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Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Reproduktiv hälsa/Sundström Poromaa)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Reproduktiv hälsa/Sundström Poromaa)
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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.

Place, publisher, year, edition, pages
2009. Vol. 201, no 2, 139.e1- p.
Keyword [en]
add-back, clinical trial, estradiol, GnRH agonist, premenstrual dysphoric disorder, progesterone
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-122328DOI: 10.1016/j.ajog.2009.03.016ISI: 000268460900004PubMedID: 19398092OAI: oai:DiVA.org:uu-122328DiVA: diva2:309725
Available from: 2010-04-08 Created: 2010-04-08 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Is it Just the Hormones?: Sex Steroids, Chronic Stress and Violence in Premenstrual Dysphoric Disorder
Open this publication in new window or tab >>Is it Just the Hormones?: Sex Steroids, Chronic Stress and Violence in Premenstrual Dysphoric Disorder
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
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:nbn:se:uu:diva-145384 (URN)978-91-554-8004-2 (ISBN)
Public defence
2011-03-25, Rosénsalen, Akademiska Sjukhuset Ing 95/96, Uppsala, 13:00 (Swedish)
Opponent
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Available from: 2011-03-04 Created: 2011-02-08 Last updated: 2011-05-04

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