Article

Changes in the sleep electroencephalogram (EEG) during male to female transgender therapy

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Abstract

Steroids, including estrogens, participate in sleep regulation. For example estrogen replacement therapy improved sleep quality in postmenopausal women. Patients, who undergo a cross-gender hormone therapy, receive high doses of estrogens. The effects of this treatment on sleep are unknown. To clarify this issue, we examined seven male to female transsexual patients (age range 31-44 years, mean±SD 35.9±4.2 years). The patients spent two nights on 2 separate occasions in our sleep laboratory. The first night of each session served for adaptation to laboratory conditions. In the second night sleep electroencephalogram [EEG] was recorded from 2300h to 0700h. The first examination was performed before and the second about 3 months after initiation of cross-gender hormone therapy with a dose of 80-100mg estrogen applied every 2 weeks. Additionally patients were treated with a starting dose of the anti-androgen cyproteronacetate of 100mg/day and after about 6 weeks with a maintenance therapy of 50mg/d in order to suppress androgenic effects. Statistical analysis was performed with the Wilcoxon rank test. Under this estrogen therapy we found a significant increase in stage 1 sleep during the whole night (at baseline [b]: 33.29±9.94min; treatment [t]: 51.57±24.26min; p<0.05) Beta activity in nonREM sleep was significantly increased (p=0.02) during hormone therapy compared to before treatment. Other sleep EEG parameters showed no significant changes. Administration of estrogen and anti-androgens in male to female transsexual patients had only a small influence on sleep EEG, with an increase in the duration of shallow sleep.

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... Similarly, studies in women report that resting-state EEG varies with estrogen level, menstrual cycle phase, and use of oral contraceptives (Brotzner et al., 2014), which influence inter-hemispheric transfer time of information (Hausmann et al., 2013). Interestingly, some changes in the oscillatory pattern of the sleep EEG have been documented in transgender persons on cross-sex hormone therapy (Kunzel et al., 2011) indicating alterations in basic neural synchronization. ...
... Moreover, the potential impact of hormone therapy was assessed by examining the influence of circulating sex hormones on resting-state activity. Based on limited available evidence (Kunzel et al., 2011;Rametti et al., 2012), we anticipated a shift toward resting-state activity consistent with their gender identity in transgender persons with treatment. ...
... This study investigated differences in local functional connectivity as measured by intensity (LFF) and synchronization of spontaneous fluctuations (ReHo) of brain activity in transgender persons. Based on limited available evidence (Kunzel et al., 2011;Rametti et al., 2012), we had hypothesized a shift toward gender identity in resting-state activity in transgender persons on crosssex hormone therapy. Three main findings pertinent to this study hypothesis emerged. ...
Article
Despite mounting evidence regarding the underlying neurobiology in transgender persons, information regarding resting-state activity, particularly after hormonal treatment, is lacking. The present study examined differences between transgender persons on long-term cross-sex hormone therapy and comparisons on two measures of local functional connectivity, intensity of spontaneous resting-state activity (low frequency fluctuations, LFF) and local synchronization of specific brain areas (regional homogeneity, ReHo). Nineteen transgender women (TW, male-to-female), 19 transgender men (TM, female-to-male), 21 non-transgender men (NTM) and 20 non-transgender women (NTW) underwent a resting-state MRI scan. The results showed differences between transgender persons and non-transgender comparisons on both LFF and ReHo measures in the frontal cortex, medial temporal lobe, and cerebellum. More interestingly, circulating androgens correlated for TM in the cerebellum and regions of the frontal cortex, an effect that was associated with treatment duration in the cerebellum. By comparison, no associations were found for TW with estrogens. These data provide first evidence for a potential masculinization of local functional connectivity in hormonally-treated transgender men.
... Others have also shown that T administration is associated with sleep apnea (84 -87); however, blocking androgen action, via flutamide administration, does not affect sleep architecture or breathing parameters in men with sleep apnea (88). Interestingly, total sleep times in males undergoing male-to-female transgender therapy, which consists of high levels of estrogens and antiandrogens remain relatively unchanged (89). Stage 1 sleep and ␤-activity during NREM sleep significantly increased in individuals during the hormone replacement period, but all other sleep parameters remained the same (89). ...
... Interestingly, total sleep times in males undergoing male-to-female transgender therapy, which consists of high levels of estrogens and antiandrogens remain relatively unchanged (89). Stage 1 sleep and ␤-activity during NREM sleep significantly increased in individuals during the hormone replacement period, but all other sleep parameters remained the same (89). Together these data suggest that the male brain in humans, as in rodents, is relatively resilient to changes in gonadal steroids. ...
Article
The paucity of clinical and preclinical studies investigating sex differences in sleep has resulted in mixed findings as to the exact nature of these differences. Although gonadal steroids are known to modulate sleep in females, less is known about males. Moreover, little evidence exists concerning the origin of these sex differences in sleep behavior. Thus, the goal of this study was to directly compare the sensitivity of sleep behavior in male and female Sprague Dawley rats to changes in the gonadal steroid milieu and to test whether the sex differences in sleep are the result of brain sexual differentiation or differences in circulating gonadal steroids. Here we report the magnitude of change in sleep behavior induced by either estradiol or T was greater in females compared with males, suggesting that sleep behavior in females is more sensitive to the suppressive effects of gonadal steroids. Furthermore, we demonstrated that the organizational effects of early gonadal steroid exposure result in male-like responsivity to gonadal steroids and directly alter the activity of the ventrolateral preoptic area (VLPO), an established sleep-promoting nucleus, in adult masculinized females. Moreover, the nonaromatizable androgen dihydrotestosterone did not suppress sleep in either males or females, suggesting that the T-mediated effect in females was due to the aromatization of T into estradiol. Together our data suggest that, like sex behavior, sex differences in sleep follow the classical organizational/activational effects of gonadal steroids.
... 29 However, another study argued that these effects are perhaps only slight, as administration of estrogen and antiandrogens in transgender women only had a small influence on sleep electroencephalogram, with an increase in the duration of shallow sleep. 30 Taken together, the existing literature hints at disparities in sleep health among sexual and gender minorities while highlighting the need for further studies, especially for TGNB individuals. This need for further research is particularly important given that a number of factors disproportionately experienced by TGNB people (e.g., experiences of discrimination, employment challenges, financial concerns, and housing instability) 31 could also play a part in sleep health. ...
