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Hot flushes are common and troublesome symptoms of menopause. The neuropeptide calcitonin gene-related peptide (CGRP) is increased in plasma during hot flushes but it has not been clear if CGRP is causally involved in the mechanism underpinning the flushes. Here, we examined the effect of interventions with CGRP in a mouse model of hot flushes based on flush-like temperature increases triggered by forced physical activity in ovariectomized mice. Compared to normal mice, ovariectomized mice reacted with an exaggerated, flush-like, temperature increase after physical exercise. This increase was completely blocked by the non-peptide CGRP-antagonist MK-8825 (-0.41 degrees Celsius, 95% CI: -0,83 to 0,012, p < 0.0001) at a dose that had no obvious effects on locomotor activity (50 mg/kg). Further, the flush-like temperature increases were strongly attenuated in ovariectomized mice lacking αCGRP due to a genetic modification. Collectively, our findings suggest that CGRP is an important mediator of experimentally induced hot flushes and they identify CGRP antagonists as promising treatment candidates for women and possibly also men with hot flushes.

Objectives: Hot flushes and night sweats affect 75% of all women after menopause and is a common reason for decreased quality of life in mid-aged women. Hormone therapy is effective in ameliorating symptoms but cannot be used by all women due to contraindications and side effects. Engagement in regular exercise is associated with fewer hot flushes in observational studies, but aerobic exercise has not proven effective in randomized controlled trials. It remains to be determined whether resistance training is effective in reducing hot flushes and improves quality of life in symptomatic postmenopausal women. The aim of this study is to investigate the effect of standardized resistance training on hot flushes and other health parameters in postmenopausal women., Study Design: This is an open, parallel-group, randomized controlled intervention study conducted in Linköping, Sweden. Sixty symptomatic and sedentary postmenopausal women with a mean of at least four moderate to severe hot flushes per day or 28 per week will be randomized to an exercise intervention or unchanged physical activity (control group). The intervention consists of 15 weeks of standardized resistance training performed three times a week under supervision of a physiotherapist., Main Outcome Measures: The primary outcome is hot flush frequency assessed by self-reported hot flush diaries, and the difference in change from baseline to week 15 will be compared between the intervention group and the control group., Conclusion: The intention is that this trial will contribute to the evidence base regarding effective treatment for hot flushes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48-51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50-55% vs 46%, 95% CI 43-48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Menopausal symptoms such as hot flashes and night sweats may persist for 10 to 20 years or even longer. Information about the extent to which older women use hormone therapy is limited. The aim of this study was to determine the use of hormone therapy in Swedish women aged 80 years or older., Methods: The study is based on national register data on dispensed drug prescriptions (ie, prescribed therapy that has been provided to individuals by pharmacies) for hormone therapy and local low-dose estrogens., Results: Of 310,923 Swedish women who were aged at least 80 years, 609 (0.2%) were new users of hormone therapy. A total of 2,361 women (0.8%) were current users of hormone therapy. The median duration of hormone therapy use in new users was 257 days (25th to 75th percentiles, 611-120 d). About one in six women aged 80 years or older had used local vaginal estrogen therapy for at least four 3-month periods. The drugs were mainly prescribed by gynecologists and general practitioners., Conclusions: Our results show that a number of women aged 80 years or older still use hormone therapy and that most women who started a new treatment period had only one or two dispensations despite the median duration of treatment being more than half a year. Because at least some of the women aged 80 years or older who used hormone therapy probably did so owing to persistent climacteric symptoms, vasomotor symptoms and hormone therapy are still relevant issues that need to be discussed when counseling women around and after age 80.

Purpose: Acupuncture has been suggested as therapy for hot flashes in women with breast cancer and men with prostate cancer. In this systematic review, we sought to evaluate the long-term effects on vasomotor symptoms after the end of a defined treatment period of acupuncture in women with breast cancer and men with prostate cancer., Methods: A literature search revealed 222 articles within the field. With defined exclusion criteria, we identified 17 studies. We also used the Jadad quality score and identified seven studies with a score of at least 3., Results: Six of seven identified studies qualified for inclusion in an analysis that measured frequency of hot flashes weighted in relation to number of patients (n=172). The average reduction from baseline to end of acupuncture (ranging between 5 and 12 weeks of treatment) showed 43.2 % reduction of hot flashes. At the last follow-up (mean 5.8 months, range 3-9 months) after the end of therapy, the weighted reduction from baseline was sustained at 45.6 % in the 153 of 172 patients (89 %) who were followed up., Conclusions: Data from six prospective analyzed studies indicate at least 3-month effects after the end of acupuncture treatment for flashes in women with breast cancer and men with prostate cancer. However, larger randomized trials with long-term follow-up will be needed to confirm these preliminary findings.

