The WHO defines quality of life as an individual's perception of their life position in the context of the culture and value systems in which they live, and in relation to their goals, expectations, standards, and concerns (WHO). Predictors of quality of life (QOL) in women identified by various studies are:

  • the woman's environmental characteristics,
  • education,
  • employment,
  • marital status,
  • experiencing stressful life events,
  • social situation and financial status,
  • cultural differences,
  • ethnicity,
  • physical exercise,
  • overweight or obesity,
  • menopausal symptomatology (Mirhaghjou et al., 2016, Giannouli et al., 2012).

Menopause

Middle age, a period of natural ovarian aging, is characterized by a changing hormonal environment that accompanies the transition to menopause. The subsequent hormonal decline has a significant impact (medical, psychological) on women's health and well-being and increases the likelihood of developing degenerative diseases (Giannouli et al., 2012).

The transition to menopause begins with a decline in reproductive capacity after the age of 40, representing a transition from a reproductive to a non-reproductive stage of life. It is a period in a woman's life that begins with the date of the last menstrual cycle. It is confirmed only after twelve consecutive months of absence of menstruation (amenorrhea) (Hachul, Polesel, Tufik, 2020). Menopause therefore denotes the permanent cessation of menstruation due to reduced ovarian estrogen secretion (Mirhaghjou et al., 2016).

However, this definition cannot be applied to women who have amenorrhea before the transition to menopause due to a previous hysterectomy, endometrial ablation, levonorgestrel-releasing intrauterine system, or use of combined oral contraceptives. Therefore, natural menopause is more appropriately defined as the permanent cessation of ovarian function in cis women, which occurs on average between the ages of 45 and 55 (Davis, Baber, 2022).

This change affects the entire organism and produces various (climacteric) symptoms:

  1. vasomotor symptoms — hot flashes and night sweats;
  2. somatic symptoms — bone and joint complaints and loss of muscle mass;
  3. psychological symptoms — sleep disturbances, mood swings, impaired memory, lack of concentration, nervousness, depression, and insomnia;
  4. sexual symptoms — sexual dysfunction, vaginal dryness or atrophy, and dyspareunia (Mirhaghjou et al., 2016).

The duration and severity of these changes vary among individuals, affecting overall quality of life (Giannouli et al., 2012). According to some authors, menopause is also a major cause of obesity, cardiovascular and metabolic diseases, which has a negative impact on QOL in menopausal women (Mirhaghjou et al., 2016).

Terminology

In connection with menopause, we may encounter several professional terms denoting different periods. These are:

  • Perimenopause: the period around menopause, immediately before menopause and the first year after menopause;
  • Menopausal transition: the period before menopause characterized by significant variability in the menstrual cycle; women may have longer or even shorter menstrual cycles;
  • Climacterium: the period denoting the transition from the reproductive to the non-reproductive phase; it encompasses longer periods than perimenopause (1–2 years before and after it), and when women experience symptoms during this period, it is called climacteric syndrome;
  • Premenopause: the period before menopause; it encompasses the entire reproductive period before the definitive cessation of menstruation;
  • Postmenopause: the period after menopause;
  • Early postmenopause: the first eight years after menopause;
  • Late postmenopause: more than eight years after menopause (Hachul, Polesel, Tufik, 2020).

Symptoms

The onset of menopausal symptoms is directly related to the increase in FSH (follicle-stimulating hormone) and LH (luteinizing hormone) levels and the decline in estrogen concentration. The period of hypoestrogenism promotes a number of negative consequences for women's health. Some occur around menopause, such as insomnia, anxiety, irritability, and hot flashes (the latter occur in nearly 70% of women). Other symptoms, such as an increased incidence of sleep-related breathing disorders and cardiovascular risk, qualitative changes in skin and hair, and physiological changes promoting the development of osteoporosis, occur over a longer time horizon. In addition, there is a modification of body fat distribution, with more fat accumulating in the abdominal area after menopause. Other difficulties include atrophy, nocturia, body pain, depression, impaired memory, and decreased libido. The prevalence of depression in this phase results from both decreased steroids and tryptophan, as well as social factors such as empty nest syndrome (a feeling of sadness and loneliness after children move out). Depression in this phase is often closely associated with insomnia (Hachul, Polesel, Tufik, 2020). Approximately 90% of women have menopausal symptoms, which are severe in approximately 20%. The average duration of vasomotor symptoms is 4–5 years (Ameratunga, Hickey, 2012).