... Overall, sleep health among TGNB individuals is an understudied area in need of further investigation. Because existing gender minority sleep research has been limited and has only utilized quantitative methods among transgender individuals, 29,30 there is a need to identify unanticipated factors contributing to poor sleep among not only transgender but also gender non-binary individuals through a qualitative approach. This is the first study, to the best of our knowledge, to examine the perceived role of mental health, gender identity, and coping mechanisms on the sleep quality of TGNB individuals through qualitative means. ...
Article
Background: A vast amount of research has demonstrated the numerous adverse health risks of short sleep duration and poor sleep health among the general population, and increasing studies have been conducted among lesbian, gay, and bisexual individuals. However, although poor sleep health is disproportionately experienced by sexual and gender minority populations, little research has examined sleep quality and associated factors among transgender and gender nonbinary (TGNB) individuals. This study qualitatively explored the relationship that factors such as gender identity, mental health, and substance use have with sleep health among a sample of TGNB individuals in New York City. Methods: Forty in-depth interviews were conducted among an ethnically diverse sample who identified as transgender male, transgender female, and gender nonbinary from July to August 2017. All interviews were transcribed, coded, and thematically analyzed for domains affecting overall sleep, including mental health, gender identity, and various coping mechanisms to improve overall sleep. Results: TGNB interview participants frequently described one or more problems with sleeping. Some (15%) participants suggested that mental health issues caused them to have difficulty falling asleep, but that psychiatric medication was effective in reducing mental health issues and allowing them to sleep. An even larger number (35%) told us that their gender identity negatively impacted their sleep. Specifically, participants described that the presence of breasts, breast binding, stress and anxiety about their identity, and concerns about hormonal therapy and gender-affirming surgery were all reported as contributing to sleep problems. Given these sleep challenges, it is not surprising that most (60%) participants used various strategies to cope with and manage their sleep problems, including prescription and over-the-counter sleep medications (33%) and marijuana (18%). Conclusions: Our findings document that sleep health is frequently an issue for TGNB individuals, and they also offer insight into the various ways that TGNB individuals attempt to cope with these sleep problems. Sleep health promotion interventions should be developed for TGNB people, which would promote positive mental health, reduce the risk of pharmaceutical adverse events, and help alleviate psychosocial stress in this target population.
... The available reports suggest transgender youth and adults may be at a higher risk of sleep problems as compared to other sexual minority subgroups (Dai & Hao, 2017). Only four publications specifically examined sleep in transpeople (Auer et al., 2017;Dai & Hao, 2017;Harry-Hernandez et al., 2019;Kunzel et al., 2011). Auer et al. (2017) relative to other LGB subgroups, which theoretically may be linked to these observed sleep disparities. ...
... There is evidence linking birth-assigned sex, oestrogen and other sex hormones to sleep architecture and disturbances (Mong & Cusmano, 2016). Although no sex-based differences in sleep among transgender groups have been reported (Auer et al., 2017), a small European study identified changes in non-rapid eye movement (REM) sleep stage and beta activity after oestradiol hormone treatment in transwomen (Kunzel et al., 2011). ...
Article
This article reviews a growing body of research that examines sleep among lesbian, gay, bisexual and transgender (LGBT) populations. An extensive search of the literature was conducted using multiple medical and psychological search engine platforms. In total, this search yielded 31 reports that included sleep data collected from sexual and gender minority participants. Overall, research findings are mixed and include several publications of studies conducted in the same sample. Our review suggests that sleep health among LGBT individuals may be an unmet health need. Critically, sleep disturbances affected LGBT subgroups differently based on sex/gender and diverse sexual orientations (e.g., bisexual women). Although not directly tested, evidence from parallel LGBT health research suggests that minority stress may contribute to these observed sleep disparities and will need to be directly assessed in future studies. In sum, continued investigation of sleep disparities among sexual and gender minority communities is needed, as is the inclusion of sleep health in theoretical models of LGBT health disparities. Given the importance of sleep in overall mental and physical health, addressing sleep health may serve to promote and protect healthy functioning among LGBT individuals.
... However, we have to acknowledge that the sample size of treatment-naïve patients was rather small. In general, sex hormones are known to affect sleep [46] and our group has shown that SHT in TW can affect sleep architecture [47]. The mostly studied population with regard to the effects of sex steroids on sleep are hypogonadal or postmenopausal women. ...
Article
Introduction Studies in the general population suggest that determinants of QoL are often sex-dependent. Sex-dependent analyses of QoL in transgender populations have not been performed so far. Aim To identify sex-specific and potentially modifiable determinants of QoL in transgender patients Methods In this cross-sectional multicentre study including 82 transwomen (TW) and 72 transmen (TM) at different treatment stages, we investigated potential determinants for QoL focusing on the impact of mood (BDI, STAI-X), sleep quality (PSQI), chronic pain (GPQ), body image (FBeK) and social support (SSS). Main outcome measure Health-related quality of life measured with the Short Form (36) Health Survey (SF-36). Results The age-adjusted SF-36 total score and its subscales did not significantly differ between TM and TW. Using a multivariate regression analysis approach, we identified common but also sex-dependent determinants for QoL (Adjusted R2 = 0.228; 0.650 respectively). Accounting for general characteristics such as age, BMI and treatment status, sleep quality according to the PSQI was an independent and strong determinant of QoL in both sexes (β= -0.451, p =0.003 TM;β= -0.320; p = 0.0029 TW). Chronic pain was a significant independent predictor of QoL in TM (β= -0.298; p = 0.042) but not in TW. In contrast, anxiety (β= -0.451; p<0.001) being unemployed (β= -0.206; p = 0.020) and insecurity about the own appearance (FBeK) (β= -0.261; p = 0.01) were independent predictors of QoL in TW. The rate of those reporting high sleep disturbances (PSQI�5) was high with 79.2% in TW and 81.2% in TM. Accordingly, age-adjusted QoL was also significantly lower in those reporting poor sleep in both sexes. Conclusions Sleep strongly affected QoL in both genders, while other factors, like pain and body image, seem to be gender specific in transgender individuals.
... However, indirectly, sleep quality should improve if E reduces nocturnal hot flashes. In one study of MtFs [114], E in combination with antiandrogens prolonged one of the sleep stages, but the authors did not report whether the individuals subjectively reported better sleep quality. ...
