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.     

Effect of cimetidine suspension on appetite and weight in overweight subjects.

OBJECTIVE--To investigate the weight reducing effect of cimetidine, comparing it with placebo. DESIGN--Block randomised parallel group double blind study using suspensions with identical appearance and taste. SETTING--Primary care practice. SUBJECTS--55 women and 5 men aged 18-59, body mass index 25-37 kg/m2, completed the study according to the protocol. INTERVENTIONS--Cimetidine suspension 200 mg or placebo 30 minutes was given before the three main meals for eight weeks. Subjects followed a diet restricted to 5 MJ/day supplemented with 9 g fibre per day. MAIN OUTCOME MEASURES--Weight reduction; abdominal and hip circumferences and systolic and diastolic blood pressures were also recorded. RESULTS--Subjects given cimetidine lost a mean of 7.3 (95% confidence interval 6.5 to 8.3) kg more than subjects given placebo (p < 0.001); body mass index decreased 3.33 (SD 0.76) and 0.77 (0.43), respectively (p < 0.001). Abdominal and hip circumference was decreased more in the cimetidine group (8.6 (3.9) cm and 7.8 (3.1) cm) than in the placebo group (2.2 (1.5) cm and 2.1 (1.5) cm). Mean reductions in systolic and diastolic blood pressure were greater in the cimetidine group than the placebo group (mean 5.8 v 0.4 and 6.5 v 0.4, p < 0.001). CONCLUSION--Intake of cimetidine suspension 30 minutes before meals in overweight subjects may lead to reduced hunger, less food intake, and subsequent weight loss. This effect may be due to the suppression of gastric acid secretion. Cimetidine suspension may be a valuable adjunct in treating obesity.     

The safety of evening primrose oil in epilepsy

The concern that evening primrose oil might cause epilepsy or seizures, or reduce the threshold for seizures, originated from two papers published in the early 1980s. These original reports are re-examined, and the association of evening primrose oil with seizures is shown to be spurious. Not only are linoleic acid and gamma-linolenic acid safe in epilepsy, with prolonged oral administration of linoleic acid and alpha-linolenic acid (in a 4:1 mixture) protecting rats from having seizures in four different epilepsy models, but the evening primrose oil-derived omega-6 fatty acid arachidonic acid inhibits sodium ion currents and synaptic transmission, while the evening primrose oil-derived eicosanoid prostaglandin E(1) appears to have anticonvulsant activity. In light of these findings, it is suggested that formularies should now remove seizures or epilepsy as a side-effect of evening primrose oil, and should remove a history of seizures or epilepsy as a contraindication to taking evening primrose oil.     

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.     

Hot Flash,Hot Topic: Conceptualizing Menopausal Symptoms From a Cognitive-Behavioral Perspective

While most healthy women report that the menopausal transition is nondistressing, a subset of women does report that symptoms significantly interfere in their lives. The most common reason that women seek treatment during this time is for vasomotor symptoms, namely, hot flashes and night sweats. Research has suggested that reports of distress during flashing are only weakly related to more objective measures of the flash, including duration and frequency and that differences in treatment-seeking during the menopausal transition may be better accounted for by differences in symptom awareness mediated by a variety of personality and stress factors. This paper discusses hot flashes and night sweats from a cognitive-behavioral perspective, taking into account individual difference variables that may also affect the experience of menopausal symptoms.Terms such as menopause, menopausal transition, perimenopause and postmenopause have been used interchangeably with determination of reproductive status based primarily on age and symptoms. The Stages of Reproductive Aging Workshop (STRAW; Soules et al., 2001) set out to provide a better 7-level staging system to describe midlife reproductive status in healthy women. The new staging system takes into account menstrual cyclicity, endocrine changes, fertility, signs/symptoms in other organs, and uterine/ovarian anatomy. The staging system is anchored around the permanent cessation of menses (final menstrual period; FMP), with stages –5 to –3 characterizing the early, peak, and late reproductive period, –2 and –1 representing the early and late menopausal transition and +1 and +2 indicating postmenopause. Vasomotor symptoms are the most common and tend to increase in intensity in stages –1 and +1.     

