Editorial Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Sep 19, 2024; 14(9): 1289-1293
Published online Sep 19, 2024. doi: 10.5498/wjp.v14.i9.1289
Research status of hormone replacement therapy on mood and sleep quality in menopausal women
Xue-Jian Wang, Department of Neurosurgery, Affiliated Hospital 2 of Nantong University, Nantong 226000, Jiangsu Province, China
ORCID number: Xue-Jian Wang (0000-0003-0389-5674).
Author contributions: All the work was done by Wang XJ.
Supported by Research Project of Nantong Health and Health Commission, No. MS2023041, No. MA2019003, and No. MA2021017; Science and Technology Program of Nantong City, No. Key03, and No. JCZ2022040; and Kangda College of Nanjing Medical University, No. KD2021JYYJYB025, No. KD2022KYJJZD019, and No. KD2022KYJJZD022.
Conflict-of-interest statement: Dr. Wang has nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xue-Jian Wang, MD, PhD, Chief Doctor, Department of Neurosurgery, Affiliated Hospital 2 of Nantong University, No. 666 Shengli Road, Chongchuan District, Nantong 226000, Jiangsu Province, China. 6841441@163.com
Received: July 6, 2024
Revised: August 4, 2024
Accepted: August 21, 2024
Published online: September 19, 2024
Processing time: 66 Days and 21.5 Hours

Abstract

Menopausal syndrome is a common disease of clinical women, which refers to a series of physical and mental symptoms caused by the fluctuation or reduction of sex hormones before and after menopause. Many of these patients have sleep and mood abnormalities that affect their health and quality of life. At present, the understanding of it is gradually improving. This paper mainly analyzes its background and current treatment.

Key Words: Effects; Hormone replacement therapy; Menopause; Women; Mood states; Sleep quality; Sex hormones

Core Tip: Menopausal syndrome is a common disease of clinical women, which refers to a series of physical and mental symptoms caused by the fluctuation or reduction of sex hormones before and after menopause. Many of these patients have sleep and mood abnormalities that affect their health and quality of life. At present, the understanding of it is gradually improving.



INTRODUCTION

Perimenopausal syndrome (MPS), as a common clinical disorder, is mainly caused by the decline of ovarian function, which leads to a significant decrease in estrogen level in the body, and many female patients have a series of signs due to this[1]. These signs include, but are not limited to, hot flashes, sweating, heart palpitations, dizziness, chest tightness, and significant declines in physical strength, memory, and work ability[2]. At the psychological level, patients often show great emotional fluctuations, such as irritability, depression, anxiety and paranoia, etc. These symptoms pose a significant threat to the physical and mental health of perimenopausal women[3]. In addition, as a more common clinical manifestation in perimenopausal women, sleep disorders are typically characterized by difficulty falling asleep, increased number of awakenings at night, early waking in the morning and difficulty falling asleep again after waking up[4].

At the current special stage, women not only have to deal with significant changes on the physiological level, but also bear the double pressure of family and work. Among them, sleep problems have become one of the important factors affecting their physical and mental health. Therefore, in clinical practice, we must pay great attention to the sleep disorders encountered by perimenopausal women.

ANALYSIS OF THE ACTUAL SITUATION OF PERIMENOPAUSAL SLEEP DISORDERS

After women enter perimenopause, the incidence of sleep disorders increases significantly due to the significant reduction of estrogen levels. In recent years, the incidence of MPS has gradually increased. According to statistics, the incidence of MPS is as high as 75%, among which patients with more severe symptoms account for between 10% and 15%[5,6]. Epidemiological studies[7-9] also show that compared with men of the same age, the incidence of sleep disorders in perimenopausal women is between 33% and 51%. This sleep disorder is closely associated with different stages of the menopausal state, especially in the perimenopause, its incidence is significantly increased compared to the pre-menopausal. Owen and Matthews[10] further revealed that insomnia in perimenopausal women accounts for a quarter of the total cases of insomnia in women, and insomnia has become a prominent health problem among perimenopausal symptoms. It is worth noting that patients with insomnia as the main symptom often have over-amplified subjective sleep feelings, and overestimate or fear the possible physical and mental impact of insomnia, among which emotional disorders such as anxiety and depression play a significant role in promoting it[11]. Epidemiological investigations have further confirmed that anxiety and depression can cause or exacerbate insomnia symptoms[12], and the risk of anxiety and depression in insomnia patients is 10 times higher than that of the general population[13,14].

