Menopause Live ( 25 February, 2013) From IMS

In a recently published paper, two subsets were extracted from two large health studies in a Finnish population to investigate the menopausal transition including the effect of use of hormone therapy (HT) on the psychological well-being and mental health among peri- and postmenopausal women [1]. The cross-sectional nationwide study, HEALTH 2000 (www.terveys2000.fi) started with a home interview with four self-administered interviews including the modified Beck Depression Inventory (BDI) and the General Health Questionnaire-12 (GHQ-12) for the Finnish population. Thereafter, general health was assessed and a new interview, the Composite Diagnostic Interview (CIDI), was administered to measure mental health in the previous 12 months. The second cross-sectional study, the National FINRISK Survey (www.ktl.fi/finriski), has been conducted every 5 years since 1972. For the purpose of this subset study, years 1997, 2002 and 2007 were selected. The survey included a clinical health assessment and a self-administered questionnaire, which contained questions focusing on reproductive and mental health issues (including BDI). The first study was carried out in 1433 peri- or postmenopausal women while the second one studied 5354 women. Together, in these populations, there were 1870 users (mean age 58.6 years) and 4733 non-users (mean age 61.0 years) of HT. A positive association between HT use and some general symptoms, such as feeling tense and nervous, having frightening thoughts, nightmares, feelings of depression and headaches, were observed. Eight other general symptoms were not associated with the use of HT. As to psychiatric diagnosis or its medical treatment in the last year, there was a positive association with HT (odds ratio (OR) 1.44). Likewise, there was a positive association between HT use and low mood (OR 1.22), recent depression (OR 1.44), any psychiatric diagnosis, as measured by CIDI (OR 1.65), major depressive disorder (OR 2.46), and anxiety disorder (OR 2.22) in the last year. Associations were not dependent on the type of HT (estrogen therapy, cyclic, continuous combined, oral, parenteral). The authors conclude that the results show an association between current use of HT and worse psychological well-being and mental health.

Comment

The transitional period from pre- to perimenopause or from peri- to postmenopause seems to increase the risk of depression and anxiety [2-4]. In a review article, it was concluded that the OR for risk of depression in the transitional period is 1.3–3 [3]. Severe menopausal symptoms may aggravate depression or, vice versa, depression may aggravate the menopausal symptoms [5]. Estrogens are known profoundly to affect brain metabolism [6]. Therefore, it is biologically plausible that HT for menopause might exert influences on depressive symptoms and mood swings as well as actual menopausal symptoms. In fact, many studies indicate that this may be true. In a randomized, controlled trial, an estradiol patch releasing 0.1 mg estradiol daily was given for 12 weeks for depressive disorders. Remission of depression with estradiol was observed in 68% of the treated women compared with 20% in the placebo group [7]. In the WISE study, white women receiving conventional HT had fewer symptoms of depression and lower aggression and cynicism scores than non-users (p < 0.04) [8]. Studd has advocated a dose as high as 0.2 mg/day transdermally [9]. Moreover, in the Sequenced Treatment Alternatives to Relieve Depression study, consisting of 171 HT users and 562 non-users, better physical functioning, less melancholia, and less sympathetic arousal (i.e. less anxiety) were reported in HT users. On the other hand, the observed similar overall severity of depression among users and non-users suggests that estrogen is not a treatment for major depression in postmenopausal women, although it also suggests that HT does not worsen depressive symptoms [10]. It seems that HT in normal doses does not efficiently relieve depressive disorders, and higher doses are probably needed. 

The study by Toffol and colleagues [1] suggests that HT is associated with depressive conditions among postmenopausal women. They do not suggest any causal relationship. Problems may always exist when a subset of material is extracted for other purposes outside the main endpoints. Although the transition to perimenopause is an independent risk factor for depression, a history of previous depression triples the risk of depressive disorders [3]. In the study by Toffol and colleagues, any history of a previous depression before commencing the HT was not known. Some participants may have been prescribed HT for some pre-existing quality-of-life problems, including mood disorders, mental swings, sadness, depressive disorders, etc. The HT group may also differ from the non-user group in that they had used more medical/specialist level services with enhanced possibilities for diagnosing depressive disorders.

Risto Erkkola
Professor in Obstetrics and Gynecology, Emeritus, Department of Obstetrics and Gynecology, University Central Hospital, Turku, Finland

References

1. Toffol E, Heikinheimo O, Partonen T. Associations between psychological well-being, mental health, and hormone therapy in perimenopausal and postmenopausal women: results of two population-based studies. Menopause 2012 Dec 30. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/23277355
2. Bromberger JT, Kravitz HM, Chang Y, et al. Does risk for anxiety increase during the menopausal transition? Study of Womenˊs Health Across the Nation. Menopause 2013 Jan 28. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/23361169
3. Freeman EW. Associations of depression with the transition to menopause. Menopause 2010;17:823-7.
http://www.ncbi.nlm.nih.gov/pubmed/20531231
4. Bromberger JT, Kravitz HM. Mood and menopause: findings from the Study of Womenˊs Health Across the Nation (SWAN) over 10 years. Obstet Gynecol Clin North Am 2011;38:609-25.
http://www.ncbi.nlm.nih.gov/pubmed/21961723
5. Reed SD, Ludman EJ, Newton KM, et al. Depressive symptoms and menopausal burden in the midlife. Maturitas 2009;62:306-10.
http://www.ncbi.nlm.nih.gov/pubmed/19223131
6. Genazzani AR, Pluchino N, Luisi S, Luisi M. Estrogen, cognition and female ageing. Hum Reprod Update 2007;13:175-87.
http://www.ncbi.nlm.nih.gov/pubmed/17135285
7. Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 2001;58:529-34.
http://www.ncbi.nlm.nih.gov/pubmed/11386980
8. Olson MB, Bairey Merz CN, Shaw LJ, et al. Hormone replacement, race, and psychological health in women: a report from the NHLBI-Sponsored WISE Study. J Womens Health (Larchmt) 2004;13:325-32.
http://www.ncbi.nlm.nih.gov/pubmed/15130261
9. Studd JW. A guide to the treatment of depression in women by estrogens. Climacteric 2011;14:637-42.
http://www.ncbi.nlm.nih.gov/pubmed/21878053
10. Kornstein SG, Young EA, Harvey AT, et al. The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women. Menopause 2010;17:828-39.
http://www.ncbi.nlm.nih.gov/pubmed/20616669