Endometrial hyperplasia: a review

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women: endometrial cancer of endometrioid histology. It is most often diagnosed in postmenopausal women, but women at any age with unopposed estrogen from any source are at an increased risk for developing endometrial hyperplasia. Hyperplasia with cytologic atypia represents the greatest risk for progression to endometrial carcinoma and the presence of concomitant carcinoma in women with endometrial hyperplasia. Abnormal uterine bleeding is the most common presenting symptom of endometrial hyperplasia. Specific Pap smear findings and endometrial thickness per ultrasound could also suggest the diagnosis. Unopposed estrogen in women taking hormone replacement therapy increases the risk of endometrial hyperplasia. Tamoxifen has demonstrated its efficacy in treating women at risk for breast cancer, but it increases the risk of endometrial hyperplasia. The choice of treatment for endometrial hyperplasia is dependent on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk. Endometrial hyperplasia without atypia responds well to progestins. However, women with atypical hyperplasia should be treated with hysterectomy unless other factors preclude surgery. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the definition and classification of endometrial hyperplasia, to outline the clinical features of a patient with endometrial hyperplasia, to point out the natural history of endometrial hyperplasia, and to summarize the diagnostic options for patients with endometrial hyperplasia.     

Uterine abnormalities in non menopausal women who received tamoxifen for breast cancer adjuvant therapy

OBJECTIVE: To elaborate a strategy of endometrial follow-up for premenopausal women treated with Tamoxifen as adjuvant hormonal treatment of breast cancer. PATIENTS AND METHODS: Retrospective study of 152 premenopausal patients treated with Tamoxifen in Nantes Comprehensive Cancer Center for a breast cancer from January 2003 to December 2005. Vaginal sonography was used in the follow-up of 70 of them. RESULTS: Endometrial hypertrophy was found in 26 patients. Sonohysterography and hysteroscopy allowed to find 11 polyps and three hyperplasias in the 19 women who were investigated. In our study, endometrial pathology was found in 20% of premenopausal women treated with Tamoxifen (polyps or hyperplasia). Uterine bleeding was found in half patient of this group. DISCUSSION AND CONCLUSION: Vaginal sonography monitoring could be proposed to premenopausal women treated with Tamoxifen among whom endometrial pathology is usual.     

Letrozole as primary therapy for endometrial hyperplasia in young women.

OBJECTIVE: To study letrozole as a primary therapeutic agent for endometrial hyperplasia with or without atypia in young women. METHODS: Five premenopausal women presenting for infertility were diagnosed as having endometrial hyperplasia. A second biopsy was performed after they were treated for 3 months with 2.5 mg of letrozole per day. Serum levels of estradiol and progesterone were measured each month. RESULTS: Curettage of the endometrium at the end of treatment revealed no evidence of endometrial hyperplasia or atypia in any of the patients. Low serum levels of estradiol were found in all patients. CONCLUSION: This case series indicates that aromatase inhibitors deserve attention for the conservative treatment of endometrial hyperplasia. However, more studies are needed to confirm the efficacy and safety of this agent.     

Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia

OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.     

Ultrasonic evaluation of endometrial changes induced by cyclic sequential hormone substitution therapy

BACKGROUND: At present the hormonal replacement therapy on postmenopausal women with uterus needs the use of progestins additionally to estrogens, to eliminate the risk of endometrial hyperplasia and carcinoma connected with the use of estrogens alone. The check of the endometrium during these therapies can be made by transvaginal ultrasound that permits the evaluation of the thickness, structure, and contour of the endometrial rima. The aim of this study was to establish the changes of endometrial thickness during cyclic sequential hormonal replacement therapy on healthy postmenopausal women with transvaginal ultrasound. METHODS: The endometrial thickness with transvaginal ultrasound has been evaluated during the cyclic sequential hormonal replacement therapy on 20 healthy women in physiological menopause before the treatment, during the phase of treatment with estrogens alone and during the phase of treatment with the addition of the progestins. RESULTS: Significant differences during the estrogenic phase compared to before treatment have been underlined (5.7 mm vs 3.5 mm p = 0.002), but not during progestinic phase compared to estrogenic (6 mm vs 5.7 mm p = 0.712). CONCLUSIONS: Transvaginal ultrasound is a useful investigation to evaluate the modifications of the thickness and structure of the endometrium during hormonal replacement therapy and can help early diagnosis of endometrial diseases during these treatments.     