Although menopause itself is not a cause of weight gain, the decline in estrogen levels causes an increase in total adipose tissue and redistribution of body fat from the periphery to the trunk, leading to increased visceral adiposity. Abdominal fat accumulation alters adipokine secretion, leading to chronic inflammation, which not only increases the risk of CVD and diabetes mellitus II but also the risk of breast, uterine, and colorectal cancer (Davis, Baber, 2022).

The impact of menopause on quality of life

According to Giannouli et al. (2012), menopause as a life event does not affect women's quality of life. However, the presence and high intensity of climacteric symptoms has a negative impact on all aspects of QOL (Giannouli et al., 2012). Global average female life expectancy increased over the past century from approximately 50 years in 1900 to 64 years in 1990, and to 72 years at present. Women spend nearly one-third of their lives in the climacteric period, and therefore experience the consequences of hypoestrogenism for a longer time (Hachul, Polesel, Tufik, 2020).

More than 80% of women experience psychological or physical symptoms in the year approaching menopause, with varying difficulties and distribution in their lives, leading to a reduction in their quality of life (Mirhaghjou et al., 2016). The effects of climacteric symptomatology on women's quality of life are diverse. Menopausal symptoms, especially in the first years of their experience, can reduce QOL levels (Mirhaghjou et al., 2016). Reduced QOL is also influenced by overweight and obesity. In several studies, significant reductions in QOL during menopause due to high BMI levels have been recorded (Mirhaghjou et al., 2016). Women with better QOL tend to be leaner, eat healthier, exercise more, have better health awareness, and use preventive health policies more frequently (Giannouli et al., 2012).

Insomnia related to sleep quality rather than quantity is associated with impaired daytime functioning (negative effects on memory, psychomotor abilities). In addition, according to some authors, insufficient subjective sleep quality and daytime dysfunction are considered the best predictors of quality of life (Ameratunga, Hickey, 2012).

The frequency of hot flashes and night sweats shows regional differences (Giannouli et al., 2012). However, higher education levels and employment are associated with better QOL. Various studies found that menopausal women with higher education levels had fewer symptoms. Interestingly, in several populations, the intensity of vasomotor, physical, and sexual symptoms was associated with lower education. Therefore, employment and higher education levels may be considered proxies for higher income levels and increased access to healthcare services or increased awareness of available coping mechanisms for menopausal symptoms. Therefore, it is necessary to provide education focused on preparing women for the years after menopause, which could improve their QOL (Mirhaghjou et al., 2016).

Insomnia

Sleep quality is an important determinant of health and quality of life. Sleep deprivation is associated with health disorders such as obesity, cardiovascular disease, diabetes, and mood disorders. Sleep disturbances during menopause are a multifactorial problem faced by many women. Insomnia is defined as difficulties initiating and/or maintaining sleep or early morning awakening accompanied by daytime impairment for at least 3 months. Insomnia can result from social, environmental, psychological, and physiological factors. Vasomotor symptoms and changing hormone levels, circadian rhythm abnormalities, exacerbations of primary insomnia, mood disorders, coexisting health conditions, as well as lifestyle factors all play a role in this problem (Ameratunga, Hickey, 2012; Hachul, Polesel, Tufik, 2020).

Hormonal changes (decreased estrogen and increased FSH, progesterone, and testosterone) can adversely affect the sleep–wake cycle and contribute to both objective and subjective sleep problems during this period (Ameratunga, Hickey, 2012). Research shows that approximately 25% of women aged 50 to 64 have sleep problems, and 15% of them report severe sleep disturbances. Problematic sleep appears to be worse in the postmenopausal period compared to the premenopausal period and substantially worse in women after surgical menopause compared to naturally postmenopausal women. Insomnia and other sleep disorders are generally more common in women (of all age groups) compared to men (Ameratunga, Hickey, 2012). According to Hachul et al. (2020), sleep problems are more frequent in late postmenopause than in the early postmenopause group (Hachul, Polesel, Tufik, 2020).

