**4. Cervical cancer**

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

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

of EC may eliminate this publication bias.

analyzed in a personalized way.

of life and health outcomes [18, 19].

increased risk for long-term users [20].

different follow-up times, will reflect the selection bias [22].

**3. Ovarian cancer**

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

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

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

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

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

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 regard to duration, there is insufficient data on the effect of long or short

with early stage EOC who protect their uterus after primary surgery [17].

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

**90**

histology of the tumor, such patients are usually treated with radical hysterectomies without preserving the ovarian or chemo-radiation treatment, in which patients begin to have sudden menopausal symptoms [32].

Approximately 80% of cervical cancers are composed of squamous cell carcinomas (SCC), 15% are adenocarcinoma and 5% are adenosquamous. The development of squamous cell carcinomas has never been associated with HRT. In contrast, there are studies that report the risk of adenocarcinoma of the cervix as notable in women receiving estrogen therapy (OR 2.7) [33].

In 80 patients under 45 years of age with early-stage disease treated with surgery or radiotherapy, HRT was used, while the remaining 40 cervical cancer patients were used as controls. No significant difference in survival or survival was observed between the groups [34].