Incidence of endometrial carcinoma in patients with endometrial hyperplasia

OBJECTIVE: The purpose of this retrospective study was to establish the risk of developing endometrial adenocarcinoma in patients diagnosed with endometrial hyperplasia. MATERIAL AND METHODS: The incidence of endometrial hyperplasia and its relation with endometrial adenocarcinoma was evaluated in 1,139 patients who presented with abnormal bleeding between January 2000 and December 2004; D&C was performed in all cases. There were 591 (51.88%) cases of simple endometrial hyperplasia, out of which 110 (18.61% from 51.88%) cases had atypia, 60 (5.26%) cases of complex hyperplasia, out of which 19 (31.66% from 5.26%) had atypia, and the remaining 488 (42.84%) had different forms of mixed hyperplasia. RESULTS: The incidence of endometrial adenocarcinoma was 3.87% in atypical hyperplasia and 0.81% in other forms, and was related only to cases with atypia in which the incidence was 0.61%. CONCLUSIONS: The most indicated measure to prevent endometrial carcinoma in cases with complex endometria hyperplasia with atypia is hysterectomy, while for other forms of hyperplasia, hormonal treatment is used but only under strict control.     

The role of hormones for the treatment of endometrial hyperplasia and endometrial cancer

PURPOSE OF REVIEW: Hormone therapy has been palliative for advanced/ recurrent endometrial cancer. High remission rates are seen in well-selected stage I, grade 1 endometrial cancer of young women using hormone therapy (usually progestins) as fertility-preserving treatment. Many other hormones, such as gonadotropin-releasing hormone analogs (GnRHa), selective estrogen receptor modulators, aromatase inhibitors, intrauterine progestins, and others are potential modalities. This review updates the recent publications in this area. RECENT FINDINGS: Two reports investigating different scheduling of tamoxifen and progestins indicated that tamoxifen may be a valuable adjunct to progestin therapy. GnRHa has been used adjunctively to tamoxifen as second-line hormone therapy for fertility sparing after progestin failed. Aromatase inhibitors have shown their potential in treating endometrial cancer and endometrial hyperplasia as single agent or in combination with progestins. Intrauterine progestins seem efficacious in treating endometrial hyperplasia; its applications on endometrial cancer patients, however, have been limited to postmenopausal women with poor surgical risk. SUMMARY: Translational research based on molecular mechanisms is mandatory to a more appropriate utilization of hormone therapy. The role of dose, scheduling, route of administration of progestins as well as the addition of other hormonal agents should be further explored by well designed randomized controlled trials.     

Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding

PURPOSE OF INVESTIGATION: To evaluate the prevalence and epidemiologic characteristics of endometrial hyperplasias in women with abnormal uterine bleeding. METHODS: We performed a retrospective analysis on data gained from 294 patients with histologically documented endometrial hyperplasia (with or without atypia), detected among 1,469 women who underwent fractional dilatation and curettage in our department due to abnormal uterine bleeding from 1986 to 1998. Epidemiologic characteristics were abstracted from the patients' medical charts. RESULTS: 294/1469 women were found with endometrial hyperplasia (258 without atypia and 36 atypical hyperplasias). Thirty-six of them were under 40 years of age. Four of the detected endometrial hyperplasias progressed to endometrial carcinoma (one with simple hyperplasia, two with complex and one with atypical hyperplasia). Obesity and hypertension were justified as risk factors in our study population. CONCLUSIONS: The prevalence of endometrial hyperplasia according to our data was 20%. There were statistically significant differences in most epidemiologic parameters between the two types of hyperplasia. The progression of four endometrial hyperplasias to endometrial adenocarcinoma indicates the need for intense follow-up even in cases where patients undergo conservative therapy.     

高分化子宫内膜样癌及子宫内膜重度不典型增生患者孕激素治疗的临床分析

目的探讨35岁以下高分化子宫内膜样癌及子宫内膜重度不典型增生患者采用孕激素治疗以保留患者子宫的疗效,并随访其治疗后的生育情况.方法采用回顾性分析的方法对1991年至2005年北京协和医院收治的35岁以下、接受孕激素治疗（以醋酸甲羟孕酮为主）的25例高分化子宫内膜样癌及子宫内膜重度不典型增生患者的临床病理资料进行研究.其中,子宫内膜样癌8例（内膜癌组）,子宫内膜重度不典型增生17例（不典型增生组）.孕激素治疗前对患者进行全面的分期评估,治疗后每1～6个月诊刮以评价疗效,对有生育要求者随访其生育情况.结果内膜癌组患者孕激素治疗前经全面的分期评估,证实为早期、高分化子宫内膜样癌.除1例子宫内膜样癌患者尚未评估疗效外,内膜癌组其他7例及不典型增生组17例患者治疗后有效者分别为6例（6/7）、17例（100%）;缓解者分别为5例（5/7）、14例（82%）;缓解后复发者分别为1例（1/5）、3例（21%）,复发时间为缓解后6～30个月;随访缓解后要求生育的14例患者中,内膜癌组4例患者尚未生育,不典型增生组10例患者中4例妊娠共7次.1例自然受孕后失访;3例经促排卵治疗后受孕并足月分娩,其中1例产后人工流产3次.结论对于要求保留子宫的高分化子宫内膜样癌及子宫内膜重度不典型增生的年轻患者,孕激素治疗是一种治疗选择.孕激素治疗前应对子宫内膜样癌患者进行详细全面的分期评估,辅助生殖措施的介入有望提高治疗后的妊娠率.     

