- Funmilola M. OlaOlorunFunmilola M. OlaOlorunSenior Lecturer, Department of Community Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria Honorary Consultant, University College Hospital. Ibadan, Nigeria Adjunct Assistant Professor, Department of Population, Family & Reproductive Health, Johns Hopkins University
- and Wen ShenWen ShenCo-Director Women's Wellness and Healthy Aging Program Director, Menopause Clinic Editor, The Johns Hopkins Menopause App. Assistant Professor, Division of Gyn Specialties, Johns Hopkins School of Medicine Joint Appointment, Johns Hopkins School of Nursing
Menopause is the natural senescence of ovarian hormonal production, and it eventually occurs in every woman. The age at which menopause occurs varies between cultures and ethnicities. Menopause can also be the result of medical or surgical interventions, in which case it can occur at a much younger age. Primary symptoms, as well as attitudes toward menopause, also vary between cultures. Presently, the gold standard for treatment of menopause symptoms is hormone therapy; however, many other options have also been shown to be efficacious, and active research is ongoing to develop better and safer treatments.
In a high-resource setting, the sequelae/physiologic changes associated with menopause can impact a woman’s physical and mental health for the rest of her life. In addition to “hot flashes,” other less well-known conditions include heart disease, osteoporosis, metabolic syndrome, depression, and cognitive decline. In the United States, cardiac disease is the leading cause of mortality in women over the age of 65. The growing understanding of the physiology of menopause is beginning to inform strategies either to prevent or to attenuate these common health conditions. As the baby boomers age, the distribution of age cohorts will increase the burden of disease toward post-reproductive women. In addition to providing appropriate medical care, public health efforts must focus on this population due to the financial impact of this age cohort of women.
Women are living longer in most geographies, and thus a better understanding of the menopause is paramount to ensuring that women continue to live healthy and fulfilling lives.
Definition, Staging, and Classification of Menopause
Menopause is the permanent cessation of menses, and it occurs at the end of the menopausal transition, also referred to as the perimenopause. The perimenopause is a period usually characterized by irregular menstrual cycles and hormonal fluctuations, often associated with unpleasant and uncomfortable symptoms and signs. The diagnosis of menopause is made retrospectively after a woman’s menses have ceased for 12 consecutive months, in the absence of any physiologic or pathologic cause (Soules et al., 2001). Although the diagnosis is clinical, elevated serum follicle-stimulating hormone (FSH) may indicate menopause (Peacock & Ketvertis, 2018; Sarri, Davies, & Lumsden, 2015).
The Stages of Reproductive Aging Workshop (STRAW) established the STRAW+10 staging system, now considered to be the gold standard for menopause staging, largely based on the menstrual cycle (Peacock & Ketvertis, 2018). The three menopausal stages are: reproductive (menstrual cycle is regular), menopause transition (menstrual cycle varies in duration), and postmenopause (menstrual cycle has ceased). Apart from providing a uniform classification on menopausal status for researchers, the STRAW staging system also serves as a clinical tool for both women and their providers in guiding the assessment of women’s fertility and contraceptive needs, as well as healthcare decision-making (Harlow et al., 2012; Santoro et al., 2007).
Menopause may be natural or artificially induced (for instance, due to surgery, chemotherapy, or radiation). When it occurs naturally, menopause follows ovarian follicular depletion, which is associated with hypoestrogenemia and high concentrations of FSH.
Basic Physiology of Menopause
Menopause is generally accepted to be a physiological phenomenon, as evidenced by the similarity of the changes that occur in women at this stage of their lives, irrespective of their race or ethnicity.
Physiological Changes During the Menopausal Transition
As part of the aging process, the number of ovarian primary follicles diminishes, so that the follicles left cannot adequately respond to the FSH, there is no luteinizing hormone (LH) surge, there is no ovulation, less estrogen is produced, and menstruation ceases. These changes in the normal physiology lead to unabated high levels of FSH and LH. The adrenals continue to secrete testosterone, some of which is converted to estrogen, and this small amount of estrogen may be responsible for the absence of symptoms beyond the cessation of menses in some women (Peacock & Ketvertis, 2018). The reduced estrogen leads to thinning and atrophy of the vagina, bone resorption and loss, constriction of arterial walls, and accelerated increase of low-density lipoprotein (LDL). These physiological changes predispose women to urogenital, skeletal, and cardiovascular symptoms.
Timing of Menopause
The age at which natural menopause is attained varies in different parts of the world, possibly due to variability in ovarian aging (Broekmans, Soules, & Fauser, 2009). Studies from all over the world suggest that the median age of natural menopause varies over a 5- to 6-year period, and generally it is reported as earlier in low- and middle-income countries (LMICs) than in their high-income counterparts (Fenton & Panay, 2015). However, there is no clearly consistent difference in the age of natural menopause between women who reside in high-income countries and their counterparts in LMICs. Furthermore, most of the existing body of evidence comes from subnational cross-sectional studies. The median age at natural menopause, based on cross-sectional studies, is 48 years in Ghana (Kwawukume, Ghosh, & Wilson, 1993), Nigeria (Okonofua, Lawal, & Bamgbose, 1990; OlaOlorun & Lawoyin, 2009), and Iraq (Mustafa & Sabir, 2012); 49 years in Lebanon (Reynolds & Obermeyer, 2001) and Latin America (Castelo-Branco et al., 2006); 50 years in Iran (Mohammad, Sadat Hashemi, & Farahani, 2004) and Saudi Arabia; 51 years in the United States (Gold et al., 2001; Nichols et al., 2006; Stanford, Hartge, Brinton, Hoover, & Brookmeyer, 1987), United Kingdom (Sarri et al., 2015), and Greece (Adamopoulos et al., 2002); and 52 years in Turkey (Aydin, Erbas, Karakus, Aydin, & K-Ozkan, 2005).