An examination of the relationship between sunlight exposure and hot flush in working women

ABSTRACT

We examined whether sunlight affects hot flushes in working menopausal women and explored effect modification by shift work and season. In this prospective cohort study, daily hot flush score (outcome) was measured by the 7-day North Central Cancer Treatment Group Daily Vasomotor Symptoms Diary. Daily duration of sunlight (≥2000 lux) was recorded by the HOBO MX2202 pendant. Both variables were measured in two 7-day data collection phases. T0 data were collected during the Australian Summer (December 2017, January and February 2018); and T1 data were collected in the Australian winter (June, July and August 2018). Linear mixed effects model was used. Shift work and season were both confounders and effect modifiers. To detect a median effect size of R² = 0.2, 34 women were required to achieve an effective sample size of 41. A total of 49 menopausal women were recruited, 11 shift and 38 day workers. Some 13 women had various missing observations. For shift workers, an hour increase in sunlight exposure was associated with a 1.4-point reduction in hot flush score (p = .016). This relationship was not significant for day workers (p = .185). The finding of this study suggests increased sunlight exposure might improve hot flushes in menopausal shift workers who are moderately bothered by hot flushes, but probably not in day workers. The possible role of shift-work associated circadian disruption on estrogen level in regard to elevated intensity and frequency of hot flush in menopausal women is discussed.     

Prospective double-blind trial of synthetic steroid (Org OD 14) for preventing postmenopausal osteoporosis.

A double-blind trial of Org OD 14, a synthetic steroid with an unusual endocrine profile, was conducted on 100 postmenopausal women; of these, 63 completed two years'' treatment (33 Org OD 14; 30 placebo). A dose of 2.5 mg/day successfully prevented bone loss over two years, whereas a significant reduction in bone mineral content occurred in women taking placebo, the rate being comparable to that in earlier studies (p less than 0.01). At the dosage used (2.5 mg/day) Org OD 14 also significantly reduced the severity of menopausal complaints (flushing, sweating, etc). Vabra aspiration curettage in 20 cases 6-18 months after starting active treatment showed no evidence of endometrial hyperplasia, though weak proliferation of the endometrium was seen in three. Org OD 14 may provide a new approach to hormonal prevention of bone loss in postmenopausal women without inducing appreciable endometrial stimulation; the potential value of Org OD 14 in osteoporosis and other post-climacteric complaints warrants further investigation.     

Benefits and risks of hormone replacement therapy (HRT)

In western countries more than 30% of the female population are postmenopausal. Approximately 30% of postmenopausal women suffer from clinical symptoms of the climacteric such as vasomotor symptoms, associated with hot flushes, night sweat, insomnia and depressive mood. Sufficient hormonal replacement therapy (HRT) will abolish specific menopausal symptoms in over 90% of patients, unspecific symptoms such as headache respond to placebo and HRT equally well. The question of cancer risk related to HRT will be addressed in this review. In combination with progestins, estrogens are obviously protective regarding ovarian and endometrial cancer. The association between HRT and breast cancer risk is presently unclear. Epidemiological data available so far do not provide compelling evidence as to a cause and effect relationship between HRT and breast cancer risk. There seems to be an overall trend towards a slightly increased risk with increasing duration of HRT use. Guidelines for HRT use in women with a history of endometrial and breast cancer are provided in this article.     

