Gynecologic malignancies can be divided into vulvar, vaginal, cervical, endometrial, ductal and ovarian cancers according to the location of the tumor. Among them, the most common are cervical cancer, endometrial cancer and ovarian cancer, whose main treatment methods include surgery, chemotherapy and radiotherapy. Except for a few patients who can retain their ovaries, most patients need to undergo double oophorectomy, and premenopausal women, or even women who are postmenopausal for a short period of time, will have a series of problems after surgery, including menopausal symptoms such as hot flashes, excessive sweating, insomnia, emotional instability, depression; frequent urination, painful urination, painful intercourse, etc. genitourinary tract atrophy symptoms; bone and joint pain, decreased bone mass, osteoporotic fractures, and increased risk of cardiovascular disease, and these symptoms usually appear faster, are more common, are more severe, and last longer after surgery, and can seriously affect the quality of patient survival. This is closely related to the rapid decline in sex hormone levels (especially estrogen and androgens) after double ovariectomy. For patients with preserved ovaries may also have problems related to menopausal estrogen deficiency after postoperative radiotherapy and chemotherapy, when the function of the ovaries is affected and ovarian failure or premature ovarian failure occurs. In addition, gynecologic malignancies have been trending younger in recent years, and as research and treatment of gynecologic malignancies progress, there will be more and more post-treatment survivors, and these problems will increase and bring many adverse effects to families and society. How to solve these clinical problems and improve the quality of survival of patients with gynecologic malignancies after surgery without increasing the recurrence rate and mortality of tumors is a problem and challenge that clinicians must face. Estrogen can effectively relieve menopausal symptoms, avoid genitourinary tract atrophy, and inhibit bone loss. It is a simple, convenient and effective treatment method with multiple good benefits, and thus has a wide and good prospect. However, whether estrogen replacement therapy can be used in women after treatment for gynecologic malignancies is still controversial. This is because gynecologic malignancies can be estrogen-dependent, such as endometrial adenocarcinoma, uterine sarcoma, cervical adenocarcinoma, and clear cell carcinoma (originating from the cervix, uterus, or ovaries); or non-estrogen-dependent (such as squamous carcinoma of the cervix and vulvar cancer). However, because the pathogenesis of tumors is unclear, women with gynecologic malignancies who have lost or failed ovarian function have long been fearful of estrogen supplementation and doctors have been silent about it, despite the presence of severe hypoestrogenic symptoms and high-risk factors for related diseases. Does sex hormone therapy affect recurrence and survival time after surgery in patients with gynecologic malignancies? There are no large-scale clinical studies. However, according to some preliminary small-scale clinical trials, sex hormone therapy can improve the quality of survival of patients with tumors without increasing recurrence or decreasing the survival time of patients with gynecologic malignancies after surgery. Endometrial cancer (ECa) is most commonly diagnosed at the age of 62-70 years (mean 67 years), but 20%-25% of cases occur before menopause. The diagnosis is definitive and requires surgical removal of the uterus and both adnexa. The sudden drop in estrogen causes associated estrogen deficiency symptoms, especially hot flashes, sleep disturbances and depressed mood. In addition, older women may also present with estrogen deficiency symptoms such as genitourinary tract discomfort and osteoporosis. Patients with endometrial cancer are also at high risk for osteoporosis, and women with estrogen deficiency have a 3-fold increased risk of developing osteoporosis or cardiovascular disease, so estrogen therapy also needs to be considered. According to whether it depends on estrogen status, endometrial cancer can be divided into type I, which is clearly associated with high estrogen status, and type II, which is not associated with high estrogen status. Type I is clearly associated with high estrogen status, and its risk factors include obesity, anovulation, early menarche, late menopause, and often preceded by hyperplastic changes in the endometrium. Type II is not associated with a hyperestrogenic state and usually originates from postmenopausal atrophied endometrium. To date, ECa has been listed as a contraindication to hormone replacement therapy (HRT), including in women who have been diagnosed for many years and treated very