Some population-based studies from the United States, the Netherlands, and Sweden that have assessed trends in the age of menopause suggest that the median age of menopause has increased over time (Nichols et al., 2006; Rödstöm et al., 2003; van Noord, Dubas, Dorland, Boersma, & te Velde, 1997). Conversely, other studies from the United States, New Zealand, and Poland have found no trends in the age of menopause over time (Burch & Gunz, 1967; Fenton & Panay, 2015; Kaczmarek, 2007; Stadel & Weiss, 1975). Data from the multiracial SWAN study suggest that the earlier the age at onset of menopause, the longer the duration of the menopausal transition (Paramsothy et al., 2017).
Although the existing body of literature provides mixed findings, factors that have been reported to influence the timing of natural menopause have been classified as demographic, menstrual, reproductive, familial, genetic, and lifestyle-related (Gold, 2011).
Nutrition and Timing of Menopause
Studies that have examined the relationship between nutrition and the timing of menopause are limited, and their findings have been mixed. While some authors reported an association between specific dietary exposures and timing of menopause, others found no association. Many of the existing studies are limited due to small sample sizes, cross-sectional designs, and use of unsuitable markers, such as FSH, which is considered insensitive in the measurement of ovarian reserve. Recommendations favor use of anti-Mullerian hormone as a predictor of ovarian aging and the timing of menopause (Jamil, Fatima, Ahmed, & Malik, 2016). However, very few studies have used this marker, so further research is indicated.
Some associations reported in cross-sectional studies, such as a study in Scotland reporting lower odds of having attained menopause among 45–49 year old women who reported high meat consumption (Torgerson, Avenell, Russell, & Reid, 1994), and a Japanese study reporting higher odds of having attained menopause among women ages 45–55 years with high calcium and soy intake (Nagata, Takatsuka, Inaba, Kawakami, & Shimizu, 1998), could not be replicated in prospective studies in similar samples (Nagata et al., 2012; Nagata, Takatsuka, Kawakami, & Shimizu, 2000; Torgerson, Thomas, Campbell, & Reid, 1997). However, a prospective study among German women was able to show that higher meat consumption was associated with increased age at menopause (Nagel, Altenburg, Nieters, Boffetta, & Linseisen, 2005).
Furthermore, findings appear also to be dependent on the age of the women in the sample. For instance, data from the U.S.-based Nurses’ Health Study found that dairy consumption was associated with a later age at menopause, but only for women less than 51 years old (Carwile, Willett, & Michels, 2013). Additionally, a U.K.-based cohort study found that high intake of oily fish, fresh legumes, vitamin B6, and zinc, as well as being non-vegetarian, were associated with a later age at natural menopause, while high intake of refined pasta and rice, as well as being vegetarian, were associated with an earlier age at natural menopause (Dunneram, Greenwood, Burley, & Cade, 2018). Further information on the findings of studies that have focused on the association between nutrition and timing of menopause can be found in the systematic review by Moslehi and colleagues (Moslehi, Mirmiran, Tehrani, & Azizi, 2017). The pathways for the associations between nutrition and the timing of menopause are not yet clear.
Premature, Early, and Delayed Menopause
Menopause is considered to be abnormal when it occurs before age 40 (premature) or after age 60 (delayed). Premature menopause affects 1% of women, occurs before age 40, and is caused by medical (primary ovarian insufficiency, or permanent ovarian failure) or surgical premature deficiency of ovarian sex hormones (Kodaman, 2010; Mishra et al., 2017; Peacock & Ketvertis, 2018; Sarri et al., 2015). However, it is believed that ovarian failure due to primary ovarian insufficiency may not be absolute, as some women with ovarian insufficiency occasionally ovulate, and others achieve pregnancy and delivery (Alper, Jolly, & Garner, 1986). In view of this, the term primary ovarian insufficiency is preferred (Kodaman, 2010; Nelson, 2009; Welt, 2008). Primary ovarian insufficiency is characterized by hypergonadotropic hypogonadism (Kodaman, 2010), and often it is predated by irregular menses and symptoms associated with estrogen deficiency, such as hot flashes and vaginal dryness (Kodaman, 2010; Nelson. 2009).
Early menopause is also thought to be due to primary ovarian insufficiency and occurs between ages 40 and 45, affecting 5% of women (Mishra et al., 2017; Peacock & Ketvertis, 2018). Early menopause has been consistently observed in women of low socioeconomic status, women with low parity or nulliparity, those who have no history of oral contraceptive use, and those who smoke actively. Similarly, a family history of premature or early menopause, being a child of a multiple pregnancy, early menarche, and being underweight have been associated with early menopause. Details of sociodemographic, health, genetic, and environmental influences on the timing of menopause have been addressed in detail (Forman, Mangini, Thelus-Jean, & Hayward, 2013; Gold, 2011; Mishra et al., 2017). Women who experience early menopause have been reported to also experience long-term adverse effects on cognition, mood, cardiovascular health, bones, and sexual health (Shuster, Rhodes, Gostout, Grossardt, & Rocca, 2010; Wellons, Ouyang, Schreiner, Herrington, & Vaidya, 2012). Furthermore, they are reported to have an increased risk of early mortality (Biglia et al., 2017). A meta-analysis that included 32 studies and over 300,000 women has also added credence to the evidence on the effect of early menopause on cardiovascular disease and mortality (Muka et al., 2016).