However, aging itself is associated with increasing insomnia. Nearly 30% of people over 65 years of age report sleep difficulties. Menopause has a significant impact on objective sleep patterns regardless of age. Given that both female sex and aging are risk factors for insomnia, this may explain the high prevalence of this sleep disorder in postmenopause. One of the possible causes of disrupted sleep in this population is the high prevalence of hot flashes. Vasomotor symptoms and depression are significantly associated with poor sleep (Midlife Women's Health Study). Additionally, a history of smoking has been associated with insomnia and sleep disturbances (Hachul, Polesel, Tufik, 2020).

Another consequence of hypoestrogenism is atrophy of the lower genital urinary tract. This often leads to nocturia (the need to wake up during the night to urinate). Nocturia leads to disrupted sleep and insomnia — it is responsible for sleep fragmentation and a reduction in sleep hours (Hachul, Polesel, Tufik, 2020).

Sleep quality is one of the main health parameters threatened by obesity, particularly due to an increased number of respiratory events and frequent awakenings. Since insomnia can be the result of physical and hormonal changes experienced by middle-aged women, but also stress related to lifestyle (work, family, and social life demands), assessment of women by a psychologist with continuous psychological monitoring can play an important role in supporting women in this phase of life. Sleep can also be significantly affected by changes in daily life and is strongly associated with the prevalence of anxiety and depression (Hachul, Polesel, Tufik, 2020).

Therapeutic options

The main advantage of early menopause diagnosis is the possibility of using either hormonal therapy or another treatment approach aimed at alleviating unpleasant symptoms caused by hypoestrogenism (Hachul, Polesel, Tufik, 2020). When formulating treatment strategies, it is also essential to examine insufficient sleep and sleep problems during menopause and to thoroughly understand the factors contributing to these problems. Strategies may range from hormone therapy and medications to lifestyle modifications (Ameratunga, Hickey, 2012).

1. Hormonal therapy: Menopausal hormone therapy (MHT) involving estrogen or an estrogen compound alleviates menopausal symptoms while also preventing menopause-related bone mass loss and cardiometabolic changes. Comprehensive care for postmenopausal women includes lifestyle optimization (nutrition and physical activity, reduced alcohol consumption, no smoking) and treatment of other identified risk factors for chronic diseases. Menopausal hormone therapy, including tibolone, remains the most effective treatment for menopausal symptoms to date. MHT significantly reduces the risk of hip, vertebral, and other osteoporosis-related fractures in women with normal bone density, osteopenia, and osteoporosis. Fracture prevention is the primary indication for its use (Davis, Baber, 2022).

Estrogen therapy aims to mimic natural estrogens, specifically estradiol, estrone, and estriol. The most commonly prescribed estrogen formulations are oral preparations. These include oral conjugated estrogens, synthetically derived piperazine estrone sulfate, micronized estradiol, and estradiol valerate. Estradiol treatment may also be prescribed as a transdermal weekly or twice-weekly patch, as a daily gel or skin spray, or as a slow-release subcutaneous implant. The availability of different formulations varies between countries. Recommended doses are specific to the patient.

Progestogens are steroid compounds that act as agonists at progesterone receptors and can induce secretory transformation in the endometrium. Progestogens can be divided into two subgroups: natural or neutral progestogens, such as progesterone and dydrogesterone, and synthetic progestogens. The role of progestogens in MHT is to prevent endometrial hyperplasia or endometrial cancer induced by estrogen, and when used in appropriate doses for an adequate duration, all progestogens induce a secretory change in the endometrium as seen in the normal luteal phase of menstruation and prevent endometrial hyperplasia or endometrial cancer. Several studies have found an increased risk of breast cancer and thromboembolic events with certain types of MHT (Davis, Baber, 2022).

2. Other available hormonal options:

  • tibolone,
  • estrogen combined with a selective estrogen receptor modulator (bazedoxifene).

