Effects of acupuncture, applied relaxation, estrogens and placebo on hot flushes in postmenopausal women: an analysis of two prospective, parallel, randomized studies.

OBJECTIVE: To assess if transdermal or oral estrogens, acupuncture and applied relaxation decrease the number of menopausal hot flushes/24 h and improve climacteric symptoms, as assessed by the Kupperman index, more than transdermal placebo treatment. SETTING: An outpatient clinic at a Swedish university hospital. METHODS: A total of 102 postmenopausal women were recruited to two studies performed in parallel. In Study I, the women were randomized between transdermal placebo or estrogen treatment and, in Study II, between oral estrogens, acupuncture or applied relaxation for 12 weeks. Climacteric symptoms were measured with daily logbooks on hot flushes. Women completed the assessment questionnaire for the Kupperman index at baseline and after 12 weeks. RESULTS: The number of flushes/24 h decreased significantly after 4 and 12 weeks in all groups except the placebo group. Both at 4 and 12 weeks, acupuncture decreased the number of flushes more (p<0.05; p<0.01, respectively) than placebo. At 12 weeks, applied relaxation decreased the number of flushes more (p<0.05) than placebo. The Kupperman index score decreased in all groups except the placebo group. The decrease in score was significantly greater in all treatment groups than in the placebo group (p<0.01). CONCLUSION: Acupuncture and applied relaxation both reduced the number of hot flushes significantly better than placebo and should be further evaluated as alternatives to hormone therapy in women with menopausal vasomotor complaints.

Vasomotor symptoms decrease in women with breast cancer randomized to treatment with applied relaxation or electro-acupuncture: a preliminary study.

OBJECTIVE: To evaluate the effect of applied relaxation and electro-acupuncture on vasomotor symptoms in women treated for breast cancer. METHODS: Thirty-eight postmenopausal women with breast cancer and vasomotor symptoms were randomized to treatment with electro-acupuncture (n = 19) or applied relaxation (n = 19) during 12 weeks. The number of hot flushes was registered daily in a logbook before and during treatment and after 3 and 6 months of follow-up. RESULTS: Thirty-one women completed 12 weeks of treatment and 6 months of follow-up. After 12 weeks of applied relaxation, the number of flushes/24 h had decreased from 9.2 (95% confidence interval (CI) 6.6-11.9) at baseline to 4.5 (95% CI 3.2-5.8) and to 3.9 (95% CI 1.8-6.0) at 6 months follow-up (n = 14). The flushes/24 h were reduced from 8.4 (95% CI 6.6-10.2) to 4.1 (95% CI 3.0-5.2) after 12 weeks of treatment with electro-acupuncture and to 3.5 (95% CI 1.7-5.3) after 6 months follow-up (n = 17). In both groups, the mean Kupperman Index score was significantly reduced after treatment and remained unchanged 6 months after end of treatment. CONCLUSION: We suggest that applied relaxation and electro-acupuncture should be further evaluated as possible treatments for vasomotor symptoms in postmenopausal women with breast cancer.

A comparison of acupuncture and oral estradiol treatment of vasomotor symptoms in postmenopausal women.

OBJECTIVE: To compare the effects of electro-acupuncture with oral estradiol and superficial needle insertion on hot flushes in postmenopausal women. MATERIAL AND METHODS: Forty-five postmenopausal women with vasomotor symptoms were randomized to electro-acupuncture, superficial needle insertion or oral estradiol treatment during 12 weeks, with 6 months' follow-up. The number and severity of flushes were registered daily and the Kupperman index and a general estimate of climacteric symptoms were completed before, during and after therapy. RESULTS: In the electro-acupuncture group, the mean number of flushes/24 h decreased from 7.3 to 3.5 (ANOVA, p < 0.001). Eleven of the 15 women had at least a 50% decrease in number of flushes (with a mean decrease of 82%). Superficial needle insertion decreased the number of flushes/24 h from 8.1 to 3.8 (p < 0.001). In seven out of 13 women, the number of flushes decreased by at least 50% (mean decrease 83%). In the estrogen group, the number of flushes decreased from 8.4 to 0.8 (p < 0.001). The decrease in number of flushes persisted during the 24-week follow-up period in all treatment groups. The Kupperman index and the general climacteric symptom score decreased, and remained unchanged 24 weeks after treatment in all groups (p < 0.001). Electro-acupuncture decreased the number of flushes/24 h significantly over time, but not to the same extent as the estrogen treatment. No significant difference in effect was found between electro-acupuncture and the superficial needle insertion. CONCLUSION: We suggest that acupuncture is a viable alternative treatment of vasomotor symptoms in postmenopausal women and cannot recommend superficial needle insertion as an inactive control treatment.

