Publications

Vasomotor symptoms (VMS), or hot flashes and night sweats, are often considered the cardinal symptoms of menopause. SWAN, one of the largest and most ethnically diverse longitudinal studies of the menopausal transition, has allowed unique insights into VMS. Specifically, SWAN has helped yield important information about the prevalence of, racial/ethnic differences in, risk factors for, and implications of VMS for midlife women's mental and physical health. We have reviewed the literature on VMS, emphasizing findings that have emerged from SWAN and new areas of inquiry in the area of VMS.

BACKGROUND: Depression is a common problem in patients with Delayed Sleep Phase Syndrome (DSPS). This study used a randomized, double-blind, crossover, placebo-controlled approach to test the hypothesis that exogenous melatonin (5mg) can attenuate depressive symptomatology in DSPS patients.

METHODS: Twenty patients with an established diagnosis of DSPS were dichotomized into DSPS with depressive symptoms (Group I; n=8) and without depressive symptoms (Group II; n=12) based on structured clinical interviews and a score greater than 17 on Center for Epidemiologic Studies Depression Scale (CES-D). Both groups received melatonin and placebo treatment for 4 weeks with a 1-week washout period in between. Participants underwent a clinical interview and psychometric evaluation to assess depression, and overnight polysomnographic sleep studies were carried out at baseline and at the end of melatonin and placebo treatments. Furthermore, melatonin secretion rhythm as a circadian phase marker was assessed by measuring urinary 6-sulphatoxymelatonin levels.

RESULTS: Melatonin treatment significantly reduced depression scores in the depressed patients as measured by the CES-D and Hamilton Depression Rating Scale–17. Melatonin treatment improved sleep continuity in both groups compared to placebo and baseline conditions. Group I individuals showed marked alterations in melatonin rhythms compared to Group II individuals.

CONCLUSION: Exogenous melatonin treatment may be an effective treatment modality for individuals with circadian rhythm sleep disorders and associated comorbid depressive symptomatology.

OBJECTIVE: Menopause-associated insomnia is commonly associated with other symptoms (hot flashes, depression, anxiety). Given frequent symptom cooccurrence, therapies targeting sleep may provide an important approach to treatment during midlife.

STUDY DESIGN: Peri/postmenopausal women (40-65 years old) with sleep-onset and/or sleep-maintenance insomnia cooccurring with hot flashes and depressive and/or anxiety symptoms were randomized to eszopiclone 3 mg orally or placebo in a double-blinded, crossover 11 week trial. Changes in the Insomnia Severity Index (ISI) scale and secondary outcomes (diary-based sleep parameters, depression/anxiety, hot flashes, quality of life) were analyzed using repeated-measure linear models.

RESULTS: Of 59 women, 46 (78%) completed the study. Eszopiclone reduced ISI scores by 8.7 + or - 1.4 more points than placebo (P < .0001). Eszopiclone improved (P < .05) all sleep parameters, depressive symptoms, anxiety symptoms, quality of life, and nighttime but not daytime hot flashes.

CONCLUSION: Eszopiclone treats insomnia and cooccurring menopause-related symptoms. Our results provide evidence that hypnotic therapies may improve multiple domains of well-being during midlife.

Melatonin secretion is synchronized to the sleep/wake cycle and has been suggested to have somnogenic properties. Sleep/wake cycle disruption and alterations in the secretary pattern of melatonin is present in various psychiatric disorders. The objective of this study was to investigate the sleep architecture and the presence of depression in individuals with low endogenous melatonin levels. The study included 16 participants (mean age 30.3 +/- 14.9 years). The first night of testing included psychiatric evaluation followed by melatonin secretion profile evaluation by Dim Light Melatonin Onset test and then standard montage polysomnographic testing. On the second night, only polysomnographic testing was carried out with an imposed sleep period of 8 h. Low endogenous melatonin secretors (LEMS) showed no discernible peaks in melatonin secretion compared to normal secretors (controls). LEMS demonstrated significant alterations in rapid eye movement sleep but not in non-rapid eye movement sleep along with poor sleep initiation and quality compared to controls. 55.6% of the low melatonin secretors group presented with subsyndromal depression. Melatonin has significant bearing on sleep architecture and a lack of melatonin may desynchronize endogenous rhythms allowing subsyndromal depression to manifest.

BACKGROUND: Menopausal symptoms can be assessed by several tools, and can be influenced by various socio-demographic factors.

OBJECTIVES: To determine the commonly reported menopausal symptoms among Sarawakian women using a modified Menopause Rating Scale (MRS).

METHODS: By using modified MRS questionnaire, 356 Sarawakian women aged 40-65 years were interview to document of 11 symptoms (divided into somatic, psychological and urogenital domain) commonly associated with menopause.