well. However, over the last 30 years, an increasing number of patients have received HRT after Eca treatment, mainly in FIGO stage I patients, including a few in stage II. Since the 1980s, countries such as Germany and the United States no longer list Eca as an absolute contraindication to HRT, but still emphasize that there are no very good prospective, randomized controlled studies evaluating the effect of HRT on tumor recurrence [1]. Since nearly 80% of ECa patients are stage I at diagnosis, HRT is an option for many women. The main therapeutic goal of HRT remains to alleviate vasodilatory symptoms due to estrogen deficiency. The use of HRT in patients treated for ECa still needs to be evaluated with an individualized pros and cons analysis. The risk of HRT stimulating tumor growth and recurrence has to be carefully analyzed. However, there is not yet a positive prospective controlled study that can give a definite conclusion. There are five relevant studies, all retrospective, non-randomized, case-control studies, and the results of all these studies showed that none of the HRT after ECa treatment significantly increased the risk of recurrence; on the contrary, there was a trend towards a decrease or significant decrease in the frequency of tumor recurrence and a longer tumor-free interval and survival time. Creasman et al [2] retrospectively studied 221 cases of stage I ECa, including 47 cases in the estrogen treatment group and 174 cases in the control group: the treatment group started Bemelia (CEE) 0.625-1.25 mg/d (72% of which were vaginal) at a mean of 15 months (0-81 months) after surgery, with a mean treatment duration of 26 months (3-84 months) and a follow-up of 60 months. The results showed 1 recurrence and 1 death in the treatment group and 26 recurrences and 16 deaths in the control group; the HRT group showed improved survival, lower recurrence rate, lower mortality (2% vs. 15%) and longer tumor-free survival (P<0.05), and the results were independent of the stage of the tumor, the presence of metastasis and the status of the receptor. In the study by Lee et al [3], there were 44 patients with low-risk ECa (stage Ia to Ib, high and intermediate differentiation) and in the HRT group, 66% were treated with oral CEE alone (0.625 to 1.25 mg/d) and 34% sequentially with progestin. 2/3 started HRT within 1 year after surgery and the others started HRT 2 years after surgery with a follow-up of 87 months and a mean of 64 months on the drug (2 months to 11 years). During HRT, there were no recurrences in the HRT group compared with 8% recurrence and mortality in 99 patients in the control group. In a study by Chapman et al [4], which included for the first time patients with stage II ECa, the prognosis was significantly better in the HRT group in terms of tumor staging and invasion. oral CEE (0.625 mg/d) treatment was started on average 5 months (0-108 months) after surgery in the HRT group, and 33 of 62 patients (53%) in the HRT group increased progestin after 5 months of treatment The duration of HRT treatment was 39.5 months (3-107 months) with 2 relapses (3%) and 1 death. In the control group of 61 patients, there were 6 recurrences (10%) and 4 deaths, but the differences were not statistically significant. In patients aged ≤70 years with high to moderate differentiation, tumor-free survival was significantly better in the HRT than in the non-HRT group. It is suggested that estrogen does not decrease the duration of tumor-free survival after surgery for early endometrial cancer, nor does it increase the risk of recurrence. Suriano et al [5] conducted a case-control study between 1984 and 1998 on 75 pairs of endometrial carcinoma, mostly FIGO stage I B and 15% stage II A to III A or III B. Seventy-three percent of the patients were started within 1 year after surgery (the rest within 5 years) on CEE 0.625 mg/d and 49% were continuously combined with medroxyprogesterone 2.5 mg/d. Mean follow-up 83 months, control follow-up 69 months. There were 2 recurrences of intrapelvic cancer in the HRT group (1%) and 8 intrapelvic recurrences and 3 distant recurrences in the control group (14.6%) during the study period. tumor-free survival was longer in the HRT group than in the control group (82 months vs. 63 months). These studies suggest that HRT does not increase recurrence and metastasis in ECa. However, there may be a selection bias because physicians prefer to recommend HRT for patients with a good prognosis. Many studies have shown that the addition of progestin to estrogen therapy reduces the incidence of ECa and that the risk of ECa is lower with sequential combinations than with sequential combinations. Progestins have a favorable effect on endometrial hyperplasia, including atypical hyperplasia. This is especially true with non-aromatized progestins, such as