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Is it Just the Hormones?: Sex Steroids, Chronic Stress and Violence in Premenstrual Dysphoric Disorder
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Premenstrual depressive symptoms and mood swings affect 3-8% of women in fertile age. The female hormones are believed to be the cause. Progesterone is well studied, but estrogen is not, and either are other causes such as intimate partner violence and chronic stress.

The aim in this thesis was to investigate the influence of hormones as well as psychological aspects on the most common problems among women seeking care for premenstrual symptoms.

In a cross-sectional study, four groups of women were included: ongoing users of oral contraceptives, with or without adverse mood symptoms and previous users, with or without experience of adverse mood. Depression and anxiety were significantly more common in both groups with reported adverse mood, in comparison with their control groups with no adverse mood. Self-reported PMS was significantly more common in those women who reported adverse mood, however, there was no difference in prospectively defined PMS or PMDD between the two groups of previous users.

In a RCT with 25 women completing the study, GnRH treatment were tested in combination with two different HRT add-back doses of estradiol, in combination with progesterone and placebo. The higher dose of estrogen 1.5 mg in combination with progesterone induced significantly more pronounced symptoms than in combination with placebo. The lower dose, 0.5 mg gave less symptom recurrence in combination with progesterone.

Exposure to violence was investigated among PMDD patients, healthy controls and gynecological patients. Among the participating women, gynecological patients, reported physical and/or emotional abuse significantly more often than did PMDD patients, as well as healthy controls.

Chronic stress was investigated with diurnal cortisol, and low-dose dexamethasone test.  There was no difference in diurnal secretion of cortisol between PMDD patients and controls. No difference in the degree of dexamethasone suppression was found between PMDD patients and controls.

According to the results from these studies, the main symptom provoking factor in women with PMDD appears to be the estradiol and progesterone fluctuations across the menstrual cycle, whereas chronic stress and intimate partner violence appears to be less relevant.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 642
Keyword [en]
premenstrual dysphoric disorder; combined oral contraceptive; GnRH agonist; add-back; estradiol; progesterone; chronic stress; intimate partner violence; depression, anxiety; allopregnanolone
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-145384ISBN: 978-91-554-8004-2OAI: oai:DiVA.org:uu-145384DiVA: diva2:396486
Public defence
2011-03-25, Rosénsalen, Akademiska Sjukhuset Ing 95/96, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-03-04 Created: 2011-02-08 Last updated: 2011-05-04
List of papers
1. Prevalence of psychiatric disorders and premenstrual dysphoric symptoms in patients with experience of adverse mood during treatment with combined oral contraceptives
Open this publication in new window or tab >>Prevalence of psychiatric disorders and premenstrual dysphoric symptoms in patients with experience of adverse mood during treatment with combined oral contraceptives
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2009 (English)In: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 79, no 1, 50-55 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Negative mood symptoms remain one of the major reasons for discontinuation of combined oral contraceptive pills (COCs). The primary aim of this study was to compare the prevalence of mood and anxiety disorders in women with different experience of COCs. STUDY DESIGN: Thirty women currently on COCs with no report of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 33 women who had discontinued COC use due to adverse mood effects and 27 women who had discontinued COC use for reasons other than adverse mood symptoms were included. Ongoing psychiatric disorders were evaluated by a structured psychiatric interview and prevalence rates of premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) were assessed by daily prospective ratings on the Cyclicity Diagnoser scale. RESULTS: Women with ongoing or past experience of COC-induced adverse mood, more often suffered from mood disorders than women with no reports of adverse mood while on COC. The prevalence of prospectively defined PMS or PMDD did not differ between prior users with positive or negative experience. Women who had discontinued COC use due to adverse mood symptoms more often had had a legal abortion in the past. CONCLUSION: Women with ongoing or past self-reported adverse mood effects from COCs had a significantly increased prevalence of mood disorders.