The mechanisms behind hot flashes in menopausal women are not fully understood. The flashes in women are probably preceded by and actually initiated by a sudden downward shift in the set point for the core body temperature in the thermoregulatory center that is affected by sex steroids, β-endorphins, and other central neurotransmitters. Treatments that influence these factors may be expected to reduce hot flashes. Since therapy with sex steroids for hot flashes has appeared to cause a number of side effects and risks and women with hot flashes and breast cancer as well as men with prostate cancer and hot flashes are prevented from sex steroid therapy there is a great need for alternative therapies. Acupuncture affecting the opioid system has been suggested as an alternative treatment option for hot flashes in menopausal women and castrated men. The heat loss during hot flashes may be mediated by the potent vasodilator and sweat gland activator calcitonin gene-related peptide (CGRP) the concentration of which increases in plasma during flashes in menopausal women and, according to one study, in castrated men with flushes. There is also evidence for connections between the opioid system and the release of CGRP. In this paper we discuss acupuncture as a treatment alternative for hot flashes and the role of CGRP in this context.

Background: Symptoms of late-onset hypogonadism (LOH) and concentrations of testosterone (T) and bioavailable testosterone (BT) were studied in relation to the data from the same men 5 years earlier., Methods: In 2008, 282 men, aged 60-82 years, answered a questionnaire regarding demographic data, medical history, different symptoms of LOH and the 10 questions from the 'Androgen Decline in Aging Males (ADAM)-questionnaire'. Blood samples were analysed for concentrations of T and calculations were made for BT., Results: A total of 87.2% of the questionnaires were returned and analysed, and 75.2% of the responders gave blood samples. The oldest third of the men were most affected by LOH symptoms (p < 0.05). Both T and BT concentrations decreased during the 5 years (p < 0.05) but only the symptom 'less strong erections' changed significantly (p < 0.05). Men reporting one of the four specific symptoms from the 'ADAM-questionnaire' for the first time in 2008 had a higher loss of T and BT than men who had unchanged or fewer symptoms than that reported in 2003., Conclusions: The magnitude of the decrease in concentrations is a better predictor of LOH than are the actual concentrations of T and BT. A combination of symptoms predicts LOH better than any single symptom.

Objectives: The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy., Design: A randomised, double-blind, double-dummy, group comparative intervention trial., Setting: Multicentre study executed in 32 centres in 7 European countries., Sample: Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years., Methods: Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks., Main Outcome Measures: Prevalence of vaginal bleeding, hot flushes and adverse events., Results: The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001)., Conclusion: Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.

Objectives: With age there is an average decline in the concentration of biologically active testosterone. It is still controversial if this leads to a clinically relevant deficit, "partial androgen deficiency of the ageing man" (PADAM). Our objective was to investigate the prevalence of a series of symptoms possibly associated with PADAM in an assumed normal-population of older men., Methods: We developed a questionnaire including items about symptoms possibly associated with PADAM as well as background data covering demography, medical history, mood status, medication, castration therapy, as well as smoking, exercise and alcohol habits. The 10 items of the ADAM-questionnaire, designed to predict low bio-available T, were also included. The questionnaire was sent to all 1885 men 55, 65 or 75-years-old, living in Linköping, Sweden., Results: We identified a number of symptoms that differed significantly (P < 0.01) between age groups, e.g., "increased abdominal circumference", "decrease in muscle strength and/or endurance", "decreased libido", "less strong erection" and "lack of energy". From factorial analysis we found that the symptoms co-varied in four different groups., Conclusion: The prevalence of a number of symptoms differed significantly between age groups, but we cannot infer that there is a causal connection between an average age-dependent decline in testosterone function and these symptoms. There are several other ways to interpret these results like the existence of concurrent somatic and/or mood disorders or ageing as such. For this purpose further studies including measurements of testosterone concentrations relating to the findings of this study have to be performed.

Calcitonin gene-related peptide (CGRP) concentrations are increased in postmenopausal women and castrated men with symptomatic flushing. We wanted to determine if a CGRP increase exists in the plasma of healthy fertile-age women during sweating. Plasma concentrations of CGRP were measured by radioimmunoassay at maximal sweating during a sauna session and during bicycle exercise both at maximal and 70% of maximal work capacity in 8 healthy women of fertile age. Plasma concentrations of CGRP were unaffected (>90% statistical power) during both experimental sessions. We suggest that sweating itself does not explain the rise in CGRP concentrations observed in flushing postmenopausal women., (Copyright (c) 2005 S. Karger AG, Basel.)

