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Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
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2003 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 88, no 5, 2026-2030 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have indicated that the addition of progestinsduring sequential hormonal replacement therapy (HRT)causes negative mood and physical symptoms. History of premenstrualsyndrome, type of progestin, and dose of progestinhave thus far been shown to influence the progestin-inducedadverse mood symptoms during HRT.

The aim of this study was to compare adverse mood effectsof two different doses of estradiol, in combination with a progestin,during postmenopausal HRT. Twenty-eight perimenopausalwomen were included in this randomized, doubleblind,crossover study comparing 2- or 3-mg continuousestradiol, with an addition of 10 mg medroxyprogesteroneacetate on d 17–28 during each treatment cycle. The mainoutcome measures were mood and physical symptoms kept ona daily rating scale. Together with the progestin, the higherdose of estrogen caused significantly more negative moodsymptoms than the lower dose. Tension, irritability, and depressedmood were all significantly augmented during theprogestin phase of cycles with 3mg estradiol (P<0.001). Physicalsymptoms also increased during the progestin phase of3-mg estradiol cycles (P<0.001), whereas positive mood symptomswere less affected. The only positive mood that changedwith estrogen dose was friendliness, which decreased duringthe progestin phase of high estradiol cycles compared withcycles with lower estradiol (P < 0.05).

Our conclusion is that an increase of the estrogen doseaccentuates negativemoodand physical symptoms during theprogestin phase of sequential hormonal therapy.

Place, publisher, year, edition, pages
The Endocrine Society , 2003. Vol. 88, no 5, 2026-2030 p.
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:umu:diva-94591DOI: 10.1210/jc.2002-020755PubMedID: 12727949OAI: oai:DiVA.org:umu-94591DiVA: diva2:755047
Conference
88(5):2026–2030
Projects
digitalisering@umu
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Hormone replacement therapy and effects on mood
Open this publication in new window or tab >>Hormone replacement therapy and effects on mood
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: During the past 5 decades, hormone replacement therapy (HRT) has been used, and appreciated for its beneficial effects, by millions of women in their menopause. As treatment for climacteric symptoms, estrogen is outstanding, and effects on hot flushes, vaginal dryness, and insomnia have been widely documented. The increased risks of venous thrombosis and breast cancer, however, restrict the use of estrogen.

Estrogen treatment in women with a remaining uterus includes a progestin, added to protect the endometrium from hyperplasia and malignancies. The long-standing clinical impression, that progestin addition negatively influences mood, has been discussed in previous studies. Mood deterioration is, however, not mortal, although mood is important to the wellbeing and daily functioning of women treated with hormones. Studies of the mental side effects of HRT add to our understanding of steroid effects in the brain.

Aims and methods: In our studies, we aimed to establish to what extent negative side effects cause women to discontinue HRT, and find out which drug compounds lead to mood deterioration. The questions asked were whether the type and dose of progestin and the estrogen dose during the progestin addition influence the mood and physical symptoms during sequential HRT.

Compliance with HRT and reasons for discontinuing the therapy were evaluated in a retrospective longitudinal follow-up study. Treatment effects were studied in three randomized, double-blind, cross-over trials. During continuous estrogen treatment, effects of sequential addition of a progestin were studied by comparing two different progestins, medroxyprogesterone acetate (MPA) andnorethisterone acetate (NETA), comparing different doses of the same progestin, MPA, and comparing two doses of estrogen during addition of the same dose of MPA. The main outcome measure was the daily rating on mood and physical symptoms kept by the participants throughout the studies. The clinical trials were carried out at three gynecological centers in northern Sweden.

Results and conclusions: Besides fear of cancer and a wish to determine whether climacteric symptoms had meanwhile disappeared, negative side effects was the most common reason or discontinuing HRT. Tension in the breasts, weight gain, a depressed mood, abdominal bloating, and irritability were the most important side effects seen both in women who continued HRT and in women who had discontinued the therapy.

In our clinical trials, we showed that addition of a progestin to estrogen treatment induces cyclic mood swings characterized by tension, irritability, and depression, as well as increased breast tension, bloatedness, and hot flushes. Women with a history of premenstrual syndrome (PMS) appeared to be more sensitive to the progestin addition and responded with lower mood scores compared with women without previous PMS. In our studies, MPA provoked depressed mood to a lesser extent than did NETA. Surprisingly, the higher dose of MPA (20 mg) enhanced the mood, compared with 10 mg, when added to estrogen treatment. In women continuously treated with 3 mg estradiol, mood and physical symptoms worsened during the progestin addition, as compared with treatment with 2 mg estradiol. The negative side effects seen during sequential HRT have much in common with symptoms seen in the premenstrual dysphoric disorder (PMDD), which is a psychoneuroendocrine disorder with psychiatric expression. Explanations for treatment effects on mood are likely to be found in drug interactions with neurotransmitter systems of the brain.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2003. 75 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 830
Keyword
adverse effects, estradiol, hormone replacement therapy (HRT), mood, negative side effects, progestins
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-94115 (URN)91-7305-404-6 (ISBN)
Public defence
2003-05-16, Norrlands Universitets sjukhus, Betula, Lecturer Hall, byggnad 6M, bottenvåningen, Umeå universitet, Umeå, 10:00
Supervisors
Projects
digitalisering@umu
Note

Diss. (sammanfattning) Umeå : Umeå universitet, 2003

Available from: 2014-10-13 Created: 2014-10-03 Last updated: 2015-04-08Bibliographically approved

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Björn, IngerSundström-Poromaa, IngerBixo, MarieNyberg, SigridBäckström, GunnelBäckström, Torbjörn
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