Even though ovarian cancer is rare, many women who have hysterectomy for benign disease are also offered a bilateral oophorectomy, due to concerns regarding the risk of malignancy, and thus they have symptoms and signs similar to that seen with medical primary ovarian insufficiency (Kodaman, 2010). Since the early 21st century, practice guidance has suggested that the risks and benefits of making a woman prematurely menopausal be weighed carefully, especially since women who have bilateral oophorectomy before age 45 are at increased risk of mortality from cardiovascular disease, especially if they were not treated with estrogen (Rivera et al., 2009). Furthermore, compared with their counterparts who undergo natural menopause, premenopausal women who experience surgical menopause tend to have more severe symptoms for the first 5 years after surgery (Ozdemir, Celik, Go”rkemli, Kiyici, & Kaya, 2009). Other causes of primary ovarian insufficiency include genetic, autoimmune, chemotherapeutic, radiotherapeutic, viral, and idiopathic causes (Fenton, 2015). The risk for adverse health outcomes has been associated with both early and late menopause (Dunneram et al., 2018).
Contextual Differences in the Experience of Menopause
Attitudes toward menopause differ by gender, and are influenced by many contextual factors, including the attitude and response of health care providers. Additionally, the way menopausal symptoms are experienced, and the preferred management approach to address symptoms differs widely by context.
Attitudes Toward Menopause
The way menopause is perceived and therefore experienced and managed depends to a large extent on the social and cultural context in which women live (Hall, Callister, Berry, & Matsumura, 2007). Although research points to menopause as a physiological process, some people perceive it as a disease process, especially in settings where people are ill-informed about menopause and how and why it occurs.
Attitudes of Women Toward Menopause
Women from Guatemala and Costa Rica reported that they perceived menopause to be a time of more sexual freedom (Diaz, Medino, Castillo, & Vargas, 2013; Michel, Mahady, Caceres, & Soejarto, 2006). This positive attitude was also reported in a Nigerian study where menopause was said to be a period of relief and rest from childbearing, especially when a woman has had all the children she wants, particularly in contexts where fertility control is minimal or non-existent (Adekunle, Fawole, & Okunlola, 2000). Postmenopausal Arab women living in Qatar reported being able to participate in more social events and religious activities; the cultural context stipulated restrictions on their participation in the latter during menses (Murphy, Verjee, Bener, & Gerber, 2013). Arab women residing in Qatar who participated in focus-group discussions felt that a husband’s attitude and emotional support greatly influenced how his wife viewed her experience of the menopause. They also felt that the close-knit nature of Arab families was protective against women’s experiencing depression at midlife (Murphy et al., 2013).
In studies among women in West Bengal, India, and Bahrain, researchers found that postmenopausal women had a more positive attitude toward menopause than their perimenopausal counterparts (Dasgupta & Ray, 2017; Jassim & Al-Shboul, 2008). A majority (87%) of highly educated Asian female teachers residing in Pakistan reported a positive attitude toward menopause (Memon, Jonker, & Qazi, 2014). A qualitative study conducted in Singapore also reported a generally positive attitude toward menopause (Mackey, Teo, Dramusic, Lee, & Boughton, 2014). One study among women and their spouses in Turkey reported that, in general, both groups had a positive attitude toward menopause (Aksu, Sevinçok, Kücük, Sezer, & Oğurlu, 2011).
Menopausal status was not associated with women’s attitude to menopause in a clinic sample of Iranian women, where only 22.8% reported having a positive attitude toward menopause (Ghorbani, Nassaji, Shahbazi, Tabar, & Rahaei, 2014). Not all attitudes reported regarding menopause have been positive. Another study among Iranian women suggested they generally had a negative attitude toward menopause, and premenopausal women were statistically significantly more concerned than their postmenopausal counterparts about sexuality after marriage (p = 0.008; Kisa, Zeyneloğlu, & Ozdemir, 2012).
In Guatemala, women felt menopause was a taboo topic (Michel et al., 2006). Furthermore, in the African context, menopause could be a troubling time if a woman has not had any children of her own, given the importance of childbearing (Adekunle et al., 2000). Studies from Central America, Mexico, and rural Costa Rica reported that women have a reduced quality of life (QoL) due to symptom experience around the menopause (Diaz et al., 2013; Locklear et al., 2008; Locklear, Perez, Caceres, & Mahady, 2013). In Turkey, it was found that women with more negative attitudes also reported experiencing more severe symptoms (Aksu et al., 2011). The experience of hot flashes and mood swings was linked to negative attitudes to menopause among Macedonian women in a qualitative study in Australia (Strezova et al., 2017). Similarly, in a cross-sectional study conducted in the United States, anxiety, depressed mood, irritability, vaginal itching, crying spells, and breast tenderness were all associated with a negative attitude toward menopause. In this same study, however, even though hot flashes and night sweats were more frequently reported, they were not associated with a negative attitude to menopause (Sood et al., 2016). In a study conducted in Pakistan, 20 to 40% of women were afraid of the onset of menopause because they had linked menopause to visual impairment (Inayat, Danish, & Hassan, 2017).
Attitudes of Men Toward Menopause
Not much has been published on attitudes of men toward menopause. Two small qualitative studies from Turkey and Brazil suggest men are ignorant of what the menopause is about, and lack understanding of the symptoms their wives experience (Hidiroglu, Tanriover, Ay, & Karavus, 2014; Rodolpho, Quirino, Hoga, & Rosa, 2016). However, men in the Brazilian study noticed changes in their wives, both in appearance and behavior. Although initially confused by these observations, many men learned, over time, to provide emotional support for their wives. Regarding marital intimacy, men learned to observe their wives’ mood and accept her reduced desire for sex in order to preserve their relationship. Many men recognized their ignorance regarding the menopause and sought information from the Internet and relatives, making it easier to provide support for their wives (Rodolpho et al., 2016). In a separate study, men mostly derived information about the menopause from their wives (Mansfield, Koch, & Gierach, 2003). Men have expressed a desire for healthcare providers to educate them regarding the menopause, preferably using a couple’s approach (Rodolpho et al., 2016), and some researchers have recommended this as well (Mansfield et al., 2003).