medroxyprogesterone (100-500 mg) and gynecomastia (40-120 mg). may also relieve menopausal symptoms, but all progestin therapy is inferior to estrogen therapy in relieving hot flashes. Moreover, some large studies in recent years (HERS, WHI) have shown that progestins in HRT (especially medroxyprogesterone) may be associated with an increased risk of breast cancer and an increased risk of cardiovascular disease. Therefore, for postoperative ECa patients at risk of cardiovascular disease, estrogen-only therapy is more recommended than combined estrogen plus progestin therapy [6]. And this is very important because hypertension, diabetes, metabolic syndrome, polycystic ovary syndrome and obesity are all high risk factors for ECa, and they also increase the risk of cardiovascular disease themselves. Recent studies have shown that endometrial hypofractionated mesenchymal sarcoma is estrogen-sensitive. With more than 50% seen premenopausal, increased dose progestin therapy after bilateral adnexal resection significantly reduces the recurrence rate and therefore this primary type is currently listed as a contraindication to HRT [6]. In conclusion, an individualized evaluation of the pros and cons analysis is still needed for the use of HRT in patients after ECa treatment. It is currently believed that HRT can be used in postoperative patients with ECa stage I or II and is the most effective etiologic treatment for postmenopausal estrogen deficiency symptoms, but prospective, randomized studies are still needed to clarify the safety of HRT treatment after ECa. Therefore, when recommending HRT to patients, it is important to carefully analyze the risk of HRT stimulating tumor growth and recurrence, to develop individualized dosing regimens, to obtain the patient's informed consent, regular follow-up and close observation. 2.Ovarian cancer Like endometrial cancer, women with premenopausal and perimenopausal ovarian cancer will have significant menopausal symptoms after surgical removal of both adnexa, which will seriously affect the quality of life of patients. Doctors are hesitant to use HRT for treatment and patients have concerns that HRT will lead to recurrence of ovarian cancer. For ovarian cancer, a retrospective analysis was conducted by Eeles et al [7] in the UK. In 78 cases of ovarian epithelial carcinoma aged <59 years with HRT after surgery and 295 in the control group, HRT was started in 46 (59%) cases at 6 months after surgery and lasted ≥6 years in 17 (22%) cases, showing that estrogen did not affect tumor-free survival nor did it affect the survival of patients. In contrast, HRT improved survival in endometrioid and clear cell carcinoma. Guidozzi et al [8] conducted a prospective randomized controlled study in which 130 cases of ovarian epithelial carcinoma (I-IV) under 59 years of age were randomized, with CEE 0.625 mg/day alone at 6-8 weeks after CRS in the HRT group and no drug in the other group. Minimum follow-up was 48 months. The results revealed that in the ERT group: recurrence rate was 54%, tumor-free survival 34 months, and overall survival 44 months; in the control group: recurrence rate was 62%, tumor-free survival 27 months, and overall survival 34 months. There was no significant effect on tumor-free survival and overall survival of ovarian cancer in both groups. It was concluded that postoperative estrogen therapy did not affect tumor-free survival and overall survival in ovarian cancer. Bebar et al [9] used HRT in 31 cases of ovarian epithelial carcinoma after surgery and followed up for 55 months, resulting in six cases with disease progression and no significant effect on ovarian epithelial carcinoma progression. HRT may reduce FSH by up to 75%, and therefore may reduce the risk of ovarian cancer development. Ursic-Vrscaj et al [10] conducted a case-control study of 24 cases of ovarian plasmacytic cystic adenocarcinoma with a mean follow-up of 49 months. Patients started HRT at a mean of 21 months (1 to 25 months) after diagnosis and were on the drug for a mean of 24 months (1 to 70 months), 21% recurred with an estimated risk of death of 0.90 (OR=0.90), and 31% recurred in those without HRT. Biglia et al [1] in 2004 systematically analyzed the literature up to April 2002 and found no evidence that HRT increased the recurrence rate of tumors other than meningioma, breast cancer and endometrial cancer. 