**3. Ovarian cancer**

Worldwide, among patients diagnosed with gynecological malignancies, ovarian cancer is the leading cause of death. Most women affected are postmenopausal, but some are younger. Menopausal symptoms in the iatrogenic group are generally more pronounced than those following naturally occurring menopause and affect quality of life and health outcomes [18, 19].

After the treatment of a serious disease such as ovarian cancer, more attention should be paid to the women's quality of life. Presently, the WHO, Europe, and the United States (US) have guidelines on hormone therapy that do not mention ovarian cancer and conclude that evidence for the increased risk of cancer due to HRT is in sufficient to make a definite recommendation. According to the guidelines in the United Kingdom (UK), such risk is only increased by prolonged use. In the case of epithelial ovarian cancer, the World Health Organization, European and US guidelines on hormone therapy suggest, that evidence for increased risk of relapse due to HRT is in sufficient to make a definite suggestion, but the rules in the UK indicate increased risk for long-term users [20].

There is insufficient data on the effect of HRT usage period on the onset and progression of ovarian cancer. The effect of some known prognostic factors, such as residual tumor and tumor differentiation during diagnosis, are more important than the duration of HRT use [21]. Despite these results, it is very likely that the heterogeneity of samples, including factors of age, stages and classifications, different treatment modalities (chemotherapy, surgery alone, radiotherapy or both) and different follow-up times, will reflect the selection bias [22].

As we know, estrogen replacement therapy (ERT) is safe in patients who have undergone surgically induced menopause by the removal of the uterus and bilateral ovaries. In order to prevent the stimulating effect of estrogen on normal and hyperplasic endometrium, several studies have added progesterone to HRT in patients with early stage EOC who protect their uterus after primary surgery [17].

With regard to duration, there is insufficient data on the effect of long or short term use of HRT on the onset or progression of ovarian cancer. A recent metaanalysis conducted by Li et al. on 1448 patients who investigated the effect of postoperative HRT on the clinical outcome of patients treated for EOC revealed

**91**

**4. Cervical cancer**

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

that post-operative HRT did not have an impact on surveillance and recurrence

Among the HRT users diagnosed with invasive EOC (n = 649) and borderline ovarian tumors (BOT; n = 150), there was no difference in 5-year survival of invasive cancer patients among HRT users and non-users. However, survival was better for those with borderline tumors who used HRT after diagnosis [24]. In addition, tumor types classified as border type, including serous and mucinous tumors had a large heterogeneity. There have been recent studies showing that borderline serous tumors can progress to low-grade serous ovarian cancer. Low-grade serous cancers are considered hormonesensitive tumors, and therefore, it is important to avoid using HRT in patients with borderline serous tumors, although there is no definitive evidence to indicate this [25]. Evaluation of HRT after radical treatment of germ cell and cord ovarian malignancies is very important, as most of the cases are in young, premenopausal women who may be subject to several reductions in estrogen levels. However, there are no trials evaluating the use of HRT in these patients. Although HRT can be used safely for many of the germ cell tumors, we believe that it should be used carefully in a small subgroup of germ cell tumors that may secrete hormones. In the cases, the treatment of menopausal symptoms with HRT should be avoided and alternatives

In the foreground affects postmenopausal women, the improvement of climacteric symptoms following ovarian cancer diagnosis is an important concern for young women. Meta-analysis of 6 studies comparing 451 ovarian cancer patients who were treated with HRT after the diagnosis compared with 1070 women treated with HRT for control; revealed that there was no statistically significant difference

Some observational studies in this patient population have shown a possible

When we look at the results of two studies, which are very valuable because being prospective and evaluate according to whether or not patients with ovarian cancer receive random HRT. One of these studies was conducted on 59 patients who were received HRT with only estrogen and 66 control patients who did not receive any treatment. All stages of ovarian cancer were included in the study and the mean follow-up period was 42 months. In the group receiving HRT, the disease-free interval and OS were 34 and 44 months respectively, while in the non-treatment group, these durations were 27 and 34 months respectively, but the difference between the