Circadian Rhythms in Hot Flashes in Natural and Surgically-Induced Menopause

The aim of this study was to investigate arcadian and ultradian variations in menopausal hot flash. The number of hot flashes per 2-hr period was collected from 25 diurnally-active, perimenopausal women for 1 week in January or February of each year for 3 consecutive years. Fourteen women were experiencing natural menopause (NM) (mean age 51.9 years) and 11 were experiencing surgically-induced menopause (SIM) (mean age 52.0 years). The difference in the number of hot flashes between the two types of menopause at each clock time was not statistically significant; neither was the mean number of hot flashes per 24 hr different between the two groups (Student's f-test). Data when normalized for each woman and placed end-to-end revealed by cosinor analysis circadian rhythmicity in the SIM group (P =0.02) but not in the NM group. A 12-hr periodicity was detected in both groups (P< 0.001 for both). An 8-hr rhythm was detected only for the NM group (P = 0.04). Both groups combined exhibited statistically significant rhythmicities with periods of 24 hr (p= 0.003), 12 hr (P<0.001) and 8 hr (P= 0.005). Regardless of the type of menopause, the women could be separated into two groups based on the temporal pattern of hot flashes during the day. One group was defined by the occurrence of peak frequency of flashes during the morning (0400–0959), while the second group was defined by the occurrence of the peak in the evening (1600–2159). The difference between the two groups in the number of hot flashes during the morning wasstatistically significant (Student's r-test, P = 0.009) as was the number of hot flashes in the evening (Student's r-test, P= 0.03).     

Double-blind Evaluation of Verapamil,Propranolol, and Isosorbide Dinitrate against a Placebo in the Treatment of Angina Pectoris

In the treatment of angina pectoris a double-blind evaluation of verapamil (Cordilox) at two dose levels—namely, 80 mg thrice daily and 120 mg thrice daily—propranolol (Inderal) 100 mg thrice daily, and isosorbide dinitrate (Vascardin) 20 mg thrice daily has been made against a placebo. The assessment was based on relief from daily attacks of angina on effort and the response to a whole-body exercise test. We can find no statistically significant difference between the effects of verapamil (120 mg three times a day) and propranolol (100 mg three times a day) in the treatment of angina of effort. Both of these preparations are more effective than a placebo both in the reduction of daily attacks (P < 0·01) and in the prolongation of exercise test (P < 0·05). Isosorbide dinitrate (20 mg three times a day) appears to be no more effective than a placebo in the treatment of angina on effort, but 14 out of 32 patients experienced headache of such severity that even when the dose was reduced to 10 mg thrice daily this drug therapy had to be withdrawn. Both propranolol (100 mg three times a day) and verapamil (120 mg three times a day) had a significant lowering effect on the diastolic blood pressure as measured with the patient standing (P < 0·01).     

ENDOCRINE RESPONSE TO AN ULTRA-MARATHON IN PRE- AND POST-MENOPAUSAL WOMEN

Ultra-endurance competitions are becoming increasingly popular but there is limited research on female participants. The purpose of this study was to examine changes in estrogen and the IGF-I system in women after an ultra-marathon. Six pairs of pre- and post- menopausal women were matched for race finish times;mean finish time was 20 hours. Blood samples were drawn 24 hours before the race, at the finish, and 24 hours into recovery. Samples were analysed for estradiol, total IGF-I, IGFBP-1, and intact IGFBP-3. There was a significant increase in estradiol following the race in both groups (P < 0.05). Total IGF-I decreased after the race (P < 0.01) and remained lower in recovery. IGFBP-1 increased after the race (P < 0.001) but returned to pre-race levels after 24 hours, while intact IGFBP-3 was significantly lower post-race and in recovery (P < 0.001). Postmenopausal women had significantly lower estradiol at baseline, but there were no other group differences. These results demonstrate that among recreational female runners, an ultra-marathon is associated with IGF system changes that are consistent with an energy-deficient, catabolic state. Further research is needed to confirm the effect of these endocrine changes on health and performance.     

Attempts at dietary alteration of prostaglandin pathways in the management of pre-eclampsia

It has been suggested that dietary supplementation with prostaglandin precursors may enhance the synthesis of PGE which lowers vascular sensitivity to increased levels of angiotensin II in pregnancy. Therefore the effect of dietary supplementation with evening primrose oil (linoleic acid and gamma-linoleic acid) in African primigravidae with established pre-eclampsia was studied. Patients were randomly allocated to one of two groups. Group A (23 patients) received 8 capsules/day of evening primrose oil and group B (24 patients) received 8 capsules of placebo. No significant differences were found between the groups in respect to perinatal outcome, blood pressure lowering effect and haematological indices.     

