**4. Menopause and hormones**

Menopause is a period of life when the ovaries are depleted of oocytes and the cyclical action of gonadotrophins, peptides, and steroids is disappeared. Age at menopause reveals the complex networks of health and socioeconomic aspects involving ethnicity, diet, education, oral contraceptive use, weight, occupation, exposure to endocrine disturbing substances, alcohol consumption, smoking, and physical activity [27]. Menopause is an indicator event in a woman's life that marks the end of reproductive capability. Although the age-related loss of vaginal bleeding in women has been described throughout history has been recognized the dramatic reduction in the amount of follicles within the ovary as a function of age, determining that the loss of both germ cells and the hormone-producing cells that help them is critical to the disappearing of menstrual function in women. Menopause is identified by the final menstrual period (FMP), but this diagnosis can only be made

retrospectively after a year of amenorrhea and happens at an average age of 51 [28]. In Mexico, the average age is 47.6 [29].

The development of reproductive aging, though, is slow, starts before the FMP, and can be defined as limiting (1) an early phase in which compensatory modifications in the hypothalamus, hypophysis, and ovary facilitate the preservation of both reproductive capability and gonadal hormone secretion; (2) an interval categorized by clear irregularity in follicle progress, ovarian secretion, and resulting symptoms precede to the FMP; and (3) constant and low ovarian hormone secretion [28]. The menopause has important effects on the functions of endocrine, cardiovascular, skeletal, immune, and genitourinary systems. Gonadal hormones affect much of the processes mainly by their effects on steroid binding proteins and receptors, but the changes in lifestyle with aging are also influential [27]. Detailed ultrasonographic show the changes in ovulatory function with reproductive aging largely define the hormonal changes, menstrual cycle patterns, and symptomatology that occur as the FMP approach [30].

Reproductive aging in women is mainly produced by the continuing, and finally quickening deficit of ovarian follicles. The related decay in inhibin B secretion from the ovaries ends in the disappearing of negative feedback on FSH. Inside the ovary, FSH stimulated follicle growth and estrogen synthesis and secretion. With additional follicle loss, these compensatory hormonal processes are no longer enough and follicle development come to be irregular in advance to additional loss of ovarian function results in the stable but very low estradiol levels that exemplify the postmenopause [28].

Several of the biochemical variations at climacteric period are due to estrogen and or progesterone diminution. Both steroids act through cytoplasmic receptors and two receptors for respectively steroid, alpha, and beta (ER-α and ER-β; PR-α and PR-β) are now recognized, occasionally antagonize each other. Isoforms of every receptor be present that have dissimilar tissue expression conformations and purpose which marks gene expression in normal and tumor tissue, therefore ligand treatment. ER-α is largely expressed in reproductive tissues, breast, kidney, bone, adipose tissue, and liver. ER-β is existent in ovary, CNS, lung, colon, kidney, and immune system. PR-α and PR-β are almost equal in configuration with the exception of PR-β having a supplementary 164 amino acids at the N terminus. PR-α and PR-β are expressed similarly in human tissues [27].

The 2001 Stages of Reproductive Aging Workshop (STRAW) and the 2011 STRAW + 10 proposed nomenclature and a staging system for ovarian aging including menstrual and qualitative hormonal criteria to define each stage. The STRAW staging system is extensively considered in the gold standard for describing reproductive aging through menopause. The menopausal shift signs a stage of physiologic changes as patients get close to reproductive senescence. Proof endorses the clinical significance of the transition for many patients as a phase of progressive fluctuations in health and QoL (i.e., vasomotor symptoms, insomnia, and MDD) and longer-term variations in numerous physical consequences (i.e., urogenital symptoms, bone, and lipids) that might impact women's QoL and the probability of healthy aging. As a standardized staging scheme for reproductive aging, STRAW is a huge influence to patient's health investigation by giving trustworthy categorization of menopause status for investigations of midlife patients. Significantly, STRAW helped investigation that proposed to differentiate the health effects of ovarian versus somatic aging. The STRAW staging system also helps as a clinical instrument for women and their healthcare providers to monitor the valuation of fertility, contraceptive needs, and healthcare decision making [31].

STRAW distributed the adult female life into three extensive phases: reproductive, the menopausal transition, and postmenopause. The late reproductive

**89**

end of life [31].

*Quality of Life and Menopause*

first variable length cycle [31].

*DOI: http://dx.doi.org/10.5772/intechopen.88983*

phase indicates the time when fecundability starts to decay and during which a woman might observe variations in her menstrual cycles. Given that significant endocrine factors start to change before obvious variations in menstrual cyclicity and that these endocrine fluctuations are crucial to fertility assessment. Early menopausal evolution is discernible by amplified inconsistency in menstrual cycle extent, conceptualized as a persistent difference of 7 days or more in the length of consecutive cycles. Persistence is defined as recurrence within 10 cycles of the

