Anna-Clara Spetz

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.

Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate.

PURPOSE We evaluated the incidence and frequency of, and distress due to hot flashes after castration therapy with polyestradiol phosphate and complete androgen ablation. MATERIALS AND METHODS A total of 915 men with metastatic prostate carcinoma enrolled in the Scandinavian Prostatic Cancer Group-5 trial study were randomized to intramuscular injections of 240 mg. Polyestradiol phosphate every 2 weeks for 8 weeks followed by monthly subcutaneous injections or complete androgen ablation, that is bilateral orchiectomy or 3.75 mg. of the gonadotropin-releasing hormone analog triptorelin monthly combined with 250 mg. of the antiandrogen flutamide 3 times daily. The incidence and frequency of, and distress due to hot flashes were recorded at regular intervals using a questionnaire. RESULTS Of the 915 men 901 were evaluated at a median followup of 18.5 months. The incidence of hot flashes was 30.1% and 74.3% in the polyestradiol phosphate and complete androgen ablation groups, respectively (p <0.001). In the polyestradiol phosphate group the frequency of and distress due to hot flashes were significantly lower than in the androgen ablation group. There was complete relief from hot flashes in 50% of the men on polyestradiol phosphate during followup compared with none on androgen ablation. The incidence of hot flashes did not differ in men with and without tumor progression. CONCLUSIONS Endocrine treatment with polyestradiol phosphate induced fewer and less distressing hot flashes than complete androgen ablation. Flashes also disappeared to a greater extent during polyestradiol phosphate than during androgen ablation. The data in this study enable us to provide thorough individual information to patients on the risk and grade of expected distress and duration of hot flashes during polyestradiol phosphate or complete androgen ablation treatment.

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. (Menopause 2000;7:25‐30.

Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate

PURPOSE In women the vasodilatory neuropeptides calcitonin gene-related peptide and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed whether plasma calcitonin gene-related peptide and neuropeptide Y change during hot flashes in men after castration. MATERIALS AND METHODS We evaluated 10 men 61 to 81 years old who underwent castration due to cancer of the prostate and had frequent hot flashes for changes in plasma calcitonin gene-related peptide and neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples were obtained between flashes and 4 were obtained during each flash. The samples were analyzed for calcitonin gene-related peptide and neuropeptide Y using radioimmunoassay technique. Hot flashes were objectively recorded by measuring peripheral skin temperature and skin conductance. RESULTS Plasma calcitonin gene-related peptide increased 46% (95% confidence interval 21 to 71) during flashes in the 6 men in whom it was measurable. This change was statistically significant (p = 0.028). The concentration of neuropeptide Y was below the detection limit. Skin conductance and temperature increased significantly during flashes. CONCLUSIONS Calcitonin gene-related peptide is involved in the mechanisms of hot flashes in men who underwent castration due to prostate carcinoma. Thus, there may be a similar mechanism of hot flashes in women and in men deprived of sex steroids.

HOT FLUSHES IN A MALE POPULATION AGED 55, 65, AND 75 YEARS, LIVING IN THE COMMUNITY OF LINKOPING, SWEDEN

Objective Hot flushes are as common in castrated men as in menopausal women. We investigated whether hot flushes exist in a normal aging male population and to what extent. Design A questionnaire was sent to all men living in Linköping, Sweden, who were 55, 65, and 75 years old (N = 1,885). The questionnaire asked for demographic data, medical history, mood status, medication, castrational therapy, and smoking, exercise, and alcohol habits, among other items. We asked specifically for current hot flushes unrelated to exercise or a warm environment. Results Of the questionnaires received, 1,381 were eligible for evaluation; 33 were analyzed separately because these men had been castrated. Hot flushes of any frequency were reported by 33.1% of noncastrated men, 4.3% reported flushes at least a few times per week, and 1.3% reported daily flushes. Half of the men reporting flushes were also bothered by them, ie, almost every sixth man in total. We found a relation between occurrence of hot flushes and other symptoms thought to be related to low testosterone concentration, such as decreased muscle strength or endurance, decreased enjoyment of life, sadness or grumpiness, and lack of energy (P < 0.05). Conclusions Hot flushes occur in one third of a population of noncastrated older men, approximately half of whom consider flushes as bothersome. Neither the mechanisms nor whether the symptoms would respond to testosterone supplementation is known. Androgen substitution to treat symptoms possibly related to a male climacteric is still controversial. Studies are needed to evaluate the needs for and the effects of androgen treatment on vasomotor symptoms.

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.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.

Symptoms in peri- and postmenopausal women in relation to testosterone concentrations: data from The Women's Health in the Lund Area (WHILA) study

Objectives The aim of this study was to investigate possible associations between androgen concentrations in perimenopausal women and symptoms that may be associated with low androgen concentrations in the blood. Methods All women born in the period 1935–1945 and living in a defined geographic area in Sweden (n = 10 766) were invited to a screening program that included physical and laboratory examinations and a questionnaire. Three groups were identified: premenopausal women, women on hormone replacement therapy (HRT) and postmenopausal women without HRT. Concentrations of testosterone, androstendione, sex hormone binding globulin and estradiol were measured. Waist–hip ratio, body mass index and free testosterone index (FTI) were calculated. Results A total of 6908 women participated. The women on HRT had lower testosterone and FTI and were less satisfied with mood and energy (p < 0.05). Women with hot flushes had higher testosterone and FTI and women reporting coldness had lower concentrations (p < 0.05). Sexual well-being was not correlated to testosterone or FTI (p > 0.05). Conclusions Lower testosterone concentrations were associated with lower quality of life in perimenopausal women but not to sexual well-being. There must be factors other than decrements in sex hormones that contribute to the emergence of some perimenopausal symptoms.

Calcitonin gene-related peptide during sweating in young healthy women

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.

Use of hormone therapy in Swedish women aged 80 years or older.

ObjectiveMenopausal 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. MethodsThe 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. ResultsOf 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. ConclusionsOur 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.

Hot flushes in men : Prevalence and possible mechanisms

In men treated with castration because of prostatic carcinoma hot flushes are as common as in women after menopause. Flushes also occur in normal ageing men, but the prevalence is unknown. Hot flushes are probably caused by an instability in the thermoregulatory centre, because of decreased sex hormone concentrations. Calcitonin gene-related peptide (CGRP) is involved in menopausal hot flushes in women and possibly in men with castrational therapy. Serotonin may also be implicated. Alternative treatments for hot flushes are needed, since men with prostatic carcinoma may not be treated with testosterone, and oestrogen therapy in men has many draw-backs. Therefore, development of a CGRP-antagonist may be useful. In conclusion vasomotor symptoms are common in men with castrational therapy and also exist in normal, ageing men. Since CGRP, serotonin and a decrease in sex steroids seem to be involved in hot flushes, the mechanisms behind hot flushes in men and women may be similar.