Endometrial Hyperplasia: A Clinicopathological Study in a Tertiary Care Hospital

Objective

To evaluate the clinical as well as histomorphologic features in different cases of endometrial hyperplasia along with its relative occurrence.

Materials and Methods

A one-and-a-half-year prospective study was conducted on histopathologically diagnosed cases of endometrial hyperplasia in a tertiary care hospital. Apart from relevant clinical findings, histomorphologic details were noted and statistically analyzed.

Observations

Maximum number (46.5 %) of endometrial hyperplasia occurred in patients of 41–50 years age group. Majority (55.2 %) of the patients were found to be premenopausal. Menorrhagia was the most common (49.6 %) clinical presentation followed by postmenopausal bleeding (30.8 %). Simple hyperplasia without atypia was the most common type (95.6 %) followed by complex hyperplasia without atypia (3.6 %) and complex hyperplasia with atypia (0.8 %), respectively. The study of gland–stroma ratio revealed 65:35 to be the most frequent (34 %) ratio; variable-sized glands with cystic dilatation (60.4 %) was the commonest gland architecture and most of the cases (99.2 %) showed the absence of atypia. Associated histopathological findings included a case each of endometrial adenocarcinoma and undifferentiated endometrial stromal sarcoma along with the common leiomyoma and progesterone effects.

Conclusion

Menorrhagia was the most common presenting complaint in cases of endometrial hyperplasia. The cases were mostly in the premenopausal age group. Simple endometrial hyperplasia without atypia was the commonest type diagnosed histopathologically. Histopathological examination along with clinical details is essential to give the final opinion regarding the diagnosis.     

Endometrial abnormalities in infertile women

OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.     

The malignant potential of endometrial polyps

OBJECTIVES: To determine the pre-malignant and malignant potential of endometrial polyps and to assess whether different clinical parameters are associated with malignancy in the polyps. STUDY DESIGN: Four hundred and thirty consecutive cases of hysteroscopic diagnosis of endometrial polyp were retrieved. The medical records, preoperative vaginal sonography results and histopathology findings were reviewed. Statistical analysis was performed. RESULTS: Hysteroscopy truly identified endometrial polyps in 95.7% of the cases. In 11.4% cases, hyperplasia without atypia was found in the endometrial polyp. In 3.3 and 3.0% of women pre-malignant or malignant conditions were found in the polyp. Older age, menopause status and polyps larger than 1.5 cm were associated with significant pre-malignant or malignant changes, although the positive predictive value for malignancy was low. All the malignant polyps were diagnosed only in postmenopausal women. The presence of postmenopausal or irregular vaginal bleeding, was not a predictor of malignancy in the polyp. CONCLUSIONS: Postmenopausal women with endometrial polyps are at increased risk of malignancy in the polyp. Those patients, whether symptomatic or not should be evaluated by hysteroscopic resection of the polyps. Asymptomatic premenopausal patients with polyps smaller than 1.5 cm can be observed.     

Preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia

OBJECTIVES: To determine the preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia. MATERIAL AND METHODS: One hundred and three patients with endometrial hyperplasia detected by surgical curettage performed due to various gynecologic pathologies were treated by hysterectomy. We compared retrospectively the histopathological diagnoses found on curettage with those found on hysterectomy specimens. The classification scheme endorsed by the International Society of Gynecological Pathologists was used to classify the endometrial hyperplasia. The histologic findings found on the endometrial tissue of curettage specimens were correlated with those from hysterectomy specimens. Histopathologic evaluation was performed by a single skilled gynecologic pathologist. RESULTS: A total number of 103 women--76 (73.8%) premenopausal and 27 (26.2%) postmenopausal--were determined to have endometrial hyperplasia on histopathological evaluation of endometrial tissues obtained by endometrial curettage performed for evaluation of various bleeding abnormalities. These included 94 patients with simple hyperplasia without atypia (91.3%), two patients with simple hyperplasia with atypia (1.9%), five patients with complex hyperplasia without atypia (4.9%), and two patients with complex hyperplasia with atypia (1.9%). Histopathological evaluation of endometrial tissue obtained from hysterectomy specimens (of patients diagnosed with hyperplasia on curettage) revealed a total number of 65 cases (63.1%) with endometrial hyperplasia, and 38 cases (36.9%) with various histopathological findings. The correlation between preoperative and postoperative endometrial histologic findings was found to be statistically insignificant (r = 0.105, p = 0.29). Among 94 patients who were found to have simple hyperplasia without atypia on curettage specimens, 55.3%, were found to have simple hyperplasia without atypia, 1.1% simple hyperplasia with atypia, 5.3% complex hyperplasia without atypia, 9.6% secretory endometrium, 4.3% proliferative endometrium, 21.3% disorganized proliferative endometrium, 1.1% corpus luteum persistency, 1.1% basal endometrium, and 1.1% endometrium cancer on final hysterectomy specimens. CONCLUSION: Postoperative diagnosis of endometrial pathology might be different from that of preoperative especially in cases with simple endometrial hyperplasia without atypia.     