RESULTS: The mean age of menopause was 51.3 years (range 47 - 56 years). The most prevalent symptoms reported were joint and muscular discomfort (80.1%); physical and mental exhaustion (67.1%); and sleeping problems (52.2%). Followed by symptoms of hot flushes and sweating (41.6%); irritability (37.9%); dryness of vagina (37.9%); anxiety (36.5%); depressive mood (32.6%). Other complaints noted were sexual problem (30.9%); bladder problem (13.8%) and heart discomfort (18.3%). Perimenopausal women (n = 141) experienced higher prevalence of somatic and psychological symptoms compared to premenopausal (n = 82) and postmenopausal (n = 133) women. However urogenital symptoms mostly occur in the postmenopausal group of women.

CONCLUSIONS: The prevalence of menopausal symptoms using modified MRS in this study correspond to other studies on Asian women however the prevalence of classical menopausal symptoms of hot flushes, sweating was lower compared to studies on Caucasian women.

Sleep disturbances in midlife women are common and have been associated with the menopause transition itself, symptoms of hot flashes, anxiety and depressive disorders, aging, primary sleep disorders (i.e., obstructive sleep apnea, periodic limb movement disorder), comorbid medical conditions and medications, as well as with psychosocial and behavioral factors. Because there are several common sources of sleep problems in midlife women, the cause of an individual woman's sleep disturbance may be multifactorial. Effective behavioral and pharmacological therapies are available to treat sleep disturbances of different etiologies. This review provides an overview of different types of sleep disturbance occurring in midlife women and presents data supporting the use of hormone therapy, hypnotic agents, and behavioral strategies to treat sleep problems in this population. The review aims to equip clinicians evaluating menopause-age women with the knowledge and evaluation tools to diagnose, engage sleep experts where appropriate, and treat sleep disturbance in this population. Sleep disorders in midlife women should be treated because substantial improvements in quality of life and health outcomes are achievable.

OBJECTIVE: Hot flashes are a major quality-of-life issue for breast cancer survivors, interrupting sleep, reducing quality of life, and diminishing treatment adherence to adjuvant endocrine therapies. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are used widely but are only partially effective for hot flashes. Alternative strategies are needed. We hypothesized that augmentation of SSRI/SNRI therapy with hypnotic agents would optimize hot flash therapy by improving sleep and quality of life.

METHODS: Women with breast cancer or at high risk for developing the disease who had hot flashes in association with nocturnal awakenings were randomized to double-blinded treatment with zolpidem 10 mg or placebo for 5 weeks. SSRI/SNRI nonusers (81%) started venlafaxine XR 75 mg/day concurrently, whereas SSRI/SNRI users continued that therapy. We compared the proportion of responders, defined as study completers with improved subjective sleep quality (Pittsburgh Sleep Quality Index) and/or objectively assessed wake time after sleep onset on actigraphy, between groups.

RESULTS: Of 53 women (aged 51 ± 8 y) randomized to zolpidem augmentation (n = 25) or placebo augmentation (n = 28), 38 completed the protocol (57% on placebo, 88% on zolpidem). More women augmented with zolpidem than placebo were responders on the sleep outcome (40% vs 14%; P = 0.035). Quality of life improved more with zolpidem than with placebo (P = 0.01). Treatment effects on hot flashes and mood did not differ between groups.

CONCLUSIONS: Augmentation of SSRI/SNRI with zolpidem improves sleep and quality of life in breast cancer survivors with hot flashes and associated sleep disturbance. Adding a hypnotic agent to an SSRI/SNRI helps women to sleep through nighttime hot flashes. Treatments targeting sleep may be an important supplemental strategy to optimize well-being.

The lifetime risk for major depression in women is well known to be twice the risk in men and is especially high during the reproductive years between menarche and menopause. A subset of reproductive-age women experience depressive episodes that are triggered by hormonal fluctuations. Such "reproductive depressions" involve episodes of depression that occur specifically during the premenstrual, postpartum, and perimenopausal phases in women. These reproductive subtypes of depression can be conceptualized as a specific biological response to the effects of hormonal fluctuations in the brain. The different types of reproductive depressions are associated with each other, have unique risk factors that are distinct from nonreproductive depression episodes, and respond to both hormonal and nonhormonal interventions. This review uses a PubMed search of relevant literature to discuss clinical, animal, and genetic evidence for reproductive depression as a specific subtype of major depression. Unique treatment options, such as hormonal interventions, are also discussed, and hypotheses regarding the underlying biology of reproductive depression-including interactions between the serotonergic system and estrogen, as well as specific effects on neurosteroids-are explored. This review will provide evidence supporting reproductive depression as a distinct clinical entity with specific treatment approaches and a unique biology that is separate from nonreproductive depression.