Article
Full-text available
Androgen deprivation therapy (ADT) for prostate cancer (PCa) treatment causes sexual dysfunction. We review here the effects of estrogen on the sexual performance of androgen-deprived males. The major findings are: We discuss the general benefits of estrogen therapy to quality of life of men on ADT, the potential risks of this treatment, and possible treatment regimes for estrogen therapy in males. Unless contraindicated, we propose that PCa patients on ADT would benefit from supplemental parenteral estrogen.
... For instance, one study with transgender women in Brazil found that while multiple aspects of their functioning improved following gender affirming surgery, sleep and rest remained poor [81]. In many cases, the explicit purpose of these studies was to better understand the effect of certain hormones (e.g., estrogen) on sleep health [44,82,83]. These findings generally suggest links between gender affirming medical practices and sleep health, but the samples in all of these studies were limited. ...
Chapter
While sexual and gender minority populations have been increasingly identified as an at-risk population for negative health outcomes, research has only recently begun to focus on sleep health among sexual and gender minority populations. This chapter defines terms relevant for discussing sexual and gender minority populations, focuses on the theoretical rational for understanding vulnerabilities to poor sleep outcomes among sexual and gender minority populations, reviews the existing literature examining sleep health among sexual and gender minority populations, and suggests directions for future research examining sleep health among sexual and gender minority populations. Indeed, the emerging literature suggests that important sleep disparities may occur across sexual and gender minority identity, and that these sleep disparities may have important consequences for other health outcomes. More work, however, is needed to understand why sexual and gender minority status places individuals at risk for specific sleep outcomes, and why particular sexual and gender minority subgroups may be particularly vulnerable to poor sleep health.
... Estrogen therapy in women and androgen therapy in both men and women are commonly employed for various other indications, and there are data concerning OSA in most. However, Robertson et al are breaking new ground, since the entire literature on sleep and gender reassignment appears to be: (1) sleep quality is unchanged 4 ; (2) scores on the Pittsburgh Sleep Quality Index worsen 5 ; (3) polysomnography (PSG) in MtF reveal changes in sleep architecture 6 ; and (4) one clinical practice guideline recommends monitoring for OSA in FtM individuals on hormone therapy. 7 Virtually all other reviews covering both FtM and MtF management, including one focusing on the elderly, do not mention OSA. ...
... One assessed the sleep electroencephalogram (EEG) of seven transwomen before and 3-months after initiation of hormones, finding an increase in stage 1 sleep and beta activity in non-rapid eye movement sleep after estrogen initiation. 43 One study used multicenter observational data of transgender individuals in Germany and found that sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), was associated with quality of life in both transwomen and transmen (r= −0.622, p<0.001; r= −0.530, p<0.001, respectively). Rates of poor sleep (PSQI ≥ 5) were high for transwomen (79.2%) and transmen (81.2%). ...
Article
Importance Little is known about the neurologic health needs of sexual and gender minority (SGM) individuals, and existing research indicates health care disparities for this group. Objective To describe the current state of science in SGM neurology and highlight areas of knowledge and gaps to guide future research. Evidence Review All articles published before April 12, 2020, in PubMed, Embase, Web of Science, PsycInfo, CINAHL, and BIOSIS Previews were searched using a search string encompassing SGM descriptors and neurologic disorders. A total of 8359 items were found and entered into EndNote, and 2921 duplicates were removed. A blind title and abstract review was performed followed by full-text review in duplicate, with conflicts settled through consensus, to identify 348 articles eligible for data abstraction. Articles presenting primary data about an identified adult SGM population addressing a clinical neurology topic were included. Descriptive statistics were used for abstracted variables. Findings Of 348 studies, 205 (58.9%) were case reports or series, 252 (72.4%) included sexual minority cisgender men, and 247 (70.9%) focused on HIV. An association was found between autism spectrum disorder and gender dysphoria in 9 of 16 studies (56.3%), and a higher risk of ischemic stroke in transgender women was shown in other studies. Literature in neuroinfectious disease, the most common topic, largely focused on HIV (173 of 200 studies [86.5%]). Findings in other neurologic topics were limited by lack of data. Conclusions and Relevance In this rigorous compendium of SGM neurology literature, several deficiencies were found: most studies focused on a limited breadth of neurologic pathology, included only a portion of the overall SGM community, and did not assess other aspects of sociodemographic diversity that may contribute to disparities in health care access and outcomes among SGM individuals. Expanding neurologic research to include broader representation of SGM individuals and incorporating sociodemographic factors, like race/ethnicity and socioeconomic status, are essential steps toward providing equitable neurologic care for this community.
... However, we have to acknowledge that the sample size of treatment-naïve patients was rather small. In general, sex hormones are known to affect sleep [46] and our group has shown that SHT in TW can affect sleep architecture [47]. The mostly studied population with regard to the effects of sex steroids on sleep are hypogonadal or postmenopausal women. ...
Article
Full-text available
Introduction Studies in the general population suggest that determinants of QoL are often sex-dependent. Sex-dependent analyses of QoL in transgender populations have not been performed so far. Aim To identify sex-specific and potentially modifiable determinants of QoL in transgender patients Methods In this cross-sectional multicentre study including 82 transwomen (TW) and 72 transmen (TM) at different treatment stages, we investigated potential determinants for QoL focusing on the impact of mood (BDI, STAI-X), sleep quality (PSQI), chronic pain (GPQ), body image (FBeK) and social support (SSS). Main outcome measure Health-related quality of life measured with the Short Form (36) Health Survey (SF-36). Results The age-adjusted SF-36 total score and its subscales did not significantly differ between TM and TW. Using a multivariate regression analysis approach, we identified common but also sex-dependent determinants for QoL (Adjusted R2 = 0.228; 0.650 respectively). Accounting for general characteristics such as age, BMI and treatment status, sleep quality according to the PSQI was an independent and strong determinant of QoL in both sexes (β = -0.451, p =0.003 TM; β = -0.320; p = 0.0029 TW). Chronic pain was a significant independent predictor of QoL in TM (β = -0.298; p = 0.042) but not in TW. In contrast, anxiety (β = -0.451; p< 0.001) being unemployed (β = -0.206; p = 0.020) and insecurity about the own appearance (FBeK) (β = -0.261; p = 0.01) were independent predictors of QoL in TW. The rate of those reporting high sleep disturbances (PSQI �5) was high with 79.2% in TW and 81.2% in TM. Accordingly, age-adjusted QoL was also significantly lower in those reporting poor sleep in both sexes. Conclusions Sleep strongly affected QoL in both genders, while other factors, like pain and body image, seem to be gender specific in transgender individuals.
