Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.     

Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting.

In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months'' hormone treatment followed by three months'' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.     

Physiological aspects of menopausal hot flush.

Eighteen hot flushes experimenced by eight menopausal women were studied and compared with the effects of warming in six premenopausal women. The hot flushes were associated with an acute rise in skin temperature, peripheral vasodilatation, a transient increase in heart rate, fluctuations in the electrocardiographic (ECG) baseline, and a pronounced decrease in skin resistence. Although premenopausal women had greater maximum increases in skin temperature and peripheral vasodilatation, they showed a much smaller decrease in skin resistance and no changes in heart rate or ECG baseline. These findings suggest that the onset of the hot flush is associated with a sudden and transient increase in sympathetic drive. Further investigations may lead to the development of a more specific alternative to oestrogen for relieving menopausal hot flushes.     

Effect of oral gamolenic acid from evening primrose oil on menopausal flushing.

OBJECTIVE--To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN--Randomised, double blind, placebo controlled study. SETTING--District general hospital and teaching hospital. SUBJECTS--56 menopausal women suffering hot flushes at least three times a day. INTERVENTION--Four capsules twice a day of 500 mg evening primrose oil with 10 mg natural vitamin E or 500 mg liquid paraffin for six months. MAIN OUTCOME MEASURES--Change in the number of hot flushes or sweating episodes a month. RESULTS--56 diaries were analysed, 28 from women taking gamolenic acid and 28 from those taking placebo. Only 18 women given gamolenic acid and 17 given placebo completed the trial. The mean (SE) improvement in the number of flushes in the last available treatment cycle compared with the control cycle was 1.9 (0.4) (P < 0.001) for daytime flushes and 0.7 (0.3) (P < 0.05) for night time flushes in women taking placebo; the corresponding values for women taking gamolenic acid were 0.5 (0.4) and 0.5 (0.3). In women taking gamolenic acid the only significant improvement was a reduction in the maximum number of night time flushes (1.4 (0.6); P < 0.05). CONCLUSION--Gamolenic acid offers no benefit over placebo in treating menopausal flushing.     

Progesterone and the premenstrual syndrome: a double blind crossover trial.

A double blind, randomised, crossover trial of oral micronised progesterone (two months) and placebo (two months) was conducted to determine whether progesterone alleviated premenstrual complaints. Twenty three women were interviewed premenstrually before treatment and in each month of treatment. They completed Moos''s menstrual distress questionnaire, Beck et al''s depression inventory, Spielberger et al''s state anxiety inventory, the mood adjective checklist, and a daily symptom record. Analyses of data found an overall beneficial effect of being treated for all variables except restlessness, positive moods, and interest in sex. Maximum improvement occurred in the first month of treatment with progesterone. Nevertheless, an appreciably beneficial effect of progesterone over placebo for mood and some physical symptoms was identifiable after both one and two months of treatment. Further studies are needed to determine the optimum duration of treatment.     

焦虑、抑郁及社会支持情况对短暂性脑缺血发作患者睡眠的影响

目的:讨论焦虑、抑郁和社会支持情况对短暂性脑缺血患者睡眠的影响情况。方法:将2012年1月至2014年1月于我院治疗的164名短暂性脑缺血患者为研究对象,采用社会支持评定量表SSRS、自评焦虑量表SAS、匹兹堡睡眠指数PSQI及自评抑郁量表SDS评估病人的抑郁、焦虑与社会支持情况对患者的影响,并分析相关性。在对患者进行一个月的治疗过程中,对伴有焦虑及抑郁症状的患者给予盐酸舍曲林片,并考察药物治疗对患者睡眠质量的影响情况。结果:164名患者中出现焦虑的几率为37.4%,出现抑郁的几率为18.9%,二者同时出现的几率为12.8%,存在睡眠障碍的患者约占68.4%,匹兹堡睡眠指数与自评焦虑量指数、自评抑郁量指数与社会支持评定量的主观支持与患者对支持和利用得分均存在相关性(r=0.66、0.53、-0.39,-0.40,P0.05),且差异有统计学意义。对采集的数据进行多因素回归分析,结果显示,焦虑、抑郁、社会主观支持和患者对支持的利用度是影响睡眠的重要因素。通过Logistic回归分析,结果显示患者对支持利用度的增加及自评焦虑量指数、自评抑郁量指数与发作次数的减少有利于改善患者的睡眠障碍(OR=0.221、2.412、1.938、0.321,P0.05)。结论:抑郁、焦虑和社会支持是导致短暂性脑缺血患者存在睡眠障碍的重要因素,对三者情况进行改善可辅助药物治疗,改善患者睡眠质量。     