Cycles in the initial menopausal transition are also defined by high but varying early follicular phase FSH levels and low antimüllerian hormone (AMH) levels and antral follicle count (AFC). The late menopausal transition is apparent by the manifestation of amenorrhea of 60 days or longer. Menstrual cycles in the late menopausal transition are exemplified by augmented inconsistency in cycle length, severe changes in hormonal amounts, and elevated frequency of anovulation. In this stage, FSH levels are occasionally raised into the menopausal range and sporadically within the span typical of the initial reproductive years, mainly in relationship with elevated estradiol levels. The elaboration of international criteria and the accessibility to fundamental population-based information now allow the definition of quantitative FSH criteria, with levels greater than 25 IU/L in a random blood draw typical of being in late transition, founded on actual international pituitary criteria that approximate more than 40 IU/L in the earlier used urine-based gonadotropin standards. First-hand analyses should be initiated to verify this reference, and investigators and clinicians should prudently estimate the proper FSH value, subject on the test they employ. Founded on investigations of menstrual calendars and on changes in FSH and estradiol, this phase is expected to persist, on average, 1–3 years. Vasomotor symptoms are probable to be present during this phase. Novel data on the routes of change in mean levels of FSH and estradiol indicate that FSH continues to rise and that estradiol continues to decline until around 2 years after the FMP, after which the levels of each of these hormones stabilize. The late postmenopause characterizes the interval in which supplementary variations in reproductive endocrine function are more delimited and processes of somatic aging become of principal worry. Symptoms of vaginal dryness and urogenital atrophy become progressively more prevalent at this time. Nevertheless, several years after menopause, it has been perceived that there may be an added drop in levels of FSH in very old women; forthcoming investigations will be required to define whether a supplementary stage is necessary close to the

Investigations in younger and older climacteric patients insinuate that consequences of aging on the hypothalamus and pituitary are present and those are autonomous of the disappearance of steroid feedback. Following menopause there is a 30–40% reduction in LH and FSH between the ages of 50 and 75. Lie beneath these gonadotropin differences are intricate consequences of aging on GnRH secretion, with a 22% reduction in GnRH pulse frequency that is slightly balanced by a 14% rise in the total quantity of GnRH secreted over that owing to the deficit of ovarian function only. There are also age-related outcomes at the pituitary, with a 30% lessening in both LH and FSH responses to GnRH in older in comparison with younger climacteric patients. Estrogen-negative feedback at the hypothalamic point continues complete in older contrasted with younger postmenopausal patients; low-dose estrogen prescription is related with a substantial descent in circulating levels of LH, FSH, and free alpha-subunit and a parallel reduction in the total concentration of GnRH, with no effect on pulse frequency. Adding of progesterone diminished pulse frequency in younger and older climacteric patients with an associated reduction in total quantity of GnRH.

#### *Quality of Life and Menopause DOI: http://dx.doi.org/10.5772/intechopen.88983*

*Quality of Life - Biopsychosocial Perspectives*

In Mexico, the average age is 47.6 [29].

FMP approach [30].

the postmenopause [28].

similarly in human tissues [27].

retrospectively after a year of amenorrhea and happens at an average age of 51 [28].

The development of reproductive aging, though, is slow, starts before the FMP, and can be defined as limiting (1) an early phase in which compensatory modifications in the hypothalamus, hypophysis, and ovary facilitate the preservation of both reproductive capability and gonadal hormone secretion; (2) an interval categorized by clear irregularity in follicle progress, ovarian secretion, and resulting symptoms precede to the FMP; and (3) constant and low ovarian hormone secretion [28]. The menopause has important effects on the functions of endocrine, cardiovascular, skeletal, immune, and genitourinary systems. Gonadal hormones affect much of the processes mainly by their effects on steroid binding proteins and receptors, but the changes in lifestyle with aging are also influential [27]. Detailed ultrasonographic show the changes in ovulatory function with reproductive aging largely define the hormonal changes, menstrual cycle patterns, and symptomatology that occur as the

Reproductive aging in women is mainly produced by the continuing, and finally

Several of the biochemical variations at climacteric period are due to estrogen and or progesterone diminution. Both steroids act through cytoplasmic receptors and two receptors for respectively steroid, alpha, and beta (ER-α and ER-β; PR-α and PR-β) are now recognized, occasionally antagonize each other. Isoforms of every receptor be present that have dissimilar tissue expression conformations and purpose which marks gene expression in normal and tumor tissue, therefore ligand treatment. ER-α is largely expressed in reproductive tissues, breast, kidney, bone, adipose tissue, and liver. ER-β is existent in ovary, CNS, lung, colon, kidney, and immune system. PR-α and PR-β are almost equal in configuration with the exception of PR-β having a supplementary 164 amino acids at the N terminus. PR-α and PR-β are expressed

The 2001 Stages of Reproductive Aging Workshop (STRAW) and the 2011 STRAW + 10 proposed nomenclature and a staging system for ovarian aging including menstrual and qualitative hormonal criteria to define each stage. The STRAW staging system is extensively considered in the gold standard for describing reproductive aging through menopause. The menopausal shift signs a stage of physiologic changes as patients get close to reproductive senescence. Proof endorses the clinical significance of the transition for many patients as a phase of progressive fluctuations in health and QoL (i.e., vasomotor symptoms, insomnia, and MDD) and longer-term variations in numerous physical consequences (i.e., urogenital symptoms, bone, and lipids) that might impact women's QoL and the probability of healthy aging. As a standardized staging scheme for reproductive aging, STRAW is a huge influence to patient's health investigation by giving trustworthy categorization of menopause status for investigations of midlife patients. Significantly, STRAW helped investigation that proposed to differentiate the health effects of ovarian versus somatic aging. The STRAW staging system also helps as a clinical instrument for women and their healthcare providers to monitor the valuation of fertility,