Among men in Turkey, some believed that as women lose their femininity, they become more masculine, are more mature, better respected, and equal to men. Some Turkish men associated women’s loss of interest in sex with menopause and thus wanted their wives to continue to menstruate. Others wanted menstruation to resume in their wives because they felt that the relaxing effect of ejaculation on men should apply to women, whereby their symptoms of irritability and nervousness would be relieved by menstruation (Hidiroglu et al., 2014). Men from a Brazilian study felt women’s lack of interest in sex was not solely due to the onset of menopause, but that the length of their relationship by the time women were experiencing menopause had an important role to play in their lack of interest in sex (Rodolpho et al., 2016).
Men interviewed using oral histories expressed their concerns about their belief that their wives were exaggerating the intensity of the menopause-related symptoms they were experiencing. Men acknowledged that they eventually found out that the nature and intensity of the symptoms experienced varied across women, and this realization made them more understanding and supportive. These Brazilian men noted how symptoms like hot flashes affected their wives’ QoL (Rodolpho et al., 2016). Men reported that they were often confused by the sudden changes they noticed in their wives, and they wanted to be supportive, but they often did not know how they could help. However, they learned how to help to support and maintain their marital relationship through patience, love, and adapting to the behavior changes they observed (Mansfield et al., 2003; Rodolpho et al., 2016). Men are often reluctant to share their feelings, and this extends to husbands’ feelings about their wives’ experiences during menopause, in part because men are reported to want to appear to be emotionally strong (Addis & Mahalik, 2003). A study conducted in the United States found a positive and statistically significant correlation between men’s attitude to menopause and that of their wives (Papini, Intrieri, & Goodwin, 2002). Furthermore, structural equation modeling was used to show that men’s attitudes to menopause were negatively related to the frequency of menopause-related symptoms reported by their wives (Papini et al., 2002).
Attitudes of Providers
The management of women’s health at midlife is complex and multifaceted. Despite the fact that most providers will treat women at midlife at some point in their career, very little information is provided to physicians during their basic and specialty training to equip them to manage these women in a holistic way. As such, many physicians have a knowledge deficiency in management of women at midlife and avoid any controversy, such as use of hormone therapy (Baber, 2017). Christianson, Ducie, Altman, Khafagy, and Shen (2013) surveyed all obstetrics/gynecology (OB/GYN) residency programs in the United States, and of 258 residency program directors they contacted, 79 (30.6%) confirmed forwarding the survey. In all, 1,799 people received the survey, with 510 completions, for a response rate of 28.3%. Most residents reported that they had limited knowledge and needed to learn more about the following aspects of menopause medicine: pathophysiology of menopause symptoms (67.1%), hormone therapy (68.1%), nonhormone therapy (79.0%), bone health (66.1%), cardiovascular disease (71.7%), and metabolic syndrome (69.5%). Among fourth-year residents who would enter clinical practice soon after the survey, a large proportion also reported a need to learn more in the following areas: pathophysiology of menopause symptoms (45.9%), hormone therapy (54.2%), nonhormone therapy (69.4%), bone health (54.2%), cardiovascular disease (64.3%), and metabolic syndrome (63.8%; Christianson et al., 2013). Christianson and colleagues subsequently conducted a 2-year menopause medicine curriculum for OB/GYN residents utilizing lectures and a lab with case studies, and they concluded that a menopause curriculum is an effective modality for improving residents’ knowledge of how to manage menopause patients (Christianson, Washington, Stewart, & Shen, 2016).
Common Symptoms Associated with Menopause
The symptoms that have been associated with menopause are similar across contexts, although the symptoms most commonly reported by women differ, and the sociocultural context within which the menopausal transition is experienced varies (Jones, Jurgenson, Katzenellenbogen, & Thompson, 2012; Locklear et al., 2017; Melby, Lock, & Kaufert, 2005). An examination of the literature suggests that the most commonly reported symptoms in a given context are intricately related to the sociocultural context, including work-related factors. For instance, studies from Asia, Africa, and Latin America often find joint and muscular discomfort or pain, as well as physical and mental exhaustion or tiredness, as the most common symptoms reported (Chim et al., 2002; Diaz et al., 2013; Kwawukume et al., 1993; Locklear et al., 2017; Okonofua et al., 1990; OlaOlorun & Lawoyin, 2009), while studies from North America and Europe tend to find that the commonly reported complaints are vasomotor symptoms (VMS), such as hot flashes, night sweats, palpitations, and migraines, which may affect as many as 75% of older women (Peacock & Ketvertis, 2018).
The well-known Study of Women’s Health Across the Nation (SWAN study) reported that 60% to 80% of women in the United States experience VMS during the menopausal transition (Thurston, Sutton-Tyrrell, Everson-Rose, Hess, & Matthews, 2008), and these symptoms may persist for over a decade (Avis et al., 2015). Hot flashes, in particular, can be very disruptive for women. Research suggests that hot flashes affect women’s QoL, impair their sleep, and affect their mood (Grady, 2006; Santoro, Epperson, & Mathews, 2015; Thurston et al., 2008). These symptoms tend to increase their healthcare utilization and missed work days, and thus the cost of care (Sarrel, 2012; Sarrel et al., 2015). It is now thought that hot flashes are not just due to decreased estrogen levels, but are rather a complex phenomenon with multiple causes, including genes, physical changes, and medication, as well as influences of culture, individual experiences, and expectations (Biglia et al., 2017). Moreover, there is growing evidence that suggests that VMS (most commonly experienced as hot flashes and night sweats) may serve as a biomarker for chronic conditions, such as cardiovascular disease, osteoporosis, and cognitive decline (Biglia et al., 2017; Herber-Gast, Brown, & Mishra, 2015).