Effect of temazepam on oxygen saturation and sleep quality at high altitude: randomised placebo controlled crossover trial

Objective: To determine the effects of temazepam on the quality of sleep and on oxygen saturation during sleep in subjects at high altitude. Design: Randomised, blinded, crossover, placebo controlled trial. Setting: Base camp at Mount Everest (altitude 5300 m). Subjects: 11 members of British Mount Everest Medical Expedition recently arrived at base camp. Intervention: Participants were randomly allocated to receive either temazepam 10 mg or placebo on their first night at base camp and the other treatment on the second night. Main outcome measures: Quality of sleep (assessed subjectively), mean arterial oxygen saturation value, and changes in saturation values (as measure of periodic breathing) while participants taking temazepam or placebo. Results: All participants noted subjective improvements in sleep. Mean saturation value remained unchanged when temazepam was compared with placebo (74.65% v 75.70%, P=0.5437). There were fewer changes in oxygen saturation when participants took temazepam and when measured as decreases >4% below the mean value of saturation each hour (P=0.0036, paired Student’s t test (two tailed)). Conclusions: Participants taking temazepam at 5300 m showed no significant drop in mean oxygen saturation values during sleep. Both the number and severity of changes in saturation during sleep decreased and the quality of sleep improved. This may be a result of a reduction in the number of awakenings and might lead to greater respiratory stability and fewer episodes of periodic breathing. This has the effect of improving the quality of sleep and reducing the number of periods of desaturation during sleep

Key messages

• Poor sleep at high altitude is common and may be due to a combination of physiological and physical factors
• Frequent arousals, periodic breathing, and episodes of oxygen desaturation lead to poor sleep and daytime symptoms of drowsiness and reduced performance
• In this study 10 mg temazepam improved subjective reports of the quality of sleep and reduced episodes of arterial desaturation, with no significant effect on mean oxygen saturation during sleep

     

Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised,double blind,placebo controlled trial (the DIABHYCAR study)

Objective To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria.Design Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years.Setting Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries.Participants 4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion ≥ 20 mg/l in two consecutive samples), and serum creatinine ≤ 150 μmol/l.Main outcome measures The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure.Results Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study.Conclusions Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.     

Urinary excretion of prostacyclin and thromboxane metabolites in climacteric women: effect of estrogen-progestin replacement therapy

To study the role of vasodilatory prostacyclin and vasoconstrictory thromboxane A2 in climacteric vascular instabilities, overnight urine samples were collected from sixteen women suffering from hot flushes and sweating before, during and after the six months' cyclic estradiol-desogestrel therapy as well as from ten non-climacteric control women. The urine was assayed for 6-keto-PGF1a and 2,3-dinor-6-keto-PGF1a (metabolites of prostacyclin) as well as for thromboxane B2 and 2,3-dinor-thromboxane B2 (metabolites of thromboxane A2) by means of HPLC and radioimmunoassay. No difference was seen in baseline prostaroid output between the climacteric and non-climacteric study groups. Furthermore, no relation was observed between individual prostanoid excretion and severity of vasomotor symptoms before replacement therapy. The replacement therapy abolished or markedly alleviated hot flushes and sweating, but prostanoid output did not change. Our data imply that climacteric symptoms are not accompanied by changes in the production of prostacyclin and thromboxane A2.     

A Behavioral Group Treatment Program for Menopausal Hot Flashes: Results of a Pilot Study

In the present study, we tested the effectiveness of a cognitive-behavioral group treatment (CBGT) for hot flashes in menopausal women. Treatment was administered over 8, 90 min weekly sessions and consisted of education, relaxation training and cognitive restructuring. Nineteen women meeting STRAW staging criteria for the menopause transition (stages –1 to +1) were randomly assigned to immediate or delayed treatment (wait list) and were asked to monitor their hot flashes and night sweats prospectively. They also completed questionnaires, including the Womens Health Questionnaire and the Menopause Specific Quality of Life Questionnaire to determine psychosocial benefits of treatment. Results suggested that the CBGT was moderately successful in reducing the frequency of total vasomotor symptoms [F (1, 17) = 6.16, p < .01], as measured by daily symptom diaries. While there were arithmetic improvements in psychosocial functioning in this sample, these results were not significant. Despite the limitations of small sample size and possible placebo effect, this pilot study supports the notion that cognitive-behavioral interventions aimed at reducing vasomotor symptoms may be of value for menopausal hot flashes when administered in a small-group format.     

