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.

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.

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.

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.

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.

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.

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.