Urogenital symptoms are also prevalent, affecting up to 60% of women, and include urethral atrophy symptoms of stress incontinence, frequency, urgency, dysuria (painful urination), as well as vaginal atrophy symptoms of vaginal dryness, pruritus, and dyspareunia (painful intercourse). Four to five in 10 women experience psychogenic symptoms, such as anger, irritability, anxiety, depression, sleep disturbance, loss of concentration, and loss of self-esteem/confidence (Peacock & Ketvertis, 2018).
Sexual concerns have been widely reported by women undergoing the menopausal transition (Avis et al., 2017; Kling et al., 2017). Sexual dysfunction is known to increase with age and has been reported to reduce the QoL of menopausal women. Factors associated with sexual dysfunction in these women may be psychosocial, may be related to medication, or may be a result of vulvovaginal atrophy, chronic illness, or hypoactive sexual desire disorder (Thornton, Chervenak, & Neal-Perry, 2015).
Weight gain is another symptom reported by women undergoing the menopausal transition (Lovejoy, 2003). Women are reported to gain an average of 2.1 kg ± 5.1 kg over the menopausal transition, and they may also lose height due to osteoporosis, thus making the weight gain appear more obvious (Guthrie, Dennerstein, & Dudley, 1999).
Management of Menopause
Approaches to management of menopause include hormonal, nonhormonal or behavioral, and alternative treatments or natural remedies.
The use of hormones in the management of menopausal symptoms remains controversial. Hormonal treatment has been used to manage VMS, to prevent and reverse vaginal or urogenital atrophy, and to prevent bone loss. Where indicated, it is recommended that hormonal treatment (estrogen and/or progestogen) be used for only a short duration, and with the lowest effective dose. If there are no systemic symptoms, localized estrogen treatment is preferred (i.e., application via creams, rings, and patches). Oral tablets are used in the presence of systemic symptoms. Depending on the indication, hormonal treatment may use continuous or cyclical modalities. The risks and benefits must always be assessed carefully before commencing hormonal therapy due to the increased associated risk of breast cancer, ovarian cancer, thromboembolism, stroke, and coronary heart disease. The use of selective estrogen receptor modulators (SERMs) produces the same outcomes as hormonal treatment, but SERMs have the advantage of not stimulating endometrial growth and not increasing the risk of reproductive cancers. An example is Raloxifene, which acts as an estrogen agonist in bone and with lipids, but as an estrogen antagonist in the uterus and breast (Peacock & Ketvertis, 2018; Sarri et al., 2015).
Nonhormonal/Behavioral, Including Self-Care Strategies
A variety of nonhormonal approaches have been reported to be beneficial for women experiencing menopausal symptoms. Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), have been used to treat VMS, such as hot flashes. For the treatment of osteoporosis, calcium and vitamin D supplementation have been used successfully (Peacock & Ketvertis, 2018). Hormone replacement therapy and cognitive behavioral therapy have been used to treat the low mood associated with menopause (Sarri et al., 2015).
Alternative Treatments/Natural Remedies
To abate symptoms, natural methods, such as massage, dietary changes, and herbal medicines, have been reported to be preferred by some women to improve their QoL (Doyle, Frasor, Perez, Locklear, & Mahady, 2009; Locklear et al., 2008, 2013, 2017).
Phytoestrogens (such as in soy, red clover, and black cohosh), vitamin E, and omega-3 fatty acids have been used in the management of VMS (Sarri et al., 2015), but some studies suggest these remedies may be no better than the use of placebo (Peacock & Ketvertis, 2018).
Extracts from herbs used by women in Costa Rico for their menopause-related symptoms have been found to bind to estrogen receptors (ER-alpha and ER-beta), and thus may have estrogenic agonist/antagonist effects. It has also been suggested that some of the herbs used by Costa Rican women to treat menopause-related symptoms may have progesterone agonist and chemopreventative effects, but safety and efficacy studies are lacking (Locklear et al., 2017).
Further details on the management of menopause can be found in the National Institute for Health and Care Excellence (NICE) recommendations (Sarri et al., 2015).
Medical Significance of Menopause
The significance of medical conditions related to menopause and the reasons why menopause education and treatment should be an objective of the public health agenda are reviewed here; however, studies from LMICs that go beyond age, perceptions, and symptoms of menopause are sparse, so menopause in industrialized countries is the focus here.
The average age of menopause in industrialized countries is 51 years, and life expectancy is 80.8 years. Thus, women spend a third of their lives in postmenopause. In the United States, an estimated 6,000 women reach menopause every day, or more than 2 million every year. In 2020, the estimated number of women over 50 in the United States is projected to exceed 60 million (U.S. Census Bureau, 2017).
Menopause has far-reaching effects on multiple conditions; however, this discussion focuses on the conditions with the greatest public health impact.
Cardiovascular disease (CVD) is the leading cause of death for women over 65 years old: 1 in 3 women will die of heart disease. Most of these deaths occur in the postmenopause, in women more than 55 years old (Go et al., 2013; Heron, 2016). Early onset of menopause, either natural or surgical/medical, increases a woman’s risk for CVD. Furthermore, the prevalence of metabolic syndrome and accelerated atherosclerosis has been shown to increase in the perimenopause (El Khoudary et al., 2013; Thurston et al., 2018).
Data from the Women’s Health Initiative (WHI) study show that the risk of CVD decreases when menopause hormone therapy (MHT) is started in younger menopausal women and closer to perimenopause. However, MHT has not been shown to be cardioprotective in older IN tpostmenopausal women, as the only trial that tested this hypothesis—Kronos Early Estrogen Prevention Study (KEEPS)—yielded negative results. Nonetheless, studies have shown that MHT’s effects on cardiac health can be benign (as in one study that showed initiation of MHT in women age 50 to 59, or within 10 years of menopause, does not increase the women’s risk of cardiac-related events more than the risk in women who did not use MHT), or it can be a powerful preventative treatment (as evidenced in a study that showed women who underwent menopause before they turned 35 and who failed to receive MHT had a two to three times higher risk of myocardial infarction; (Harman et al., 2005; Manson et al., 2013). The American Heart Association and American College of Cardiology recommend assessing for cardiovascular risk starting at age 40 (Goff et al., 2014).
