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Vasomotor symptoms in postmenopausal women: the role of acupuncture and calcitonin gene-related peptide
Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
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: urn:nbn:se:liu:diva-26678Local ID: 11245ISBN: 91-7373-198-6 (print)OAI: oai:DiVA.org:liu-26678DiVA: diva2:247227
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
List of papers
1. Effects of acupuncture on climacteric vasomotor symptoms, quality of life, and urinary excretion of neuropeptides among postmenopausal women
Open this publication in new window or tab >>Effects of acupuncture on climacteric vasomotor symptoms, quality of life, and urinary excretion of neuropeptides among postmenopausal women
1995 (English)In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 2, no 1, 3-12 p.Article in journal (Refereed) Published
Abstract [en]

Most perimenopausal women suffer from vasomotor symptoms. Changes in central opioid activity have been proposed to be involved in the mechanisms of hot flushes after menopause. Because acupuncture increases central opioid activity, it may affect postmenopausal hot flushes. The aim was to study if and to what extent two different kinds of acupuncture affected postmenopausal hot flushes, urinary excretion of certain neuropeptides, and quality of life in a group of postmenopausal women. Twenty-four women with natural menopause and hot flushes were included. Twenty-one women completed the study. One group was randomized to electroacupuncture at 2 Hz, whereas the other group was treated with another form of acupuncture (i.e., superficial needle insertion) for a total of 8 weeks. All women daily registered the number and severity of flushes from 1 month before to 3 months after treatment. They completed Quality of Life questionnaires before, during, and after treatment. Twenty-four-hour urine was sampled before, during, and after treatment and analyzed for neuropeptides using radioimmunoassay methods. The number of flushes decreased significantly by >50% in both groups and remained decreased in the group receiving electroacupuncture, whereas in the superficial-needle-insertion group, the number of flushes increased again during the 3 months after treatment. The Kupperman Index decreased significantly in both groups during and after treatment. The excretion of the potent vasodilating neuropeptide calcitonin gene-related peptide-like immunoreactivity decreased significantly during treatment. Acupuncture significantly affects hot flushes and sweating episodes after menopause, with effects persisting at least 3 months after the end of treatment. Changes in calcitonin gene-related peptide, which is a very potent vasodilator, could be involved in the mechanisms behind hot flushes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81633 (URN)
Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2017-12-07Bibliographically approved
2. Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide
Open this publication in new window or tab >>Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide
Show others...
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81634 (URN)10.1016/S0378-5122(98)00047-4 (DOI)
Available from: 2012-09-19 Created: 2012-09-19 Last updated: 2017-12-07Bibliographically approved
3. Concentrations of Calcitonin Gene-Related Peptide and Neuropeptide Y in Plasma Increase During Flushes in Postmenopausal Women
Open this publication in new window or tab >>Concentrations of Calcitonin Gene-Related Peptide and Neuropeptide Y in Plasma Increase During Flushes in Postmenopausal Women
2000 (English)In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 7, no 1, 25-30 p.Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25426 (URN)9871 (Local ID)9871 (Archive number)9871 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-09-19Bibliographically approved
4. A comparison of acupuncture and oral estradiol treatment of vasomotor symptoms in postmenopausal women
Open this publication in new window or tab >>A comparison of acupuncture and oral estradiol treatment of vasomotor symptoms in postmenopausal women
2004 (English)In: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 7, no 2, 153-164 p.Article in journal (Refereed) Published
Abstract [en]

Objective To compare the effects of electro-acupuncture with oral estradiol and superficial needle insertion on hot flushes in postmenopausal women.

Material and methods  Forty-five postmenopausal women with vasomotor symptoms were randomized to electro-acupuncture, superficial needle insertion or oral estradiol treatment during 12 weeks, with 6 months' follow-up. The number and severity of flushes were registered daily and the Kupperman index and a general estimate of climacteric symptoms were completed before, during and after therapy.

Results In the electro-acupuncture group, the mean number of flushes/24 h decreased from 7.3 to 3.5 (ANOVA, p  < 0.001). Eleven of the 15 women had at least a 50% decrease in number of flushes (with a mean decrease of 82%). Superficial needle insertion decreased the number of flushes/24 h from 8.1 to 3.8 (p  < 0.001). In seven out of 13 women, the number of flushes decreased by at least 50% (mean decrease 83%). In the estrogen group, the number of flushes decreased from 8.4 to 0.8 (p < 0.001). The decrease in number of flushes persisted during the 24-week follow-up period in all treatment groups. The Kupperman index and the general climacteric symptom score decreased, and remained unchanged 24 weeks after treatment in all groups (p < 0.001). Electro-acupuncture decreased the number of flushes/24 h significantly over time, but not to the same extent as the estrogen treatment. No significant difference in effect was found between electro-acupuncture and the superficial needle insertion.

Conclusion We suggest that acupuncture is a viable alternative treatment of vasomotor symptoms in postmenopausal women and cannot recommend superficial needle insertion as an inactive control treatment.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-22013 (URN)10.1080/13697130410001713814 (DOI)1041 (Local ID)1041 (Archive number)1041 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-09-19Bibliographically approved

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