Oestrone, oestradiol and oestriol glucosiduronates and sulphates in human puerperal plasma and milk

Conjugated and unconjugated oestrone, oestradiol and oestriol were measured in simultaneous milk and plasma samples obtained from 21 women in the early post-partum period. Conjugated oestrogens comprised more than 90% of the total oestrogen content of both milk and plasma. Oestrone glucosiduronate was the major oestrogen metabolite in milk (33%), the levels being significantly higher (P less than 0.01) than in plasma. Oestriol glucosiduronates were the predominant oestrogen metabolites (63%) in plasma.     

Distribution of sleep and wakefulness in 24-h light-dark cycles in the juvenile and adult magpie, Pica pica

The daily organization of sleep and wakefulness was examined electrographically under natural conditions in captive juvenile and adult magpies, Pica pica. Electrographic indices of sleep in the magpie were found to be similar to those of other avian species. The daily amount of TS in juveniles was 17% greater than in adults. The amount of paradoxical sleep (PS) in adults was one-fifth that of juveniles. In adults sleep was confined to darkness, while in juveniles it also occurred during the light period. SWS in adults was almost constant, while PS slightly increased across the night. No systematic trends were observed in juveniles. In both groups of birds, the longest sleep episodes appeared around midnight.     

"Extracts from "Clinical evidence": Menopausal symptoms

DefinitionMenopause begins one year after the last menstrual period. Symptoms often begin in the perimenopausal years.Incidence/prevalenceIn the United Kingdom the mean age for the menopause is 50 years 9 months. The median onset of the perimenopause is between 45.5 and 47.5 years. One Scottish survey (of 6096 women aged 45 to 54 years) found that 84% had experienced at least one of the classic menopausal symptoms, with 45% finding one or more symptoms a problem.¹

