Insomnia Abstracts 1 Hormones

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Effects of sex steroids on sleep.
            (Empson and Purdie, 1999) Download
Sex steroid secretions are generally synchronous with the circadian rhythm and sleep, and there is evidence that prolactin secretion is sleep-dependent. Polysomnographically assessed changes in sleep during the menstrual cycle are characterized by increased EEG activity in the 14-15-Hz (sleep spindle) range in the luteal phase accompanying an increase in core temperature. There are no other consistent changes in sleep architecture associated with the menstrual cycle. The hot sweats which disturb sleep in menopausal women are attributable to oestrogen deficiency and are reduced by oestrogen replacement therapy. Although it is often assumed that the psychological changes during the menopause are attributable to chronic sleep disturbance caused by hot sweats, the evidence for this is uncertain. Sex steroids have also been shown to have a role in the aetiology of obstructive sleep apnoea and its treatment. It is clear that the sex steroids are all implicated in sleep and thermoregulatory processes, although we cannot as yet define their precise roles.

Insomnia Symptoms, Objective Sleep Duration, and Hypothalamic-Pituitary-Adrenal Activity in Children
            (Fernandez-Mendoza et al., 2014) Download
BACKGROUND: Insomnia symptoms are the most common parent-reported sleep complaints in children; however, little is known about the pathophysiology of childhood insomnia symptoms, including their association with hypothalamic-pituitary-adrenal (HPA) axis activation. The objective of this study is to examine the association between parent-reported insomnia symptoms, objective short sleep duration, and cortisol levels in a population-based sample of school-aged children. DESIGN: A sample of 327 children from the Penn State Child Cohort (5-12 years old) underwent 9-hour overnight polysomnography and provided evening and morning saliva samples to assay for cortisol. Objective short sleep duration was defined based on the median total sleep time (i.e., < 7.7h). Parent-reported insomnia symptoms of difficulty initiating and/or maintaining sleep were ascertained with the Pediatric Behavior Scale. RESULTS: Children with parent-reported insomnia symptoms and objective short sleep duration showed significantly increased evening (0.33 +/- 0.03 mug/dL) and morning (1.38 +/- 0.08 mug/dL) cortisol levels. In contrast, children with parent-reported insomnia symptoms and "normal" sleep duration showed similar evening and morning cortisol levels (0.23 +/- 0.03 mug/dL and 1.13 +/- 0.08 mug/dL) compared to controls with "normal" (0.28 +/- 0.02 mug/dL and 1.10 +/- 0.04 mug/dL) or short (0.28 +/- 0.02 mug/dL and 1.13 +/- 0.04 mug/dL) sleep duration. CONCLUSIONS: Our findings suggest that insomnia symptoms with short sleep duration in children may be related to 24-hour basal or responsive physiological hyperarousal. Future studies should explore the association of insomnia symptoms with short sleep duration with physical and mental health morbidity. This article is protected by copyright. All rights reserved.

The association of exercise with sleep, sex steroids, sexual activities and aging in Asian men
            (Goh and Tong, 2009) Download
Background: This study sought to examine the association between the type and intensity of exercise as a lifestyle habit with sex steroid hormones, sexual activities, sleep parameters and aging in men. Methods: Exercise scores, sleep duration and sexual activities were evaluated through a self-administered questionnaire, while testosterone (T), sex hormone binding globulin (SHBG), estradiol (E2) and dehydroepiandrosterone sulfate (DHEAS) levels were measured using established immunoassay methods. Bioavailable T was calculated using Vermeulen’s formula. Results: Moderately intense exercise as a lifestyle habit was significantly associated with higher coital frequency, higher sex hormone concentrations, and more men engaging in masturbation, but fewer men

Sleep, sex steroid hormones, sexual activities, and aging in Asian men.
            (Goh and Tong, 2010) Download
This was a cross-sectional study to examine the different associations of age and sleep duration with sex steroid hormones and sexual activities in 531 Asian Chinese men aged between 29 and 72 years old. Sleep duration and sexual activities were evaluated through a self-administered questionnaire, and total testosterone (T), sex hormone-binding globulin (SHBG), estradiol (E2), and dehydroepiandrosterone sulfate (DHEAS) were measured by established immunoassay methods in a single blood sample collected between 8:00 and 11:00 am. Bioavailable T (BioT) was calculated using the Vermeulen formula. Age was a major determinant of sleep, sex steroid hormones, and sexual activities in men. BioT, DHEAS, coital frequency, masturbation, and sleep duration declined with age. On the other hand, SHBG and E2 increased with age. Sleep duration, independently of age, aerobic exercise, and body fat, was positively associated with T and BioT, but not with DHEAS, E2, or any of the sexual activities studied. Men who masturbated had higher levels of both T and BioT. DHEAS was significantly associated with coital frequency and desire for sex. The present study showed that besides age, sleep duration was associated with androgen concentrations in men, and thus the evaluation of sleep hygiene may be beneficial in the management of men with low androgen concentrations. DHEAS may be independently associated with some sexual functions in men.