STRAW distributed the adult female life into three extensive phases: reproductive, the menopausal transition, and postmenopause. The late reproductive

contraceptive needs, and healthcare decision making [31].

quickening deficit of ovarian follicles. The related decay in inhibin B secretion from the ovaries ends in the disappearing of negative feedback on FSH. Inside the ovary, FSH stimulated follicle growth and estrogen synthesis and secretion. With additional follicle loss, these compensatory hormonal processes are no longer enough and follicle development come to be irregular in advance to additional loss of ovarian function results in the stable but very low estradiol levels that exemplify

**88**

phase indicates the time when fecundability starts to decay and during which a woman might observe variations in her menstrual cycles. Given that significant endocrine factors start to change before obvious variations in menstrual cyclicity and that these endocrine fluctuations are crucial to fertility assessment. Early menopausal evolution is discernible by amplified inconsistency in menstrual cycle extent, conceptualized as a persistent difference of 7 days or more in the length of consecutive cycles. Persistence is defined as recurrence within 10 cycles of the first variable length cycle [31].

Cycles in the initial menopausal transition are also defined by high but varying early follicular phase FSH levels and low antimüllerian hormone (AMH) levels and antral follicle count (AFC). The late menopausal transition is apparent by the manifestation of amenorrhea of 60 days or longer. Menstrual cycles in the late menopausal transition are exemplified by augmented inconsistency in cycle length, severe changes in hormonal amounts, and elevated frequency of anovulation. In this stage, FSH levels are occasionally raised into the menopausal range and sporadically within the span typical of the initial reproductive years, mainly in relationship with elevated estradiol levels. The elaboration of international criteria and the accessibility to fundamental population-based information now allow the definition of quantitative FSH criteria, with levels greater than 25 IU/L in a random blood draw typical of being in late transition, founded on actual international pituitary criteria that approximate more than 40 IU/L in the earlier used urine-based gonadotropin standards. First-hand analyses should be initiated to verify this reference, and investigators and clinicians should prudently estimate the proper FSH value, subject on the test they employ. Founded on investigations of menstrual calendars and on changes in FSH and estradiol, this phase is expected to persist, on average, 1–3 years. Vasomotor symptoms are probable to be present during this phase. Novel data on the routes of change in mean levels of FSH and estradiol indicate that FSH continues to rise and that estradiol continues to decline until around 2 years after the FMP, after which the levels of each of these hormones stabilize. The late postmenopause characterizes the interval in which supplementary variations in reproductive endocrine function are more delimited and processes of somatic aging become of principal worry. Symptoms of vaginal dryness and urogenital atrophy become progressively more prevalent at this time. Nevertheless, several years after menopause, it has been perceived that there may be an added drop in levels of FSH in very old women; forthcoming investigations will be required to define whether a supplementary stage is necessary close to the end of life [31].

Investigations in younger and older climacteric patients insinuate that consequences of aging on the hypothalamus and pituitary are present and those are autonomous of the disappearance of steroid feedback. Following menopause there is a 30–40% reduction in LH and FSH between the ages of 50 and 75. Lie beneath these gonadotropin differences are intricate consequences of aging on GnRH secretion, with a 22% reduction in GnRH pulse frequency that is slightly balanced by a 14% rise in the total quantity of GnRH secreted over that owing to the deficit of ovarian function only. There are also age-related outcomes at the pituitary, with a 30% lessening in both LH and FSH responses to GnRH in older in comparison with younger climacteric patients. Estrogen-negative feedback at the hypothalamic point continues complete in older contrasted with younger postmenopausal patients; low-dose estrogen prescription is related with a substantial descent in circulating levels of LH, FSH, and free alpha-subunit and a parallel reduction in the total concentration of GnRH, with no effect on pulse frequency. Adding of progesterone diminished pulse frequency in younger and older climacteric patients with an associated reduction in total quantity of GnRH. The outcome of estrogen-negative feedback on the LH response to GnRH is not predisposed by aging even though the FSH response to GnRH is weakened with aging. Numerous reports have proposed that sensitivity to estrogen-positive feedback may be absent with aging in women [28]. Hormone measurements other than FSH during the perimenopause are usually considered to be of little diagnostic value. The transition may take four or more years [27].

