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The effect of gonadal hormones on the sensation of pain: Quantitative sensory testing in women
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Accumulating evidence points to sex differences in pain sensitivity and many chronic pain conditions preferentially affect women. Sex hormones, and in particular estrogens, have been shown to affect pain processing and pain sensitivity in animals, although the findings are divergent. The aim of the research on which this thesis is based was to examine the effect of gonadal hormones on the sensation of pain in women who either presented normal variations in hormonal levels over time or who had been given hormone treatment.

Different quantitative sensory tests (QST) examining temperature thresholds, cold, heat and pressure pain thresholds, as well as tolerance thresholds for heat and cold, were performed during different hormonal conditions: During hormonal fluctuations throughout the ovulatory cycle (papers I, II); in women undergoing in vitro fertilization (IVF), a treatment associated with extremely low and high 17β-estradiol levels (paper III); and before and after hormonal substitution treatment in postmenopausal women suffering from fibromyalgia (paper IV).

The results showed little changes in pain sensitivity during the ovulatory cycle, with an interaction between 17β-estradiol and progesterone on cold pressor pain as the major finding. No significant changes in pain sensitivity were seen even with the extreme variations in 17β-estradiol levels that occurred during the IVF-treatment. Also, the use of hormonal substitution treatment did not affect pain thresholds or tolerance in postmenopausal women suffering from fibromyalgia.

Session-to-session effects were reported in several studies and seem to be an important factor when using repeated sessions design. Additionally, the present work also emphasizes the use of actual hormonal values as essential instead of tentative calendar methods when evaluating hormonal effects on the sensation of pain during the menstrual cycle. 

The present studies thus indicate that changes in gonadal hormone levels have little effect on experimental pain in women, contrary to what has been reported in animal studies.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2011. , 84 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1258
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71210ISBN: 978-91-7393-079-6 (print)OAI: oai:DiVA.org:liu-71210DiVA: diva2:448173
Public defence
2011-11-30, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-11-08 Created: 2011-10-06 Last updated: 2011-11-08Bibliographically approved
List of papers
1. Pain thresholds and pain tolerance during the ovulatory cycle in healthy women: quantitative sensory testing
Open this publication in new window or tab >>Pain thresholds and pain tolerance during the ovulatory cycle in healthy women: quantitative sensory testing
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Hormonal influence on pain sensitivity at different menstrual phases is a field of contradictory results. One reason is methodological differences between studies and methodological limitations such as lack of confirmation of cycle phase by measurement of actual hormone levels. In the present study, 14 healthy women were followed during three menstrual cycles and were subjected to a battery of quantitative sensory tests 1-4 after start of menses (follicular phase) and 2-11 days before next menses (luteal phase). The material was analyzed in three different ways: cycle phase determined according to the calendar method; cycle phase determined by hormone values, with cycles showing hormone values outside reference values omitted; and cycles subdivided into three subgroups depending on hormone profile (“normal” cycle; high s-estrogen during the assumed luteal phase; and low progesterone during the assumed luteal phase). However, neither analysis showed any significant differences between the measurement done during immediate after onset of menses and those performed in the period before next menses. Consistent with the results of several previous studies, the findings indicate that pain sensitivity does not seem to vary as a function of the menstrual cycle.

Keyword
Estrogen, pain, hormonal levels, quantitative sensory testing
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71868 (URN)
Available from: 2011-11-08 Created: 2011-11-08 Last updated: 2011-11-08Bibliographically approved
2. Pain sensations to the cold pressor test in normally menstruating women: Comparison with men and relation to menstrual phase and serum sex steroid levels
Open this publication in new window or tab >>Pain sensations to the cold pressor test in normally menstruating women: Comparison with men and relation to menstrual phase and serum sex steroid levels
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2007 (English)In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 293, no 4Article in journal (Refereed) Published
Abstract [en]