... Additionally patients were treated with a starting dose of the anti-androgen cyproteronacetate of 100 mg/day and after about 6 weeks with a maintenance therapy of 50 mg/d in order to suppress androgenic effects. They concluded that the administration of estrogen and anti-androgens in male to female transsexual patients had only a small influence on sleep EEG, with an increase in the duration of shallow sleep [25]. ...
Article
Mannen en vrouwen verschillen van elkaar en geslachtshormonen spelen daarbij een rol; ze beïnvloeden hersenen en gedrag. De onderzoeker naar de effecten van geslachtshormonen op het brein maakt onderscheid tussen organiserende en activerende effecten. Onder organiserende effecten wordt de invloed van prenatale hormonen op de organisatie van de hersenen verstaan, terwijl de effecten van geslachtshormonen op reeds bestaande hersensystemen activerend worden genoemd. Transseksuelen ervaren een genderidentiteit die niet overeenkomt met hun geboortegeslacht. Organiserende effecten van geslachtshormonen spelen mogelijk een rol bij het ontstaan van deze discrepantie. Met behulp van beeldvormend onderzoek kunnen eventuele determinanten voor de ontwikkeling van transseksualiteit bestudeerd worden. De vraag die daarbij gesteld wordt, is of transseksuelen op verschillende uitkomstmaten meer gelijkenis vertonen met hun geboortegeslacht of met hun –wensgeslacht. Daarnaast biedt de behandeling met cross-sex-hormonen de mogelijkheid activerende effecten van geslachtshormonen op het brein te onderzoeken. In dit artikel geef ik een overzicht van recent beeldvormend onderzoek naar de effecten van geslachtshormonen bij transseksuelen.
Chapter
Sleep consists of an electrophysiological and a neuroendocrine component. Their interaction was investigated in healthy volunteers of both sexes throughout the lifespan, in patients with various disorders, after manipulation of the sleep–wake pattern and after administration of synthetic and endogenous substances acting at the central nervous system, particularly neuropeptides and neuroactive steroids. Furthermore, related animal models were studied including transgenic mice with altered endocrine activity and surgical removal of endocrine glands. A bidirectional interaction between both components was demonstrated. A specific role of certain hormones in sleep regulation was identified, particularly of growth hormone-releasing hormone und corticotropin releasing hormone.
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Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological, neurochemical, endocrinological, immunological and genetic factors are involved. The brain as both the generator and main object of sleep is obviously of particular interest, which makes a neuroscience-driven view the most promising approach to evaluate clinical implications and applications of sleep research. Polysomnography as the gold standard of sleep research, complemented by brain imaging, neuroendocrine testing, genomics and other laboratory measures can help to create composite biomarkers that allow to maximize the effects of individualized therapies while minimizing adverse effects. Here we review the current state of the neuroscience of sleep, sleep disorders and sleep therapeutics and will give some leads to promote the discovery and development of sleep medicines that are better than those we have today.
Article
Objective: To measure the attitudes and knowledge of American Academy of Neurology (AAN) member neurologists in caring for sexual and gender minority (SGM) patients (e.g., those who identify in the lesbian, gay, bisexual, transgender, queer, or questioning [LGBTQ+] spectrum) to inform future educational offerings. Methods: A questionnaire was created in an iterative process by the LGBTQ+ Survey Task Force, consisting of 21 questions examining self-reported knowledge, attitudes, and clinical preparedness in caring for SGM patients. Participants responded to each statement with a 5-point Likert scale ("strongly disagree" to "strongly agree"). The survey was distributed via electronic and conventional mail to a random, representative sample of 1,000 AAN members. Results: The response rate was 13.5% (n = 135). Most respondents (60%-66%) were aware of local and national barriers that inhibit SGM individuals from using health care services; the majority (73%-91%) felt comfortable assessing SGM patients. Over half believed sexual orientation (SO) and gender identity (GI) to be social determinants of health (61% and 57%, respectively). Yet a third would not tailor neurologic care based on a patient's SGM identity, and 43% believed that SO/GI has no bearing on the management of neurologic illness. Conclusions: Most neurologists surveyed were aware of overarching barriers to care experienced by SGM individuals; however, a minority of respondents recognized the intersection of SGM identity with neurologic health. Our results highlight awareness gaps that could be addressed via targeted educational opportunities, ensuring that neurologists provide high-quality neurologic care to patients of all sexual orientations and gender identities.
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Transgender persons identify with a gender different from the one they were assigned at birth. Although describing oneself as transgender is not a new phenomenon, media attention has lately been increasing exponentially, thanks to progressive changes in laws and change in societal attitudes. These changes also allow more people nowadays to (openly) identify as transgender and/or seek gender-affirming treatment. However, simultaneously, not much is presently understood about the underlying neurobiology, and specifically the brain structure and brain function of transgender persons. One major question in neuroimaging and neuroscience has been to determine whether, at the brain level, transgender people resemble more their gender identity, their sex assigned at birth, or have a unique neural profile. Although the evidence is presently inconsistent, it suggests that while the brain structure, at least before hormonal treatment, is more similar to sex assigned at birth, it may shift with hormonal treatment. By contrast, on “sex-stereotypical tasks,” brain function may already be more similar to gender identity in transgender persons, also before receiving gender-affirming hormone treatment. However, studies continue to be limited by small sample sizes and new initiatives are needed to further elucidate the neurobiology of a ‘brain gender’ (sex-dimorphic change according to one’s gender). Keywords: cross-sex hormones; gender; magnetic resonance imaging; neurobiology; trans
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Exogenous estradiol (E) is used occasionally to treat the side effects associated with androgen-deprivation in men, but its effects on sleep patterns have received little attention. We examined whether E modulates sleep patterns and recovery from sleep loss in castrated male rats. Adult male rats were castrated and implanted subcutaneously with Silastic tubes containing either oil (Cast+Oil) or E (Cast+E). Sham-operated male rats (Intact) were implanted with oil-filled tubes. All rats were also implanted with EEG and EMG electrodes for sleep/wake recordings. After two weeks, polysomnographic recordings were made before, during, and following 6h of sleep deprivation (SD). At baseline, the Cast+Oil group showed sleep and EEG patterns similar to those in the Intact group. Compared to these groups, the Cast+E group spent more time awake during the dark (active) phase, and showed higher EEG theta power (a measure of cortical activation) during wake and rapid eye movement (REM) sleep in both the light and dark phases. Following SD, the Cast+E group showed a larger increase from baseline in REM sleep amount, compared to the Cast+Oil group. The Cast+Oil group showed prolonged rebound in non-REM sleep and EEG delta power, and reduced REM sleep rebound, compared to the other two groups. These results indicate that E treatment in castrated male rats promotes baseline wakefulness during the active phase, and facilitates recovery of REM sleep after acute sleep loss. The possible benefit of E treatment for improving sleep quality in androgen-deprived men remains to be investigated.