In the late perimenopause, where extended cycles (≥60 days) predominate, 60–70% cycles are anovulatory. Regarding the steroid hormone secretion patterns, when ovulatory cycles do happen, the cycle may seem normal, overlaid on one another or have a prolonged follicular phase named as a lag phase. While the initial perimenopause is considered by instabilities in the timing and regulation of ovulation, the advanced perimenopause is distinguished by rareness of ovulation derived to the original ovarian follicle reduction. In the late perimenopause, although AMH has decreased to imperceptible levels, inhibin B frequently persists measureable, particularly if there is still residual follicle function. Both gonadotropins are considerably high and show substantial cyclical differences. FSH amounts can be at their most irregular throughout the late perimenopause. The function that very low AMH amounts to participate in the interference of ovulatory function in the perimenopause continues indeterminate but given its close link with the total nongrowing follicle (NGF) pool and primordial follicle recruitment and the intricacy of underlying follicle wave action, it is likely to be crucial [30]. In the initial 1–2 years after the FMP, intermittent follicle growth is obvious in single women. Harmonious with these studies, epidemiologic reports employing sensitive estradiol assays prove a farthest decrease from the FMP to the estradiol lowest point 2 years ahead. Subsequently, estradiol levels persist low and stable. FSH levels also continue steady between 2 and 8 years after the FMP but decay over time such that FSH drops by 30% by around age 75, as does LH. Nevertheless women are no longer concerned by irregular bleeding or breast tenderness, hot flashes may continue for up to 7 years after the FMP, and with lengthy hypoestrogenism, the genitourinary syndrome (GSM) of menopause may appear as a novel clinical symptom [28].

#### **5. Menopause and associated health problems**

The transition to menopause is characterized mainly by elevated levels of follicle-stimulating hormone (FSH) and low serum levels of estradiol, which gives rise to the presence of the characteristic symptoms (hot flashes, menstrual irregularities, sleep disruption, mood swings, headache, and genitourinary syndrome) [32]. 80% of women suffer physical and psychological symptoms throughout menopause with different degrees of seriousness and influence on QoL [4]. Clinicians and women usually identify the transition to menopause by the onset of menstrual irregularities [5, 6]. This period called perimenopause is variable but can range from 5 to 10 years before menopause.

The Study of Women's Health Across the Nation (SWAN) is a longitudinal, epidemiologic study designed to examine the physical, biological, psychological, and social changes during their intermediate years when they are suffering from menopausal transition that evaluated a total of 3302 women from different ethnic among 42 and 52 years old with a follow up for 15 years. The scientific areas of study assessed: bone mineral density and body composition, cardiovascular measures/risk factors, ovarian markers, vaginal, urogenital and sexual health, physical functioning, sleep quality, psychosocial factors, and epidemiologic factors. The results of this study contributed to define The Stages of Reproductive Aging Workshop (STRAW),

**91**

*Quality of Life and Menopause*

bleeding patterns [40].

or intensively.

*DOI: http://dx.doi.org/10.5772/intechopen.88983*

a staging system that categories reproductive life stages of adult women en three main categories: reproductive, menopausal transition, and postmenopause [33]. During the late reproductive year's, progesterone levels in the luteal phase decrease and the follicular phase is shortened from 14 to 10 days, including the decrease in inhibin B and a slight increase in FSH levels with preserved levels of estradiol, which gives rise to menstrual irregularities. The levels of antimüllerian hormone (AMH) and the count of antral ovarian follicles diminish too [32]. As time goes (around 2 years since last menstrual period), the FSH levels continue to rise and estradiol levels start falling and for the next 3–6 years estradiol, AMH and inhibin B levels are even lower, at this time is when the symptoms of genitourinary syndrome (GSM) could be more severe [32, 34, 35]. Contraception should be a part of any counseling during the menopausal transition due to the presence ovulatory cycles that can still occur until 12 months of amenorrhea have occurred [32].

The body mass index (BMI), lifestyle factor like tobacco use could influence the timing of the physiologic changes, but not in the path of change in bleeding patterns or hormonal levels with reproductive aging [31]. Some situations like the surgical menopause caused after a hysterectomy may not let us know when is the patient is in transition to menopause, the only way we could evaluate objectively this stage of life is by endocrine markers of ovarian aging, it is necessary to mention that 3 months after surgery high levels of transient FSH may occur, so for an accurate diagnosis, a new measurement of estradiol or serum FSH is required [36].

The bleeding patterns may not be a reliable parameter for evaluating reproductive aging owing to different endocrine disorders like polycystic ovarian syndrome or any other chronic illness or medications like cancer treatment among other situations that can also affect menstrual patterns or even cause amenorrhea [32]. It is well known that alkylating agents used as chemotherapeutic medication may lead to temporary elevated levels FSH and a decline of AMH and ovarian antral follicle count (AFC), but with time menstruation may resume [37–39]. Women in treatment with tamoxifen may also have altered hormone levels and abnormal

During this life stage period, serum cortisol levels also increases as well as adrenal androgen levels (androstenediol, dehydroepiandrosterone sulfate). In thyroid function for the moment, there is no information about disorders related to menopause so far [32]. After the cessation of ovarian function, the production of estrogen comes from the aromatization of androgens in the ovarian stroma and, in less quantity, from extragonadal sites mainly the adipose tissue. Hence, it is expected that obese women present vasomotor symptoms more frequently and/

Hot flashes, which may be accompanied with some other symptoms like flushing of the face, neck, and upper chest; palpitations; chills; and/or anxiety are some of the vasomotor symptoms [32] that occurs in up to 80% of women, frequently associated with diminished sleep quality [41, 42] irritability, difficulty concentrating, reduced quality of life (QoL) [43], and poorer health status [35]. Some researchers are looking for the relationship with the presence of hot flashes with markers of cardiovascular risk, in order to identify a vulnerable vascular phenotype [44]. Of all possible etiologies of headache, tensional headache is the most common. Migraine-type headache can increase during menopause due to hormonal changes. Tensional-type headache usually shows a favorable response to nonsteroidal therapy and can be prevented altogether with tricyclic antidepressants instead of hormonal therapy alone. Non-cyclical hormonal therapies are recommended to minimize headache due to hormonal treatment. Women who suffer migraine headache with aura or other risk factors of CVD can benefit from

