Publications

Although most women report vasomotor symptoms (hot flashes, night sweats) during midlife, their etiology and risk factors are incompletely understood. Body fat is positively associated with vasomotor symptoms cross-sectionally, but the longitudinal relation between changes in body fat and vasomotor symptoms is uncharacterized. The study aim was to examine whether gains in body fat were related to vasomotor symptom reporting over time. Measures of bioelectrical impedance for body fat, reproductive hormones, and reported vasomotor symptoms were assessed annually over 4 years from 2002 to 2006 among 1,659 women aged 47-59 years participating in the Study of Women's Health Across the Nation. Body fat change was examined in relation to vasomotor symptoms by using generalized estimating equations. Body fat gains were associated with greater odds of reporting hot flashes in models adjusted for age, site, race/ethnicity, education, smoking, parity, anxiety, and menopausal status (relative to stable body fat, gain: odds ratio = 1.23, 95% confidence interval: 1.02, 1.48; P = 0.03; loss: odds ratio = 1.07, 95% confidence interval: 0.89, 1.29; P = 0.45). Findings persisted controlling for estradiol, the free estradiol index, or follicle-stimulating hormone concentrations. The relations between body fat changes and night sweats were not statistically significant. Body fat gains are associated with greater hot flash reporting during the menopausal transition.

OBJECTIVE: Depression occurs more commonly during the menopausal transition in women with vasomotor symptoms (VMS) than in those without, but most women with VMS do not develop depression. It has been hypothesized that VMS are associated with depression because VMS lead to repeated awakenings, which impair daytime well-being. We aimed to determine if objectively measured sleep and perceived sleep quality are worse in depressed women with VMS than in nondepressed women with VMS.

METHODS: Objectively and subjectively measured sleep parameters were compared between 52 depressed women with VMS and 51 nondepressed controls with VMS. Actigraphic measures of objective sleep conducted in the home environment and subjective measures of sleep quality (Pittsburgh Sleep Questionnaire Index) were compared using linear regression models.

RESULTS: On objective assessments, depressed women with VMS spent less time in bed (by 64.8 min; P < 0.001) and had shorter total sleep time (by 47.7 min; P = 0.008), longer sleep-onset latency (by 13.8 min; P = 0.03), and lower sleep efficiency (by 3.2 percentage points; P = 0.09), but did not awaken more or spend more time awake after sleep onset than nondepressed controls with VMS. Depressed women also reported worse sleep quality (mean Pittsburgh Sleep Questionnaire Index 12.0 vs 8.3; P < 0.001). Adjustment for VMS frequency and important demographic characteristics did not alter these associations.

CONCLUSIONS: Sleep quality and selected parameters of objectively measured sleep, but not sleep interruption, are worse in depressed than in nondepressed women with VMS. The type of sleep disturbance seen in depressed participants was not consistent with the etiology of depression secondary to VMS-associated awakenings.

BACKGROUND: Delayed Sleep Phase Syndrome (DSPS) arises from biological clock desynchrony and accounts for 10% of chronic insomnia patients. Currently DSPS is diagnosed based on sleep/wake cycle disruptions rather than examining the underlying biological clock alterations. The objective of the study was to determine the sensitivity and specificity of the Dim Light Melatonin Onset (DLMO) Test in diagnosing DSPS in a clinical setting.

METHODS: Fifty-six patients (mean age 28 years) symptomatic of DSPS participated in the study. Following an initial assessment of DSPS using sleep diaries, participants underwent two consecutive nights of polysomnography (PSG), with an imposed sleep period on the second night to demonstrate the delay in the timing of habitual sleep period and to thereby confirm DSPS. Circadian phase delays were also measured using melatonin secretion profiles, and the efficacy of diagnosing DSPS using DLMO was compared to using sleep diaries and PSG. Melatonin secretion was assayed for each individual by ELISA using saliva samples.

RESULTS: Main outcome measures included the time of melatonin secretion onset, clinical sensitivity and specificity of the DLMO test. The time of melatonin secretion onset was significantly delayed in DSPS patients. Clinical sensitivity and specificity of the DLMO test in diagnosing DSPS were 90.3% and 84.0%, respectively.

CONCLUSIONS: The DLMO test is an accurate tool for differentiating between sleep disorder patients with or without underlying circadian rhythm disruption. It is effective for phase typing DSPS patients in a clinical setting.