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Oestrogen regulates various aspects of circadian rhythm physiology. The presence of oestrogen receptors within the suprachiasmatic nucleus (SCN), the principal circadian oscillator, indicates that some actions of oestrogen on circadian functions may be exerted at that site. The present study analysed sex differences, topographic distribution, and neurochemical phenotype of neurones expressing the and β subtypes of oestrogen receptors (ER and ERβ) in the mouse SCN. We found that relatively few neurones in the SCN are immunoreactive (IR) for ER (approximately 4.5% in females and 3% in males), but five- to six-fold more SCN neurones express ERβ. ER-IR neurones are primarily in the shell subdivision of the nucleus and show differences between the sexes, significantly greater numbers being found in females. Treatment of male or female gonadectomised mice with oestradiol benzoate for 24 h substantially reduced the number of ERβ-IR neurones, but not ER-IR neurones. Double-labelling immunocytochemical experiments to characterise the phenotype of the oestrogen-receptive neurones showed the presence of the calcium-binding proteins calretinin or calbindin D28K in approximately 12% and 10%, respectively, of ER-IR neurones. A higher proportion (approximately 38%) of ERβ-IR neurones contains calbindin D28K; a few (approximately 2%) express calretinin or vasopressin. These double-labelled cells appear primarily in the shell subdivision of the SCN. Neither vasoactive intestinal polypeptide- nor gastrin releasing peptide-immunoreactivity was observed in ER-IR neurones. These data indicate that the primary target cells for oestrogen are in the shell subdivision of the nucleus. The sexually differentiated expression and distribution of ER and ERβ in various cell populations of the SCN suggest multiple modes of oestrogen signalling within this nucleus, which may modulate circadian functions.
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Sex is an important determinant of the pathophysiology of several disorders that influence and/or impair sleep-wake regulation. To date, few studies have examined either the role of sex or the gonadal hormones on sleep and wakefulness. The difficulty in performing well-controlled clinical experiments on sex and sleep underscores the need for effective animal models to investigate the influence of the gonadal hormones on sleep-wake states. This study describes the influence of sex on sleep and wakefulness in mice, the primary mammalian genetic model for sleep analysis, and tests the hypothesis that gonadal function drives sex differences in sleep-wake states. Electroencephalogram/electromyogram sleep-wake patterns were recorded in intact and gonadectomized male and female C57BL/6J mice maintained on a 14-hour light:10-hour dark schedule. Following a 24-hour baseline recording, mice were sleep deprived during the light phase by gentle handling and given a 10-hour recovery opportunity during the immediate dark phase. Intact female mice spent more time awake than intact males during 24 hours of baseline recording at the expense of non-rapid eye movement (NREM) sleep. Though the recovery response of NREM sleep was similar between males and females, when examined in reference to baseline levels, females exhibited a more robust recovery response. Gonadectomy in males and females reduced or eliminated the majority of sex differences in sleep architecture and homeostasis. These data demonstrate that the gonadal hormones influence the amount, distribution, and intensity of sleep but do not account for all sex differences in the sleep-wake cycle.
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During the perimenopausal period, women often develop insomnia. To determine whether hormone replacement therapy (HRT) could affect sleep in menopause, the present study examined estrogen (E2) treatment in old female rats with an immune challenge. The rats received either E2 or vehicle s.c. for a week, and 5 or 50 µg/kg of lipopolysaccharide (LPS) i.p. on day 3. The old female rats showed an impaired sleep pattern, but it tended to be improved when E2 was administered. Furthermore, some non-treated rats did not respond to an LPS injection, but under E2 treatment, LPS induced significant increases in non-rapid eye movement (REM) sleep with hypothermia. The results indicate that the E2 supplement enhanced immune responses in old female rats, suggesting a possible mechanism of how HRT helps postmenopausal insomnia.
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Evidence for the role of androgens in the male aggressive and sexual behavior is reviewed. Medroxyprogesterone acetate (MPA; Provera, Upjohn) has a marked antiandrogen property; it is effective in lowering the testosterone level and controlling certain otherwise intractable sex deviations. The finding in 6 patients treated for sex deviation are summarized. The effects of MPA in the treatment of 11 temporal lobe epileptics and 5 other patients with severe angry-aggressive behavior disorder are reported. Most temporal lobe epileptics responded well to MPA. Weight gain and earlier sleep were consistent side effects. The values of plasma testosterone, serum luteinizing hormone, and urinary 17-ketosteroids were decreased by the treatment. Four patients were XYY individuals with lack of control over their sexual-aggressive or angry-aggressive impulses.
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A double-blind controlled study of the effect of piperazine oestrone sulphate on sleep, depression, anxiety, and hot flushes was performed in 34 perimenopausal women. Half of the patients were given six weeks' placebo followed by eight weeks' oestrogen, and half remained on placebo throughout. Sleep was recorded electrophysiologically every week, and mood and anxiety were rated daily by means of visual analogue scales. Hot flushes were counted daily. Observer rating scales of anxiety and depression were complete at intervals. During the first month of active treatment the amount of intervening wakefulness in the first six hours of sleep decreased significantly more in the oestrone group than in those on placebo. Between the baseline period and the second treatment month the oestrone group showed a significantly greater decrease in the total amount of intervening wakefulness and in the frequency of awakenings. Their total amount of rapid eye movement sleep increased. Mood and anxiety improved and the number of hot flushes decreased to a similar degree in both groups. Although oestrogen did reduce the number of episodes of wakefulness in perimenopausal women complaining of insomnia, its effects on their psychological symptoms were little different to those of placebo.