#### *Quality of Life and Menopause DOI: http://dx.doi.org/10.5772/intechopen.88983*

*Quality of Life - Biopsychosocial Perspectives*

The outcome of estrogen-negative feedback on the LH response to GnRH is not predisposed by aging even though the FSH response to GnRH is weakened with aging. Numerous reports have proposed that sensitivity to estrogen-positive feedback may be absent with aging in women [28]. Hormone measurements other than FSH during the perimenopause are usually considered to be of little

In the late perimenopause, where extended cycles (≥60 days) predominate, 60–70% cycles are anovulatory. Regarding the steroid hormone secretion patterns, when ovulatory cycles do happen, the cycle may seem normal, overlaid on one another or have a prolonged follicular phase named as a lag phase. While the initial perimenopause is considered by instabilities in the timing and regulation of ovulation, the advanced perimenopause is distinguished by rareness of ovulation derived to the original ovarian follicle reduction. In the late perimenopause, although AMH has decreased to imperceptible levels, inhibin B frequently persists measureable, particularly if there is still residual follicle function. Both gonadotropins are considerably high and show substantial cyclical differences. FSH amounts can be at their most irregular throughout the late perimenopause. The function that very low AMH amounts to participate in the interference of ovulatory function in the perimenopause continues indeterminate but given its close link with the total nongrowing follicle (NGF) pool and primordial follicle recruitment and the intricacy of underlying follicle wave action, it is likely to be crucial [30]. In the initial 1–2 years after the FMP, intermittent follicle growth is obvious in single women. Harmonious with these studies, epidemiologic reports employing sensitive estradiol assays prove a farthest decrease from the FMP to the estradiol lowest point 2 years ahead. Subsequently, estradiol levels persist low and stable. FSH levels also continue steady between 2 and 8 years after the FMP but decay over time such that FSH drops by 30% by around age 75, as does LH. Nevertheless women are no longer concerned by irregular bleeding or breast tenderness, hot flashes may continue for up to 7 years after the FMP, and with lengthy hypoestrogenism, the genitourinary syndrome

diagnostic value. The transition may take four or more years [27].

(GSM) of menopause may appear as a novel clinical symptom [28].

The transition to menopause is characterized mainly by elevated levels of follicle-stimulating hormone (FSH) and low serum levels of estradiol, which gives rise to the presence of the characteristic symptoms (hot flashes, menstrual irregularities, sleep disruption, mood swings, headache, and genitourinary syndrome) [32]. 80% of women suffer physical and psychological symptoms throughout menopause with different degrees of seriousness and influence on QoL [4]. Clinicians and women usually identify the transition to menopause by the onset of menstrual irregularities [5, 6]. This period called perimenopause is variable but can

The Study of Women's Health Across the Nation (SWAN) is a longitudinal, epidemiologic study designed to examine the physical, biological, psychological, and social changes during their intermediate years when they are suffering from menopausal transition that evaluated a total of 3302 women from different ethnic among 42 and 52 years old with a follow up for 15 years. The scientific areas of study assessed: bone mineral density and body composition, cardiovascular measures/risk factors, ovarian markers, vaginal, urogenital and sexual health, physical functioning, sleep quality, psychosocial factors, and epidemiologic factors. The results of this study contributed to define The Stages of Reproductive Aging Workshop (STRAW),

**5. Menopause and associated health problems**

range from 5 to 10 years before menopause.

**90**

a staging system that categories reproductive life stages of adult women en three main categories: reproductive, menopausal transition, and postmenopause [33].

During the late reproductive year's, progesterone levels in the luteal phase decrease and the follicular phase is shortened from 14 to 10 days, including the decrease in inhibin B and a slight increase in FSH levels with preserved levels of estradiol, which gives rise to menstrual irregularities. The levels of antimüllerian hormone (AMH) and the count of antral ovarian follicles diminish too [32]. As time goes (around 2 years since last menstrual period), the FSH levels continue to rise and estradiol levels start falling and for the next 3–6 years estradiol, AMH and inhibin B levels are even lower, at this time is when the symptoms of genitourinary syndrome (GSM) could be more severe [32, 34, 35]. Contraception should be a part of any counseling during the menopausal transition due to the presence ovulatory cycles that can still occur until 12 months of amenorrhea have occurred [32].

The body mass index (BMI), lifestyle factor like tobacco use could influence the timing of the physiologic changes, but not in the path of change in bleeding patterns or hormonal levels with reproductive aging [31]. Some situations like the surgical menopause caused after a hysterectomy may not let us know when is the patient is in transition to menopause, the only way we could evaluate objectively this stage of life is by endocrine markers of ovarian aging, it is necessary to mention that 3 months after surgery high levels of transient FSH may occur, so for an accurate diagnosis, a new measurement of estradiol or serum FSH is required [36].

