子宫内膜癌的孕激素拮抗及增敏机制

子宫内膜癌是女性生殖道最常见的恶性肿瘤之一,近年来发病率逐渐上升并呈年轻化趋势。虽然子宫内膜癌大多发生于绝经后妇女,但也有约25%的患者发生于绝经前,其中40岁以下患者占3%~14%。然而,子宫内膜癌的标准手术疗法使年轻患者失去了生育机会及卵巢内分泌功能,严重影响患者的生活质量。目前,为了满足年轻患者保留生育能力的强烈愿望,长期应用大剂量孕激素的保守疗法成为治疗子宫内膜不典型增生及子宫内膜癌的重要方法。但是部分患者在治疗的不同时期出现孕激素拮抗现象,降低了激素治疗的效果,影响患者的预后。因此,进一步研究子宫内膜癌的孕激素拮抗及增敏机制,对提高早期子宫内膜癌的疗效以及保留生殖内分泌功能具有重要意义。综述子宫内膜癌的孕激素拮抗机制及其增敏途径。     

年轻子宫内膜癌女性保留生育及卵巢功能的治疗进展

子宫内膜癌（endometrial carcinoma,EC）是女性生殖系统三大恶性肿瘤之一,年轻育龄期EC患者相对少见,但随着子宫内膜癌发病率的逐渐上升,以及现代生活习惯的改变,EC出现明显年轻化趋势。EC的标准治疗方案使得女性永久性失去生育功能以及绝经前女性提前进入更年期,严重影响年轻患者的生活质量。故年轻EC患者保留生育功能或保留卵巢功能的治疗方案逐渐受到重视。现有的保留生育功能方案主要有：孕激素、芳香化酶抑制剂、二甲双胍等药物治疗以及宫腔镜下EC病灶切除术。多项研究已经证实,肥胖与EC发生发展相关,保留生育功能治疗期间体质量管理同样也至关重要。现就年轻EC女性保留生育及卵巢功能治疗以及治疗期间体质量管理等的研究进展进行综述。     

年轻子宫内膜癌女性保留生育及卵巢功能的治疗进展

子宫内膜癌(endometrial carcinoma,EC)是女性生殖系统三大恶性肿瘤之一,年轻育龄期EC患者相对少见,但随着子宫内膜癌发病率的逐渐上升,以及现代生活习惯的改变,EC出现明显年轻化趋势。EC的标准治疗方案使得女性永久性失去生育功能以及绝经前女性提前进入更年期,严重影响年轻患者的生活质量。故年轻EC患者保留生育功能或保留卵巢功能的治疗方案逐渐受到重视。现有的保留生育功能方案主要有:孕激素、芳香化酶抑制剂、二甲双胍等药物治疗以及宫腔镜下EC病灶切除术。多项研究已经证实,肥胖与EC发生发展相关,保留生育功能治疗期间体质量管理同样也至关重要。现就年轻EC女性保留生育及卵巢功能治疗以及治疗期间体质量管理等的研究进展进行综述。     

年轻未生育妇女子宫内膜癌保留生育功能的治疗

年轻妇女子宫内膜癌保留功能治疗,包括未生育患者保留生育功能治疗和年轻患者保留卵巢内分泌功能治疗,是近年来子宫内膜癌治疗方面的热点问题之一。本文从保留生育功能治疗的必要性、病例选择和治疗等方面进行讨论。1保留生育功能治疗的必要性子宫内膜癌是妇科常见的恶性肿瘤之一,目前在国内发病率仅次于宫颈癌。但是由于生活方式的转变,其发病率在不断升高,并且随着宫颈癌筛查及预     

子宫内膜癌患者保留生理功能的治疗

子宫内膜癌是妇科常见恶性肿瘤之一,约75%的患者为早期病例,对于Ⅰ期子宫内膜癌的首选治疗方法为筋膜外全子宫切除、双附件切除及盆腔、腹主动脉旁淋巴结取样和（或）清扫术,术后5年存活率达83%～93%,预后较好.但标准的手术治疗使年轻的子宫内膜癌患者失去了生育机会及卵巢内分泌功能,严重影响患者的生存质量.因此,子宫内膜癌患者保留生理功能的治疗,包括保留年轻子宫内膜癌患者的生育功能或卵巢内分泌功能,以及对手术治疗后的子宫内膜癌患者进行激素替代治疗,成为近年较为关注的问题.     