The role of gonadal hormones on pain sensations was investigated in normally menstruating women (n = 16) using the cold pressor test. Tolerance time, pain threshold, and pain intensity were examined once a week during a 4-wk period, and serum concentrations of 17β-estradiol and progesterone were determined at each test session, which were classified into the early follicular phase, late follicular phase, early luteal phase, and late luteal phase, as determined by the first day of menses and the actual hormone levels recorded. A group of men (n = 10) of the same age interval was examined for comparison. The data show that pain threshold was reduced during the late luteal phase compared with the late follicular phase, and hormone analyses showed significant positive correlation between the progesterone concentration and lowered pain threshold and increasing pain intensity. Hormone analysis also showed an interaction between S-estradiol and S-progesterone on pain intensity, demonstrating that the increased perceived pain intensity that was associated with high progesterone concentrations was significantly reduced with increasing levels of estradiol. While no statistically significant sex differences in pain measurements were found, women displayed much more pronounced, and statistically significant, session-to-session effects than men, with increased pain threshold and decreased pain intensity with each test session. Hence, these data suggest that the changes in the serum concentration of gonadal hormones that occur during the menstrual cycle influence pain sensations elicited by noxious tonic cold stimulation and show that adaptation to the cold pressor test may be sex dependent. © 2007 the American Physiological Society.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-39946 (URN)10.1152/ajpregu.00127.2007 (DOI)51815 (Local ID)51815 (Archive number)51815 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2011-11-08Bibliographically approved
3. Influence of estrogen levels on thermal perception, pain thresholds and pain tolerance: Studies on women undergoing in vitro fertilization
Open this publication in new window or tab >>Influence of estrogen levels on thermal perception, pain thresholds and pain tolerance: Studies on women undergoing in vitro fertilization
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2012 (English)In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 13, no 5, 459-466 p.Article in journal (Refereed) Published
Abstract [en]

We examined the relationship between estrogen and pain in women undergoing in vitro fertilization (IVF). Quantitative sensory tests (QST) were performed twice during the IVF-regimen: once during hormonal down-regulation and once during hormonal upregulation. A group of healthy men and a group of women using monophasic contraceptives were also examined, to control for session-to-session effects. Among the women undergoing IVF, serum 17β-estradiol levels differed strongly between treatments as expected, and increased from 65.7 (SD = 26) pmol/l during the downregulation phase, to 5188 (SD = 2524) pmol/l during the up-regulation phase. Significant outcomes in the QST were only seen for temperature perception thresholds (1.7°C vs. 2.2°C; P = 0.003) and cold pain threshold (11.5°C vs. 14.5°C; P = 0.04). A similar change in cold pain threshold was also seen in the two control groups, however, and statistical analysis suggested that this change was due to a session-to-session effect rather than being the result of hormonal modulation. Heat pain thresholds, heat tolerance, pressure pain thresholds, and the cold pressor test showed no significant differences between sessions. These data demonstrate that pain perception and pain thresholds in healthy women show little, if any, changes even with major variations in serum estradiol levels.

Keyword
Estrogen, pain, hormonal levels, quantitative sensory testing
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71869 (URN)10.1016/j.jpain.2012.01.446 (DOI)000304228700005 ()
Note

funding agencies|Swedish Research Council| 7879 |Konung Gustav V:s 80-arsfond||Health Research Council in the South-East of Sweden||Linneus University, Kalmar, Sweden||

Available from: 2011-11-08 Created: 2011-11-08 Last updated: 2017-12-08Bibliographically approved
4. Hormonal replacement therapy does not affect self-estimated pain or experimental pain responses in post-menopausal women suffering from fibromyalgia: a double-blind, randomized, placebo-controlled trial
Open this publication in new window or tab >>Hormonal replacement therapy does not affect self-estimated pain or experimental pain responses in post-menopausal women suffering from fibromyalgia: a double-blind, randomized, placebo-controlled trial
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2011 (English)In: RHEUMATOLOGY, ISSN 1462-0324, Vol. 50, no 3, 544-551 p.Article in journal (Refereed) Published
Abstract [en]

Methods. Twenty-nine post-menopausal women were randomized to either 8 weeks of treatment with transdermal 17 beta-oestradiol (50 mu g/day) or placebo according to a double-blind protocol. A self-estimation of pain, a set of quantitative sensory tests measuring thresholds to temperature, thermal pain, cold pain and pressure pain, and a cold pressor test were performed on three occasions: before treatment, after 8 weeks of treatment and 20 weeks after cessation of treatment. Results. Hormonal replacement treatment significantly increased serum oestradiol levels as expected (P andlt; 0.01). However, no differences in self-estimated pain were seen between treatment and placebo groups, nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points. Conclusion. Eight weeks of transdermal oestradiol treatment does not influence perceived pain, pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM.

Place, publisher, year, edition, pages
Oxford University Press, 2011
Keyword
Oestrogen, Substitution, Pain, Hormonal levels, Quantitative sensory testing, Cold pressor test
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66851 (URN)10.1093/rheumatology/keq348 (DOI)000287745600016 ()
Available from: 2011-03-22 Created: 2011-03-21 Last updated: 2011-11-08

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