The bleeding patterns may not be a reliable parameter for evaluating reproductive aging owing to different endocrine disorders like polycystic ovarian syndrome or any other chronic illness or medications like cancer treatment among other situations that can also affect menstrual patterns or even cause amenorrhea [32]. It is well known that alkylating agents used as chemotherapeutic medication may lead to temporary elevated levels FSH and a decline of AMH and ovarian antral follicle count (AFC), but with time menstruation may resume [37–39]. Women in treatment with tamoxifen may also have altered hormone levels and abnormal bleeding patterns [40].

During this life stage period, serum cortisol levels also increases as well as adrenal androgen levels (androstenediol, dehydroepiandrosterone sulfate). In thyroid function for the moment, there is no information about disorders related to menopause so far [32]. After the cessation of ovarian function, the production of estrogen comes from the aromatization of androgens in the ovarian stroma and, in less quantity, from extragonadal sites mainly the adipose tissue. Hence, it is expected that obese women present vasomotor symptoms more frequently and/ or intensively.

Hot flashes, which may be accompanied with some other symptoms like flushing of the face, neck, and upper chest; palpitations; chills; and/or anxiety are some of the vasomotor symptoms [32] that occurs in up to 80% of women, frequently associated with diminished sleep quality [41, 42] irritability, difficulty concentrating, reduced quality of life (QoL) [43], and poorer health status [35]. Some researchers are looking for the relationship with the presence of hot flashes with markers of cardiovascular risk, in order to identify a vulnerable vascular phenotype [44].

Of all possible etiologies of headache, tensional headache is the most common. Migraine-type headache can increase during menopause due to hormonal changes. Tensional-type headache usually shows a favorable response to nonsteroidal therapy and can be prevented altogether with tricyclic antidepressants instead of hormonal therapy alone. Non-cyclical hormonal therapies are recommended to minimize headache due to hormonal treatment. Women who suffer migraine headache with aura or other risk factors of CVD can benefit from progesterone-only therapy, like the levonorgestrel intrauterine system, etonogestrel subdermal implant, depo-medroxyprogesterone acetate, or progestin-only contraceptives [32].

The symptoms of genitourinary syndrome (GUS), which may comprise signs and symptoms associated to the hypoestrogenism of the menopause involving changes to the labia, vagina, urethra, and bladder and includes vulvovaginal atrophy [45]. Symptoms are genital dryness, burning, and/or irritation; sexual symptoms of diminished lubrication and pain; and urinary symptoms of urgency, dysuria, and recurrent urinary tract infections (UTIs) [35]. Signs include changes in the skin consequently of the reduction blood flow to the vagina and vulva, the external genitalia reveals less pubic hair and less elasticity of the vulvar skin with introital narrowing and possible changes in the architecture, such as the loss of the labia minora, usually we could appreciate this changes about 3 years after menopause, although approximately 20% of women may report some symptoms in the early or late transition of menopause [46]. Topical estrogen is the best treatment for the relief of vulvovaginal symptoms and current therapeutic therapy, among the options for topical administration include creams, gel, vaginal tablets, or even vaginal ring [34]; other therapeutic options are vaginal lubricants and moisturizers. It is necessary to mention that also systemic estrogen preparations with or without progesterone provide excellent vaginal therapy [32].

Low-dose vaginal estrogen preparations are effective and generally safe treatments in women with actual diagnosis or history of breast cancer and treatment with tamoxifen, that with the non-hormonal treatments did not present relief of the symptomatology, there is lees information about treatment with aromatase inhibitors, taking into account that vaginal estrogen preparations can be absorbed systemically in a minimal amount. Less data are available on the creams containing conjugated estrogens than on those containing 17B-estradiol [47].

Menopause is associated with an increase in skeletal, joint, and muscle symptoms [43]. Estrogen binds on estrogenic receptor on joint tissues, protecting their biomechanical structure and function and maintaining overall joint health, but the exact effect of estrogen on osteoarthritis remains controversial [48–50]. Arthralgias increase with age, also rheumatic disorders incidence has an augment. Women who are obese or depressed may have marked symptoms, nevertheless it seems to be an association with joint pain or stiffness and menopausal transition, these symptoms could be alleviated with estrogen therapy alone or with combination therapy of estrogen and progestin, women in the WHI and some other studies have shown less joint pain or stiffness compared with those on placebo [32, 51].

In 2010, it was estimated that 21% of women in the European Union between 50 and 84 years old have osteoporosis. Osteoporosis, along with osteoarthritis, sarcopenia, and frailty, is considered a part of the so-called musculoskeletal aging phenotype. Adverse outcomes such as falls, fractures, functional deterioration, and increased morbidity can impact quality of life. The clinical complications of osteoporosis are fractures of the hip, wrist, and vertebral bodies. Worldwide, 8.9 million fractures occur annually due to osteoporosis, resulting in a fragility fracture every 3 seconds, which is associated with pain and decreased physical and social function in menopausal women [52].

Cardiovascular disease (CVD) is main etiology responsible of mortality in postmenopausal population. Menopause, itself, increases the risk of CVD no matter the age [53]. There is evidence that the use of estrogenic therapy has beneficial effects in cardiovascular mortality in many ways, some of them includes the reduction diminish of low-density lipoproteins levels and increased levels of highdensity lipoprotein as well as the improved endothelial function in the coronary vasculature [32].