子宫内膜癌保留生育非适应证患者治疗的探索

正子宫内膜癌(endometrial carcinoma, EC)是指原发于子宫内膜的一组上皮性恶性肿瘤,最常见类型为子宫内膜样腺癌,高发于绝经后女性,包括子宫切除在内的全面分期手术是其主要治疗方案。近年来随着EC患者发病呈现年轻化的趋势,个体化的治疗从保留生命到保留生理乃至保留生育的目标不断提高。目前,保留生育功能治疗已成为EC治疗的重要组成部分。1 EC保留生育功能治疗适应证EC保留生育功能治疗既保留了胎儿生长发育的场所,     

子宫内膜癌保留生育功能相关辅助生殖技术

正子宫内膜癌(endometrial cancer, EC)指子宫内膜上皮恶性肿瘤,是妇科最常见恶性肿瘤之一。EC年轻患者发病率呈逐年上升趋势,研究表明约有7%～8%的EC发生在育龄期女性~([1])。同时,随着我国全面放开生育政策和女性生育计划推迟,约70%年轻EC患者在确诊时尚未生育~([2])。目前相关指南及共识推荐对有强烈生育要求的早期EC年轻患者,经详细的病情告知及知情理解,可考虑行保留生育功能治疗~([3,4])。     

年轻子宫内膜癌保留生育功能治疗评估的几点思考

<正>子宫内膜癌(endometrial cancer, EC)是女性生殖道常见恶性肿瘤。好发于绝经期和围绝经期妇女。治疗方法以手术为主。近年来,子宫内膜癌的发病率有升高和年轻化的趋势。北京市肿瘤登记办公室数据显示,2008年以后,子宫内膜癌已居北京市女性生殖系统恶性肿瘤首位^[1]。其中20%～25%发生于绝经前,3%～5%的患者年龄小于40岁,70%以上发病时未完成生育[2]。除了有强烈的保留生育功能的愿望,与其他年龄的患者相比,年轻子宫内膜癌患者有其特殊的临床及病理特点：(1)月经不规律或不规则     

早期子宫内膜癌保留生育功能的治疗

子宫内膜癌是常见的妇科恶性肿瘤,多数发生在绝经后女性。传统治疗方法切除了全子宫及双附件,使患者丧失生育功能。目前,文献报道了较多关于子宫内膜癌保守治疗成功的案例,使得年轻的早期患者保留了生育功能。但保留子宫存在肿瘤复发的风险。且药物的剂量、治疗时间,患者的入选标准、随访等尚未达成共识。现就保守治疗的可行性及这些相关问题做一综述。     

左炔诺孕酮宫内缓释系统在子宫内膜癌保留生育功能治疗中的应用

<正>子宫内膜癌(EC)是女性生殖系统三大恶性肿瘤之一,约3%~14%发生在40岁以下的年轻女性,其中80%以上未曾生育或仍有生育愿望。如何保留年轻EC患者的女性特征和生育功能是当前妇科临床亟待解决的问题。左炔诺孕酮宫内缓释系统(LNG-IUS)通过每天恒定释放20μg的左炔诺孕酮至宫腔,拮抗雌激素作用,逆转增生或癌变的内膜组织,在早期EC保留生育功能治疗中的应用越来越受到关注。本文重点就其治疗机制、适应     

Pregnancy outcomes of women who received conservative therapy for endometrial carcinoma or atypical endometrial hyperplasia

Case

Approximately 3%‐25% of cases of endometrial carcinoma (EC) or atypical endometrial hyperplasia (AH) occur in women aged <40 years and conservative treatment with high‐dose medroxyprogesterone acetate (MPA) is administered to women who wish to preserve their fertility. Here is reported the pregnancy outcomes of patients with EC or AH who received MPA therapy at Tokushima University Hospital, Tokushima, Japan. The frequency of pregnancy and live births among the patients with EC or AH who received conservative treatment, followed by fertility treatment, were analyzed retrospectively.

Outcome

Twelve patients underwent fertility examinations and received fertility treatment immediately after the completion of conservative treatment for EC or AH. One patient had the complication of severe diabetes and total embryo cryopreservation was performed before her diabetes was treated. Among the other 11 patients, 8 (72.7%) became pregnant at least once and 6 (54.5%) experienced at least 1 live birth. Three patients (25.0%) suffered disease recurrence during or after the infertility treatment and all of the recurrences occurred in the EC cohort.

Conclusion

When patients with EC or AH wish to preserve their fertility, it is recommended that prompt and effective fertility treatment, including assisted reproductive technology, should be initiated just after conservative treatment because EC and AH exhibit relatively high recurrence rates among conservatively treated patients.     

