Mats Hammar

Increased Risk of Recurrence After Hormone Replacement Therapy in Breast Cancer Survivors

BACKGROUND Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. METHODS HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. RESULTS Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test). CONCLUSION After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.

Physical exercise and vasomotor symptoms in postmenopausal women

BACKGROUND The mechanisms causing postmenopausal vasomotor symptoms are unknown, but changes in hypothalamic beta-endorphins have been suggested to be involved. beta-endorphin production may be increased by regular physical exercise. OBJECTIVE To assess if physically active women suffered from vasomotor symptoms to a lower extent than sedentary women. MATERIAL AND METHODS All women (n = 1323) in the ages ranging from 55-56 years in the community of Linköping Sweden, were included. In a questionnaire these women were asked about their physical exercise habits and their complaints from vasomotor symptoms. Only those 793 women who had reached a natural menopause were grouped into sedentary, moderately or highly active women, based on a physical activity score. RESULTS Only 5% of highly physically active women experienced severe hot flushes as compared with 14-16% of women who had little or no weekly exercise (P < 0.05; relative risk 0.26; CI 95%: 0.10-0.71). This was not explained by differences in body mass index, smoking habits or use of hormone replacement therapy. Women who used hormone replacement therapy were more physically active than non-users (P < 0.05). CONCLUSION Fewer physically active women had severe vasomotor symptoms compared with sedentary women. This may be due to a selection bias but also to the fact that physical exercise on a regular basis affects neurotransmitters which regulate central thermoregulation.

Pros and cons of vertical integration between clinical medicine and basic science within a problem-based undergraduate medical curriculum: examples and experiences from Linkoping, Sweden.

Problem-based learning (PBL), combined with early patient contact, multiprofessional education and emphasis on development of communications skills, has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping (FHS), Sweden, which was started in 1986. Important elements in the curriculum are vertical integration, i.e. integration between the clinical and basic science parts of the curriculum and horizontal integration between different subject areas. This article discusses the importance of vertical integration in an undergraduate medical curriculum, according to experiences from the Faculty of Health Sciences in Linköping, and also give examples on how it has been implemented during the latest 15 years. Results and views put forward in published articles concerning vertical integration within undergraduate medical education are discussed in relation to the experiences in Linköping. Vertical integration between basic sciences and clinical medicine in a PBL setting has been found to stimulate profound rather than superficial learning, and thereby stimulates better understanding of important biomedical principles. Integration probably leads to better retention of knowledge and the ability to apply basic science principles in the appropriate clinical context. Integration throughout the whole curriculum entails a lot of time and work in respect of planning, organization and execution. The teachers have to be deeply involved and enthusiastic and have to cooperate over departmental borders, which may produce positive spin-off effects in teaching and research but also conflicts that have to be resolved. The authors believe vertical integration supports PBL and stimulates deep and lifelong learning.

Effects of acupuncture on climacteric vasomotor symptoms, quality of life, and urinary excretion of neuropeptides among postmenopausal women

Most perimenopausal women suffer from vasomotor symptoms. Changes in central opioid activity have been proposed to be involved in the mechanisms of hot flushes after menopause. Because acupuncture increases central opioid activity, it may affect postmenopausal hot flushes. The aim was to study if and to what extent two different kinds of acupuncture affected postmenopausal hot flushes, urinary excretion of certain neuropeptides, and quality of life in a group of postmenopausal women. Twenty-four women with natural menopause and hot flushes were included. Twenty-one women completed the study. One group was randomized to electroacupuncture at 2 Hz, whereas the other group was treated with another form of acupuncture (i.e., superficial needle insertion) for a total of 8 weeks. All women daily registered the number and severity of flushes from 1 month before to 3 months after treatment. They completed Quality of Life questionnaires before, during, and after treatment. Twenty-four-hour urine was sampled before, during, and after treatment and analyzed for neuropeptides using radioimmunoassay methods. The number of flushes decreased significantly by >50% in both groups and remained decreased in the group receiving electroacupuncture, whereas in the superficial-needle-insertion group, the number of flushes increased again during the 3 months after treatment. The Kupperman Index decreased significantly in both groups during and after treatment. The excretion of the potent vasodilating neuropeptide calcitonin gene-related peptide-like immunoreactivity decreased significantly during treatment. Acupuncture significantly affects hot flushes and sweating episodes after menopause, with effects persisting at least 3 months after the end of treatment. Changes in calcitonin gene-related peptide, which is a very potent vasodilator, could be involved in the mechanisms behind hot flushes.