Epilepsy, bipolar disorder, and migraines are common disorders that are often associated with disturbances in menstrual function in adolescent girls. Women with untreated epilepsy are more likely to have irregular menstrual cycles than are nonepileptic controls, indicating that the disease itself plays a role in the etiology of these reproductive abnormalities. In addition, many girls with these disorders require chronic maintenance treatment with agents that may perturb the hypothalamic-pituitary-ovarian axis. Valproate is a highly effective antiepileptic drug used widely to treat epilepsy, bipolar disorder, and migraines. Valproate induces features of the polycystic ovary syndrome (PCOS) in approximately 7% of women. Girls with epilepsy, and possibly bipolar disorder, appear particularly susceptible to developing PCOS features on valproate, perhaps on account of the relative immaturity of their hypothalamic-pituitary-ovarian axes. Antipsychotics are highly effective drugs used widely to treat adolescents with bipolar disorder, psychotic disorders, and behavioral disturbances. Some, but not all of the antipsychotic, induce hyperprolactinemia, which may result in oligo- or amenorrhea. Prolonged amenorrhea in association with hyperprolactinemia incurs significant risks for bone health in adolescent girls. Because of the potential reproductive health risks associated with use of specific antiepileptic drugs and selective antipsychotics, these agents are vital treatments for adolescents with severe illnesses. Use of these agents should be considered and weighed against the risk of using alternative agents, which have their own side effects, or not treating these serious neurologic and psychiatric disorders.

OBJECTIVE: Most menopausal women report vasomotor symptoms (hot flashes, night sweats). However, not all women with vasomotor symptoms, including frequent symptoms, are bothered by them. The primary aim was to identify correlates of vasomotor symptom bother beyond symptom frequency.

DESIGN: The Study of Women's Health Across the Nation participants reporting vasomotor symptoms at annual visit 7 comprised the sample (N = 1,042). Assessments included hot flash and night sweats frequency (number per week) and bother (1, not at all- 4, very much). Negative affect (index of depressive symptoms, anxiety, perceived stress, negative mood), symptom sensitivity, sleep problems, and vasomotor symptom duration (number of years) were examined cross-sectionally in relation to bother in ordinal logistic regression models with symptom frequency and covariates. Hot flashes and night sweats were considered separately.

RESULTS: In multivariable models controlling for hot flash frequency, negative affect (odds ratio [OR] = 1.27, 95% CI: 1.08-1.51), symptom sensitivity (OR = 1.18, 95% CI: 1.03-1.37), sleep problems (OR = 1.38, 95% CI: 1.04-1.85), poorer health (OR = 1.24, 95% CI: 1.03-1.48), duration of hot flashes (OR = 1.14, 95% CI: 1.06-1.23), younger age (OR = 0.94, 95% CI: 0.89-0.99), and African American race (vs white, OR = 1.59, 95% CI: 1.12-2.26) were associated with hot flash bother. After controlling for night sweats frequency and covariates, sleep problems (OR = 1.84, 95% CI:1.33-2.55) and night sweats duration (OR = 1.10, 95% CI: 1.02-1.20) were associated with night sweats bother.

CONCLUSIONS: Beyond frequency, factors associated with bothersome hot flashes include mood, symptom sensitivity, symptom duration, sleep problems, age, and race. Correlates of bothersome night sweats include sleep problems and symptom duration. In addition to reducing frequency, interventions for vasomotor symptoms might consider addressing modifiable factors related to symptom bother.

OBJECTIVE: Concerns about hormone therapy have led many menopausal women to discontinue hormone treatment. This study examines the efficacy of paroxetine controlled-release versus placebo for the treatment of women with vasomotor symptoms after discontinuing hormone therapy.

METHODS: Sixty-four perimenopausal and postmenopausal women without depression or anxiety but reporting vasomotor symptoms after hormone discontinuation entered a 1-week, single-blind, placebo lead-in phase, followed by a 6-week, flexible-dose, double-blind phase with paroxetine controlled-release (12.5-25 mg/d) or placebo. The primary outcome measure was a change in vasomotor symptoms. Other measures included changes in depressive symptoms and overall functioning.

RESULTS: Fifty subjects (paroxetine controlled-release, n=27; placebo, n=23) completed the study. At study entry, subjects had an average of 17 hot flushes per week, had used hormones for more than 5 years (median=66 months, interquartile range=18-120 months), and had discontinued treatment for less than 1 year (median=5 months, interquartile range=2-10 months) before study enrollment. Paroxetine controlled-release was more efficacious than placebo for the alleviation of vasomotor symptoms (mean reduction of 6.1 vs 2.8 hot flashes per week, respectively; P=.03). Depressive symptoms also improved with paroxetine (mean reduction of 3.6 points vs 0.4 points in Montgomery-Asberg Depression Rating Scale total scores; P=.01).

CONCLUSION: Treatment with paroxetine controlled-release may constitute an efficacious alternative for symptomatic perimenopausal and postmenopausal women after menopausal hormone discontinuation.