Keyword
Combined oral contraceptive pills, Estrogen, Progestogen, Depression, Anxiety, Premenstrual syndrome, Premenstrual dysphoric disorder
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-98210 (URN)10.1016/j.contraception.2008.08.001 (DOI)000261721000008 ()19041441 (PubMedID)
Available from: 2009-02-18 Created: 2009-02-17 Last updated: 2011-05-04Bibliographically approved
2. Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder
Open this publication in new window or tab >>Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder
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2009 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 201, no 2, 139.e1- p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy. STUDY DESIGN: Three different add-back hormone replacement treatments were evaluated in a randomized, double-blinded, cross-over clinical trial in 27 patients premenstrual dysphoric disorder. The add-back treatments consisted of 1.5 mg estradiol and 400 mg progesterone, 1.5 mg estradiol and placebo, and 0.5 mg estradiol and 400 mg progesterone. The primary outcome measure was daily symptom ratings for mood and physical symptoms. RESULTS: The highest dose of estradiol in combination with progesterone was associated with the most pronounced symptom recurrence, both in comparison with a lower dose of estradiol together with progesterone and estradiol-only treatment. CONCLUSION: Based on the findings of the present study, long-cycle add-back treatment to avoid frequent progestagen use appears to be most beneficial for patients with premenstrual dysphoric disorder.

Keyword
add-back, clinical trial, estradiol, GnRH agonist, premenstrual dysphoric disorder, progesterone
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-122328 (URN)10.1016/j.ajog.2009.03.016 (DOI)000268460900004 ()19398092 (PubMedID)
Available from: 2010-04-08 Created: 2010-04-08 Last updated: 2011-05-04Bibliographically approved
3. Prevalence of violence exposure in women with premenstrual dysphoric disorder in comparison with other gynecological patients and asymptomatic controls
Open this publication in new window or tab >>Prevalence of violence exposure in women with premenstrual dysphoric disorder in comparison with other gynecological patients and asymptomatic controls
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2011 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 7, 746-752 p.Article in journal (Refereed) Published
Abstract [en]

Objective. The aim of the present study was to estimate prevalence rates of physical,emotional and sexual abuse in women with premenstrual dysphoric disorder(PMDD) in comparison with gynecological outpatients and asymptomatic healthycontrol subjects. Design. Cross-sectional study. Settings. Departments of obstetricsand gynecology in three different Swedish hospitals. Population. Fifty-eightwomen meeting strict criteria for PMDD, a control group of 102 women seekingcare at the gynecological outpatient clinic (ObGyn controls) and 47 asymptomatichealthy control subjects were included in this study. Methods. The Swedish versionof the Abuse Assessment Screen was used to collect information on physical andsexual abuse, and the screening instrument was administered as a face-to-face interview.Main Outcome Measures. Previous and ongoing physical and sexual abuse.Results. Any lifetime abuse (physical, emotional or sexual) was reported by 31.0%of PMDD patients, by 39.2% of ObGyn controls and by 21.3% of healthy controls.The ObGyn controls reported physical and/or emotional abuse significantly moreoften than PMDD patients as well as healthy controls (p<0.05). Lifetime sexualabuse was reported significantly more often by ObGyn controls than by healthycontrols (p<0.05). Conclusions. Patients with PMDD appear not to have sufferedphysical, emotional or sexual abuse to a greater extent than other gynecologicalpatients or healthy control subjects. However, exposure to violence was common inall groups of interviewed women, and for the individual patient these experiencesmay contribute to their experience of symptoms.

Keyword
physical abuse, emotional abuse, sexual abuse, premenstrual dysphoric disorder
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-145183 (URN)10.1111/j.1600-0412.2011.01151.x (DOI)000292436500009 ()
Available from: 2011-02-08 Created: 2011-02-07 Last updated: 2015-07-22Bibliographically approved
4. Diurnal cortisol variation and low-dose dexamethasone test in women with premenstrual dysphoric disorder and healthy controls
Open this publication in new window or tab >>Diurnal cortisol variation and low-dose dexamethasone test in women with premenstrual dysphoric disorder and healthy controls
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(English)Manuscript (preprint) (Other academic)
Keyword
Premenstrual dysphoric disorder; hypothalamus-pituitary-adrenal axis, cortisol, dexamethasone
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-145344 (URN)
Available from: 2011-02-08 Created: 2011-02-08 Last updated: 2011-05-04

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