**93**

*Quality of Life and Menopause*

evidence is requiring.

other pathologies [32].

risks of osteopenia [32].

best option for this kind of patients [61].

*DOI: http://dx.doi.org/10.5772/intechopen.88983*

The reanalysis of older studies such as the WHI study and the recent studies suggest that in case of no contraindication, the benefits of hormone therapy outweigh

Venous thromboembolism (VTE) has an augmented incidence when is related to the usage of hormonal therapies for menopause, it is supposed to increase twofold or threefold the risk, presenting a higher risk with oral formulations. Transdermal preparations of estrogen or estrogen and progestins combined and vaginal estrogen preparations did not appear to increase the risks of VTE [55]. In a meta-analysis of women who started HRT less than 10 years following menopause beginning or who were younger than 60 years, robust sign of augmented jeopardy of VTE was seen in the horn therapy group related to placebo (RR 1.74; 95% CI, 1.11–2.73) [56]. Minor doses of oral ET may give reduced VTE risk than higher doses [57], but related RCT

Talking about hormone therapy and breast cancer may result controversial, the effect of hormone therapy on breast cancer risk may depend on the type of the formulation, dose, and duration regimen, route of administration, prior exposure, and individual characteristics [35]. In the WHI study, the incidence of breast cancer increased in the estrogen-progestogen cohort and decreased in the estrogen-only and placebo groups. Contrarily, hormone therapy users had more localized tumors and improved survival rates [32]. The NAMS do not recommended the prescription of systemic hormone therapy for survivors of breast cancer, although selected cases may be discussed in conjunction with an oncologist after non-hormone options have been unsuccessful. If the patient refers moderate to severe GSM symptoms, low-dose vaginal estrogens, may be considered after a failed trial of non-hormone therapies and with consultation of the oncologist in charge of the case [35]. Options for symptom management include non-hormonal moisturizers, vaginal estrogens,

its risks, with fewer CVD events in younger versus older women [54].

androgens, selective modulators of the estrogen receptor (SERM).

The skin is another target where the hypoestrogenism may have manifestations after menopause, it is altered by epidermal and dermal thickness, decreased collagen and elastin content, consequently more laxity and wrinkles, many women could also experience hair loss. Estrogen therapy may benefit wound healing through modifying inflammation, stimulating granulation tissue formation, and accelerating re-epithelialization. In studies, ET increased epidermal and dermal thickness, increased collagen and elastin content, and improved skin moisture, with fewer wrinkles [58]. It may be relevant to perform scrutiny studies to those women with hair loss like thyroid function, serum iron, and androgens in order to exclude

Cholelithiasis, cholecystitis, and cholecystectomy occur more frequently in women who take oral estrogen, presumably because of the first-pass hepatic effect after oral ingestion, so systemic hormone therapy should be prescribed with caution in women with known gallbladder disease [32, 35]. Estrogens increase biliary cholesterol secretion and saturation, promote precipitation of cholesterol in the bile, and reduce gallbladder motility, with increased bile crystallization [59, 60]. The transdermal route of administration could be the

In epileptic patients, menopause can present at earlier age. The cause of this could be related to the number of crisis the woman presents during her life and the anticonvulsants she uses as treatment, specifically the ones that are metabolized by the hepatic enzyme cytochrome p450, which also affects estrogen levels. It is common that women with epilepsy present seizures during the menopausal transition due to the hormonal fluctuations. It is important to note that some anticonvulsants agents may accelerate the metabolism of vitamin D, which possibly increasing the

#### *Quality of Life and Menopause DOI: http://dx.doi.org/10.5772/intechopen.88983*

*Quality of Life - Biopsychosocial Perspectives*

progesterone provide excellent vaginal therapy [32].

conjugated estrogens than on those containing 17B-estradiol [47].

joint pain or stiffness compared with those on placebo [32, 51].

contraceptives [32].

progesterone-only therapy, like the levonorgestrel intrauterine system, etonogestrel subdermal implant, depo-medroxyprogesterone acetate, or progestin-only

The symptoms of genitourinary syndrome (GUS), which may comprise signs and symptoms associated to the hypoestrogenism of the menopause involving changes to the labia, vagina, urethra, and bladder and includes vulvovaginal atrophy [45]. Symptoms are genital dryness, burning, and/or irritation; sexual symptoms of diminished lubrication and pain; and urinary symptoms of urgency, dysuria, and recurrent urinary tract infections (UTIs) [35]. Signs include changes in the skin consequently of the reduction blood flow to the vagina and vulva, the external genitalia reveals less pubic hair and less elasticity of the vulvar skin with introital narrowing and possible changes in the architecture, such as the loss of the labia minora, usually we could appreciate this changes about 3 years after menopause, although approximately 20% of women may report some symptoms in the early or late transition of menopause [46]. Topical estrogen is the best treatment for the relief of vulvovaginal symptoms and current therapeutic therapy, among the options for topical administration include creams, gel, vaginal tablets, or even vaginal ring [34]; other therapeutic options are vaginal lubricants and moisturizers. It is necessary to mention that also systemic estrogen preparations with or without