The decreased melatonin production in humans and animals caused by environmental lighting, especially short wavelength lighting (between 470 and 525 nm) has been shown to be associated with an increased risk of cancer. The purpose of this study was to investigate whether blocking light in this wavelength range under bright light may prevent the suppression of melatonin, which could help to prevent cancer. Optical filter lenses were designed, allowing selective exclusion of all wavelengths below 530 nm. Salivary melatonin levels were measured under dim light (<5 lux), bright light (800 lux) and filtered light (800 lux) at hourly intervals between 2000 and 0800 h in 11 healthy young male participants (mean age 23.5+/-1.5 years). The measurements were taken during three nonconsecutive nights over a 2-week period. The Dim Light Melatonin Onset test was used as a marker of circadian phase. Nine of the 11 participants demonstrated preserved melatonin levels in filtered light similar to their dim light secretion profile. With filtered light, the participants had a mean relative amount of melatonin of 91.2 (P>0.05 between dim light and experimental condition). Unfiltered bright light drastically suppressed melatonin production with a mean relative amount of melatonin of 25.4 (P<0.05 between dim light and experimental condition). Preventing melatonin deficiencies using lenses that block light of low wavelength from reaching the retina presents a cost-effective, practical solution to the problem of increased malignancy rates in shift workers.

OBJECTIVE: Despite the efficacy of antidepres-sants, depression can break through premenstrually. Oral contraceptive pills (OCPs) stabilize reproductive hormones and treat premenstrual dysphoric disorder. Management of depression that breaks through premenstrually has not been studied.

METHOD: Women taking antidepressants with successfully treated depression, except during the late luteal phase (Montgomery-Asberg Depression Rating Scale [MADRS] score >or= 15) and high late-luteal phase (Daily Rating of Severity of Problems scores) were randomly assigned to open-label ethinyl estradiol (EE) 30 mug/day plus drospirenone 3 mg/day (EE/DRSP) for 21 days and double-blinded treatment with EE 30 mug/day or placebo for days 22 through 28 of 2 cycles. Participants were recruited from community and psychiatry outpatient clinics and enrolled into this study in 2004-2005.

RESULTS: Of 25 subjects who received EE/DRSP (N = 12 with EE and N = 13 with placebo), 21 completed treatment. For study completers, premenstrual MADRS (p = .0019) and Daily Rating of Severity of Problems scores (p = .0001) improved significantly in both groups. Outcome did not differ between groups.

CONCLUSION: This study provides preliminary evidence that addition of EE/DRSP (+/- EE) to antidepressants may treat premenstrual breakthrough of depression. Stabilizing hormone levels with EE/DRSP may provide an important therapeutic option for women taking antidepressants whose symptoms break through premenstrually.

CONTEXT: Postpartum psychosis occurs in 1 to 2 cases per 1000 live births. Most studies have not distinguished postpartum psychosis from bipolar disorder or the proportion of the incidence attributable to prepregnancy psychiatric morbidity.

OBJECTIVE: To determine the incidence of postpartum psychosis and bipolar disorder attributable to previous psychiatric hospitalization.

DESIGN: Population-based study using linked registry data to determine postpartum onset of psychotic and bipolar episodes within 90 days after the first birth, by women with and without prepregnancy or prenatal psychiatric hospitalization. We assessed the type, number, and recency of previous hospitalizations on the incidence of hospitalization for postpartum psychotic and bipolar episodes.

SETTING: Nationwide Swedish Hospital Discharge and Medical Birth registers.

PATIENTS: Swedish women delivering a first live infant between January 1, 1987, and December 31, 2001.

MAIN OUTCOME MEASURES: Postpartum hospitalization for psychosis or bipolar disorder.

RESULTS: The cumulative incidences for postpartum psychotic and bipolar episodes (adjusted for age at first birth) were 0.07% and 0.03%, respectively. The incidence of psychiatric hospitalizations for postpartum psychotic or bipolar episodes among women without previous psychiatric hospitalizations was 0.04% and 0.01% of first births, respectively; for women with any psychiatric hospitalization before delivery, the incidence was 9.24% and 4.48%, respectively. For postpartum psychotic and bipolar episodes, the risk increased significantly with the recency of prepregnancy hospitalizations, number of previous hospitalizations, and length of most recent hospitalization. More than 40% of women hospitalized during the prenatal period for a bipolar or a psychotic condition were hospitalized again during the postpartum period. Approximately 90% of all postpartum psychotic and bipolar episodes occurred within the first 4 weeks after delivery.

CONCLUSIONS: Almost 10% of women hospitalized for psychiatric morbidity before delivery develop postpartum psychosis after their first birth. This underscores the need for obstetricians to assess history of psychiatric symptoms and, with pediatric and psychiatric colleagues, to optimize the treatment of mothers with psychiatric diagnoses through childbirth.

This article reviews the literature on the use of antidepressants for symptoms associated with perimenopause. In some perimenopausal women, mood instability, insomnia and vasomotor symptoms cause significant distress. Studies of antidepressants for perimenopausal symptoms are summarized, with a focus on perimenopausal depression and vasomotor symptoms. Antidepressants should be considered as an alternative to hormone therapy for perimenopausal depression and hot flashes, especially when hormone therapy is contraindicated, or as an augmentation strategy for women who are only partially responsive to hormone therapy.