Effects of modafinil on heat thermoregulatory responses in humans at rest

The effects of modafinil on heat thermoregulatory responses were studied in 10 male subjects submitted to a sweating test after taking 200 mg of modafinil or placebo. Sweating tests were performed in a hot climatic chamber (45 degrees C, relative humidity <15%, wind speed = 0.8 m x s(-1), duration 1.5 h). Body temperatures (rectal (Tre) and 10 skin temperatures (Tsk)), sweat rate, and metabolic heat production (M) were studied as well as heart rate (HR). Results showed that modafinil induced at the end of the sweating test higher body temperatures increases (0.50 +/- 0.04 versus 0.24 +/- 0.05 degrees C (P < 0.01) for deltaTre and 3.64 +/- 0.16 versus 3.32 +/- 0.16 degrees C (P < 0.05) for deltaTsk (mean skin temperature)) and a decrease in sweating rate throughout the heat exposure (P < 0.05) without change in M, leading to a higher body heat storage (P < 0.05). AHR was also increased, especially at the end of the sweating test (17.95 +/- 1.49 versus 12.52 +/- 1.24 beats/min (P < 0.01)). In conclusion, modafinil induced a slight hyperthermic effect during passive dry heat exposure related to a lower sweat rate, probably by its action on the central nervous system, and this could impair heat tolerance.     

Circadian variations in the sweating mechanism.

Sweat rates and body temperatures of human subjects were measured at 0200, 1000, and 1800 h during a heat exposure of 90 min. The latent period of sweating was not significantly altered in the evening but significantly shortened during the night. Mean body temperature corresponding to the onset of sweating was nearer to the basal body temperature during the night, while during the day the difference between these two temperatures became larger. This phenomenon seems related to the circadian cycle of vasomotor adjustment, since during the night body conductance was higher than during the day and corresponded to a state of a vasodilatation similar to that observed at the onset of sweating. During the day, this situation was reversed. During steady state, the following changes were observed: sweating rate, night less than morning less than evening; skin temperatures, night less than morning less than evening; and rectal temperature increase, morning less than evening less than night. It is hypothesized that these changes are due to either different metabolic rates or an imbalance between heat gains and losses which preserve the circadian rhythm of the body temperature, even under thermal loads.     

Similarities between morphine withdrawal in the rat and the menopausal hot flush

Skin temperature, cardiovascular and neuroendocrine responses to morphine withdrawal in the rat were evaluated in an effort to develop a potential animal model for the menopausal hot flush in women. Morphine dependency was produced by s.c. implantation of pellets containing morphine alkaloid. In response to precipitous, naloxone-induced withdrawal, rats showed surges in tail skin temperature (TST) which were similar in magnitude (4.8 to 7.2 degrees C) and duration (60 to 90 min.) to peripheral skin temperature increases reported during menopausal hot flushes. Additionally, a brief period of accelerated heart rate (59%) and a 9-fold hypersecretion of luteinizing hormone (LH) preceded the TST response to morphine withdrawal. These cardiovascular and neuroendocrine responses are observed to precede or coincide with the menopausal hot flush. Additionally, protracted morphine withdrawal subsequent to abstention, resulted in TST instability characterized by spontaneous, high amplitude TST fluctuations. Thus, the alteration in skin temperature, heart rate and LH secretion during precipitated morphine withdrawal in the rat are similar in magnitude, duration and in their temporal relationship to those observed during the hot flush. These data suggest a possible opioid etiology in this vasomotor disturbance. Acute withdrawal in the morphine addicted rats may serve as an animal model by which to study the neural mechanism underlying the menopausal hot flush.