Low-dose vaginal estrogen preparations are effective and generally safe treatments in women with actual diagnosis or history of breast cancer and treatment with tamoxifen, that with the non-hormonal treatments did not present relief of the symptomatology, there is lees information about treatment with aromatase inhibitors, taking into account that vaginal estrogen preparations can be absorbed systemically in a minimal amount. Less data are available on the creams containing

Menopause is associated with an increase in skeletal, joint, and muscle symptoms [43]. Estrogen binds on estrogenic receptor on joint tissues, protecting their biomechanical structure and function and maintaining overall joint health, but the exact effect of estrogen on osteoarthritis remains controversial [48–50]. Arthralgias increase with age, also rheumatic disorders incidence has an augment. Women who are obese or depressed may have marked symptoms, nevertheless it seems to be an association with joint pain or stiffness and menopausal transition, these symptoms could be alleviated with estrogen therapy alone or with combination therapy of estrogen and progestin, women in the WHI and some other studies have shown less

In 2010, it was estimated that 21% of women in the European Union between 50 and 84 years old have osteoporosis. Osteoporosis, along with osteoarthritis, sarcopenia, and frailty, is considered a part of the so-called musculoskeletal aging phenotype. Adverse outcomes such as falls, fractures, functional deterioration, and increased morbidity can impact quality of life. The clinical complications of osteoporosis are fractures of the hip, wrist, and vertebral bodies. Worldwide, 8.9 million fractures occur annually due to osteoporosis, resulting in a fragility fracture every 3 seconds, which is associated with pain and decreased physical and social function

Cardiovascular disease (CVD) is main etiology responsible of mortality in postmenopausal population. Menopause, itself, increases the risk of CVD no matter the age [53]. There is evidence that the use of estrogenic therapy has beneficial effects in cardiovascular mortality in many ways, some of them includes the reduction diminish of low-density lipoproteins levels and increased levels of highdensity lipoprotein as well as the improved endothelial function in the coronary

**92**

vasculature [32].

in menopausal women [52].

The reanalysis of older studies such as the WHI study and the recent studies suggest that in case of no contraindication, the benefits of hormone therapy outweigh its risks, with fewer CVD events in younger versus older women [54].

Venous thromboembolism (VTE) has an augmented incidence when is related to the usage of hormonal therapies for menopause, it is supposed to increase twofold or threefold the risk, presenting a higher risk with oral formulations. Transdermal preparations of estrogen or estrogen and progestins combined and vaginal estrogen preparations did not appear to increase the risks of VTE [55]. In a meta-analysis of women who started HRT less than 10 years following menopause beginning or who were younger than 60 years, robust sign of augmented jeopardy of VTE was seen in the horn therapy group related to placebo (RR 1.74; 95% CI, 1.11–2.73) [56]. Minor doses of oral ET may give reduced VTE risk than higher doses [57], but related RCT evidence is requiring.

Talking about hormone therapy and breast cancer may result controversial, the effect of hormone therapy on breast cancer risk may depend on the type of the formulation, dose, and duration regimen, route of administration, prior exposure, and individual characteristics [35]. In the WHI study, the incidence of breast cancer increased in the estrogen-progestogen cohort and decreased in the estrogen-only and placebo groups. Contrarily, hormone therapy users had more localized tumors and improved survival rates [32]. The NAMS do not recommended the prescription of systemic hormone therapy for survivors of breast cancer, although selected cases may be discussed in conjunction with an oncologist after non-hormone options have been unsuccessful. If the patient refers moderate to severe GSM symptoms, low-dose vaginal estrogens, may be considered after a failed trial of non-hormone therapies and with consultation of the oncologist in charge of the case [35]. Options for symptom management include non-hormonal moisturizers, vaginal estrogens, androgens, selective modulators of the estrogen receptor (SERM).

The skin is another target where the hypoestrogenism may have manifestations after menopause, it is altered by epidermal and dermal thickness, decreased collagen and elastin content, consequently more laxity and wrinkles, many women could also experience hair loss. Estrogen therapy may benefit wound healing through modifying inflammation, stimulating granulation tissue formation, and accelerating re-epithelialization. In studies, ET increased epidermal and dermal thickness, increased collagen and elastin content, and improved skin moisture, with fewer wrinkles [58]. It may be relevant to perform scrutiny studies to those women with hair loss like thyroid function, serum iron, and androgens in order to exclude other pathologies [32].

Cholelithiasis, cholecystitis, and cholecystectomy occur more frequently in women who take oral estrogen, presumably because of the first-pass hepatic effect after oral ingestion, so systemic hormone therapy should be prescribed with caution in women with known gallbladder disease [32, 35]. Estrogens increase biliary cholesterol secretion and saturation, promote precipitation of cholesterol in the bile, and reduce gallbladder motility, with increased bile crystallization [59, 60]. The transdermal route of administration could be the best option for this kind of patients [61].

In epileptic patients, menopause can present at earlier age. The cause of this could be related to the number of crisis the woman presents during her life and the anticonvulsants she uses as treatment, specifically the ones that are metabolized by the hepatic enzyme cytochrome p450, which also affects estrogen levels. It is common that women with epilepsy present seizures during the menopausal transition due to the hormonal fluctuations. It is important to note that some anticonvulsants agents may accelerate the metabolism of vitamin D, which possibly increasing the risks of osteopenia [32].