Metabolic syndrome, which increases the risk for CVD and type 2 diabetes, includes: hypertension (HTN), dyslipidemia, central obesity, and increased fasting glucose level. One or more of these conditions occur in 50% to 80% of postmenopausal women. However, conditions like inflammation may have an equal or greater impact than metabolic syndrome (López-Suárez et al., 2014).
Type 2 diabetes mellitus (DM) occurs in 28% of adults over 65 years old (Cheng et al., 2013). Type 2 DM is undiagnosed in about a third of women (Cowie et al., 2009). Screening should be considered for all women, starting at age 45 (American Diabetes Association, 2015). WHI and Heart and Estrogen/Progestin Replacement Study (HERS) data showed that, after 5.6 years, self-reported DM was lower in women who received MHT compared to women who received a placebo (Kanaya et al., 2003; Margolis et al., 2004). The North American Menopause Society (NAMS) does not recommend MHT to prevent diabetes (NAMS, 2010).
Overall prevalence of HTN is higher in men than in women until the age of 60. However, after age 60, women have a higher prevalence of HTN, with an incidence rate of greater than 75%. Blood pressure steadily increases with age, and a “bump” occurs at menopause. If left untreated, HTN can lead to coronary heart disease, heart failure, atrial fibrillation, dementia, and stroke (Burt et al., 1995; Eaton et al., 2016; Haring et al., 2013; Howe & Mccullough, 2015; Rodriguez et al., 2016).
Triglycerides (TG), LDL, and non-high-density lipoprotein-cholesterol (non-HDL-C) increase the risk of CVD. LDL levels have been shown to increase within 1 year of menopause (Derby et al., 2009; Matthews et al., 2009).
Women have a 1 in 3 chance of developing cancer in their lifetimes, and the risk of cancer increases with aging and obesity. Breast cancer is the most common cancer diagnosed in women (Siegel, Miller, & Jemal, 2016). It is the second leading cause of death among women in the United States (Heron, 2016). Due to advances in detection and treatment, breast cancer survivors number more than 3.5 million women. Risk factors include sex, age, menstrual life, genetics, obesity, alcohol use, hormone therapy, and thoracic radiation therapy. WHI data shows that breast cancer risk is increased with estrogen and progestogen therapy beyond 3 to 5 years. Some data link progestogen use with (lobular) breast cancer (American Cancer Society, 2018; Chlebowski et al., 2013; NAMS, 2010).
Other cancers common in postmenopausal women are cancers of the endometrium, cervix, ovary, lung, colorectum, and skin. Treatment for these cancers can result in severe menopause-related conditions and may complicate care for the survivors. Additionally, these patients are also at increased risk for CVD and osteoporosis (Colzani et al., 2011; Yang, Neugut, Wright, Accordino, & Hershman, 2016).
Prevalence of osteoporosis is 6.8% among women 50 to 59 years old; however, it escalates to 34.9% in women 80 years and older (Wright et al., 2014). Bone loss accelerates 2 to 3 years before menopause, and the rate then slows 3 to 4 years after menopause (Recker, Lappe, Davies, & Heaney, 2000). Lower estrogen levels have been associated with higher risk of fracture in older women (Devine et al., 2005). Among postmenopausal women, 40 to 50% have osteoporosis, more than 15% have hip fractures, and 50% will have an osteoporotic fracture in their lifetime. Risk factors for osteoporosis include age, low body weight, genetics, smoking, alcohol use, history of fracture, and medications.
Hip fractures due to osteoporosis result in a 5- to 8-fold increase in mortality within the first 3 months after the fracture, and a greater than 20% increase in mortality within 1 year of the fracture. Additionally, hip fracture results in increased morbidity in older women, and 25% of these women will require long-term care and 50% will have long-term loss of mobility. Vertebral fractures incur a 10% increase in mortality within a year of the fracture. These fractures also result in chronic pain, height loss, and adverse sequelae for pulmonary function and ambulation (Pinkerton & McClung, 2019).
Mood changes are observed in 23% of perimenopausal and postmenopausal women (Bromberger et al., 2007). Certain time periods that are associated with hormonal changes (such as premenstrual, postpartum, and perimenopause) are known to precipitate mood symptoms in a subgroup of women. Overall, studies suggest that the greatest at-risk time for new-onset depression in midlife women is the perimenopause, not the postmenopause (Freeman, Sammel, Lin, & Nelson, 2006). It has been suggested that a decline in estrogen occurring around the time of menopause is associated with mood changes.
Individuals going through menopause are diagnosed with depression at rates two to four times the average. Of those diagnosed at menopause, depression rates were highest in the 40- to 59-year-old age group. Several studies found that VMS could amplify depression. Many studies suggest that the menopause transition is an independent risk factor for the development of depression. Bromberger et al. found that the likelihood of depressive symptoms was significantly higher—about 1.30-fold—in women in the early menopause transition, 1.71-fold in women in late transition, and 1.57-fold in women in postmenopause compared to women in premenopause (Bromberger et al., 2007). This finding was confirmed by data from the Penn Ovarian Aging Study (POAS) by Freeman et al. (2004) and data from the Seattle Midlife Women’s Health Study by Woods et al. (2008).
In comparison to depression, relatively less is known about the course of anxiety during peri- and postmenopause. The menopausal transition is associated with new-onset anxiety in women without a history of anxiety. Risk factors include a history of high premenopausal anxiety.