Due to the diversity of definitions, diagnostic criteria, and investigation methods of sleep disorders, the incidence of menopausal sleep disorders is somewhat variable. However, the phenomenon that perimenopausal women generally suffer from sleep disorders has been widely recognized in the academic community.

CAUSE ANALYSIS OF PERIMENOPAUSAL SLEEP DISORDERS
Regional and ethnic differences

The occurrence of perimenopausal sleep disorders is not only directly affected by the menopausal status of women, but also significantly affected by different factors such as race and region. In a large-scale survey, Kravitz et al[15] included a total of 12603 female samples aged 40 to 55 years old (including Caucasian, African American, Chinese, Japanese, Spanish and other ethnicities), and found significant racial differences in the incidence of sleep disorders through detailed data analysis. Among them, the incidence of sleep disorders in Japanese women at this stage is relatively low, 28%; For Caucasian women, the rate was higher, at 64 percent. This finding provides new insights into the complex causes of perimenopausal sleep disorders.

Analysis of the effects of low estrogen levels

During perimenopause and post menopause, the secretory function of female ovaries gradually declines or even stops, which leads to a significant decrease in endogenous estrogen secretion. As an important physiological regulatory hormone, estrogen has a clear targeting effect on multiple intracranial regions, including the neurotransmitter system involved in sleep regulation. When estrogen levels decrease, its regulatory effect on the neurotransmitter system is weakened, which may affect the quality of sleep[16].

In addition, changes in estrogen levels have a significant effect on melatonin levels produced by the pineal gland, and this effect may increase the amplitude of changes in body temperature rhythms. At the same time, estrogen can reduce the activity of monoamine oxidase, thereby reducing its breakdown of the hypnotic 5-hydroxytryptamine (5-HT). However, after perimenopause, decreased estrogen levels may trigger a range of symptoms such as vasomotor, mood changes and irritability, and these indirect factors may also have an adverse effect on sleep quality.

Currently, the relationship between estrogen and sleep has been widely understood. The low estrogen level of menopausal women patients is an important cause of sleep disorders. There have been a lot of previous studies on this aspect, and corresponding understanding has been obtained, and after supplementing estrogen and other levels for such patients, the sleep disorders of patients have also been improved to a certain extent, which further explains the correlation with low estrogen levels. But the pattern of sleep disorders in menopause, and the specific mechanism of estrogen expression in it, still need to be studied.

Vasomotor related effects in perimenopause

According to statistics, about 58.5% of women will experience symptoms of vasomotor dysfunction such as hot flashes, sweating, and cold hands and feet after entering perimenopause. Otte et al[17] revealed a significant correlation between vasomotor symptoms and sleep disorders in perimenopausal women, which are often accompanied by psychological changes such as menstrual disorders, mood swings, irritability, anxiety, and depression, which may lead to increased nighttime wakefulness. In addition, another study[18] pointed out that vasomotor symptoms such as hot flashes and sweating not only directly have a negative impact on sleep quality, but also indirectly affect sleep through affecting individuals' emotional states. Notably, these women experienced significant improvements in their sleep quality after taking estrogen replacement therapy. However, the specific mechanism of the correlation between menopausal vasomotor symptoms such as hot flashes and sleep disorders still needs further research and discussion.

Anxiety and depression factors

Anxiety depression, also known as anxiety neurosis, is characterized by generalized anxiety disorder (chronic anxiety disorder) and episodic panic states (acute anxiety disorder). Patients are often accompanied by a series of physiological symptoms, such as dizziness, chest tightness, palpitation, dyspnea, dry mouth, frequent urination, urgent urination, sweating, tremor and motor restlessness[19]. It is important to note that anxiety and depression are particularly common in perimenopausal women.

