**1. Introduction**

Menopause is defined by the World Health Organization (WHO) as the complete disappearance of cyclic menstruation over a period of 12 months due to a reduction in the production of estrogen and progesterone hormones from a woman's ovaries [1]. Menopause can be defined by more concrete values in laboratory tests. According to the findings of amenorrhea and hypestrogenemia studies, serum FSH levels above 40 IU/L were defined. Subjectively, menopause can also be diagnosed by vasomotor symptoms, such as hot flashes. The permanent cessation of menstrual periods can occur naturally or can be induced by surgery, chemotherapy or radiation, leading to estrogen deficiency and loss of reproductive function [2]. Symptoms are more pronounced with a sudden drop in circulating estrogen levels. These symptoms are severe in premature ovarian failure and surgical menopause. Natural menopause is often seen between the ages of 45 and

55, but its onset varies from woman to woman. The average age of natural menopause in our country (Turkey) is 47 [3].

A menopausal statement can disrupt a woman's personal and social life. Vasomotor symptoms (e.g., hot flashes and night sweats) are the most common symptoms and can be treated very effectively with estrogen-based hormone therapy. The decision to use estrogen (usually only hormone therapy or hormone replacement therapy or HT) treatment involves balancing potential benefits with potential risks. A woman who desires HRT and has an intact uterus must also receive progestogen with the estrogen to protect her uterus from endometrial hyperplasia or malignancy. It is assumed that if a woman has had a hysterectomy that she no longer needs a progestin. However, progesterone is different, as it can provide symptom relief from sleep disturbance and mood instability, and there is increasing evidence to support its offering protection to breast tissue [4].

The relationship between early surgical menopause and poor cognitive outcomes has been demonstrated. Increased risk of cognitive impairment especially in patients undergoing oophorectomy at a young age revealed that this relationship is age-related [5].

Furthermore, cancer treatment often accelerates menopause and then affects quality of life. Postmenopausal women are at increased risk for vaginal dryness, dyspareunia, urogenital atrophy and sexual dysfunction. Hormone replacement therapy (HRT) has been proven to be highly effective in alleviating menopausal symptoms, such as hot flashes, night sweats, dyspareunia, sexual disorders and insomnia, as well as preventing osteoporosis. Life satisfaction and social functioning can be improved by overcoming menopausal symptoms and increasing resistance to age-related pathologies.

The number of menopausal women will also increase as the population ages. Accurate estimation of the postmenopausal population is an important point for health care providers to consider, as the incidence of all cancers increases with aging. If life satisfaction, social functioning and psychological resources are enhanced by increasing resistance to against age-related pathologies, the experience of aging can be improved.

To clarify the possible effective management of menopausal symptoms, the main evidence in the literature was analyzed to investigate the role of hormone replacement therapy in patients affected by endometrial, ovarian or cervical cancer.

## **2. Endometrial cancer**

A number of clinical trials have reported that HRT does not increase the risk of recurrence of endometrial cancer (EC) even after treatment [6, 7]. In contrast, studies' showing that estrogen exposure is associated with an increase in mitosis of endometrial cells, placing them in a specific molecular configuration sensitive to DNA damage [8].

The most common gynecological cancer, endometrial cancer is seen in the postmenopausal period, but 25% of diagnosed patients are premenopausal with approximately 2.5–14.4% of the patients less than 40 years old [9].

As a result, a large number of women will be exposed to the sudden iatrogenic onset of postmenopausal morbidity, consisting of standard abdominal hysterectomy and bilateral oophorectomy procedures. In addition, surgery-induced menopausal symptoms tend to be more severe than those caused by normal menopause, and in these patients, surgery is usually followed by chemotherapy or radiotherapy [10]. Since EC is typically diagnosed with a good prognosis in the early stage of the

**89**

group [14].

group [12].

nodes or other organs [15].

*The Role of Hormone Replacement Therapy in the Treatment of Menopausal Symptoms…*

disease, relieving these symptoms is an important issue in terms of quality of life

The endometrioid EC type is associated with estrogen exposure and endometrial hyperplasia. The role of estrogens in providing relapse after hysterectomy for EC is less clear and controversial. Since it does not increase recurrence, there are a number of current clinical studies that report HRT should be considered even after EC therapy [12]. For relief of menopause-related vasomotor symptoms (VMS), systemic usage of HRT with either (1) conventional estrogens/progestogens or (2) conjugated estrogens/bazedoxifene is the most effective regime. Currently, method 2 conjugated estrogens, with a selective estrogen receptor modulator such as bazedoxifene, is a very popular replacement of progestin. This method is useful for