Effects of electro-acupuncture on psychological distress in postmenopausal women.

OBJECTIVES: To evaluate effects of electro-acupuncture (EA) on general psychological distress and relate to experience of climacteric symptoms in 30 postmenopausal women. DESIGN: A randomised single-blind controlled design was used to evaluate effects of EA and extremely superficial needle insertion, with the latter serving as a near-placebo control. SETTINGS: The Linköping University Hospital in Sweden. INTERVENTIONS: Fourteen treatments during 12 weeks with follow-ups at 3 and 6 months. OUTCOME MEASURES: General psychological well-being, mood and experience of climacteric symptoms. RESULTS: Mood Scale improved only in EA group and not until 12 weeks compared to baseline, from 110 to 129 (P = 0.01), and to 120 at 3-month follow-up (P = 0.04). Mood was significantly better than control at 8 (P = 0.05) and 12 weeks (P = 0.01). Visual analogue scale estimation of climacteric symptoms was decreased at 4 weeks in both groups, and lasted throughout the study period, in EA group from 5 to 2 (P = 0.04) and in control group from 5 to 3 (P = 0.02) at 6-month follow-up. Well-being was ameliorated from 4 weeks in EA and from 8 weeks in control group until end of study (P = 0.01, P = 0.03). No significant differences on climacteric symptoms or well-being existed between the groups. CONCLUSIONS: This study does not show that EA is better than superficial needle insertion for the amelioration of general psychological distress and experience of climacteric symptoms in women with vasomotor symptoms after menopause. However, the more pronounced effect on mood suggests that EA might have additional effects compared with superficial needle insertion.

Urinary excretion of calcitonin gene-related peptide in males with hot flushes after castration for carcinoma of the prostate.

OBJECTIVE: The majority of men who undergo surgical or medical castration due to prostatic carcinoma develop vasomotor symptoms with hot flushes. The mechanisms behind these symptoms are poorly understood. One possible explanation is a release of the vasodilatory peptide calcitonin gene-related peptide (CGRP) from perivascular nerves, which seem to be involved in the mechanisms behind vasomotion and sweating in postmenopausal women. The aim of this report was to investigate whether CGRP is involved in vasomotion in men after castration therapy. MATERIAL AND METHODS: Twenty-four hour urine excretion of CGRP was analysed in 15 men with prostatic carcinoma, using radioimmunoassay before and 3 months after surgical or medical castration. RESULTS: Eleven of the 15 men developed hot flushes during the observation period of 3 months. Twenty-four hour urine excretion of CGRP did not change significantly after castration, either in the group as a whole or in those 11 men who developed hot flushes. CONCLUSIONS: Even though we did not observe any significant changes in 24-h urine excretion of the potent vasodilator CGRP after castration it is possible that serum levels of CGRP increase during hot flushes, without having an effect on the 24-h urine excretion of the peptide.

Few oligo-amenorrheic athletes have vasomotor symptoms.

OBJECTIVE: To assess whether women with athletic oligo-amenorrhea have vasomotor symptoms. MATERIAL AND METHODS: A mailed questionnaire was sent to 252 female athletes about vasomotor symptoms. Identical questions were also mailed to 1523 peri- and postmenopausal women. RESULTS: The prevalence of vasomotor symptoms was low in female athletes with oligo- and amenorrhea and similar to that found in athletes with regular menstruations. The prevalence was significantly lower than in menopausal women. Although more than a third of the menopausal women had hormone replacement therapy, 30% of them still had vasomotor symptoms at least every week compared with only 2% of the oligo-amenorrheic athletes. CONCLUSION: Vasomotor symptoms are very uncommon in oligo-amenorrheic athletes, although many of them are hypoestrogenic. It was suggested that one factor contributing to these symptoms around menopause is low hypothalamic activity of beta-endorphins, which makes the thermoregulatory centre labile. On the other hand, supraphysiological activity in hypothalamic beta-endorphins may cause the oligo-amenorrhea in athletes, but may stabilise the thermoregulatory centre and thus prevent hot flushes.

Concentrations of calcitonin gene-related peptide and neuropeptide Y in plasma increase during flushes in postmenopausal women.