Effect of Endogenous Sex Steroids on Sleep Habits in Male Medical Students
            (Khan et al., 2015) Download
Background: To study the relationship of age and sleep habits with total testosterone levels in younger age group. Methods: This randomized cross sectional study was conducted on 66 male medical students. Anthropometric characteristics were measured and a standardized questionnaire proforma was completed regarding sleep habits. Serum total testosterone level was analyzed by Enzyme Linked Fluorescent Assay technique. Data was analyzed using student‘t’ test and Pearson bivariate correlation. Results: Total testosterone was positively associated with age (r=0.102, p=0.018) and total sleep duration (r=0.753, p=0.000). Total sleep duration showed a positive association with age (r=0.270, p=0.000).Academic performance showed a positive relation with sleep duration (r=0.623, p=0.000) and sleeping time (r=0.188, p=0.000). Conclusion: Low concentration of total testosterone was associated with less healthy sleep. Total sleep duration and timing of sleep were related with academic performance.

Sleep in menopause: differential effects of two forms of hormone replacement therapy.
            (Montplaisir et al., 2001) Download
OBJECTIVES:  The aim of the present study was to evaluate differences between two regimens of estrogen/progestogen replacement therapy on nocturnal sleep in postmenopausal women. METHODS:  Twenty-one (21) postmenopausal women were studied. They were randomized into two treatment groups: (1) estrogen (Premarin 0.625 mg) and medroxyprogesterone acetate (Provera 5 mg) (n = 11) or (2) estrogen (Premarin 0.625 mg) and oral micronized progesterone (Prometrium 200 mg) (n = 10). Postmenopausal women were recorded for two consecutive nights in the sleep laboratory at baseline and again after 6 months of treatment in a randomized trial. The women also had to fill out evening and morning sleep and vigilance questionnaires for 7 days before baseline recordings and for 23 days before month 6 recordings. RESULTS:  Sleep efficiency was found to be significantly improved in the micronized progesterone group. It increased by 8% (p = 0.014) with no such increase observed in the medroxyprogesterone acetate group. Time spent awake after sleep onset was also significantly improved in the micronized progesterone group but not in the medroxyprogesterone acetate group. On the other hand, menopausal symptoms and subjective measures of sleep (questionnaires) improved in both groups after treatment. CONCLUSION:  This study suggests that medroxyprogesterone acetate and micronized progesterone are both effective for treating menopausal symptoms but that the latter might better improve the quality of sleep in postmenopausal women taking estrogen.


 

Sleep and Women's Health.
            (Nowakowski et al., 2013) Download
Sex differences in sleep begin at a very early age and women report poorer sleep quality and have higher risk for insomnia than do men. Sleep may be affected by variation in reproductive hormones, stress, depression, aging, life/role transitions, and other factors. The menstrual cycle is associated with changes in circadian rhythms and sleep architecture. Menstruating women (even without significant menstrual-related complaints) often report poorer sleep quality and greater sleep disturbance during the premenstrual week compared to other times of her menstrual cycle. In addition to these sleep disturbances, women with severe premenstrual syndrome often report more disturbing dreams, sleepiness, fatigue, decreased alertness and concentration during the premenstrual phase. Sleep disturbances are also commonly reported during pregnancy and increase in frequency and duration as the pregnancy progresses. The precipitous decline in hormones and unpredictable sleep patterns of the newborn contribute to and/or exacerbate poor sleep and daytime sleepiness during the early postpartum period. Insomnia is also among the most common health complaints that are reported by perimenopausal women. Women are particularly vulnerable to developing insomnia disorder during these times of reproductive hormonal change. In this review, we present a discussion on the most relevant and recent publications on sleep across the woman's lifespan, including changes in sleep related to menstruation, pregnancy, postpartum, and the menopausal transition. Treatment for sleep disturbances and insomnia disorder and special considerations for treating women will also be discussed.