Endometrial adenocarcinoma in young patients: evaluation and fertility-preserving treatment

Carcinoma of the endometrium is the most common female pelvic malignancy in the US. Although it is primarily a disease of the postmenopausal female, 25% of patients are premenopausal, with 3-5% in women 40 years old or younger. The younger group of women with endometrial carcinoma are frequently nulligravid with a history of infertility, and a strong desire to preserve fertility. This may pose a therapeutic dilemma for both patients and treating physicians. Medical treatment for young patients with grade 1 endometrial carcinoma who wish to preserve fertility is a reasonable and appealing option. A comprehensive evaluation prior to counseling the patient should include. A complete history and physical examination. A formal D&C with review of histology with an experienced gyn-onc pathologist. Evaluation of the pelvic and abdomen preferably with contrast-enhanced MRI or transvaginal ultrasound. In patients found to have a clinical stage I grade 1 tumor and who want to preserve fertility, thorough counseling including risks and benefits, and explanation that the data is partial and incomplete due to the lack of appropriate controlled studies is mandatory. In patients considered for medical treatment, a high dose progestin regimen should be started with endometrial sampling every 3 months until complete regression of the tumor is documented. For patients willing to conceive at this stage, treatment options should be discussed. In women who do not want pregnancy at this stage, a maintenance treatment with oral contraceptive agent or Depo-provera (medroxyprogesterone acetate 150 mg i.m. q 12 weeks) should be recommended, with periodic ultrasound evaluation of the endometrium. When the patient finishes her fertility plans, the option of hysterectomy should be considered. Although most responses are long standing, there is a small risk of progression during or after cessation of progestin therapy.     

Impact of pelvic radiotherapy on the female genital tract and fertility preservation measures

Radiotherapy to the pelvis can have a major and deleterious impact on the female genital tract. Despite significant advances in the technical delivery of radical pelvic radiotherapy there remains no way to avoid delivering substantial radiation doses to the ovaries and uterus for patients undergoing treatment for gynaecological cancers. Due to improved cure rates from radical chemo-radiotherapy and social trends toward delayed childbirth many women treated for cervical cancer with radical chemo-radiotherapy will wish to attempt to preserve their fertility. Whilst there are now established and emerging techniques for preserving ovarian function and ovarian tissue, there remains the difficulty of the irradiated uterus which, even if pregnancy can be achieved, results in an increased risk for pregnancy-related complications. Future developments may offer women in this difficult situation more and improved options for fertility preservation.     

Endometrial adenocarcinoma in women under 25 years of age

Ten cases of endometrial carcinoma in young women aged 15 to 25 years are presented. Seven of these ten patients exhibited the clinical characteristics of Stein-Leventhal syndrome; of these, three had evidence of polycystic ovaries. Nine of the tumors were well-differentiated, adenoacanthomas (six) or adenocarcinomas (three) and limited to the endometrium. In one case, a moderately differentiated adenosquamous carcinoma involved an ovary and the pelvic wall. Treatment consisted of curettage and progestogens in three patients, one of whom later bore two children. The remainder of the women were treated with abdominal hysterectomy and bilateral salpingo-oophorectomy and/or radiation therapy. All patients for whom follow-up data are available are alive and well without evidence of disease. It is concluded that in selected young patients with well-differentiated endometrial carcinoma limited to the endometrium, conservative hormonal therapy and curettage may be adequate treatment and may preserve fertility.     

Current therapy for dysgerminoma of the ovary

It is important that therapy of ovarian dysgerminoma be optimized because of the young age of women affected and the threat that therapy may pose to fertility. Our understanding of dysgerminoma has improved, so that treatment schemes with better therapeutic ratio may now be used. Approximately 65% of patients present with stage IA disease. For those wishing to preserve fertility, conservative surgery with close clinical, radiologic, and serologic follow-up is the treatment of choice, with chemotherapy for relapse. Cure rates should approach 100%, and fertility is usually preserved. Intra-abdominal relapse in those not wishing to preserve fertility should be treated with modest-dose pelvic and abdominal irradiation. For those patients with disease presenting in stages IB, II, and III who wish to maintain fertility, unilateral oophorectomy followed by combination chemotherapy may be curative and spare ovarian function. Otherwise, complete surgery, followed by abdominopelvic radiation therapy, is recommended. This treatment produces less morbidity than chemotherapy and will cure approximately two-thirds of patients. Chemotherapy should be used for salvage of subsequent relapse. Both radiation and chemotherapy are highly effective treatment modalities for dysgerminoma. This information, coupled with better understanding of the patterns of disease spread and improved ability to identify nondysgerminomatous elements using serum tumor markers, means that a more conservative approach can be taken to management without compromising the chance of cure. Cure rates for dysgerminoma should now approach the role of 97% achieved in the comparable tumor, testicular seminoma.     