Objective: To establish whether estrogen treatment affects well-being in postmenopausal women without current or previous vasomotor symptoms., Design: Forty postmenopausal women, aged 45-59 years, without current or previous vasomotor complaints, were included. They were randomized to masked treatment with either transdermal 17beta-estradiol 50 microg/24 h or to placebo. At baseline and after 12 and 14 weeks of treatment, the women completed a questionnaire which reflects well-being, the Psychological General Well-Being (PGWB) Index., Results: The women scored high on the PGWB Index, both at baseline and after 12 and 14 weeks of treatment. There was no significant difference in well-being according to PGWB Index between the groups treated with estrogen and placebo, neither at baseline, nor after therapy. Furthermore, there was no difference in change during therapy between the treatment groups., Conclusion: There is a gradual decline in estrogen during the climacteric, and it is controversial to which extent this affects women's mental health. The PGWB scores in this study were high before therapy, reflecting that these women without previous or current vasomotor complaints represented a selected sample. Neither short-term estrogen treatment over 12 weeks nor addition with medroxyprogesterone acetate during 2 weeks improved well-being in postmenopausal women without vasomotor symptoms who had high well-being at baseline.

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.

Female sex hormones have been suggested to affect the risk of low back pain. One reason is the fact that back pain is a very common symptom during pregnancy. It also seems to be a more common problem among female than male athletes, e.g. in soccer. Although there are few scientific data supporting a relationship between female sex hormones, use of oral contraceptives and low back pain, many doctors and physiotherapists advise women with low back pain to avoid oral contraceptives. The aim of this study was to evaluate whether low back pain fluctuated during the menstrual cycle and differed between women using and not using oral contraceptives. A questionnaire was sent to 12 female soccer teams; 261 players answered and 50 players (28 with back pain and 22 controls) fulfilled the prospective study. At baseline the players underwent a thorough clinical examination and then filled in a diary concerning menstrual data, back pain, training and matches during one season. A total of 296 menstrual cycles was analysed. No difference in prevalence or severity of back pain was seen between the different phases of the menstrual cycle or between users and non-users of oral contraceptives. Our data do not support the hypothesis that low back pain is influenced by hormonal fluctuations during the menstrual cycle or by use of oral contraceptives.

Objective: To establish whether hormone replacement therapy affects postural balance in postmenopausal women., Methods: Nineteen healthy postmenopausal women with vasomotor symptoms were included. Median age was 54 years, median time since menopause was 3 years. They underwent dynamic posturography before and after 4 and 12 weeks of transdermal estrogen treatment (17 beta-estradiol 50 micrograms/day) as well as after 2 additional weeks of combined estrogen-progestagen treatment. The dynamic posturography method quantifies the amplitude, frequency, and pattern of body sway and tests the visual, vestibular, and somatosensory systems, which together maintain balance. The two most difficult tests either cancel visual and distort somatosensory inputs or give distorted information from both the visual and somatosensory systems., Results: Hormone replacement therapy increased static balance performance assessed by dynamic posturography. A highly significant improvement was seen in the two most difficult tests between the pretreatment test and the test performed after 4 weeks of estrogen therapy (P < .01, P < .001, respectively). This improvement was sustained after 12 weeks and also during the 14th week, with the women on combined estrogen-progestagen treatment., Conclusion: Estrogen treatment increased balance performance measured by dynamic posturography, indicating that the beneficial effects from estrogens on postmenopausal fracture risk may include central nervous system effects on balance. Two weeks' addition of gestagen to the treatment regimen did not counteract the estrogen effects.

There has been increasing interest in curriculum innovation in many medical schools. The pedagogic principles for learning and for assessment should be congruent. Changing the curriculum and pedagogic principles for medical education implies that the examinations should also be adapted to the new principles. At the Faculty of Health Sciences, Linköping University, we use a student-oriented programme with problem-based learning, early patient contact, multiprofessional integrated education, and integration between basic science and clinical medicine and between traditional medical subjects. We also encourage the students to adopt a scientific attitude from the very beginning. To assess the students at the conclusion of the medical curriculum, we have developed a new form for the final examination containing measurements of clinical ability based on a videotaped patient consultation, an assessment of the student's performance and presentation of a scientific project, the student's analysis of a published scientific paper and an extensive oral examination based on the students' own scientific papers. Our experience, including results from questionnaires to students and teachers, is that the method is suitable for a final examination and assesses qualities that we previously were not able to assess.

Urinary citrate affects the ion-activity products of calcium oxalate and calcium phosphate and inhibits the growth of these crystals. Women are less prone to develop calcium stones and because they also excrete more citrate than men, an effect of sex steroids on citrate excretion might be important. We therefore analysed urinary citrate and creatinine before and during treatment with estrogen alone or together with medroxyprogesterone acetate in 29 postmenopausal women and at different gestational ages in 19 pregnant women. Urinary citrate and creatinine was also determined before and after orchidectomy in ten men with carcinoma of the prostate. The excretion of citrate and the ratios between citrate and creatinine were not significantly altered by pregnancy or orchidectomy. Neither did treatment with estrogen or estrogen/medroxyprogesterone acetate affect these variables. We were unable to explain the difference in citrate excretion between men and women by effects of sex steroids.