Poor sleep includes insomnia, sleep apnea, and nocturnal awakening, and it occurs in 40 to 60% of menopausal women. Reduced sleep quality in menopause has been linked to depressive symptoms (Bolge, Balkrishnan, Kannan, Seal, & Drake, 2010; Gold et al., 2000; Shaver & Woods, 2015).
A systematic review and meta-analysis in 2014 showed that the prevalence of sleep disturbance is higher in perimenopause and postmenopause than in premenopause. The authors concluded that the menopause transition conveyed poor sleep beyond anticipated age effects. They also found that the perceptions of sleep are not translatable from detectable physical sleep changes and may be affected by an emotional overlay (Xu & Lang, 2014). Night sweats and disturbed sleep caused excessive daytime sleepiness, fatigue, relationship problems, and reduced QoL. Recent studies have shown a relationship between sleep disturbance and increased risk of depression, weight gain, and heart disease. Wang and Holtzman (2020) demonstrated a bidirectional relationship between sleep and the neuropathological hallmarks of Alzheimer’s disease (AD).
Cabeza de Baca and colleagues (2019) found that sleep debt was associated with poorer cardiovascular health in older women, despite taking into account socioeconomic status and psychosocial factors. Better sleep habits were associated with more favorable cardiovascular health among women. Similarly, sleep debt is associated with long-term metabolic disruption, which may promote the progression of type 2 DM.
The prevalence of subjective cognitive complaints during the menopause transition ranges from 31 to 92%. It has been hypothesized that declines in estrogen during the menopause transition are associated with reduced cognitive functioning. There is an accelerated deterioration of cognitive function once menopause begins (Alzheimer’s Association, 2019).
AD is three times more common in women than in men, with more women than men dying of the disease. In cultured cells and animal models, estrogen has a protective effect on neurons. There is support for the timing hypothesis of the impact of early MHT on AD development. Different formulations of MHT also have different impacts on AD (Henderson, Guthrie, Dudley, Burger, & Dennerstein, 2003; Joffe et al., 2006; Resnick et al., 2006).
Maki (2013) demonstrated that neuroimaging studies showed enhanced hippocampal and prefrontal function with MHT, findings that provide support for the hypothesis that early initiation of MHT is associated with cognitive benefits (Leblanc, Janowsky, Chan, & Nelson, 2001).
Two meta-analyses of 14 retrospective and four prospective observational studies showed significant reduction (29–44%) of risk of AD in MHT users (Nelson, Humphrey, Nygren, Teutsch, & Allan, 2002). However, overall studies to date have lacked consistency in testing outcomes and specific aspects of memory function with the use of estrogen therapy.
The Cost of Menopause-Related Symptoms and Disease
The need for more education on menopause in the workplace has been well documented. An exhaustive 2017 research report by Brewis and colleagues looked at 104 English language publications on the effects of menopause transition on women’s economic participation in the United Kingdom from 1990 to 2016 (Brewis, Beck, Davies, & Matheson, 2017). The studies surveyed found an increase in population of older employed women in the workforce, highlighting the reality that a larger proportion of the workforce will have to cope with menopause symptoms while working. Menopause is not well understood by the general population and workplace interventions are not commonly in place. Additionally, attitudes of colleagues and managers can severely impact a woman’s QoL. Gendered ageism is a significant problem that requires organizational culture changes. Studies have shown both positive and negative effects of menopause on working women, and the positive variations may be due to job type, especially among women in more senior positions. Several areas exist where more data are needed, including studies that can contribute to how the experience of the menopause transition can affect the labor force. Data from these studies will “allow a recognition of the potential productivity losses which organizations will incur if they do not make use of the full array of experience, skill and knowledge possessed by older female workers” (Brewis et al., 2017).
In a retrospective analysis of the medical expenditure survey data, it was determined that menopausal symptoms were associated with significantly higher annual costs than osteoporosis, disorders of lipid metabolism, and esophageal disorders. More than 6 million women experience menopausal symptoms annually. In this cross-sectional U.S. population–based survey of 4,402 women age 40 to 65 years, approximately 60% of respondents said they had consulted a healthcare provider regarding menopausal symptoms. These are underestimates, because few women seek help from a healthcare professional for menopausal problems, or they mention only some of their symptoms, but not others, to their healthcare providers, usually due to embarrassment or confusion about treatment options (Assaf et al., 2017).
Total health expenditures for menopausal symptoms were estimated at $3 billion annually in the United States. Women with menopausal symptoms had $1,343 higher overall direct costs, $457 higher prescription drug costs, $48 more sick leave costs, 0.27 more sick leave days annually, lower hourly productivity rates by 2 units of work, and lower annual productivity rates by 2,600 units of work. Direct costs that impact menopause are physician and emergency department visits, medications, laboratory testing, and the management of side effects (Pinkerton, 2015). The U.S. Bureau of Labor Statistics reported that 68 million women, or half the total workforce, worked either full time or part time in 2011. In the United States, up to 75% of women have VMS, and more than 90% of women with surgical menopause have VMS that can interfere with daily life and have significant negative effects on their work. It is estimated that women who did not receive medical therapy for VMS incurred 1.5 million outpatient healthcare visits, with a 57% increase in loss of indirect work productivity. The cost of this indirect work productivity loss is estimated at U.S. $27,668,410 (Pinkerton, 2015).
Dibonaventura and colleagues reported that patients with menopausal symptoms were more likely to have depression and anxiety and incurred significantly higher follow-up healthcare costs than women who did not experience depression ($7,237 versus $6,739). Of women currently experiencing menopause symptoms with hot flashes, 32% report suffering from depression. In this population, absenteeism from work was higher (5.31 versus 2.80%), as well as impairment while at work (25.00 versus 14.32%), and impairment of daily activities as compared to women who did not experience menopause hot flashes (37.32 versus 23.16%). Also increased were the numbers of physician visits (2.47 versus 1.77), emergency room visits (0.27 versus 0.16), and days hospitalized (0.36 versus 0.18) in the preceding 6 months (Dibonaventura, Wagner, Alvir, & Whiteley, 2012).