3. Non-hormonal management of menopausal symptoms: This includes lifestyle and dietary modifications, dietary supplements, non-hormonal medications, and behavioral and alternative therapies. However, there is a lack of convincing evidence that exercise, dietary supplements, or a diet rich in phytoestrogens are effective in alleviating vasomotor symptoms. Growing evidence points to the effectiveness of antidepressants (venlafaxine, paroxetine, gabapentin, oxybutynin) in alleviating menopausal vasomotor symptoms (VMS). Cognitive behavioral therapy helps reduce difficulties associated with VMS and may have additional benefits for sleep and mood (Davis, Baber, 2022).

However, in cases where hormonal therapy is declined, patients may try other alternatives, although with limited evidence of efficacy: Healthy diet and beneficial lifestyle A healthy diet focused on:

  • including 5 portions of fruit or vegetables daily,
  • reducing refined foods,
  • reducing fats and sugars,
  • reducing caffeine and alcohol to limit hot flashes and osteoporosis risk,
  • weight reduction — high BMI increases the risk of hot flashes, heart disease, and breast cancer.

Regular physical activity to:

  • reduce weight,
  • reduce hot flashes (although highly intense irregular activity may even worsen symptoms),
  • reduce the risk of heart disease,
  • reduce the risk of osteoporosis.

Vitamins and minerals:

  • vitamin E may protect against heart disease, although there is limited evidence for reducing hot flashes; it may also help with vaginal dryness;
  • calcium and vitamin D are important for maintaining optimal bone density (Holloway, 2008).

4. Promising prospects also include:

  • estetrol (15,16-dihydroxyestradiol),
  • neurokinin B receptor antagonists,
  • fezolinetant.

Estetrol and NK3B receptor antagonists are promising new treatment options for bothersome postmenopausal VMS. Further studies are needed to determine whether estetrol protects against menopause-associated central adiposity accumulation and associated changes in glucose tolerance and lipid profiles, and whether it has a clinically significant anti-resorptive effect on bone (Davis, Baber, 2022).

Current international guidelines recommend initiating MHT in healthy symptomatic women within 10 years of their last menstruation to maximize benefits and minimize risks. The risks associated with MHT use in women aged 65 or older who started treatment within 10 years of their last menstruation are considerably lower than in those who started MHT at age 65 or later. Premature discontinuation of MHT, for example within less than 5 years of use, may be unwise for many women. VMS will recur in 50% of women regardless of whether MHT is tapered or abruptly discontinued. Furthermore, a large population study found that in women under 60 years of age, MHT discontinuation was associated with an increased risk of cardiac death (1.5-fold after ≤5 years of use and 2-fold after >5 years of use) and stroke-related death (2.6-fold after ≤5 years of use and 3.2-fold after >5 years of use). An appropriate management protocol should include annual reassessment with a review of comorbidities and consideration of dose reduction and transition to transdermal therapy with increasing age (Davis, Baber, 2022).

This is a very brief overview of possible therapeutic approaches for individual menopausal symptoms with varying levels of evidence of efficacy. A detailed review exceeds the scope of this paper. The variability in symptom presence among postmenopausal women clearly reflects that not all women can be treated in the same way. It is always essential to consult a doctor on how to treat any given symptom. The physician should always consider evidence-based therapy in combination with the specific patient's wishes.

Conclusion

Menopausal and postmenopausal symptoms significantly affect women's quality of life. However, their frequency and severity show interpersonal differences. Menopausal age should be considered a fundamental aspect in assessing health risks for women, regardless of whether it is caused by a natural factor (due to aging) or a surgical procedure (due to hysterectomy or oophorectomy). Furthermore, their impact may distort the results of other observations (quality of life studies, sleep quality studies, etc.). It would therefore be appropriate for researchers to always inquire about concomitant symptoms of the climacteric state and postmenopause in women, even when the study has a primarily different focus. This also applies to healthcare providers treating these women.

Authors: Mgr. Lívia Kaňuková, Institute of Public Health and Hygiene, UPJŠ in Košice prof. MUDr. Kvetoslava Rimárová, CSc., Institute of Public Health and Hygiene, UPJŠ in Košice MVDr. Martina Tejová, Institute of Public Health and Hygiene, UPJŠ in Košice

Work supported by 2 grant projects of the Ministry of Education, Science, Research and Sport of the Slovak Republic KEGA: KEGA 008 UPJŠ-4/2020; KEGA 010UPJŠ-4/2021.

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