Interventions

• Beneficial:OestrogensTibolone

• Likely to be beneficial:ProgestogensClonidine

• Unknown effectiveness:Phyto-oestrogensTestosteroneAntidepressants

PrognosisMenopause is a physiological event. Its timing may be genetically determined. Although endocrine changes are permanent, menopausal symptoms such as hot flushes, which are experienced by about 70% of women, usually resolve with time.² However, some symptoms, such as genital atrophy, may remain the same or worsen.AimsTo reduce or prevent menopausal symptoms, and to improve quality of life with minimum adverse effects.OutcomesFrequency and severity of vasomotor, urogenital, and psychological symptoms; quality of life.MethodsClinical Evidence search and appraisal December 1999. We included only randomised controlled trials (RCTs) and systematic reviews that met Clinical Evidence quality criteria.BenefitsVasomotor symptoms: We found no systematic review. We found over 40 RCTs comparing oestrogen versus placebo and various preparations and/or routes against each other. Most found that oestrogen reduced vasomotor symptoms (data from one RCT in 875 women: odds ratio 0.53, 95% confidence interval 0.31 to 0.93).³ Two RCTs found that transdermal oestrogen at a low dose of 25 μg daily reduced severity of vasomotor symptoms compared with placebo.^4,5 Urogenital system: We found one systematic review (search date 1995) and three subsequent RCTs. The review pooled data from six RCTs.⁶ It found that oestrogen improved urogenital symptoms regardless of the route of administration (no figures available). One subsequent RCT (n=136) found that low dose transdermal oestrogen (25 μg daily) combined with norethisterone acetate significantly reduced vaginal dryness and dyspareunia compared with placebo over six months.⁴ Two other RCTs (n=192) found that local administration of oestrogen using a silicone oestradiol releasing vaginal ring over 24-36 weeks improved vaginal oestrogenisation and pH compared with placebo.^7,8 One of these trials also found a significant reduction in incidence of urinary tract infection in treated women (P=0.008).⁷ Psychological symptoms: We found one systematic review (search date 1995, 14 RCTs, 12 cohort studies), which found that oestrogen reduced depressed mood among menopausal women.⁹ Duration of treatment ranged from one month to two years. Data pooling for oestrogen versus placebo (10 studies) found that oestrogen reduced depressive symptoms (no figures available). We found no RCTs of oestrogen treatment in women with clinically proved depression. We found one systematic review (search date 1996, 10 controlled trials, 9 observational studies) of the effects of oestrogen on cognitive function in postmenopausal women and women with Alzheimer''s disease.¹⁰ Studies were too weak to allow reliable conclusions. An additional crossover RCT (n=62) found a beneficial effect of oestrogen on sleep quality compared with placebo over seven months.¹¹ Quality of life: We found no systematic review. We found four RCTs (639 women, 3 RCTs placebo controlled, 3 versus progestogen), which found significant improvement in quality of life in women treated with oestrogen compared with baseline or placebo.^12–15 The largest RCT (242 women) found that oestrogen improved quality of life (P=0.0003) and wellbeing (P=0.003) compared with placebo over 12 weeks.¹²HarmsMany RCTs have found that oestrogen causes weight gain and breast tenderness in the short term. Although many women report an increase in weight when starting oestrogen, we found no evidence from RCTs that oestrogen causes significant weight gain in the long term. The most important long term adverse effects are increased risk of venous thromboembolic disease, endometrial cancer, and breast cancer.^16–18 The relation between oestrogen (as hormone replacement therapy) and breast cancer was reviewed in a reanalysis of 51 studies of more than 160 000 women.¹⁹ The review found that the risk of breast cancer increased by 2.3% (1.1% to 3.6%) each year in women using hormone replacement therapy. Five or more years after hormone replacement therapy was stopped, there was no significant excess of breast cancer.¹⁹CommentMany studies used selected populations such as women attending hospital clinics, who may be different in their behaviour, personality, and symptom profile to women of the same age seen in primary care or those who do not seek medical advice. Option: ProgestogensSummary We found good evidence from RCTs that progestogens reduce vasomotor symptoms. We found no good quality evidence on other outcomes, including quality of life.BenefitsWe found no systematic review. Vasomotor symptoms: We found five RCTs (257 women, all trials less than a year long), which found that women taking progestogens experienced a significant reduction in vasomotor symptoms compared with placebo.^20–24 The single RCT comparing oestrogen alone with progestogen (150 mg of depot medroxyprogesterone for 25 days a month) found that over three months, 18% of women taking oestrogens and 33% taking progestogen reported no vasomotor symptoms.²¹ One RCT (n=102) found that transdermal progesterone cream 20 mg daily improved vasomotor symptoms compared with placebo (P<0.001) but had no beneficial effect on bone density.²⁵ Urogenital system: We found no RCTs evaluating the effects of progestogens alone on urinary incontinence, the lower genital tract, or sex life. Psychological symptoms: We found no RCTs. Quality of life: One RCT of cyclical progestogen plus oestrogen for six months found no evidence of an effect on quality of life.²⁶ We found no studies of progestogen alone on quality of life.HarmsWe found two RCTs that evaluated harms of progestogens. The first compared continuous progestogen (norgestrel) and placebo in 321 women who had undergone hysterectomy and were already taking conjugated oestrogen. It found no difference in symptoms (including weight gain and bloating).