Protection of ovarian function and fertility using a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist during cancer treatment in young females

Cytotoxic treatment can cause early loss of ovarian function associated with loss of fertility in younger women. To investigate if co-treatment with a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist may be useful in preserving ovarian function and fertility in younger women during chemotherapy, we prospectively observed nine young patients receiving different chemotherapies for various malignant diseases and other severe medical conditions who also received simultaneous GnRH agonist and GnRH antagonist. Mean age of the patients was 26.56 ± 8.78 years, all were ≤35 years old. Eight (88.9%) patients regained normal basal hormonal profile within 3 – 6 months after the completion of chemotherapy. Median level of follicle-stimulating hormone, luteinizing hormone and estradiol was 6.3 ± 8.8 U/l, 8.2 ± 25.4 U/l and 118.0 ± 130.8 pg/ml, respectively. Eight (88.9%) patients resumed spontaneous menses within 3 – 11 months following discontinuation of chemotherapy. Two (22.2%) patients conceived: one spontaneously, and the second following induction of ovulation by injection of gonadotropins. It seems that combined usage of GnRH agonist and GnRH antagonist during chemotherapy may be useful in preserving ovarian function and fertility in a group of young females receiving chemotherapy treatment.     

Protection of ovarian function and fertility using a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist during cancer treatment in young females.

Cytotoxic treatment can cause early loss of ovarian function associated with loss of fertility in younger women. To investigate if co-treatment with a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist may be useful in preserving ovarian function and fertility in younger women during chemotherapy, we prospectively observed nine young patients receiving different chemotherapies for various malignant diseases and other severe medical conditions who also received simultaneous GnRH agonist and GnRH antagonist. Mean age of the patients was 26.56 +/- 8.78 years, all were < or =35 years old. Eight (88.9%) patients regained normal basal hormonal profile within 3 - 6 months after the completion of chemotherapy. Median level of follicle-stimulating hormone, luteinizing hormone and estradiol was 6.3 +/- 8.8 U/l, 8.2 +/- 25.4 U/l and 118.0 +/- 130.8 pg/ml, respectively. Eight (88.9%) patients resumed spontaneous menses within 3 - 11 months following discontinuation of chemotherapy. Two (22.2%) patients conceived: one spontaneously, and the second following induction of ovulation by injection of gonadotropins. It seems that combined usage of GnRH agonist and GnRH antagonist during chemotherapy may be useful in preserving ovarian function and fertility in a group of young females receiving chemotherapy treatment.     

Polycystic ovary syndrome in adolescence and early adulthood

Polycystic ovaries and the associated syndrome are recognized as the most common cause of endocrine disturbances in adult women, but much less research has been performed to examine how polycystic ovary syndrome (PCOS) presents in girls and young women. Polycystic ovaries have been demonstrated in childhood, and there is evidence to show that even very young women may show symptoms and signs of the associated syndrome. Closer examination of younger populations (ˇ- 25 years of age), and in particular, studies of girls during the transition from puberty into early adulthood (adolescence), may provide new insights into the pathogenesis and natural history of polycystic ovaries and PCOS, and may indicate whether polycystic ovaries could potentially be considered as a marker for health screening. Consideration should be given to the management of girls and young women with polycystic ovaries and PCOS as this group may have different needs and health risks compared with older women.     

Polycystic ovary syndrome in adolescence and early adulthood

Polycystic ovaries and the associated syndrome are recognized as the most common cause of endocrine disturbances in adult women, but much less research has been performed to examine how polycystic ovary syndrome (PCOS) presents in girls and young women. Polycystic ovaries have been demonstrated in childhood, and there is evidence to show that even very young women may show symptoms and signs of the associated syndrome. Closer examination of younger populations (less-than-or-eq, slant 25 years of age), and in particular, studies of girls during the transition from puberty into early adulthood (adolescence), may provide new insights into the pathogenesis and natural history of polycystic ovaries and PCOS, and may indicate whether polycystic ovaries could potentially be considered as a marker for health screening. Consideration should be given to the management of girls and young women with polycystic ovaries and PCOS as this group may have different needs and health risks compared with older women.     

Endometrial cancer in women 45 years of age or younger

OBJECTIVE: The clinical characteristics and outcomes of endometrial cancer in women 45 years of age or younger evaluated and treated at the community hospital level are presented. METHODS: A series of 500 consecutive women with endometrial cancer operated on by the author over a nine-year period of time was used to identify women 45 years of age or younger and compared to older patients from the author's data base. RESULTS: Although the majority of patients presented with clinical stage I disease, 30% of women 45 years of age or younger had occult metastatic disease and 5.0% had clear cell or papillary serous histology, similar to the older patient population. In addition, survival was similar in both groups of patients. Serum CA-125 was useful in identifying patients with possible occult metastatic disease in the group of women 45 years old or younger. CONCLUSION: Patients 45 years of age or younger with uterine cancer are not ipso facto a "lower risk" group of patients; efforts to preserve fertility should be balanced against a thorough effort to identify those individuals at higher risk for occult metastases.