According to the study of Guidozzi et al[20], there is a significant correlation between depression and sleep. Perimenopausal women are at significantly increased risk for insomnia and mood disorders due to the effects of low estrogen and progesterone levels. In addition, sleep disorders themselves are also one of the typical manifestations of anxiety and depression patients.

Influence of genetics, chronic diseases and drug therapy

The occurrence of sleep disorders in perimenopausal women is the result of the combined effect of environmental factors and genetic factors, in which genetic factors play a central determining role. According to the study[21], genetic factors can explain about 57% of the genetic variation in sleep disorders, and in particular, there is a direct correlation between the 5-HT gene and sleep disorders during menopause in women. In addition, obesity, heart disease, endocrine disease, the use of stimulant medications, chronic pain, and the intake of certain medications (such as bronchodilators, antiepileptics, etc.) may contribute to a significant decrease in sleep quality in perimenopausal women. The study of Kravitz et al[15] further revealed the significant correlation between pain, arthritis and other diseases and sleep disorders in perimenopausal women.

TREATMENT STRATEGIES FOR PERIMENOPAUSAL SLEEP DISORDERS
Enhance the awareness of perimenopausal sleep disorders

In view of the fact that perimenopausal women are experiencing significant physiological and psychological changes, as well as the increasing pressure of social life and work, it is of great significance to build a sound family and social support system to reduce the psychological impact caused by stressful events and reduce negative emotions, so as to reduce the adverse factors affecting sleep quality. Therefore, to enhance the overall social awareness of the common diseases of perimenopausal women and their prone sleep disorders at this stage is the primary prerequisite for effective intervention and treatment.

Optimize the sleep environment

To improve the quality of sleep, it is important to optimize the sleeping environment. This includes maintaining the right temperature and humidity in the room (generally recommended 16 to 20 degrees Celsius in winter and 25 to 28 degrees Celsius in summer, with humidity controlled in the range of 50% to 60%). At the same time, the selection of pillows with the right height and the reduction of noise interference in the sleeping environment can help to increase the duration of sleep[22]. In addition, moderate exercise has also been shown to improve sleep disorders in some perimenopausal women; Aerobic exercise, in particular, can not only promote physical and mental health, but also effectively increase the total sleep time, shorten the time to fall asleep, and reduce the number of awakenings.

Estrogen replacement therapy

Changes in estrogen levels in perimenopausal women have been identified as a key contributor to menopausal related sleep disorders. Estrogen (or combined with progesterone) supplementation through different pathways (including percutaneous and oral) has shown significant potential to improve sleep disorders in perimenopausal and postmenopausal women[23].Although estrogen replacement therapy has caused widespread controversy in the past, in 2013 the International Menopause Society reached a clear consensus that hormone replacement therapy (HRT) is the most effective way to relieve menopausal symptoms for women younger than 60 years of age and less than 10 years after menopause. A study by Silva et al[24] showed that perimenopausal women treated with estrogen showed significant improvement in sleep disorders compared to the placebo group. Therefore, hormone therapy, as one of the overall strategies to maintain the health of perimenopausal and postmenopausal women, together with other lifestyle adjustment measures (such as diet, exercise, tobacco control and alcohol restriction), constitutes the cornerstone of total health management[25].

At present, the amount and duration of HRT are not well regulated. This paper proposes “Estradiol valerate tablets were administered orally at a dose of 1 mg once a day for 14 days. In addition to administering estradiol valerate tablets on the 15th day, hydroxyprogesterone acetate tablets were administered orally at a dose of 8 mg once a day for 14 days; The treatment cycle comprised three courses (28 days)”. The results of the study in this paper have achieved satisfactory therapeutic effects. In fact, other literature has different doses, which need to be adjusted according to different symptoms and hormone levels, and there is no unique identification.

Other treatments

For patients with significant insomnia symptoms, especially those with severe sleep disorders before perimenopause, sedative hypnotic drugs can be used as adjuvant therapy. When choosing drugs, priority should be given to anti-anxiety drugs and sedative hypnotics with short half-life, slight adverse reactions and small dependence, and taken before going to bed to prevent drug dependence. According to Schofield and Khan's study[26], for female patients with sleep disorders accompanied by anxiety and depression symptoms, appropriate addition of antidepressant anxiety drugs can simultaneously improve their sleep disorders.