For ovarian cancer, the available evidence suggests either a neutral effect on survival or a possible benefit from HRT. In view of the limitations of available evidence, factors such as the age of the patient, the presence of menopausal symptoms, and the molecular and hormonal characteristics of the tumor affect the initiation of

A number of problems could not be resolved. For example, what the best HRT regimens are for patients with ovarian cancer and how long patients should take HRT after surgery, as well as how the use of HRT affects the clinical outcomes of patients with previous EOC diagnoses, require further study. At present, we know that in ovarian cancer patients there is no published study confirming the growth of

The mean age of cervical cancer is 48 years, and when diagnosed 70% of patients are under 54 years of age. Depending on the patient's age, the stage and

benefit, as there is no increase in the risk of recurrence with HRT [29].

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

should be investigated after diagnosis [26].

groups was not statistically significant [30].

HRT in some histological types of ovarian cancer [31].

microscopic residues that are encouraged by the use of HRT.

in survival results [27, 28].

(HR = 0.68, 95% CI: 0.54–0.86) [23].

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

that post-operative HRT did not have an impact on surveillance and recurrence (HR = 0.68, 95% CI: 0.54–0.86) [23].

Among the HRT users diagnosed with invasive EOC (n = 649) and borderline ovarian tumors (BOT; n = 150), there was no difference in 5-year survival of invasive cancer patients among HRT users and non-users. However, survival was better for those with borderline tumors who used HRT after diagnosis [24]. In addition, tumor types classified as border type, including serous and mucinous tumors had a large heterogeneity. There have been recent studies showing that borderline serous tumors can progress to low-grade serous ovarian cancer. Low-grade serous cancers are considered hormonesensitive tumors, and therefore, it is important to avoid using HRT in patients with borderline serous tumors, although there is no definitive evidence to indicate this [25].

Evaluation of HRT after radical treatment of germ cell and cord ovarian malignancies is very important, as most of the cases are in young, premenopausal women who may be subject to several reductions in estrogen levels. However, there are no trials evaluating the use of HRT in these patients. Although HRT can be used safely for many of the germ cell tumors, we believe that it should be used carefully in a small subgroup of germ cell tumors that may secrete hormones. In the cases, the treatment of menopausal symptoms with HRT should be avoided and alternatives should be investigated after diagnosis [26].

In the foreground affects postmenopausal women, the improvement of climacteric symptoms following ovarian cancer diagnosis is an important concern for young women. Meta-analysis of 6 studies comparing 451 ovarian cancer patients who were treated with HRT after the diagnosis compared with 1070 women treated with HRT for control; revealed that there was no statistically significant difference in survival results [27, 28].

Some observational studies in this patient population have shown a possible benefit, as there is no increase in the risk of recurrence with HRT [29].

When we look at the results of two studies, which are very valuable because being prospective and evaluate according to whether or not patients with ovarian cancer receive random HRT. One of these studies was conducted on 59 patients who were received HRT with only estrogen and 66 control patients who did not receive any treatment. All stages of ovarian cancer were included in the study and the mean follow-up period was 42 months. In the group receiving HRT, the disease-free interval and OS were 34 and 44 months respectively, while in the non-treatment group, these durations were 27 and 34 months respectively, but the difference between the groups was not statistically significant [30].

For ovarian cancer, the available evidence suggests either a neutral effect on survival or a possible benefit from HRT. In view of the limitations of available evidence, factors such as the age of the patient, the presence of menopausal symptoms, and the molecular and hormonal characteristics of the tumor affect the initiation of HRT in some histological types of ovarian cancer [31].

A number of problems could not be resolved. For example, what the best HRT regimens are for patients with ovarian cancer and how long patients should take HRT after surgery, as well as how the use of HRT affects the clinical outcomes of patients with previous EOC diagnoses, require further study. At present, we know that in ovarian cancer patients there is no published study confirming the growth of microscopic residues that are encouraged by the use of HRT.
