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Hormone replacement therapy and effects on mood
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
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 [en]
adverse effects, estradiol, hormone replacement therapy (HRT), mood, negative side effects, progestins
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:umu:diva-94115ISBN: 91-7305-404-6 (print)OAI: oai:DiVA.org:umu-94115DiVA: diva2:754955
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
List of papers
1. Drug related negative side effects is a common reason for poor compliance in hormone replacement therapy
Open this publication in new window or tab >>Drug related negative side effects is a common reason for poor compliance in hormone replacement therapy
1999 (English)In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 32, no 2, 77-86 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: The reasons for poor compliance with hormone replacement therapy (HRT) and, in particular drug-related reasons, have not yet been fully elucidated. In this study, a cohort of peri- or postmenopausal women—mainly workers from a small town and surrounding rural area—was studied. The aim of the study was to investigate why some women never start or discontinue HRT, even when great effort has been made to inform and fulfill the demands of the patient. Methods: All women who were given a HRT prescription at a gynecological practice between September 1991 and December 1992 participated in a longitudinal study. A written questionnaire was mailed to these patients in 1996. Data from the questionnaire was supplemented with information from the medical records. Care of patients included initial information, follow-up within 4 months, yearly visits supplemented with contacts on demand. Results: 356 women received the questionnaire, among which 92% replied. A total of 2% never started HRT. Seventy-five percent continued the therapy for more than 3 years. Reasons for discontinuing HRT were negative side-effects (35%), desire to find out if climacteric symptoms had ended (26%), fear of cancer and thrombosis (25%), weariness of bleeding (19%) and a wish to deal with the problems ‘naturally’ (15%). Conclusions: Compliance with HRT can be high if adequate information is given and follow-ups are made. The main reason for poor compliance was negative side-effects, most likely progestin-related. The results of this study suggest that the future challenge will be to minimize negative side-effects of HRT.

Place, publisher, year, edition, pages
Elsevier, 1999
Keyword
Compliance, Estrogen, HRT
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-94585 (URN)10.1016/S0378-5122(99)00018-3 (DOI)
Projects
digitalisering@umu
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved
2. Negative mood changes during hormone replacement therapy: a comparison between two progestogens
Open this publication in new window or tab >>Negative mood changes during hormone replacement therapy: a comparison between two progestogens
Show others...
2000 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 183, no 6, 1419-1426 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of this study was to compare side effects of medroxyprogesterone acetate and norethindrone acetate during postmenopausal hormone replacement therapy in women with and without a history of premenstrual syndrome. Study Design: Fifty-one postmenopausal women were randomly selected in a double-blind crossover study. The women received 2 mg of estradiol continuously during five 28-day cycles and 10 mg of medroxyprogesterone or 1 mg of norethindrone sequentially for 12 days of each cycle. Daily symptom rating scales were kept. Results: The women showed cyclic changes, with negative mood and physical symptoms culminating during the late progestogen phase and positive mood during the estrogen-only phase. Symptoms declined with time but remained after 5 months. Women with a history of premenstrual syndrome responded strongly to both progestogens. Medroxyprogesterone acetate induced less negative and more positive mood symptoms than norethindrone in women with no history of premenstrual syndrome. In both groups medroxyprogesterone caused more physical symptoms than norethindrone. Conclusion: The addition of medroxyprogesterone to estrogen is preferable to norethindrone with respect to mood symptoms in women without a history of premenstrual syndrome.

Place, publisher, year, edition, pages
Elsevier, 2000
Keyword
Hormone replacement therapy, progestogen, mood, negative side effects, adverse effects
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-94586 (URN)10.1067/mob.2000.107781 (DOI)
Projects
digitalisering@umu
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved
3. The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy
Open this publication in new window or tab >>The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy
Show others...
2002 (English)In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 16, 1-8 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to compare adverse mood effects of two different doses of medroxyprogesterone acetate (MPA) during postmenopausal hormone replacement therapy (HRT) in women with and without a history of premenstrual syndrome (PMS). The study was designed as a randomized double-blind cross-over study and included 36 postmenopausal women at three health care areas in northern Sweden. The women received 2 mg estradiol continuously during five 28-day cycles and 10 mg or 20 mg MPA sequentially for 12 days during each cycle. The main outcome measures were mood and physical symptoms noted on a daily rating scale. We found that physical symptoms did not differ between 10 and 20 mg MPA. Both women with a history of PMS and women without responded with more negative mood symptoms with the lower dose of MPA. In women with previous PMS the higher dose of MPA enhanced positive mood symptoms. With respect to mood and physical symptoms, the aim to lower MPA doses in HRT is unwarranted.

Place, publisher, year, edition, pages
Informa Healthcare, 2002
Keyword
HRT, Progestogen, mood adverse effects
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-94587 (URN)10.1080/gye.16.1.1.8 (DOI)
Projects
digitalisering@umu
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved
4. Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy
Open this publication in new window or tab >>Increase of estrogen dose deteriorates mood during progestin phase in sequential hormonal therapy
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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
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-94591 (URN)10.1210/jc.2002-020755 (DOI)12727949 (PubMedID)
Conference
88(5):2026–2030
Projects
digitalisering@umu
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved

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