using PubMed, Embase and Cochrane databases. STUDY SELECTION: Prospective cohort studies regarding menopause prediction using serum AMH levels were selected by consensus discussion. DATA SELECTION: Individual cases were included if experiencing a regular cycle at baseline. Exclusion criteria were hormone use and gynecological surgery. DATA SYNTHESIS: 2596 women were included, 1077 experienced menopause. A multivariable Cox regression analysis assessed time to menopause (TTM) using age and AMH. AMH predicted TTM, however, added value on top of age was poor (age alone C-statistic 84%; age + AMH HR 0.66 95% CI 0.61-0.71, C-statistic 86%). Moreover, the capacity of AMH to predict early (≤45 years) and late menopause (≥55 years) was assessed. An added effect of AMH was demonstrated for early menopause (age alone C-statistic 52%; age + AMH HR 0.33, 95% CI 0.24-0.45, C-statistic 80%). A Weibull regression model calculating individual age at menopause revealed that predictive inaccuracy remained present and increased with decreasing age at menopause. Lastly, a check of non-proportionality of the predictive effect of AMH demonstrated a reduced predictive effect with increasing age. CONCLUSION: AMH was a significant predictor of TTM and especially of time to early menopause. However, individual predictions of age at menopause demonstrated a limited precision, particularly when concerning early age at menopause, making clinical application troublesome.

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.

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.

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.

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.

Course of premenstrual syndrome symptom severity after treatment.

OBJECTIVE: Patients from a randomized, double-blind, placebo-controlled study of progesterone suppository treatment for premenstrual syndrome (PMS) were followed up to determine poststudy PMS symptom levels and medication use. METHOD: An average of 1 year after the end of the treatment study, 129 subjects were contacted for telephone interviews. All subjects met criteria for PMS before the progesterone suppository treatment, and their symptoms were confirmed by daily symptom reports throughout the study. The outcome measure at follow-up was the patient's global assessment of symptom severity, which was also rated by the subjects during the treatment study. The ratings at enrollment, end of study, and follow-up were compared. RESULTS: Only 27% of the subjects (N = 35) were taking medications for PMS at follow-up. Symptom severity at follow-up was less than at enrollment but greater than at the end of the study. CONCLUSIONS: Some of the improvement gained during treatment was maintained, but overall the subjects remained moderately symptomatic. Validation of the PMS condition, education, and support and caring may account for the symptom decreases during treatment, and the end of treatment and withdrawal of these conditions may account for the moderate return of symptoms.

Late luteal phase dysphoric disorder in 670 women evaluated for premenstrual complaints.

OBJECTIVE: The American Psychiatric Association's DSM-IV Work Group on Late Luteal Phase Dysphoric Disorder (LLPDD) reanalyzed existing data from prospective, daily symptom ratings to evaluate the DSM-III-R criteria for LLPDD. The objectives were to 1) evaluate the individual symptoms presently required for the diagnosis and other symptoms, 2) determine the proportion of treatment-seeking women who meet the LLPDD criteria, and 3) explore the association between LLPDD and other mental disorders. METHOD: Data from over 1,000 women seeking evaluation for premenstrual complaints at five U.S. sites were examined. The data from 670 of these women were sufficiently complete to warrant evaluation by four different methods of assessing symptom change. RESULTS: Depending on the assessment method used, 14% to 45% of the women met the criteria for LLPDD. The current DSM-III-R symptoms were classified as positive for 7% to 54% of the women. Each of these symptoms was significantly more common among women with LLPDD regardless of the assessment method used. Five symptoms not presently included were also significantly more common. Women who had had mental disorders in the past, but not present, showed a significantly greater, but very small, relative risk of LLPDD. CONCLUSIONS: The variability in the frequency of LLPDD diagnosis according to method of assessing symptom change underscores the need for a uniform assessment method. The five additional symptoms with frequencies comparable to those of the DSM-III-R symptoms should be studied further for possible inclusion in the criteria.

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.

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.

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.

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.

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.

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.

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.

Symptom reports from a cohort of African American and white women in the late reproductive years.

OBJECTIVE: To identify symptoms experienced in a cohort of healthy women in the late reproductive years; to compare symptom reports between African American and Caucasian women; and to determine the extent to which other factors in reproductive health, mood and behavior, lifestyle, and demographic background are associated with the reported symptoms. DESIGN: A cohort of women aged 35 to 47 years (mean age, 41 years) was identified through random digit dialing. This study is a cross-sectional analysis of data collected at enrollment from a subset of 308 women who completed daily symptom reports (DSR) for one menstrual cycle. Data were obtained in structured interviews and self-administered standard questionnaires. The associations of the study variables with symptoms as assessed by the DSR were examined using analysis of variance and general linear models. RESULTS: The African American women were significantly more likely to report in interview that they experienced menopausal symptoms (46% vs. 30%; p < 0.001) and had significantly higher ratings on the physiological symptom factor of the DSR, which included hot flashes, dizziness, poor coordination/clumsiness, urine leaks, and vaginal dryness. The DSR yielded two other factors of psychological and somatic symptoms. Race was associated only with the physiological symptom factor in the multivariable analyses. Neither race nor age were associated with psychological symptoms, which were predicted by current or past mood problems. CONCLUSIONS: Symptoms commonly associated with the menopause are experienced in the late reproductive years before observable changes in menstrual cycles. African American women reported more physiological symptoms than white women. These data provide an essential baseline for longitudinal study of symptoms associated with the ovarian decline in the perimenopausal years.

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.

Effects of medical history factors on symptom severity in women meeting criteria for premenstrual syndrome.

Medical history variables were examined to identify their effects on the severity of premenstrual syndrome (PMS) in women seeking medical treatment. Symptoms were monitored daily for two untreated cycles and two placebo-treated cycles to establish the diagnosis of PMS. Data from 60 women who reported moderate to severe premenstrual mood changes and met criteria for PMS were analyzed statistically. Step regression analysis showed that 34% of the variance in symptom severity was explained by four variables: PMS in the patient's mother, low level of exercise, younger age, and more children. These significant relationships with severity of PMS have not previously been identified and suggest a role of familial and daily stress factors in this complex syndrome.