²⁷ The second RCT (875 women) compared various oestrogen-progestogen combinations over three years.³ It found that additional progestogen increased breast discomfort (odds ratio 1.92, 1.16 to 3.09). Neither trial found evidence of an effect on cardiovascular events.CommentProgestogen is seldom given alone, which makes it hard to isolate its effects. When it was given without oestrogen, doses of progestogens were high, the lowest dose being 20 mg medroxyprogesterone acetate per day. Option: TiboloneSummary RCTs found that tibolone significantly improved vasomotor symptoms, libido, and vaginal lubrication.BenefitsWe found no systematic review. Vasomotor symptoms: We found three RCTs, two of tibolone versus continuous combined oestrogen/progestogen treatment over 48 and 52 weeks (672 women with menopausal symptoms)^28,29 and one versus placebo over 16 weeks (82 women with menopausal symptoms).³⁰ The first RCT found a slightly greater reduction in hot flushes with the combined regimen than with tibolone over 48 weeks (P=0.01). The second trial found a significant reduction in vasomotor symptoms from baseline in both groups (67/72 women on HRT and 58/68 women on tibolone, P<0.001) but no significant difference between groups. The third trial found tibolone reduced vasomotor symptoms by 39% compared with placebo (P=0.001). Urogenital system: We found two RCTs. The first RCT found no significant difference between tibolone and combined hormonal treatment in terms of subjective reports of vaginal lubrication; both interventions improved lubrication compared with baseline.²⁸ The second RCT (437 women) found that tibolone improved sexual satisfaction compared with oestradiol plus norethisterone (P<0.05).³¹ We found no RCTs examining effects on urinary incontinence. Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs. Bone density: We found nine RCTs, which found that tibolone increased bone density over periods from 6 to 36 months compared with baseline or placebo.³²HarmsWe found no evidence on adverse effects from RCTs. One non-randomised controlled trial found that the main unwanted effect of tibolone was breakthrough bleeding, which occurred in about 10% of users.³³ We found no good evidence of androgenic adverse effects such as hair growth and greasiness of the skin. Two RCTs of short term use found a 33% reduction in plasma high density lipoproteins with tibolone,^34,35 although the long term effects on cardiovascular disease are unknown.CommentNone. Option: Phyto-oestrogensSummary Limited evidence from small RCTs suggests that soy flour, which contains phyto-oestrogens, may relieve vasomotor menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found three placebo controlled RCTs. Two evaluated soy supplements, which contain phyto-oestrogen, using double blind designs; the other, which was not blinded, evaluated isoflavone. The first RCT (58 postmenopausal women) compared soy flour versus wheat flour for 12 weeks and found that hot flushes were reduced significantly more in the group of women using soy flour (40% v 25% reduction).³⁶ The second RCT used a crossover design to evaluate six weeks'' administration of 34 mg soy protein daily. It found reduced severity but not frequency of vasomotor symptoms.³⁷ The third RCT (n=51) used a crossover design to compare isoflavone 40 mg daily with placebo. It found benefit from placebo compared with baseline, but not with isoflavone.³⁸ Urogenital system: We found no RCTs. Psychological symptoms: We found no RCTs. Beneficial effects of treatment on quality of life: We found no RCTs.HarmsWe found no evidence of significant adverse effects.CommentNone. Option: ClonidineSummary Two RCTs found that clonidine reduced vasomotor symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found two RCTs.^39,40 One crossover RCT (66 women) found that clonidine reduced the mean number of flushing attacks in the 14 days after crossover compared with placebo (56.8 v 64.3, P<0.05).³⁰ The second RCT (30 women) found that more women taking clonidine reported reduced flushes at 8 weeks (12/15 v 5/14, P<0.04).⁴⁰ Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs.HarmsThe two RCTs found no significant difference in the incidence of unwanted effects between placebo and active treatment groups.^39,40CommentNone. Option: TestosteroneSummary We found evidence from RCTs that testosterone improves sexual enjoyment and libido. We found no studies evaluating effects on other commonly experienced menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found no RCTs evaluating testosterone alone in women with menopausal symptoms. We found one RCT (93 postmenopausal women) comparing oestrogen alone and oestrogen plus methyltestosterone. This concluded that addition of a small dose of methyltestosterone reduced the dose of oestrogen needed to control menopausal symptoms.⁴¹ Urogenital system: We found two RCTs, one in 40 women and one crossover study in 53 women. Both found benefit from exogenous testosterone on self reported sexual enjoyment, desire, and arousal.^42,43 Psychological symptoms: We found no RCTs. Beneficial effects of therapy on quality of life: We found no RCTs.HarmsWe found no evidence from RCTs or other controlled studies on the incidence of androgenic adverse effects with testosterone.CommentNone. Option: AntidepressantsSummary We found insufficient evidence on the effects of antidepressants on menopausal symptoms.BenefitsWe found no systematic review or RCTs that specifically addressed the effects of antidepressants on menopausal symptoms or quality of life in menopausal women.HarmsWe found no evidence on adverse effects in postmenopausal women. Antidepressants as a group can cause many central nervous system adverse effects, including sedation and agitation, as well as urinary and vision problems, liver dysfunction, and cardiac dysrhythmias.⁴⁴CommentNone.     

Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation

The neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) regulate sleep and nocturnal hormone secretion in a reciprocal fashion, at least in males. GHRH promotes sleep and GH and inhibits hypothalamo-pituitary-adrenocortical (HPA) hormones. CRH exerts opposite effects. In women, a sexual dimorphism was found because GHRH impairs sleep and stimulates HPA hormones. Sleep deprivation (SD) is the most powerful stimulus for inducing sleep. Studies in rodents show a key role of GHRH in sleep promotion after SD. The effects of GHRH and CRH on sleep-endocrine activity during the recovery night after SD are unknown. We compared sleep EEG, GH, and cortisol secretion between nights before and after 40 h of SD in 48 normal women and men aged 19-67 yr. During the recovery night, GHRH, CRH, or placebo were injected repetitively. After placebo during the recovery night, non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) increased and wakefulness decreased compared with the baseline night. After GHRH, the increase of NREMS and the decrease of wakefulness were more distinct than after placebo. Also, after CRH, NREMS increased higher than after placebo, and a positive correlation was found between age and the baseline-related increase of slow-wave sleep. REMS increased after placebo and after GHRH, but not after CRH. EEG spectral analysis showed increases in the lower frequencies and decreases in the higher frequencies during NREMS after each of the treatments. Cortisol and GH did not differ between baseline and recovery nights after placebo. After GHRH, GH increased and cortisol decreased. Cortisol increased after CRH. No sex differences were found in these changes. Our data suggest that GHRH and CRH augment NREMS promotion after SD. Marked differences appear to exist in peptidergic sleep regulation between spontaneous and recovery sleep.     

Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks

ObjectivesTo assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.DesignRandomised, double blind, multicentre, parallel group trial for 8 weeks.SettingTrained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.Participants263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32.1 and F33.1.Interventions1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.ResultsHypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean −15.4 (SD 8.1), −12.1 (7.4), and –14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).ConclusionsAt an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

Key messages

• Hypericum extract (STEI 300) was effective after 4, 6, and 8 weeks of treatment in patients with moderate depression
• Simultaneous analysis confirmed hypericum extract to be at least as efficacious as imipramine 100 mg daily after eight weeks of treatment
• Besides better antidepressive efficacy both hypericum extract and imipramine improved quality of life
• Patients tolerate hypericum extracts much better than they do tricyclics and therefore by improving patients'' compliance hypericum extracts are promising drugs for long term treatment

     