Although these finding were based on retrospective or cohort controlled study results, HRT use does not seem to increase the risk of EC recurrence. Creasman et al. reported a retrospective study of 47 cases of stage I endometrial cancer patients treated with via the oral or vaginal route using conjugated estrogen (0.625 or 1.25 mg/dl). HRT was initiated within 15 months (range 0–81 months) of the median interval after cancer treatment and patients were followed up for 32 months (range 6–84 months) after the onset of HRT. In the control group, 174 patients who began treatment at the same time were compared. No difference was observed between the groups in terms of prognostic aspects. Only one recurrence (2.1%) was observed in the estrogen-treated group and 26 recurrences (14.9%) were observed in the control group. The recurrent patient in the HRT group had been treated with estrogen only for 3 months and had discontinued HRT use 18 months before relapse. Disease-free survival (DFS) and overall survival (OS) were significantly

A retrospective paired cohort study was conducted with 75 women being treated for stages I–III EC who received an average of 83 months of HRT (conjugated equine estrogen-oral, 0.625 mg/dl with or without medroxyprogesterone acetate-oral, 2.5 mg/dl). These women were then compared with matched controls who received an average of 69 months of treatment. The study revealed lower recurrence rate (1 vs. 14% in the control group) and significantly longer DFS (P = 0.006) in the HRT

A total of 50 patients with stage I or stage II EC who had combined HRT (0.625 mg conjugated equine estrogen plus continuous oral daily regimen and 2.5 mg medroxyprogesterone acetate) of 4–8 weeks postoperatively were compared to 52 patients for control purposes. In the first prospective paired cohort study, no recurrence was observed in the HRT group but a relapse was observed in the control

A retrospective case-control study was conducted with 44 clinical stage I patients (defined as grade 1 or 2 tumors), using oral estrogens (0.625 or 1.25 mg/dl) with or without combined progesterone. The study revealed no metastases to lymph

and the application of HRT in these sarcomas should be avoided [16].

Serous papillary and clear cell carcinomas, which are mostly seen in postmenopausal women and constitute approximately 8% of all ECs, have poor prognosis even if they are caught at an early stage. Since they do not have estrogen and progesterone receptors, it is not thought that they are not stimulated when HRT is used after surgical treatment. A safe recommendation cannot be raised because no study has addressed the use of HRT after treatment in all of the above histological subtypes of EC. As for uterine sarcomas, endometrial stromal sarcomas are considered estrogen-dependent because they express estrogen and progesterone receptors,

*DOI: http://dx.doi.org/10.5772/intechopen.88047*

after treatment [11].

protection of the endometrium.

longer in the estrogen-treated group [13].

*The Role of Hormone Replacement Therapy in the Treatment of Menopausal Symptoms… DOI: http://dx.doi.org/10.5772/intechopen.88047*

disease, relieving these symptoms is an important issue in terms of quality of life after treatment [11].

The endometrioid EC type is associated with estrogen exposure and endometrial hyperplasia. The role of estrogens in providing relapse after hysterectomy for EC is less clear and controversial. Since it does not increase recurrence, there are a number of current clinical studies that report HRT should be considered even after EC therapy [12]. For relief of menopause-related vasomotor symptoms (VMS), systemic usage of HRT with either (1) conventional estrogens/progestogens or (2) conjugated estrogens/bazedoxifene is the most effective regime. Currently, method 2 conjugated estrogens, with a selective estrogen receptor modulator such as bazedoxifene, is a very popular replacement of progestin. This method is useful for protection of the endometrium.

Although these finding were based on retrospective or cohort controlled study results, HRT use does not seem to increase the risk of EC recurrence. Creasman et al. reported a retrospective study of 47 cases of stage I endometrial cancer patients treated with via the oral or vaginal route using conjugated estrogen (0.625 or 1.25 mg/dl). HRT was initiated within 15 months (range 0–81 months) of the median interval after cancer treatment and patients were followed up for 32 months (range 6–84 months) after the onset of HRT. In the control group, 174 patients who began treatment at the same time were compared. No difference was observed between the groups in terms of prognostic aspects. Only one recurrence (2.1%) was observed in the estrogen-treated group and 26 recurrences (14.9%) were observed in the control group. The recurrent patient in the HRT group had been treated with estrogen only for 3 months and had discontinued HRT use 18 months before relapse. Disease-free survival (DFS) and overall survival (OS) were significantly longer in the estrogen-treated group [13].

A retrospective paired cohort study was conducted with 75 women being treated for stages I–III EC who received an average of 83 months of HRT (conjugated equine estrogen-oral, 0.625 mg/dl with or without medroxyprogesterone acetate-oral, 2.5 mg/dl). These women were then compared with matched controls who received an average of 69 months of treatment. The study revealed lower recurrence rate (1 vs. 14% in the control group) and significantly longer DFS (P = 0.006) in the HRT group [14].

A total of 50 patients with stage I or stage II EC who had combined HRT (0.625 mg conjugated equine estrogen plus continuous oral daily regimen and 2.5 mg medroxyprogesterone acetate) of 4–8 weeks postoperatively were compared to 52 patients for control purposes. In the first prospective paired cohort study, no recurrence was observed in the HRT group but a relapse was observed in the control group [12].

