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Vasomotor symptoms in men and the role of Calcitonin Gene-Related Peptide
Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Department of Biomedicine and Surgery, Urology. Linköping University, Faculty of Health Sciences.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hot flushes is a cotmnon phenomenon in women during the menopausal transition. In men treated with castration because of prostate cancer, hot flushes are probably the most cotmnon and distressing side-effect and are as common in these men as in menopausal women but the course of the flushes is unknown. Flushes also occur in healthy aging men, but the prevalence is unknown. The mechanisms behind hot flushes are not fully understood. They are probably caused by instability in the thermoregulatory centre due to a decrease in sex hotmone concentrations. Calcitonin Gene-Related Peptide (CGRP) and perhaps also Neuropeptide Y (NPY) are probably involved in menopausal hot flushes in women and could also be involved in men following therapeutic castration.

The aims of this thesis were to compare different methods of castration as regards the occunence and course of hot flushes, and to investigate the prevalence of hot flushes in an unselected population of elderly men. A further aim was to see if CGRP and NPY are involved in hot flushes in men, in the same way as has previously been suggested in women.

In this thesis two different modalities of castration therapy were compared: 1. castration by means of estrogens (Polyestradiol phosphate) and 2. total androgen blockade (a. bilateral orchiectomy or b. GnRH-analogue combined with oral anti-androgen). A much lower incidence of hot flushes were seen in the first group (1). Flushes induced by castration with estrogen were also milder and tended to disappear with time.

The prevalence of hot flushes in a male population 55 years of age and above was investigated by means of a questionnaire. Thirty per cent of the men repotted flushes and half of these found the flushes distressing, i.e. every sixth man in the study. There was an association between flushes and a number of symptoms that are often related to low testosterone concentrations in the blood.

The 24-hour urinaty excretion of CGRP was investigated in 17 men with prostate cancer before and after castration. Thirteen of the 17 men developed hot flushes after castration, but the urinary excretion of CGRP was not significantly altered.

Blood-samples were taken during hot flushes in 10 men for analysis of CGRP- and NPY-plasma concentrations. CGRP increased in 6 men (we failed to obtain CGRP measurements in the other men due to technical problems). NPY concentrations were below the detection limit for the analysis in all samples.

In conclusion vasomotor symptoms are common in men subjected to castration therapy. Different castration modalities result in different prevalence of hot flushes, something that should be considered when choosing the method of castration for men with prostate cancer. Hot flushes also occur in normal, aging men. The mechanisms behind hot flushes in men and women may be similar. CGRP may be involved in hot flushes in castrated men.

In order to be able to develop new treatment regimens for these vasomotor symptoms fmther studies on the mechanisms behind hot flushes should be undertaken, in both castrated and in otherwise healthy elderly men.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2002. , 78 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 758
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25712Local ID: 10089ISBN: 91-7373-202-8 (print)OAI: oai:DiVA.org:liu-25712DiVA: diva2:246260
Public defence
2002-12-06, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-19Bibliographically approved
List of papers
1. Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate
Open this publication in new window or tab >>Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate
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2001 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, no 2, 517-520 p.Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25368 (URN)10.1016/S0022-5347(05)65973-3 (DOI)9811 (Local ID)9811 (Archive number)9811 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
2. Hot flushes in a male population aged 55, 65, and 75 years, living in the community of Linköping, Sweden
Open this publication in new window or tab >>Hot flushes in a male population aged 55, 65, and 75 years, living in the community of Linköping, Sweden
2003 (English)In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 10, no 1, 81-87 p.Article in journal (Refereed) Published
Abstract [en]

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 ( = 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 ( < 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26461 (URN)10.1097/00042192-200310010-00013 (DOI)11009 (Local ID)11009 (Archive number)11009 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
3. Urinary excretion of calcitonin gene-related peptide in males with hot flushes after castration for carcinoma of the prostate
Open this publication in new window or tab >>Urinary excretion of calcitonin gene-related peptide in males with hot flushes after castration for carcinoma of the prostate
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2001 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 35, no 2, 92-96 p.Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25429 (URN)10.1080/003655901750170380 (DOI)9875 (Local ID)9875 (Archive number)9875 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
4. Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate
Open this publication in new window or tab >>Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate
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2001 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 166, no 5, 1720-1723 p.Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25313 (URN)10.1016/S0022-5347(05)65660-1 (DOI)9754 (Local ID)9754 (Archive number)9754 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved

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