Sleep-waking cycle and behaviour after diethyldithiocarbamate in the rat

Young adult Louis rats were implanted for chronic sleep recording to test the effect of diethyldithiocarbamate (DDC) on sleep. Recordings of EEG and EMG were done continuously for 12 h during the 12 consecutive days. There were 2 days of baseline recording, 3 days of recording with a single daily injection of placebo, 3 days of recording with a single daily injection of DDC (500 mg/kg i.p.), and 3 days of DDC withdrawal recording with placebo injection. Placebo injections did not change the proportion of time spent in different behavioural states. With daily injection of DDC there was an increase in wakefulness, no change in slow-wave sleep and elimination or drastic reduction in paradoxical sleep (PS). There was no PS rebound during the DDC withdrawal days. These results suggest that the reduction of PS produced by DDC and the absence of PS rebound may be due to a lowering in norepinephrine in the brain. In other experiments rats were injected with DDC (500 mg/kg i.p.) daily for 3 days and whole brains were analysed chemically. Norepinephrine was significantly decreased, while 5-hydroxytryptamine, 5-hydroxyindolacetic acid, dopamine and homovanilic acid were unchanged. Seizure activity appeared during relaxed wakefulness in all rats treated with DDC. Taken together it seems that lowering of brain NE is responsible for the appearance of seizure activity and also, for PS reduction. PS reduction might, per se, produce seizure activity.     

更年期潮热与体温调节

由于潮热是更年期女性的最常见和最特异的症状,也是最痛苦的症状之一。潮热主要发生在更年期过渡期的妇女,主要表现为忽冷忽热,其发生严重的影响了更年期妇女的情绪、睡眠及生活质量。但是其发病的病理学机制仍然不清楚。研究表明,潮热的发生与体温调节的异常有关,大多数学者认为潮热发生的机制是体温调节中枢的异常,并通过改变外周和中心体温而实现。因此,本文对潮热时体温调定点,其外周和中心体温的变化情况,作出综述。     

Monitoring ovarian function and pregnancy by evaluating excretion of urinary oestrogen conjugates in semi-free-ranging Przewalski's horses (Equus przewalskii).

Immunoreactive urinary oestrogen conjugates were assessed in daily urine samples (approximately 5 samples/week) collected from 8 Przewalski's mares maintained under semi-free-ranging pasture conditions. The relative percentage contributions of immunoreactive urinary oestrogens during different reproductive stages (oestrus, luteal phase, early, mid- and late gestation) were determined using high-pressure liquid chromatography. In general, conjugated forms of oestrone (oestrone sulphate and oestrone glucuronide) were the major excreted immunoreactive oestrogens in nonpregnant and pregnant Przewalski's mares. Variations in urinary oestrogen conjugates indicated that the onset of oestrous cyclicity coincided with increasing daylengths, and the non-conception oestrous cycle was 24.1 +/- 0.7 days (n = 17) in duration. Most copulations (29/35, 82.9%) were observed between Day -4 and Day +1 from the preovulatory oestrogen conjugates peak (Day 0). Based on known copulation dates, the mean gestation length was 48.6 +/- 0.4 weeks (range 47.3-50.3 weeks). During pregnancy, urinary excretion of oestrogen conjugates increased approximately 300-fold over levels in non-pregnant mares, reaching peak concentrations by Week +24 (51% of gestation). These results demonstrate that longitudinal reproductive events, including oestrous cyclicity and pregnancy, can be monitored precisely by evaluating urinary oestrogen conjugates in samples from Przewalski's mares maintained under semi-free-ranging conditions.     

Peripheral blood flow in menopausal women who have hot flushes and in those who do not.