In 2017, the annual AD death rate was 37.3/100,000 people per year in the United States, and a total of 5.8 million Americans have AD. Women have AD more often than men. Presently, two thirds of AD patients in America are in women: 3.5 million women versus 2.1 million men. Of the number of people 85 years old or older in 2050, 7 million will have AD. The responsibilities for caring for dementia patients often fall to women, and nearly half are unpaid family members or friends. The amount of unpaid care is estimated at 18.5 billion hours, valued at $233.9 billion. In addition, Medicare and Medicaid paid $290 billion in medical costs for AD in 2019.
Osteoporosis is a major public health problem resulting in high societal costs and physical impairment, with direct annual costs estimated to be over $17 billion (for fractures attributed to osteoporosis). Menopause is the single greatest risk factor for osteoporosis. Studies have shown that the most cost-effective screening strategy was combined dual-energy x-ray absorptiometry (DXA)/quantitative computed tomography (CT), with screening initiation at age 55 and a quantitative CT screening interval of 5 years. This practice can reduce the lifetime risk of fractures to 12.8% with early therapy for those found to be at increased risk. (Agten, Ramme, Kang, Honig, & Chang, 2017).
Components of Preventative Medicine in Mature Women’s Health
A multidisciplinary approach to menopause health was advocated in a position paper published by the European Menopause and Andropause Society (EMAS) in 2016 (Armeni et al., 2016). In this paper EMAS proposed a care pathway for post-reproductive health with a focus on prevention or delaying disorders associated with menopause. EMAS recommended “assessment should be holistic and include menopausal symptoms . . . cardiovascular and osteoporotic risk factors as well as gynecological and breast health. Strategies to maintain post-reproductive health encompass optimizing diet and lifestyle.”
Trudeau and her group conducted a feasibility study of educational needs of menopausal women, and they concluded that “the need for information and social support during the menopause transition is paramount, considering that over 30 million women are within the associated age range” (Trudeau, Ainscough, Trant, Starker, & Cousineau, 2011). They noted that too much disparate and inaccurate information is available to patients. This causes confusion for patients at a time “when healthcare is in a crisis.” Patients need excellent medical care, and it is equally important for patients to have evidence-based health education to help them age well.
Why Menopause Should Be on the Public Health Agenda
Perimenopause should be viewed as a window of opportunity to improve women’s health, this opportunity can improve women’s health in the post-reproductive years, and provide benefits for a public health perspective, just as CVD, smoking and obesity have been addressed.
The present population of the world is over 7.5 billion, and 50% of the population are female. The United States alone has 50 million women over the age of 51 in 2020. Over 2 million U.S. women enter menopause annually, and more than 6 million women worldwide. Policymakers may believe that interventions targeted at older adults are less beneficial and cost effective. However, data from productivity studies and the work of economists offer alternative views (World Health Organization, 2017).
Joseph F. Coughlin, founder and director of the AgeLab at the Massachusetts Institute of Technology, stated, “One of the greatest under-appreciated sources of innovation and new business may in fact be women over 50, with new ideas, lots of life ahead of them, and with the verve to get it done” (Coughlin, 2017). According to Coughlin, today’s older women live longer and have more education than at any time in history. Women are the main caregivers for the family, including aging parents. They are also the chief consumer, making decisions about 80 to 90 cents on the dollar of healthcare spending for the family. Older women are changing the workplace with entrepreneurship and are acting as engines of innovation.
Borsch-Supan and Weiss (2008) found that in knowledge-based jobs, productivity increases with age and then levels off, but it does not decrease. He also found that there is evidence in some sectors that teams with mixed-age members were the most productive. His study showed that the combination of knowledge and experience of the older workers in conjunction with the skill and speed of the younger workers contributed to productivity gains (Borsch-Supan & Weiss, 2008).
Clark and Shoven (2019) proposed creating a paid-up status for Social Security in their report “Enhancing Work Incentives for Older Workers: Social Security and Medicare Proposals to Reduce Work Disincentives.” Their proposal was that employees who have been working for over 40 years and their corresponding employers should be exempt from paying into Social Security. This would decrease the cost to the employer and effectively lower the marginal cost of labor for the employee, thereby increasing their take-home pay and incentivizing them to work more. The study also proposed allowing older workers to work part time or to take longer time off, which would make them less expensive for employers. A similar paid-up policy change for Medicare would also contribute to decreased cost. These policy changes should “encourage continued employment of older people who are able and willing to remain in the labor force.”
Major research institutions have recognized the necessity of dedicating more resources to putting healthy aging (by extension, menopause in women) on the public health agenda. The Stanford Center on Longevity has as their mission “to accelerate and implement scientific discoveries, technological advances, behavioral practices, and social norms so that century-long lives are healthy and rewarding.”
Women’s health has generally been equated with reproduction, but due to increased longevity and continued productivity, a new metric for women’s health is needed. Women need to be seen as more than mothers (Psaki & OlaOlorun, 2012). Recommendations can be made based on the concept that early in the menopause transition there is a window of opportunity to identify and prevent chronic diseases later in life:
Provide an integrated, holistic approach to preventive care that is patient centric rather than disease centric.
Promote lifestyle modifications (changes in diet, physical activity, smoking, and alcohol/drug use) through social support and education.
Advocate for a shift away from viewing menopause as a disease state, and instead as a time of significant physiologic changes that requires more research and better education of patients and medical practitioners.
Finally, in concordance with the WHO’s The Decade of Healthy Ageing 2020–2030 there is an opportunity “to bring together governments, civil society, international agencies, professionals, academia, the media, and the private sector for ten years of concerted, catalytic and collaborative action to improve the lives of older people, their families, and the communities in which they live.”
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