When does estrogen replacement therapy improve sleep quality
            (Polo-Kantola et al., 1998) Download
OBJECTIVE:  Our purpose was to evaluate the effect of estrogen replacement therapy on sleep complaints by postmenopausal women and to assess the predictive factors involved. STUDY DESIGN:  Sixty-three postmenopausal women entered a 7-month prospective, randomized, double-blind, crossover study consisting of two 3-month treatments with estrogen and placebo with a 1-month washout period between. Eight Visual Analogic Scale statements about different sleep complaints, the Basic Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression Inventory, and serum estradiol and follicle-stimulating hormone level controls were the main outcome measures. RESULTS:  Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p < 0.001). The subjects were less tired in the mornings and in the daytime (p < 0.001) when taking estrogen replacement therapy. Estrogen-induced sleep improvement was associated with alleviation of vasomotor symptoms (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range 0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia predicted only one estrogen-induced sleep improvement effect: the more the subjects experienced insomnia, the better the estrogen replacement therapy facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep improvement was also reported by the 15 climacterically asymptomatic subjects. In these subjects initial insomnia scores strongly predicted estrogen-induced sleep improvement (r range 0.50 to 0.75). CONCLUSIONS:  Estrogen replacement therapy significantly diminished sleep complaints among postmenopausal women. Alleviation of climacteric symptoms was the most important predictive factor for the beneficial effect of estrogen replacement therapy on sleep complaints. The use of estrogen replacement therapy in women without self-reported climacteric symptoms could also be considered because women do not always recognize their climacteric symptoms or they ignore them.

Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women.
            (Polo-Kantola et al., 1999) Download
OBJECTIVE:  To evaluate the effect of estrogen replacement therapy on sleep architecture, arousals, and body movements. DESIGN:  A 7-month, prospective, randomized, double-blind, placebo-controlled crossover trial. SETTING:  Departments of obstetrics and gynecology and a university sleep center in Turku, Finland. PATIENT(S):  Seventy-one postmenopausal women, 4 of whom were excluded and 5 of whom withdrew from the study; the final study group consisted of 62 women. INTERVENTION(S):  Two periods of treatment with either estrogen or placebo. MAIN OUTCOME MEASURE(S):  Polysomnography for measurement of sleep and arousals and a static charge-sensitive bed for monitoring of movements and breathing. Self-reports of climacteric symptoms for 14 days. RESULT(S):  Estrogen effectively alleviated hot flashes, sweating, sleep complaints, and headaches. Estrogen decreased the total frequency of movement arousals but increased alpha-arousals, especially during light non-rapid eye movement sleep (stage 1). Sleep latency, distribution of sleep stages, sleep efficiency, and total sleep time were similar during treatment with estrogen and placebo. Changes in serum E2 concentrations correlated with neither subjective nor objective sleep quality. CONCLUSION(S):  Estrogen replacement therapy improves objective sleep quality by alleviating the frequency of nocturnal movement arousals. It also reduces climacteric symptoms, especially vasomotor symptoms. Estrogen replacement therapy does not seem to have any effect on sleep architecture.


 

The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study.
            (Ruiz and Daniels, 2014) Download
Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy; however, clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking. The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor, mood, and other quality-of-life symptoms in post-menopausal women. This was a prospective, observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1, 2003 and October 1, 2010 in a community pharmacy. Data collection included patient demographics, comorbidities, hormone regimens, and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of-life symptoms as absent, mild, moderate, or severe at baseline, at one to three months follow-up, and three to six months follow-up. Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test. A total of 200 patients met study criteria; 160 received topical bioidentical hormone replacement therapy, and 40 received sublingual bioidentical hormone replacement therapy. Most sublingually-treated patients (70%) received an estrogen combination and 100% received progesterone. Nearly half (43%) of the topically treated patients received an estrogen combination (43%) and 99% received progesterone. The percentage of sublingually treated patients reporting "moderate" or "severe" symptoms was significantly reduced at one to three months follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night sweats (38%, P < 0.01), irritability (36%, P = 0.01), anxiety (42%, P < 0.01), emotional lability (38%, P < 0.01), sleep disturbances (35%, P < 0.01), memory loss (35%, P = 0.04), fatigue (33%, P = 0.04), and libido (26%, P = 0.03). Similar reductions were seen at three to six months follow-up compared to baseline. Patients who received topical therapy did not experience significant symptom reductions at one to three months follow-up; however, significant symptom reduction was seen at three to six months for the following: emotional lability (31%, P < 0.01), irritability (29%, P = 0.02), and night sweats (20%, P = 0.04). Compounded sublingual bioidentical hormone replacement therapy is effective in reducing vasomotor, mood, and quality-of-life symptoms experienced in post-menopausal women. Topical therapy does not appear to improve symptoms as extensively or rapidly as sublingual therapy.


 

Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double-blind, placebo-controlled investigations on the effects of a novel estrogen-progestogen combination (Climodien, Lafamme) versus estrogen alone.
            (Saletu-Zyhlarz et al., 2003) Download
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.