A retrospective case-control study was conducted with 44 clinical stage I patients (defined as grade 1 or 2 tumors), using oral estrogens (0.625 or 1.25 mg/dl) with or without combined progesterone. The study revealed no metastases to lymph nodes or other organs [15].

Serous papillary and clear cell carcinomas, which are mostly seen in postmenopausal women and constitute approximately 8% of all ECs, have poor prognosis even if they are caught at an early stage. Since they do not have estrogen and progesterone receptors, it is not thought that they are not stimulated when HRT is used after surgical treatment. A safe recommendation cannot be raised because no study has addressed the use of HRT after treatment in all of the above histological subtypes of EC. As for uterine sarcomas, endometrial stromal sarcomas are considered estrogen-dependent because they express estrogen and progesterone receptors, and the application of HRT in these sarcomas should be avoided [16].

*Hormone Therapy and Replacement in Cancer and Aging-Related Diseases*

pause in our country (Turkey) is 47 [3].

age-related [5].

tance to age-related pathologies.

of aging can be improved.

**2. Endometrial cancer**

DNA damage [8].

55, but its onset varies from woman to woman. The average age of natural meno-

A menopausal statement can disrupt a woman's personal and social life. Vasomotor symptoms (e.g., hot flashes and night sweats) are the most common symptoms and can be treated very effectively with estrogen-based hormone therapy. The decision to use estrogen (usually only hormone therapy or hormone replacement therapy or HT) treatment involves balancing potential benefits with potential risks. A woman who desires HRT and has an intact uterus must also receive progestogen with the estrogen to protect her uterus from endometrial hyperplasia or malignancy. It is assumed that if a woman has had a hysterectomy that she no longer needs a progestin. However, progesterone is different, as it can provide symptom relief from sleep disturbance and mood instability, and there is

increasing evidence to support its offering protection to breast tissue [4].

The relationship between early surgical menopause and poor cognitive outcomes has been demonstrated. Increased risk of cognitive impairment especially in patients undergoing oophorectomy at a young age revealed that this relationship is

Furthermore, cancer treatment often accelerates menopause and then affects quality of life. Postmenopausal women are at increased risk for vaginal dryness, dyspareunia, urogenital atrophy and sexual dysfunction. Hormone replacement therapy (HRT) has been proven to be highly effective in alleviating menopausal symptoms, such as hot flashes, night sweats, dyspareunia, sexual disorders and insomnia, as well as preventing osteoporosis. Life satisfaction and social functioning can be improved by overcoming menopausal symptoms and increasing resis-

The number of menopausal women will also increase as the population ages. Accurate estimation of the postmenopausal population is an important point for health care providers to consider, as the incidence of all cancers increases with aging. If life satisfaction, social functioning and psychological resources are

enhanced by increasing resistance to against age-related pathologies, the experience

To clarify the possible effective management of menopausal symptoms, the main evidence in the literature was analyzed to investigate the role of hormone replacement therapy in patients affected by endometrial, ovarian or cervical cancer.

A number of clinical trials have reported that HRT does not increase the risk of recurrence of endometrial cancer (EC) even after treatment [6, 7]. In contrast, studies' showing that estrogen exposure is associated with an increase in mitosis of endometrial cells, placing them in a specific molecular configuration sensitive to

The most common gynecological cancer, endometrial cancer is seen in the postmenopausal period, but 25% of diagnosed patients are premenopausal with

As a result, a large number of women will be exposed to the sudden iatrogenic onset of postmenopausal morbidity, consisting of standard abdominal hysterectomy and bilateral oophorectomy procedures. In addition, surgery-induced menopausal symptoms tend to be more severe than those caused by normal menopause, and in these patients, surgery is usually followed by chemotherapy or radiotherapy [10]. Since EC is typically diagnosed with a good prognosis in the early stage of the

approximately 2.5–14.4% of the patients less than 40 years old [9].

**88**

Although it is mainly based on retrospective, case or cohort controlled studies based on various biases, the use of HRT, in women with stage I and/or II EC, the risk of relapse was demonstrated with data that did not increase. Selecting healthier and younger women to explain the protective effect of HRT on recurrence in survivors of EC may eliminate this publication bias.

Although it is based on retrospective or cohort-controlled studies, nowadays, a number of clinical studies have reported that HRT should be considered even after treatment of endometrial cancer (EC) without increasing the risk of recurrence [17].

Although the results related to EC do not completely exclude the possibility of increasing the risk of recurrence, they argue that HRT does not matter the magnitude of such a risk. The positive effect of HRT on quality of life outweighs the unfounded risk of recurrence. Additional well-designed RCTs are needed for the definite recommendations including the factors that may be related to recurrence such as characteristics and treatment of cancer, different types of HRT, the diseasefree interval before the onset of HRT, and the duration of HRT use. To determine the best therapeutic option between new hormones and non-hormonal regimens every EC survivor dealing with HRT must be informed of the available data and analyzed in a personalized way.