Climacteric symptoms among women aged 60–62 in Linköping, Sweden, in 1986

By means of a simple postal questionnaire, all women aged 60, 61 and 62 (n = 2015) living in the community of Linköping, Sweden, were screened for vasomotor symptoms and local vaginal complaints. After one reminder, answers were received from 73% of the women. At the time of the survey (April 1986) all the women were post-menopausal, the median period since menopause being 11 yr. Slightly over one in four of the women (27%) were suffering from sweating and hot flushes. Ten percent (10%) of the women who were more than 15 yr post-menopausal still had moderate to severe climacteric symptoms. Vasomotor symptoms were significantly more common among oophorectomized women than among those whose ovaries were intact. Local vaginal symptoms were positively correlated with urinary problems, repeated urinary tract infections and a high risk of disturbance of sexual activity. It was concluded that climacteric symptoms often persist for more than 15 yr after the menopause.

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.

DOES PHYSICAL EXERCISE INFLUENCE THE FREQUENCY OF POSTMENOPAUSAL HOT FLUSHES

The frequency of moderate and severe hot flushes was investigated in a group of women (n=142) who took part in organized physical exercise on a regular basis, and a control group of all women 52 and 54 years old in the city of Linkoping, Sweden (n = 1,246). Only women with natural menopause and without a history of hormonal replacement treatment were statistically compared in the study. It appeared that moderate and severe vegetative symptoms with hot flushes and sweatings were only half as common among the physically active postmenopausal women (21.5%) as in the control group (43.8%). Although this could be due to a positive selection of these physically active women, it might also be due to the fact that exercise may affect the mechanisms that elicit hot flushes in peri‐ and postmenopausal women.

Treatment of menopausal symptoms with applied relaxation: a pilot study.

Applied relaxation (AR) was tested in a series of six women with postmenopausal hot flushes. The AR program consisted of group instructions 1 hour per week over a 12 week duration. The number of flushes were registered from 1 month before to 6 months after training AR. Menopausal symptoms (Kupperman Index), psychological well-being (Symptom Checklist), and mood (MOOD Scale) were measured at various moments during the study. For the six patients the number of flushes decreased from the baseline period to 6 months follow-up with 59, 61, 62, 67, 89 and 100% respectively, in mean 73%. While the scores on the Kupperman Index and the Symptom Checklist followed the pattern of the flushes, a similar trend was not seen for the scores on the MOOD Scale.

The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial

Objective: This study compared the effectiveness of individualized acupuncture plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women. Methods: This study involved a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing, on average, seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received 10 acupuncture treatment sessions and advice on self-care, and the control group received advice on self-care only. The frequency and severity (0-10 scale) of hot flashes were registered in a diary. Urine excretion of calcitonin gene-related peptide was assessed at baseline and after 12 weeks. The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. The secondary endpoint was change in health-related quality of life measured by the Womens Health Questionnaire. Results: Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n = 133), a difference of 2.1 (P < 0.001). Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4 (P < 0.001). The acupuncture group experienced statistically significant improvements in the vasomotor, sleep, and somatic symptoms dimensions of the Womens Health Questionnaire compared with the control group. Urine calcitonin gene-related peptide excretion remained unchanged from baseline to week 12. Conclusions: Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women.

Vasomotor symptoms and quality of life in previously sedentary postmenopausal women randomised to physical activity or estrogen therapy

OBJECTIVE To assess if regular physical exercise or oral oestradiol therapy decreased vasomotor symptoms and increased quality of life in previously sedentary postmenopausal women. SETTING A prospective, randomised trial at a University Hospital. METHODS 75 postmenopausal, sedentary women with vasomotor symptoms were randomised to: exercise three-times weekly over 12 weeks (15 women), oral oestradiol therapy for 12 weeks (15 women) and 45 women to three other treatment arms. Results from the exercise and oestradiol groups are presented here. The effects on vasomotor symptoms and wellbeing were assessed with logbooks and validated questionnaires. RESULTS Ten women fulfilled 12 weeks of exercise. The number of flushes was rather unchanged in five women and decreased to 28% (range 18-42%) of baseline in the other five women. Five of the ten women continued to exercise another 24 weeks, thus in all 36 weeks. The mean number of flushes decreased by about 50% in these five women (from 6.2/24 to 3.2 flushes/24 h at 36 weeks). In the same group a score made as the product of reduction in number and severity of flushes decreased by 92% at 12 weeks, 75% at 24 weeks and 72% at 36 weeks compared with baseline. In the estrogen group flushes decreased from 8.4 to 0.8 (P<0.001) after 12 weeks of therapy and remained at this level after 36 weeks. Well-being according to different measurements improved significantly in both groups, albeit more markedly in the estrogen group. CONCLUSIONS Apart from many other health benefits regular physical exercise may decrease vasomotor symptoms and increase quality of life in postmenopausal women, but this has to be further evaluated scientifically. Exercise should be introduced gradually to ensure compliance.