 

A randomized, controlled pilot trial of hormone therapy for menopausal insomnia
            (Silva et al., 2011)  Download
Insomnia is a frequent climacteric symptom. This pilot, double-blind, randomized placebo-controlled trial compared estradiol associated with trimegestone or placebo in 12 women with perimenopausal insomnia. The Pittsburgh Sleep Quality Index (PSQI) was administered, and polysomnography was performed at baseline and after 28 days. Sleep efficiency and median score of the PSQI improved significantly in the hormone therapy group (HT) (p=0.041 and p=0.027, respectively) and not in placebo group. Perimenopausal insomnia improved after short-term HT.

The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.
            (Stephenson et al., 2013) Download
Menopause impacts 25 million women world wide each year, and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030. Menopause has been associated with symptoms of hot flashes, night sweats, dysphoric mood, sleep disturbance, and conditions of cardiovascular disease, depression, osteoporosis, osteoarthritis, depression, dementia, and frailty. Conventional hormone replacement therapy results in increased thrombotic events, and an increased risk of breast cancer and dementia as evidenced in large prospective clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women's Health Initiative. A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors. Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile, yet long-term studies of this treatment model are lacking. The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol, estradiol, progesterone, DHEA, and testosterone on cardiovascular biomarkers, hemostatic, inflammatory, immune signaling factors; quality-of-life measures; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care. A prospective, cohort, closed-label study received approval from the Human Subjects Committee. Recruitment from outpatient clinics at an academic medical center and the community at large resulted in three hundred women giving signed consent. Seventy-five women who met strict inclusion/exclusion criteria were enrolled. Baseline hormone evaluation was performed along with baseline experimental measures. Following this, women received compounded transdermal bioidentical hormone therapy of BiEst (80%Estriol/20%Estradiol), and/or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women. The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic, ischemic, or neuronal injury. Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of androgens of DHEA and Testosterone if indicated. Experimental subjects were monitored for 36 months. Baseline, 2-month, and annual values were obtained for: blood pressure, body mass index, fasting glucose, Homeostasis Metabolic Assessment of Insulin Resistance (HOMA-IR), fasting triglycerides, total Factor VII, Factor VIII, fibrinogen, Antithrombin III, Plasminogen Activator Inhibitor1(PAL-1), C-reactive protein (CRP), Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), Tumor Necrosis Factor-alpha (TNF), Insulin-like Growth Factor (IGF-1), and sex steroid levels. Psychosocial measures included: Greene Climacteric Scale, Visual Analog Pain Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Holmes Rahe Stress Scale, Job Strain, and Home Strain. Health outcome measures included the number of prescribed medications used, number of co-morbidities, and endometrial thickness in postmenopausal women with intact uteri. Subjects receiving compounded transdermal bioidentical hormone therapy showed significant favorable changes in: Greene Climacteric Scale scores, Hamilton Anxiety Scale, Hamilton Depression Scale, Visual Analog Pain Scale, fasting glucose, fasting triglycerides, MMP-9, C-reactive Protein, fibrinogen, Factor VII, Factor VIII, Insulin-Like Growth Factor 1, and health outcomes of co-morbidities and a number of prescribed medications. Antithrombin III levels were significantly decreased at 36 months. All other measures did not exhibit significant effects. Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women. Cardiovascular biomarkers, inflammatory factors, immune signaling factors, and health outcomes were favorably impacted, despite very high life stress, and home and work strain in study subjects. The therapy did not adversely alter the net prothrombotic potential, and there were no associated adverse events. This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in populations with high perceived stress and a history of stressful life events prior to, or during the menopausal transition.

Effects of estrogen therapy on postmenopausal sleep quality regardless of vasomotor symptoms: a randomized trial.
            (Tansupswatdikul et al., 2015) Download
OBJECTIVE:  To determine the effects of estrogen therapy on objective sleep quality in insomniac postmenopausal women without severe vasomotor symptoms and/or recognized hot flushes during sleep. Study design Randomized, double-blinded, placebo-controlled trial, parallel design (ClinicalTrials.gov Identifier: NCT01501422). METHODS:  Forty insomniac postmenopausal women with no severe vasomotor symptoms and/or recognized hot flushes during sleep were randomized into 2 months' treatment with a 50-μg transdermal estradiol patch or placebo. Sleep quality was determined objectively with wrist actigraphy. Sleep efficiency, total sleep time, wake up after sleep onset and number of awakenings were compared before and after treatment. The Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) questionnaires were used for subjective sleep quality assessment before and after treatment. RESULTS:  The study showed no significant difference in sleep efficiency improvement between women having estrogen alone or placebo (median 85.7% vs. 85.2%, respectively, p = 0.71). Similarly, sleep quality scores assessed by ISI and ESS were not significantly different. CONCLUSION:  Estrogen therapy in insomniac postmenopausal women without severe vasomotor symptoms and/or recognized hot flushes during sleep was not found to improve sleep efficiency during the study period.

Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications.
            (Vgontzas et al., 2001) Download
Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-h ACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pM, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 nM, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss, which is usually associated with no change or decrease in cortisol secretion or a circadian disturbance. Chronic activation of the hypothalamic-pituitary-adrenal axis in insomnia suggests that insomniacs are at risk not only for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeutic goal in insomnia should be to decrease the overall level of physiologic and emotional arousal, and not just to improve the nighttime sleep.

Efficacy and tolerability of compounded bioidentical hormone replacement therapy.
            (Vigesaa et al., 2004) Download
The primary purpose of this six-week survey study of women currently taking compounded bioidentical hormone replacement therapy was to determine if compounded bioidentical hormone replacement therapy relieves symptoms of menopause and is well tolerated. The secondary purpose of this study was to compare the symptom relief and tolerability of compounded bioidentical hormone replacement therapy to previously used commercially available products. All strengths and dosage forms of bi-estrogen and tri-estrogen were included, whether used alone or in combination with progesterone, dehydroepiandrosterone or testosterone. The survey instrument consisted of nineteen questions and evaluated the outcomes and side effects for commercially available versus compounded bioidentical hormones. A total of 160 surveys was distributed and 78 were completed. Overall, 57.7% of the women surveyed reported fewer side effects and 71.8% of the women had better relief of menopausal symptoms when using bioidentical hormone replacement therapy. The occurrence and severity of menopausal symptoms decreased significantly after beginning bioidentical hormone replacement therapy. Before treatment, moderate-to-severe symptoms of hot flashes, night sweats, sleep problems, dry skin/hair, vaginal dryness, foggy thinking, mood swings and decrease in sex drive were reported in 52 % to 70% of the women. After initiating treatment the moderate-to-severe range of symptoms dropped to between 4% and 20%. The most commonly reported side effects with bioidentical hormone replacement therapy were weight gain (37.2%), breast tenderness (19.2%) and bloating (23.1%). Weight gain (56.2%), breast tenderness (54.5%), bloating (40%) and mood swings (36.4%) were most commonly seen with commercially available products. Bioidentical hormone replacement relieved the symptoms of menopause and was well tolerated.

Alterations in hypothalamus-pituitary-adrenal/thyroid axes and gonadotropin-releasing hormone in the patients with primary insomnia: a clinical research
            (Xia et al., 2013) Download
The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes' hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman's correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the "stepwise" method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.

A community-based study on the association between insomnia and hypothalamic-pituitary-adrenal axis: Sex and pubertal influences
            (Zhang et al., 2014) Download
CONTEXT: The association between insomnia disorder and the hypothalamic-pituitary-adrenal (HPA) axis needs to be explored in both adults and adolescents. OBJECTIVES: Our objective was to investigate the associations of the HPA axis (via serial salivary cortisol) with insomnia disorder and subjective and objective sleep quality in a community-based study. DESIGN AND SETTING: This was a community-based case-control family study. PARTICIPANTS: Participants included 205 adolescents (14.2 +/- 2.8 years old, 51.7% females, and 57 with insomnia) and 244 adults (46.4 +/- 4.1 years old, 52.8% females, and 69 with insomnia). MAIN OUTCOME MEASURES: Outcome measures included a diagnostic interview for assessment of insomnia disorder, 3-day actigraphy and sleep diary, and serial salivary cortisol measurement. RESULTS: Adults with insomnia had a significantly greater cortisol awakening response (CAR) reference to increase (CARi) but a comparable CAR reference to ground and a comparable cortisol level during afternoon and evening when compared with noninsomniac adults. The association between insomnia disorder and larger CARi was also found in adolescents at late/post puberty but not in pre/early pubertal adolescents. There was an interaction effect between sex and insomnia disorder on CARi level with adult females having larger CARi than adult males. Among subjects with insomnia disorder, those with lower subjective sleep efficiency had higher cortisol levels in the late evening (10:00 pm) in both adults and adolescents. CONCLUSIONS: Our study suggests that a series of insomniac indices at both syndromal and symptomatic levels including clinical diagnosis and poor sleep quality are associated with dysfunction of the HPA axis. The association between insomnia and increased CARi emerges at late puberty, and the sex difference in this association occurs in adulthood but not in adolescence.

 


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