OBJECTIVE: To assess whether the plasma concentrations of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), or neurokinin A (NKA) increase during hot flushes in postmenopausal women with vasomotor symptoms. DESIGN: Eight postmenopausal women (age range = 49-63 years) with vasomotor symptoms were included. During 1 day, repeated blood samples were taken between and during flushes; four samples were taken during each flush. The samples were analyzed for CGRP, NPY, and NKA using radioimmunoassay technique. RESULTS: The serum concentrations of CGRP and NPY increased significantly-73% and 34%, respectively-during the flushes (p = 0.018; p = 0.028), whereas the concentrations of NKA did not change significantly. CONCLUSIONS: CGRP and NPY may be involved in the mechanisms that cause vasomotor symptoms.

Postmenopausal women without previous or current vasomotor symptoms do not flush after abruptly abandoning estrogen replacement therapy.

BACKGROUND: Most but not all women suffer from vasomotor symptoms around menopause. The exact mechanisms behind these symptoms are unknown, but the rate of decline in estrogen concentrations has been suggested to affect the risk of hot flushes. OBJECTIVE: The objective was to assess whether vasomotor symptoms were induced in women without previous such symptoms, when the women were given combined estradiol and progestagen therapy for 3 months, whereafter therapy was abruptly withdrawn. MATERIALS AND METHOD: After randomization, 40 postmenopausal women without previous or current vasomotor symptoms were treated transdermally with either 50 micrograms/day 17 beta-estradiol or placebo during 14 weeks. During the 13th and 14th weeks, treatment was combined with oral medroxyprogesterone acetate 10 mg/day. Serum estradiol and follicle-stimulating hormone (FSH) concentrations were analysed before and after 12 weeks of therapy. Climacteric symptoms were assessed at the same intervals as well as 8 weeks after the end of therapy. RESULTS: All women had low pretreatment levels of estradiol and high FSH concentrations. During estradiol therapy estradiol levels increased significantly, whereas FSH only decreased slightly. No woman developed vasomotor symptoms after withdrawal of therapy. CONCLUSION: Postmenopausal women without previous or current vasomotor symptoms did not develop such symptoms when estrogen replacement therapy was first instituted and then abruptly stopped. Probably other factors than the rate with which estrogen concentrations decrease determine whether or not a woman will develop vasomotor symptoms. Evidently, estrogens can be prescribed to a woman who has no vasomotor symptoms, without much risk of inducing such symptoms if she decides to abandon therapy, even after 3 months of treatment.

Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma: a pilot study.

PURPOSE: Most men who undergo castration therapy for prostatic carcinoma will have vasomotor symptoms that usually persist for years. Vasomotor symptoms are elicited from the thermoregulatory center, possibly due to a decrease in hypothalamic opioid activity induced by low sex steroid concentrations. Acupuncture treatment in women, which stimulates hypothalamic opioid activity, alleviates vasomotor symptoms. We report on men treated with acupuncture for relief of vasomotor symptoms after castration therapy. MATERIALS AND METHODS: We asked 7 men with vasomotor symptoms due to castration therapy to receive acupuncture treatment 30 minutes twice weekly for 2 weeks and once a week for 10 weeks. Effects on flushes were recorded in logbooks. RESULTS: Of the 7 men 6 completed at least 10 weeks of acupuncture therapy and all had a substantial decrease in the number of hot flushes (average 70% after 10 weeks). At 3 months after the last treatment the number of flushes was 50% lower than before therapy. Therapy was discontinued after 10 weeks because of a femoral neck fracture in 1 man and after 3 weeks due to severe back pain in 1. CONCLUSIONS: Acupuncture may be a therapeutic alternative in men with hot flushes after castration therapy and merits further evaluation.

Effects of physical activity and acupuncture on calcitonin gene-related peptide immunoreactivity in different parts of the rat brain and in cerebrospinal fluid, serum and urine.

Calcitonin gene-related peptide (CGRP) is a very potent vasodilator in the nervous system, and may be involved in hot flushes experienced by most women around menopause. Flushing post-menopausal women had higher urinary excretion of CGRP before than after successful treatment of their flushes with acupuncture. The prevalence of vasomotor symptoms is lower in physically active women. In a rat model we therefore intended to assess whether acupuncture and exercise affected CGRP concentrations in different parts of the brain and peripherally. The aim of the study was to elucidate the short- and long-term effects of exercise and acupuncture on CGRP concentrations in the nervous system of normal adult rats. In a rat model, we examined the effects of single interventions and long-term treatment with physical exercise and manual or electro-acupuncture on CGRP concentrations in urine, cerebrospinal fluid and serum and different parts of the brain. In all compartments studied, but significantly only in the cerebrospinal fluid, CGRP increased after a single session of physical exercise or electro-acupuncture. Manual acupuncture did not change CGRP concentrations in any compartment. Rats had the highest concentrations of CGRP in the pituitary and hypothalamus but the concentrations did not differ significantly between control rats and those subjected to long-term treatment with manual or electro-acupuncture or running rats. Rats treated with electro-acupuncture had twice the CGRP concentration in the frontal cortex compared to control rats, albeit the difference did not reach statistical significance. Evidently manual and electro-acupuncture have different effects, whereas electro-acupuncture and physical exercise have more similar effects on CGRP production and/or release. To elucidate the role of CGRP in vasomotor symptoms, further studies with older flushing rats should be performed.

Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.

OBJECTIVES: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. MATERIAL AND METHODS: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. RESULTS: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. CONCLUSION: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

[Estrogen and natural products in the treatment of postmenopausal complaints. Oral contraceptives prepare the way for hormonal substitution]. / Ostrogen och naturmedel vid postmenopausala besvär. P-piller banar väg för hormonsubstitution.

To chart current and previous use of hormone replacement therapy (HRT) and alternative remedies in a postmenopausal population, in relation to previous oral contraceptive (OC) usage, all 1,323 55-56-year-old women living in Linköping in 1995 were sent a questionnaire concerning health status and climacteric symptoms, and previous and/or current use of HRT, OCs and alternative remedies. Current HRT was more common among previous OC users than among those who had never used OCs (41.4 vs. 23.1 percent). As compared with non-HRT users, HRT users were characterised by greater physical activity but less strenuous occupations, and a higher prevalence of hysterectomy. Of the series as a whole, 35 per cent were currently on HRT, half of them having been so for at least two years, and only 5 per cent had abandoned HRT after trying it for some time. Alternative remedies were used by 5 per cent of the women as therapy for climacteric complaints, but about four times as many women had tried such therapy and abandoned it. The sole characteristic feature of alternative remedy usage was that it was less common among hysterectomised women. Of women treated for breast cancer, none used HRT and few used alternative remedies. Thus, in this postmenopausal population, the prevalence of HRT was high, as was the level of compliance. Previous OC usage was probably a determinant of current attitudes toward HRT.

Problem-based medical education: development of a theoretical foundation and a science-based professional attitude.

Problem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evidence as to whether our present evaluation is correct.

Hormone replacement therapy and previous use of oral contraceptives among Swedish women.

OBJECTIVES: To assess the current and previous use of hormone replacement therapy (HRT) and alternative remedies in a postmenopausal population and to relate HRT use to previous use of oral contraceptives. MATERIAL AND METHODS: All 1323 women living in Linköping of 55 or 56 years old during 1995 were sent a questionnaire asking for data with relation to health and climacteric symptoms as well as to previous and current use of HRT, oral contraceptives and alternative remedies. RESULTS: Current use of HRT was more common among women who previously used oral contraceptives (41.3%) than among women who had never used oral contraceptives (23.1%). HRT users were also more often physically active, had undergone hysterectomy and had lighter occupation than non-users. Of all women 35% were current users of HRT, half of them for at least 2 years, whereas only 5% had tried HRT and abandoned therapy. Alternative remedies were used by 5% of the women as therapy for climacteric complaints, and about four times as many women had tried such therapy but abandoned it. The only characteristic about use of alternative medicines was that they were used less often by women who had been hysterectomized. No women treated for breast cancer used HRT and only few of them used alternative remedies. CONCLUSIONS: The prevalence of HRT use, as well as compliance, was high. Previous use of oral contraceptives probably affected the attitude towards using HRT.

[Acupuncture against climacteric disorders? Lower number of symptoms after menopause]. / Akupunktur mot klimakteriebesvär? Färre vegetativa symtom efter menopaus.

Vasomotor symptoms are very common among perimenopausal women, but also among orchidectomized men. The cause of the symptoms is not the low steroid concentrations per se, but probably changes in central neuropeptide activity. Twenty-four healthy women with natural menopause, suffering from hot flushes, were included in the study and randomly assigned to either of two groups, one group received treatment with electrostimulated acupuncture (EA), the other with superficial needle position (SNP) acupuncture. Treatment was given for totally of eight weeks, twice a week during the first two weeks, and then once a week for the remaining six weeks. As recorded in logbooks kept by the participants, the frequency of flushes decreased significantly by more than 50 per cent in both groups, and remained decreased in the EA group, whereas in the SNP group it increased slightly again over the three months after treatment. Values for the Kupperman Index decreased in both groups during treatment, changes still evident at three-month follow-up, whereas the self-rated general climacteric symptoms (VAS) decreased significantly in the EA group only. The PGWB (Psychological General Well-Being) index did not change significantly in either group during treatment.