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Ontogenetically the brain is female and, regardless of genetic sex, would remain so if not exposed to gonadal hormones at a critical stage in its development. Research in animals in which this exposure occurs after birth is providing evidence that the differentiation of the neural substrates that regulate pituitary activity and sexual behavior is localized to a particular hypothalamic region.
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This study reports the short term effects in five pedophiles of the antiandrogenic drug cyproterone acetate (CPA) on nocturnal penile tumescence (NPT); penile responses to erotic stimuli in the laboratory; and sex hormones (testosterone, LH, FSH and prolactin). During the administration of CPA, NPT, laboratory arousal and hormone measures (except prolactin) all decreased. Waking laboratory measures were influenced less and were more variable (one subject showed greater arousal) than NPT measures. The changes in NPT closely paralleled the reduction in testosterone. The results are discussed with reference to the known psycho-neuroendocrinology of sleeping and waking erections.
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An ovulatory menstrual cycle is characterized by fluctuating levels of progesterone. Progesterone, a gonadal hormone known for its soporific and thermogenic effects, is present in negligible levels prior to ovulation and in high levels after ovulation. To describe and compare sleep patterns in relation to ovulatory cycles and premenstrual mood state, sleep was monitored in healthy women at two phases of the menstrual cycle. Results indicated that rapid-eye-movement (REM) latency was significantly shorter during the postovulatory (luteal) phase compared to the preovulatory (follicular) phase, but there was no significant difference in latency to sleep onset or the percentage of REM sleep. While there were no menstrual cycle phase differences in the percentages of various sleep stages, the women with negative affect symptoms during the premenstruum demonstrated significantly less delta sleep during both menstrual cycle phases in comparison with the asymptomatic subjects.
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Three-dimensional images of nuclei facilitate morphological comparisons between differing animal groups. As revealed by computer-assisted techniques, the greater volume in male rats of the sexually dimorphic nucleus of the preoptic area was not proportional in all directions. The nucleus was more elongated in males than females, indicating a sex-dependent shape. This study also indicated that the volume of the suprachiasmatic nucleus was larger in males.
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To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest the menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy.
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Cyclic changes in hormones, body temperature, and metabolic rate characterize the menstrual cycle. To investigate whether these changes are associated with changes in sleep and the sleep electroencephalogram (EEG), a total of 138 sleep episodes from 9 women with no premenstrual syndrome symptoms were recorded every second night throughout one ovulatory menstrual cycle and analyzed in relation to menstrual phase. Ovulation and menstrual cycle stage were confirmed by measurements of temperature, urinary LH, and midluteal plasma levels of estrogen and progesterone. No significant variation across the menstrual cycle was observed for subjective ratings of sleep quality and mood as well as for objective measures of total sleep time, sleep efficiency, sleep latency, rapid eye movement sleep latency, and slow wave sleep. In nonrapid eye movement sleep, EEG power density in the 14.25-15.0 hertz band, which corresponds to the upper frequency range of the sleep spindles, exhibited a large variation across the menstrual cycle, with a maximum in the luteal phase. The data show that in healthy young women, sleep spindle frequency activity varies in parallel with core body temperature, whereas homeostatic sleep regulatory mechanisms, as indexed by the time course of EEG slow wave activity are not substantially affected by the menstrual cycle.
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Previously, we reported that paradoxical sleep (PS) is sexually dimorphic in mice and rats. Since some early studies indicate that PS is suppressed during proestrus night, it is important to know whether the estrus cycle and accompanying circulating ovarian hormones could explain the sexual dimorphism of PS. To examine this, sleep patterns of male rats were compared with those of normal cycling female rats and ovariectomized females in a 12:12 h light/dark cycle. Slow wave sleep and total sleep time are indistinguishable between the males, cycling females and ovariectomized females. However, normal males display significantly more PS than cycling females during both daytime and nighttime (average of all estrus stages). On the other hand, while ovariectomy has no visible effect on daytime sleep--the sexual dimorphism of PS is unchanged by ovariectomy--during nighttime, ovariectomy produces a selective increase of PS, eliminating the sex difference during the night. In sum, normal cycling females show no change in daytime sleep patterns across the estrus cycle, but have significantly less PS during proestrus nights than during metestrus and diestrus nights. The results indicate that the sex difference in nighttime PS is due to the suppression of PS by ovarian hormones during proestrus and, to a less extent, estrus nights. The sex difference in daytime PS, on the other hand, appears to be independent of circulating ovarian hormones.
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Centrally administered vasoactive intestinal polypeptide (VIP) promotes rapid eye movement (REM) sleep in rats, rabbits, and cats. We studied the effect of 4 x 10 micrograms VIP (expt 1, n = 7) and 4 x 50 micrograms VIP (expt 2, n = 10) administered hourly as intravenous boluses between 2200 and 0100 on sleep electroencephalogram and secretion of plasma adreno corticotropic hormone, cortisol, growth hormone, and prolactin in humans. In experiment 2, the sleep cycles were decelerated during the first three cycles because of increased duration of both REM and non-REM sleep periods, and there was a tendency to increased REM-to-non-REM ratios. With a low VIP dose, prolactin levels were decreased during the whole night, whereas, with a high dose, they were increased during the first half of the night. In experiment 2, the cortisol nadir was advanced, after midnight the serum cortisol levels were enhanced, and the growth hormone peak was blunted. It appears that VIP may have a phase-advancing effect on sleep cycles and cortisol secretion, possibly through actions that involve the suprachiasmatic nucleus.
