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Studies on Premenstrual Dysphoria
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated.

Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood.

The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition.

The partial 5-HT1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT2 receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function.

The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels.

Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2005. , p. 73
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 42
Keywords [en]
Obstetrics and gynaecology, premenstrual dysphoria, PMDD, premenstrual syndrome, estrogen challenge test, gonadotropin feedback response, LH, FSH, neuroendocrine regulation, buspirone, nefazodone, PCO, testosterone, irritability, depressed mood, bloating, visual analogue scale, VAS, 11C-5-hydroxytryptophan, positron emission tomography, right caudate nucleus
Keywords [sv]
Obstetrik och kvinnosjukdomar
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-5812ISBN: 91-554-6260-X (print)OAI: oai:DiVA.org:uu-5812DiVA, id: diva2:166480
Public defence
2005-05-20, Auditorium Minus, Gustavianum, Uppsala, 13:15
Opponent
Supervisors
Available from: 2005-04-29 Created: 2005-04-29Bibliographically approved
List of papers
1. Gonadotropin feedback response to Estrogen challenge test differs in women with Premenstrual Dysphoria, and is related to symptom severity
Open this publication in new window or tab >>Gonadotropin feedback response to Estrogen challenge test differs in women with Premenstrual Dysphoria, and is related to symptom severity
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Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-93100 (URN)
Available from: 2005-04-29 Created: 2005-04-29Bibliographically approved
2. Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria
Open this publication in new window or tab >>Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria
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2006 (English)In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 146, no 2, p. 107-116Article in journal (Refereed) Published
Abstract [en]

The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-93101 (URN)10.1016/j.pscychresns.2005.02.012 (DOI)16515859 (PubMedID)
Available from: 2005-04-29 Created: 2005-04-29 Last updated: 2017-12-14Bibliographically approved
3. Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparisonof buspirone, nefazodone, and placebo
Open this publication in new window or tab >>Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparisonof buspirone, nefazodone, and placebo
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2001 In: Psychopharmacology, no 155, p. 292-298Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-93102 (URN)
Available from: 2005-04-29 Created: 2005-04-29Bibliographically approved
4. Ovarian ultrasound morphology and serum levels of androgen hormones in women with premenstrual dysphoria
Open this publication in new window or tab >>Ovarian ultrasound morphology and serum levels of androgen hormones in women with premenstrual dysphoria
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Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-93103 (URN)
Available from: 2005-04-29 Created: 2005-04-29 Last updated: 2010-01-13Bibliographically approved

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