3. Cervical cancer The cervix, like other female reproductive organs, responds to changes in endogenous hormone levels. Receptors for estrogen and progesterone are found in the cervix. The squamous-columnar junction is the most frequent site of cancer, and its location varies with endogenous or exogenous sex hormone levels. Currently, cervical adenocarcinoma is considered estrogen-dependent and surgical treatment should be accompanied by total hysterectomy with both adnexa, while the common squamous cervical cancer is non-estrogen-dependent. For women who are infertile but have reproductive requirements, the uterus and ovaries can be preserved depending on the clinical situation, but the function of ovaries can also be greatly affected in most patients after postoperative radiotherapy and chemotherapy, and ovarian failure or premature ovarian failure can occur rapidly. There are also problems associated with menopausal estrogen deficiency. There is no evidence that HRT is associated with increased recurrence of cervical cancer. Levgur [11] summarized four case-control studies including 537 patients with tumors and showed that 228 of these patients who received HRT had a tumor recurrence rate of 3.5% compared to 16.5% in the untreated control group, and there was no difference in survival or mortality between the two groups. The tissue type of the tumor is still an important consideration before starting HRT. HRT is not associated with the development of cervical squamous carcinoma, but hormone replacement therapy is still contraindicated in patients with a history of cervical adenocarcinoma. Are there other treatments for patients with estrogen-dependent gynecologic malignancies that can relieve the symptoms and discomfort caused by estrogen deficiency and prevent related complications, while alleviating or removing the medication concerns of patients and families? In fact, this question has always been a concern and consideration for clinicians, and in recent years, the development of some drugs has provided the conditions for this. Surgical removal of ovaries for gynecologic malignancies increases the risk of coronary heart disease and osteoporosis. For the management of coronary artery disease, statins are preferred, while for osteoporosis, diphosphonates and raloxifene may be considered. Raloxifene, unlike triamcinolone, does not cause hyperplasia of the endometrium [12] and does not increase the risk of ECa, but is still listed as a contraindication to ECa due to the lack of data in this regard. Similarly, tibolone has no proliferative effect on the endometrium [13] and is effective in relieving menopausal symptoms and genitourinary tract atrophy compared to raloxifene, but is also currently listed as a contraindication to ECa, again due to lack of adequate safety data. However, it is a new option for postoperative ECa. Phytoestrogens can also alleviate menopausal symptoms in patients, but the risk of endometrial hyperplasia or ECa cannot be ruled out, so ECa is also listed as a contraindication to their use. The composition of these drugs is very complex, variable, incompletely understood, the effects of their active ingredients are poorly understood, their side effects are difficult to determine, and the results of studies are often conflicting. In recent years, there have been increasing reports from abroad showing that a large number of patients with breast cancer who are more sensitive to estrogen choose the botanical black asclepias to control menopausal symptoms without increasing the recurrence of breast cancer [14-15]. Black Cohosh is one of the most widely used herbs in Europe for the relief of menopausal symptoms, containing triterpenoids and glycosides as active ingredients. For example, black asclepiad Livermin tablets, extracted from black asclepiad in a special process? have good effect on relieving menopausal symptoms in women. In recent years, more and more studies have shown that whether it is in vivo or in vitro studies, or the source of Livermin, the extraction process, or increasing the dose of Livermin or delaying its use, Livermin has no estrogenic activity [16], and its mechanism of action is still unclear, and it is now believed that Livermin may be a neurotransmitter modulator, which does not act through estrogen receptors and thus has no effect on FSH, LH E2, and PRL, but acts directly on the nociceptors, either by acting directly on 5-HT7 receptors or by acting directly on μ-opioid receptors in the brain of postmenopausal women [17]. Currently, from our preliminary findings, it appears that Livermin significantly alleviates menopausal symptoms in patients with gynecological malignancies without increasing the risk of tumor recurrence. It is also a worthy and promising treatment to try. In conclusion, there is a lack of large-scale, prospective, randomized double-blind controlled studies of HRT in patients with gynecologic malignancies at home and abroad. As the treatment of gynecologic malignancies progresses, the survival time of patients is prolonged, and thus more and more patients with gynecologic malignancies will have the requirement to improve their quality of life, and HRT is an optional method. Meanwhile, clinicians need to explore safer and more effective treatment methods.