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The objective of this pilot study was to evaluate the effects of conjugated estrogens on the rates of cyclic alternating patterns of sleep (CAPS) and nocturnal hot flushes in symptomatic postmenopausal women. Seven postmenopausal or posthysterectomy women aged 45 to 60 years with nocturnal diaphoresis and/or hot flushes participated in this study. The study was conducted with a single-masked design using a matching placebo. The placebo baseline was followed by a 4-week, single-masked treatment of conjugated estrogens 0.625 mg taken 4 hours before bedtime. Each patient's sleep was monitored in the laboratory for 3 consecutive nights during placebo baseline and again for 3 consecutive nights after an at-home period of at least 24 days of estrogen replacement therapy. Estrogen therapy resulted in a statistically significant decrease in the overall number of hot flushes and the number of hot hot flushes associated with awakenings, as well as improvement in sleep efficiency and a reduction in the rate of CAPS. These data confirm earlier well-established reports that estrogens reduce the frequency of hot flushes and suggest that the frequency of nocturnal arousals decreases and sleep quality improves in conjunction with a reduction in the rate of CAPS.
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The differential effects of ageing on polysomnographic and EEG spectral characteristics of sleep were explored in men and women between the ages of 20 and 40. Men and women in their twenties were found to have similar percentages of slow-wave sleep (SWS) (% Stage 3 and 4) and mean EEG slow wave activity (quantified by spectral analysis). Significant reductions in the percentage of SWS and mean slow wave activity over the night occurred in men during their thirties but not in the women. This suggests that gender difference in SWS may emerge between age 30 and 40 in young adults. Men in this sample were also found to have significant increases in Stage 2 sleep, and decreases in REM sleep time, REM activity, REM density and REM intensity. No significant effects of age were found for women in any visually scored sleep variables. Both men and women had age related reductions in spectral power in the spindle frequencies. Taken together, these findings suggest that the sleep of men and women over age 20-40 may age differently.
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To investigate whether sleep homeostasis in the female rat is modulated by the estrous cycle, the vigilance states, EEG power spectra and cortical temperature (TCRT) were assessed on the basis of 4-day continuous recordings. A regulatory response was elicited by 6-h sleep deprivation (SD) during the proestrous (PRO) and the estrous (EST) day and compared to the baseline recordings. The vigilance states varied across the estrous cycle. In the PRO dark period the amount of sleep was reduced. The decrease in rapid-eye-movement (REM) sleep was already evident towards the end of the preceding light period, and an increased fragmentation of sleep was present throughout PRO. Compared to the other days of the estrous cycle, slow-wave activity (SWA; EEG power density 0.75-4.75 Hz) in nonREM (NREM) sleep was lower in PRO at the end of the light period and in the beginning of the dark period. High-frequency activity (HFA; EEG power density 10.25-25.0 Hz) was increased in the dark period of PRO. The SD performed during the first 6 h of the light period of PRO and EST enhanced SWA in NREM sleep and reduced sleep fragmentation during the subsequent 6 h. The extent and time course of the response to SD did not differ between the two phases of the estrous cycle. It is concluded that despite the marked baseline variations of the vigilance states and the EEG, homeostatic regulation is little affected by the estrous cycle.
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The present article reviews direct and indirect evidence of the effects of sex steroids on different aspects of sleep. It begins with a review of what is known about the effects of steroid hormones on sleep and on central nervous system processes related to sleep, such as the GABA-ergic system, in animals. It continues with a review of the effects of exogenous hormones on human sleep and a review of studies comparing sleep during hypogonadal states secondary to surgical or natural menopause. The article proceeds to review the data on the effects of the menstrual cycle on both subjective and objective aspects of sleep and circadian temperature and melatonin rhythms in samples of healthy women, women with premenstrual dysphoric disorder, and women with primary insomnia. Then, the article reviews gender differences in sleep during depression and raises the possibility that sex steroids moderate these differences. Finally, the article concludes with a discussion of the implications of the data reviewed for basic clinical, and methodological aspects of sleep research.
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Sleep-endocrine regulation in humans involves high activity of the somatotropic axis at the beginning of the night and an increase in the hypothalamic-pituitary-adrenocortical (HPA) system during the night. Gender differences were examined with regard to sleep-endocrine regulation in young healthy controls (10 men, 9 women). The sleep EEG was recorded (23:00-07:00 h) and plasma samples were collected and analyzed for GH, cortisol and ACTH at 20-min intervals. Cortisol secretion was significantly higher in females during the first half of the night (F = 9.9, p < 0.05), while ACTH was not different. In women, sleep-EEG analysis showed less slow wave sleep (SWS) during the second half of the night (F = 4.5, p < 0.05) and a significantly greater decrease in SWS and delta activity from the first to the second half of the night (F = 3.7 and 7.4, respectively, p < 0.05). Sigma activity increased during the night in women only (F = 3.7, p < 0.05). Our data are compatible with the hypothesis that in women compared to men activity of hypothalamic CRH neurons and central CRH release is greater, but is not reflected by greater HPA activity.
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We performed an examination of the effects of estrogen replacement on the sleep electroencephalogram in postmenopausal women. A sleep electroencephalogram was recorded in 11 postmenopausal women with and without estrogen administered by skin patch (50 microg of estradiol per day). Estrogen enhanced rapid-eye-movement sleep (50 +/- 4 vs 39 +/- 5 minutes, P <.05) and reduced time awake (12 +/- 5 vs 20 +/- 6 minutes, P <.05) during the first 2 sleep cycles. The normal decrease in slow-wave sleep and delta activity from the first to the second cycle (in percentage from the first cycle) was restored by estrogen (-56% +/- 9% vs -5% +/- 14% and -20% +/- 6% vs -2% +/- 5%; P <.05, respectively). Sigma electroencephalographic activity was increased by estrogen from the first to the second half of the night but decreased during baseline. Estrogen treatment after menopause can help to restore the normal sleep electroencephalogram pattern, which in turn might contribute to improved cognitive functioning.
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In patients with depression, enhanced secretion of ACTH and cortisol, a reduction in slow wave sleep (SWS) and a blunted nocturnal growth hormone (GH) surge have been described and attributed, at least partly, to an elevation of corticotropin-releasing hormone (CRH), hence a shift in the ratio between growth hormone-releasing hormone (GHRH) and CRH. We investigated the effects of pulsatile administration of GHRH (4x50 microgram, at hourly intervals between 2200 and 0100 h) on the sleep EEG (2300-0700 h) in patients with depression (16 females, 19 males, age range 19-76 years) and matched controls (20 females, 20 males). In patients compared with controls, NREM sleep and in particular stage 2 sleep was greatly decreased at baseline. GHRH treatment enhanced NREM sleep, and in particular stage 2 sleep in men, regardless of diagnosis, while decreasing it in women (F=6.0 and 7.1, p<0.05). In controls, aging was associated with a decrease in NREM sleep, including both SWS and stage 2 sleep (r= -0.45 r= -0.39, p<0.05), while in patients only SWS declined with age (r= -0.49, p<0.05). The significant decrease in NREM sleep including stage 2 sleep in patients with depression and elderly control subjects is compatible with the suggested role of sleep continuity and stage 2 sleep in cognitive functioning. GHRH promoted NREM sleep, stage 2 sleep and sleep continuity and might prove beneficial for improvement of cognitive function, at least in men. These data support the hypothesis that female gender, aging and depression are associated with a shift in the GHRH/CRH ratio towards CRH.
