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.

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.

Interrelationship of serum testosterone, dominance and ovarian cyclicity status in female African elephants.

The African elephant population in North American zoos is not self-sustaining, in part due to the prevalence of ovarian acyclicity. While little is known about the cause of this condition, earlier research has shown that females without cyclic corpus luteum (CL) function rank higher in the dominance hierarchy than females with cyclic CL function. The goal of this study was to measure longitudinal serum testosterone concentrations in captive female African elephants to determine if there is a relationship among serum testosterone concentrations, social dominance rank and ovarian cyclicity status. Weekly blood samples from 49 female African elephants (24 having and 25 not having cyclic CL function at 22 facilities) were collected over a 12-month period and analyzed for serum testosterone using an enzymeimmunoassay. A progesterone radioimmunoassay was used to quantify serum progestagen concentrations and categorize ovarian cyclicity status. The dominance hierarchy of individual elephants within each herd was assessed by a written temperament survey, which identified 19 dominant, 15 middle and 15 subordinate females. No clear patterns of serum testosterone secretion were observed in females with and without cyclic CL function. Furthermore, no significant relationships were found among serum testosterone concentrations, dominance rank, and ovarian cyclicity status. These data suggest that increased circulating testosterone concentrations are not associated with greater rates of ovarian acyclicity or dominance status in captive female African elephants.

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.

Prevalence of hot flushes and night sweats around the world: a systematic review.

OBJECTIVE: Many studies have evaluated the relationships between ethnicity and culture, prevalence of menopausal symptoms, and attitudes toward them, but few have assessed menopausal symptoms across cultures world-wide. This paper aims to systematically review the prevalence of hot flushes and night sweats, two prevalent symptoms of menopause, across the menopausal stages in different cultures and considers potential explanations for differences in prevalence rates. DESIGN: Sixty-six papers formed the basis for this review. Studies were organized by geographic region, and results are presented for North America, Europe, East Asia, Southeast Asia, Australia, Latin America, South Asia, Middle East, and Africa. Studies were included if they provided quantitative information on the occurrence of hot flushes. This report focuses on hot flushes and night sweats, the most common menopausal symptoms reported in epidemiologic studies. RESULTS: Studies reviewed indicate that vasomotor symptoms are highly prevalent in most societies. The prevalence of these symptoms varies widely and may be influenced by a range of factors, including climate, diet, lifestyle, women's roles, and attitudes regarding the end of reproductive life and aging. Patterns in hot flush prevalence were apparent for menopausal stages and, to a lesser degree, for regional variation. CONCLUSIONS: Caregivers should recognize that variations exist and ask patients specific questions about symptoms and their impact on usual functioning.

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.

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.

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.

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.

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.

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.

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.

Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.

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.

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.

Hot flashes in the late reproductive years: risk factors for Africa American and Caucasian women.

Hot flashes are a primary reason that midlife women seek medical care, but there is little information about the onset or the predictors of hot flashes in the years before the menopause. This study examines women's experience of hot flashes in the late reproductive years, comparing African American and Caucasian women, and identifies hormonal, behavioral, and environmental risk factors for hot flashes associated with ovarian aging. Data are from a population-based prospective cohort study of ovarian aging in women who were ages 35--47, in general good health, and had regular menstrual cycles at study enrollment. Hot flashes were assessed by subject report in a structured interview at the first follow-up period and correlated highly with previous prospective daily ratings of hot flashes (p = 0.0001). Blood samples were obtained in the first 6 days of the menstrual cycle in two consecutive cycles at enrollment and two consecutive cycles at follow-up. Predictor variables include hormone measures, structured interview, and standard questionnaire data. Thirty-one percent of the sample (n = 375) reported hot flashes (mean age 41 years). In bivariate analysis, more African American than Caucasian women reported hot flashes (38% vs. 25%, p = 0.01). Significant predictors of hot flashes in the final multivariable logistic regression model were higher follicle-stimulating hormone (FSH) levels (odds ratio [OR] 3.19), anxiety (OR 1.06), baseline menopausal symptoms (OR 4.91), alcohol use (OR 1.09), body mass index (BMI) (OR 1.04), and parity (OR 1.20). Race did not predict hot flashes after adjusting for these variables. Hot flashes commonly occur before observable menstrual irregularities in the perimenopause and are associated with both hormonal and behavioral factors. The association of hot flashes with increased body mass (BMI) challenges the current "thin" hypothesis and raises important questions about the role of BMI in hormone dynamics in the late reproductive years.

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.