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Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide
Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
Department of Pharmacology and Physiology, Karolinska lnstitutet, Stockholm, Sweden.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
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1998 (English)In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 30, no 3, 289-294 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age.

Material and methods: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immuno assay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase.

Results: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24h; P=0.028). CGRP concentrations were stable throughout the ovulatory cycles.

Conclusion: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

Place, publisher, year, edition, pages
1998. Vol. 30, no 3, 289-294 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-81634DOI: 10.1016/S0378-5122(98)00047-4OAI: oai:DiVA.org:liu-81634DiVA: diva2:555324
Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Vasomotor symptoms in postmenopausal women: the role of acupuncture and calcitonin gene-related peptide
Open this publication in new window or tab >>Vasomotor symptoms in postmenopausal women: the role of acupuncture and calcitonin gene-related peptide
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A majority of postmenopausal women experience vasomotor symptoms, which have a significant impact on the women's quality of life. Estrogens are the treatment of choice but can for different reasons not be used by all women. There is therefore a great need for viable alternative treatments. The patophysiology behind hot flushes and sweatings is so far not fully understood. Several studies have concluded that low levels of estrogens after menopause will lead to instability in the thermoregulatory center in the hypothalamus probably due to low [ß-endorphin levels. Since acupuncture is known to increase central [ß-endorphin activity, we wanted to evaluate if this treatment could ameliorate vasomotor symptoms which, to our knowledge, has not been scientifically evaluated previously. We also aimed to reveal if the vasoactive neuropeptides Calcitonin Gene-related peptide (CGRP), neuropeptide Y (NPY), neurokinin A, and substance P were involved in the mechanisms behind these symptoms.

Results: Electro-acupuncture decreased flushes by 50 %, and superficial needle insertion by 30 %. The difference in reduction between the groups was not significant. Along with the decrease of flushes we found a significant reduction of the 24h urinary excretion of the neuropeptide CGRP, which is one of the most potent vasodilators known. When we later compared electro-acupuncture (EA), superficial needle insertion (SNI) and estrogen treatment, we found a significant reduction of 24h flushes by almost 60 % after EA and SNI. However, about 20% were non-responders in both groups. The responders in the EA group reduced their flushes and sweatings by 82 % and in the SNI group the reduction was 68%. We found no significant difference in effect between the acupuncture groups. Estrogen was the most effective treatment with a 91% reduction of flushes (range 58-100 %). We found a higher excretion of CGRP/24h urine in postmenopausal women with vasomotor symptoms, than in women without symptoms. Furthermore we found a 73 % elevation of CGRP in plasma, along with a 34% increase ofNPY concentration, during flushes in postmenopausal women.

Conclusion: The results indicate that acupuncture is as a viable alternative or complement to traditional pharmacological treatments in postmenopausal women with vasomotor symptoms. The vasoactive neuropeptide CGRP is most likely involved in the mechanisms of vasomotor symptoms, probably as an executor or mediator of the skin vasodilatation and sweating that occur during the hot flush.

Abstract [sv]

Majoriteten av alla kvinnor dmbbas av vasomotoriska besvär i form av värmevallningar och svettningar. Besvären påverkar ofta påtagligt kvinnans livskvalile · och välbefinnande. Symtomen varar vanligen under några år, men en av fem kvinnor har besvären i mer än femton år. Orsaken till besvären är delvis oklar. Många studier har visat en koppling mellan låga östrogennivåer och minskad nivå av opiaten ß-endorfin i hypothalamus efter menopaus som även leder till minskad stabilitet i termoregleringen. Man vet att östrogenbehandling höjer nivån av 6-endorfin, och verkar på så sätt även stabilisera termoregleringen. Många kvinnor i behov av hjälp för dessa besvär, kan av olika skäl inte använda östrogenbehandling, trots intensiva besvär. En stor grupp är bl.a kvinnor som behandlats för bröstcancer och kvinnor med hereditet för bröstcancer, som idag inte rekommenderas östrogenbehandling. Andra avstår behandlingen pga biverkningar. Behovet av effektiva alternativa behandlingar är därför stort.

Då det är visat att även akupunktur behandling ökar den centrala B-endorfin aktiviteten, har vi i två studier undersökt effekten av akupunktur behandling mot vasomotoriska besvär, och fann då att besvären minskade signifikant med ca 50-60 %. Vi såg även att ca 20 % av de som behandlats inte svarade på behandlingen, och att de övriga minskade sina besvär med ca 75%. I den ena studien jämfördes effekten av akupunktur med östrogenbehandling som minskade besvären med ca 90 %. I den första studien försökte vi även klargöra om man kunde finna någon påverkan på vissa specifika neuropeptider under denna behandling. Vi fann då en tydlig sänkning av den kraftigt kärlvidgande peptiden Calcitonin Gene-related peptide (CGRP), som även visats påverka svettning. Vi har vidare även funnit att kvinnor med värmevallningar och svettningar har en högre dygnsutsöndring i urin av denna peptid än kvinnor utan dessa besvär. Vi fann vidare att koncentrationen av CGRP i blod ökar under pågående värmevallning.

Resultaten visar att akupunktur behandling kan utgöra ett alternativ för de kvinnor som av olika skäl inte kan använda behandling med östrogen, samt att den kärlvidgande peptiden CGRP med stor sannolikhet är involverad i mekanismerna bakom dessa besvär.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 71 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 758
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26678 (URN)11245 (Local ID)91-7373-198-6 (ISBN)11245 (Archive number)11245 (OAI)
Public defence
2002-11-29, Berzeliussalen, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-19Bibliographically approved

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Wyon, YvonneFrisk, JessicaTheodorsson, ElvarHammar, Mats

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