CONCLUSION

In summary, perimenopausal women, as a group with unique physiological characteristics, face the challenge of physiological changes before and after menopause, which significantly increase the prevalence of sleep disorders. The causes of these sleep disorders are complex and can be attributed to multiple factors such as decreased estrogen levels in the body, increased vasomotor symptoms, and mood disorders. Although current estrogen replacement therapy has been shown to improve sleep quality to some extent, the results vary from study to study because of the age of participants and the criteria used to assess sleep quality. In view of this, the research on perimenopausal sleep disorders in women still needs to be further explored.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Corresponding Author's Membership in Professional Societies: American Society for Peripheral Neurosurgery, 5300190.

Specialty type: Psychiatry

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade B, Grade D

Novelty: Grade B, Grade D

Creativity or Innovation: Grade B, Grade D

Scientific Significance: Grade B, Grade D

P-Reviewer: Zhang Y S-Editor: Lin C L-Editor: A P-Editor: Zhang XD

References
1.  Liu Q, Huang Z, Xu P. Effects of hormone replacement therapy on mood and sleep quality in menopausal women. World J Psychiatry. 2024;14:1087-1094.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (3)]
2.  Gracia CR, Freeman EW. Onset of the Menopause Transition: The Earliest Signs and Symptoms. Obstet Gynecol Clin North Am. 2018;45:585-597.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 80]  [Article Influence: 13.3]  [Reference Citation Analysis (0)]
3.  Haufe A, Baker FC, Leeners B. The role of ovarian hormones in the pathophysiology of perimenopausal sleep disturbances: A systematic review. Sleep Med Rev. 2022;66:101710.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
4.  Santoro N, Roeca C, Peters BA, Neal-Perry G. The Menopause Transition: Signs, Symptoms, and Management Options. J Clin Endocrinol Metab. 2021;106:1-15.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 62]  [Cited by in F6Publishing: 148]  [Article Influence: 49.3]  [Reference Citation Analysis (0)]
5.  Kakkis E, Marsden D. Urinary glycosaminoglycans as a potential biomarker for evaluating treatment efficacy in subjects with mucopolysaccharidoses. Mol Genet Metab. 2020;130:7-15.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 15]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
6.  Hachul H, Hachul de Campos B, Lucena L, Tufik S. Sleep During Menopause. Sleep Med Clin. 2023;18:423-433.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
7.  Santoro N. Perimenopause: From Research to Practice. J Womens Health (Larchmt). 2016;25:332-339.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 84]  [Cited by in F6Publishing: 114]  [Article Influence: 12.7]  [Reference Citation Analysis (0)]
8.  Baker FC. Optimizing sleep across the menopausal transition. Climacteric. 2023;26:198-205.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
9.  Prairie BA, Wisniewski SR, Luther J, Hess R, Thurston RC, Wisner KL, Bromberger JT. Symptoms of depressed mood, disturbed sleep, and sexual problems in midlife women: cross-sectional data from the Study of Women's Health Across the Nation. J Womens Health (Larchmt). 2015;24:119-126.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 51]  [Cited by in F6Publishing: 61]  [Article Influence: 6.8]  [Reference Citation Analysis (0)]
10.  Owens JF, Matthews KA. Sleep disturbance in healthy middle-aged women. Maturitas. 1998;30:41-50.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 206]  [Cited by in F6Publishing: 211]  [Article Influence: 8.1]  [Reference Citation Analysis (0)]
11.  Pearson O, Uglik-Marucha N, Miskowiak KW, Cairney SA, Rosenzweig I, Young AH, Stokes PRA. The relationship between sleep disturbance and cognitive impairment in mood disorders: A systematic review. J Affect Disord. 2023;327:207-216.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 14]  [Reference Citation Analysis (0)]
12.  Jermann F, Perroud N, Favre S, Aubry JM, Richard-Lepouriel H. Quality of life and subjective sleep-related measures in bipolar disorder and major depressive disorder. Qual Life Res. 2022;31:117-124.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 8]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