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EMD 68843 (EMD) has properties of a serotonin (5-HT)-reuptake inhibitor and a partial 5-HT1A agonist in one molecule in order to combine antidepressive and anxiolytic properties. We investigated the effects of EMD on the sleep EEG in order to characterize how the complex interaction between these two properties influences the sleep EEG. We performed a randomized crossover study in ten young normal male controls (20-30 years), receiving a single dose of 20 mg EMD or placebo orally at 2100 hours. Sleep EEG was recorded from 2300 to 0700 hours. After EMD, rapid eye movement (REM) sleep was nearly totally abolished. In the course of the night other effects on the sleep EEG occurred in distinct intervals. Slow wave sleep and EEG delta power increased in the first and third one-third of the night, whereas wakefulness was enhanced in the second and third one-third of the night. The sleep EEG effects of EMD fit with its pharmacological profile, which might lead to adaptive changes suggested to characterize an antidepressive substance.
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Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double-blind, placebo-controlled, comparative, randomized, three-arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2-month open-label phase in which all patients received Climodien 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well-being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea-hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug-induced changes being superior to those induced by placebo. In the open-label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved subjective sleep quality, the apnea and apnea-hypopnea indices of insomniac postmenopausal syndrome patients, while it only marginally improved variables concerning objective sleep and awakening quality.
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Sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), is more common in men than in women. However, menopause increases the risk for development of OSA. Administration of estrogen and progesterone to postmenopausal women with OSA decreases apnea and hypopnea during sleep. Because beneficial changes can be observed soon after administration of a short course of hormones, we hypothesized that suppression of these hormones would rapidly result in the development of SDB. Production of sex hormones was suppressed with daily administration of leuprolide acetate (LA), a gonadotropin-releasing hormone analogue, for 5 weeks in women who were participating in a study on pharmacologically induced menopause and physiology. The subjects underwent polysomnographic evaluation at baseline and after 5 weeks of LA administration. In the 12 healthy women aged 18 to 34 years who participated in the study, sleep architecture and respiration were normal at baseline. After LA administration, the subjects stopped their menses, and their plasma concentrations of l7beta-estradiol (preadministration, mean [SD] 33.9 [9.0] pg/mL; post administration, 10.2 [3.4] pg/mL) and progesterone (preadministration, 0.48 [0.05] ng/mL; post administration, 0.40 [0.06] ng/mL) reached menopausal levels. Sex hormone deficiency was associated with climacteric vasomotor symptoms such as hot flashes and sweating. Sleep latencies and architecture did not change significantly with LA administration. The participants subjectively noticed some increased snoring that was not confirmed by polysomnogram. Specifically, there was no change in arousal index and no evidence for sleep fragmentation to suggest the presence of increased upper-airway resistance during sleep. The apnea-hypopnea index, 0.07 (0.02) to 0.22 (0.11) events per hour of sleep, did not change with sex hormone deficiency. In this study, sex hormone deficiency in young women resulted in climacteric symptoms and cessation of menses, and was not associated with sleep fragmentation or clinically significant SDB.
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Cerebral cortical activity in healthy, full-term human neonates (10 boys and 10 girls) was evaluated using spectral estimation of electroencephalogram frequency content with new equipment and analysis technique allowing the assessment of the lowest frequencies (i.e. infraslow waves). The activity was analysed under quiet sleep and active wakefulness taking sex into consideration. During sleep, the mean amount of infraslow activity was 27% larger in boys, whereas during wakefulness the average amount of higher frequencies was 17% larger in girls. Both these differences indicate an earlier maturation of cortical function in girls than in boys.
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In children, objective data carried out from sleep EEG monitoring are scarce. Furthermore, results associating the hypothalamic-pituitary-adrenocortical (HPA)-activity with sleep EEG measurements in children are missing. Therefore, our study aimed to investigate in preschool-children the association between sleep patterns and endocrine activity. Furthermore, children's behavioral/emotional difficulties and competences were assessed in order to correlate psychological strain with sleep measures. Sixty-seven kindergarten children (35 boys and 32 girls) aged 5.34 underwent EEG-monitoring for one night. For baseline HPA-activity assessment, saliva samples were collected immediately after awakening, whereas saliva samples before, while and after a psychological challenge were used to assess the HPA-activity under stress conditions. Compared to girls, boys showed significantly more REM sleep time. After cluster analysis, children labeled as 'poor' sleepers (n=27; 40,30%) showed significantly increased morning cortisol values, as compared to 'good' sleepers (n=22; 32,83%). Furthermore, increased cortisol AUC values under stress conditions were significantly associated with an elevated number of awakenings after sleep onset, and more sleep time in stages 1 and 2. In addition, an increased sleep efficiency was significantly correlated with self-reported emotional/behavioral difficulties, i.e. with low degrees of impulsivity (r=-.31; p<.05) and lower degrees of social inhibition and peer victimiziation (r=-.26, p<.05). Our results underlined that already in preschool years, associations between objectively examined unfavorable sleep patterns, increased HPA-system activity and more difficult behavioral and psychosocial dimensions may be observed.
Sleep in female mice: a strain comparison across the estrous cycle Sleep pat-terns related to menstrual cycle phase and premenstrual affec-tive symptoms
  • M Koehl
  • S E Battle
  • F W Turek
Koehl, M., Battle, S.E., Turek, F.W., 2003. Sleep in female mice: a strain comparison across the estrous cycle. Sleep 26, 267—272. Lee, K.A., Shaver, J.F., Giblin, E.C., Woods, N.F., 1990. Sleep pat-terns related to menstrual cycle phase and premenstrual affec-tive symptoms. Sleep 13, 403—409.