OBJECTIVE--To compare blood pressure, heart rate, and peripheral vascular responsiveness in menopausal women who have hot flushes and in those who do not, and to assess the effect on these variables of treating women who have hot flushes with oestriol, a natural oestrogen, given vaginally. DESIGN--An open, non-randomised cohort study of flushing and non-flushing menopausal women. A before and after investigation of the effects of vaginal oestriol treatment on the circulation. SETTING--Referral based endocrinology clinic. PATIENTS--88 Consecutive menopausal women, 63 complaining of frequent hot flushes and 25 who had not flushed for at least a year. INTERVENTION--Treatment with vaginal oestriol 0.5 mg at night for six weeks in 18 of the women who had hot flushes. MEASUREMENTS AND MAIN RESULTS--Peripheral blood flow was measured by venous occlusion plethysmography at rest and in response to stressful mental arithmetic and anoxic forearm exercises. Blood flow in the forearm and its variability were significantly higher in flushing than in non-flushing women (4.1 (SD 1.7) and 3.1 (0.9) ml/100 ml tissue/min and 17% and 13% respectively). Blood pressure, heart rate, and blood flow in the hand were, however, similar in the two groups. No difference was found in the peripheral incremental response to either stress or anoxic exercise. Vaginal oestriol significantly lowered forearm blood flow from 4.4 (1.5) to 3.3 (1.1) ml/100 ml tissue/min but dilator responsiveness was unaffected. CONCLUSIONS--The peripheral circulation is different in menopausal women who have hot flushes compared with those who do not, with selective vasodilatation in the forearm. The lowered blood flow in the forearm after vaginal oestriol in flushing women may be relevant to the alleviation of vasomotor symptoms induced by oestrogen treatment.     

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: A systematic review and meta-analysis

OBJECTIVE: To critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women. DATA SOURCES: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and The Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed. RESULTS: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05). CONCLUSION: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.     

Sustained release choline theophyllinate in nocturnal asthma.

Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days'' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.     

Double-blind comparison of tolamolol,propranolol, practolol,and placebo in the treatment of angina pectoris.

Forty-two patients with angina pectoris have completed a randomized, double-blind trial comparing tolamolol 100 mg and 200 mg with propranolol 80 mg, practolol 100 mg, and placebo, all given three times a day. Tolamolol 200 mg thrice daily was found to be equivalent to propranolol 80 mg thrice daily in anti-anginal efficacy. Anginal attack rates and trinitrin consumption were significantly reduced by all active treatments as compared with the placebo but tolamolol and propranolol were the most effective. Tolamolol 200 mg thrice daily was most effective in reducing blood pressure, while propranolol was most effective in reducing the resting heart rate. All treatments except the placebo significantly increased the amount of exercise which could be performed before angina appeared (exercise work), while tolamolol 200 mg thrice daily significantly reduced Robinson''s index when compared with all other active agents. The degree of S-T segment depression induced by exercise was significantly lessened by both tolamolol and propranolol but not by practolol or placebo. There was no difference in patient preference between tolamolol and propranolol but tolamolol at both dose levels was preferred to practolol. Both tolamolol and propranolol are potent adrenergic beta-receptor antagonists and equal in anti-anginal efficacy but tolamolol has the advantage of being cardioselective. It is superior to practolol.     

Does menopausal transition really influence mental health? Findings from the prospective long‐term Zurich study

In the prospective long‐term Zurich study, we re‐examined the hypothesized association between mental health problems in women and the transition through menopausal stages. One hundred sixty‐eight women from a population‐based Swiss community cohort were prospectively followed up from age 21 to 50. At age 50, the occurrence of hot flushes/night sweats and sleep disturbances was significantly more frequent in peri‐ and post‐menopausal women. Irritability/nervousness was increased only in peri‐menopausal women, but that association was accounted for by neuroticism trait scores at age 30. Transitions to peri‐ or post‐menopause were not related to changes in either the prevalence rates of DSM major depressive episode or anxiety disorders, or the course of psychopathological syndromes as assessed by the Symptom Checklist 90 ‐ Revised. The null associations held when adjusting for duration of reproductive period or age at menopause. Preceding mental health problems between ages 21 and 41, increased neuroticism trait scores at age 30, and concurrent psychosocial distress were significantly related to mental health problems occurring between ages 41 and 50. Depending upon the cut‐off point that was chosen, the arbitrary dichotomization of a continuous depression outcome produced spurious associations with the menopausal transition. We conclude that mental health problems between ages 41 and 50 are probably not directly related to the menopausal transition, and that previously reported associations could be false positives due to inadequate dichotomizations, reporting bias, undisclosed multiple adjustments or overfitting.