13.  Zhang LG, Cheng LF, Wang TT, Wang LL, Zhou SJ, Luo YH, Chen JX. Chain mediating effect of insomnia, depression, and anxiety on the relationship between nightmares and cognitive deficits in adolescents. J Affect Disord. 2023;322:2-8.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
14.  Bard HA, O'Driscoll C, Miller CB, Henry AL, Cape J, Espie CA. Insomnia, depression, and anxiety symptoms interact and individually impact functioning: A network and relative importance analysis in the context of insomnia. Sleep Med. 2023;101:505-514.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 20]  [Reference Citation Analysis (0)]
15.  Kravitz HM, Zheng H, Bromberger JT, Buysse DJ, Owens J, Hall MH. An actigraphy study of sleep and pain in midlife women: the Study of Women's Health Across the Nation Sleep Study. Menopause. 2015;22:710-718.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 17]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
16.  Haufe A, Leeners B. Sleep Disturbances Across a Woman's Lifespan: What Is the Role of Reproductive Hormones? J Endocr Soc. 2023;7:bvad036.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
17.  Otte JL, Rand KL, Landis CA, Paudel ML, Newton KM, Woods N, Carpenter JS. Confirmatory factor analysis of the Pittsburgh Sleep Quality Index in women with hot flashes. Menopause. 2015;22:1190-1196.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 18]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
18.  Zhou Q, Wang B, Hua Q, Jin Q, Xie J, Ma J, Jin F. Investigation of the relationship between hot flashes, sweating and sleep quality in perimenopausal and postmenopausal women: the mediating effect of anxiety and depression. BMC Womens Health. 2021;21:293.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 9]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
19.  Alblooshi S, Taylor M, Gill N. Does menopause elevate the risk for developing depression and anxiety? Results from a systematic review. Australas Psychiatry. 2023;31:165-173.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 18]  [Reference Citation Analysis (0)]
20.  Guidozzi F, Alperstein A, Bagratee JS, Dalmeyer P, Davey M, de Villiers TJ, Hirschowitz S, Kopenhager T, Moodley SP, Roos P, Shaw A, Shimange O, Smith T, Thomas C, Titus J, van der Spuy Z, van Waart J; Council of the South African Menopause Society. South African Menopause Society revised consensus position statement on menopausal hormone therapy, 2014. S Afr Med J. 2014;104:537-543.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 15]  [Cited by in F6Publishing: 16]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
21.  Ban HJ, Kim SC, Seo J, Kang HB, Choi JK. Genetic and metabolic characterization of insomnia. PLoS One. 2011;6:e18455.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 44]  [Article Influence: 3.4]  [Reference Citation Analysis (0)]
22.  Stephens M, Bartley C. Use of night-time positioning equipment in care home residents with postural asymmetry: a pilot study. Nurs Older People. 2020;32:17-24.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
23.  Kargozar R, Azizi H, Salari R. A review of effective herbal medicines in controlling menopausal symptoms. Electron Physician. 2017;9:5826-5833.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 63]  [Cited by in F6Publishing: 52]  [Article Influence: 7.4]  [Reference Citation Analysis (0)]
24.  Silva BH, Martinez D, Wender MC. A randomized, controlled pilot trial of hormone therapy for menopausal insomnia. Arch Womens Ment Health. 2011;14:505-508.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 13]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
25.  de Villiers TJ, Gass ML, Haines CJ, Hall JE, Lobo RA, Pierroz DD, Rees M. Global consensus statement on menopausal hormone therapy. Climacteric. 2013;16:203-204.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 188]  [Cited by in F6Publishing: 150]  [Article Influence: 13.6]  [Reference Citation Analysis (0)]
26.  Schofield MJ, Khan A. Predictors of prescribed medication use for depression, anxiety, stress, and sleep problems in mid-aged Australian women. Soc Psychiatry Psychiatr Epidemiol. 2014;49:1835-1847.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]