The management of endometrial hyperplasia: an evaluation of current practice

OBJECTIVE: To identify current management practices and evaluate subsequent outcomes of treatment for women diagnosed with endometrial hyperplasia. STUDY DESIGN: All women with a histological diagnosis of endometrial hyperplasia at the Birmingham Women's Hospital were identified between October 1998 and September 2000. A retrospective case note review was performed for each woman using a standardised data abstraction sheet. Baseline characteristics including clinical presentation and treatment strategy were obtained. Results of subsequent endometrial tissue examinations were used to assess histological response to treatment and the need and indication for hysterectomy was used to assess clinical response. RESULTS: There were 351 women diagnosed with endometrial hyperplasia during the study period of which 84% presented with symptoms of abnormal uterine bleeding and 54% were postmenopausal. Complex endometrial hyperplasia was the most common diagnosis accounting for 60% of all cases. Eighty percent of women with atypical endometrial hyperplasia were treated by hysterectomy compared with 30% without evidence of cytological atypia (relative hysterectomy rate of 2.6, 95% CI 2.0-3.3). Hysterectomy was avoided in 138/172 (80%, 95% CI 74-86%) women managed conservatively during the study period. Overall 35/108 (36%, 95% CI 27-46%) of women managed conservatively had persistent or progressive disease identified (mean follow up 36 months). 20/143 (14%) women initially diagnosed with endometrial hyperplasia who subsequently underwent hysterectomy were found to have endometrial cancer, the majority of whom had been diagnosed with atypical disease (14/20, 70%). CONCLUSION(S): The majority of women with atypical endometrial hyperplasia were managed by hysterectomy and the substantial risk of diagnostic under-call supports this approach to treatment. In contrast, there is no consensus regarding the initial management of women with endometrial hyperplasia without cytological atypia.     

Classification of endometrial cells on cervical cytology

One hundred eighty-eight women who had endometrial cells on cervical cytologic specimens during the secretory phase or in the postmenopausal period were studied retrospectively. Each had undergone hysterectomy or endometrial biopsy within 12 months of the original smear. The endometrial cells were classified as typical, atypical, or suspicious for carcinoma. Among premenopausal subjects, three of 57 with typical cells had endometrial hyperplasia, one of two with atypical cells had endometrial polyps, and both with cells suspicious for carcinoma had endometrial carcinoma. In the postmenopausal group, ten (13.5%) of 74 with typical endometrial cells had either hyperplasia or carcinoma, and five (22.7%) of 22 with atypical cells and 24 77.4%) of 31 patients with suspicious cells had either hyperplasia or carcinoma. The present findings and a review of the pertinent literature demonstrate that the classification system used is helpful in predicting the risk for endometrial disease in patients with endometrial cells seen on cervical cytologic smears during the secretory phase or in the postmenopausal period.     

Resolution of endometrial hyperplasia with adjuvant anastrozole treatment in postmenopausal breast cancer: a case report

BACKGROUND: Endometrial hyperplasia in patients with a history of breast cancer presents a therapeutic dilemma. The standard conservative therapy for hyperplasia, high-dose progestins, is contraindicated in breast cancer. Anastrozole, an aromatase inhibitor, is becoming first-line adjuvant therapy for breast cancer in postmenopausal women and may have protective effects on the endometrium. CASE: A 51-year-old, obese woman with a history of breast cancer presented with a 2-day history of heavy postmenopausal bleeding. Endometrial biopsy demonstrated simple hyperplasia without cellular atypia. After consultation with the patient's oncologist, the patient received adjuvant anastrozole therapy for the breast cancer; it led to resolution of the endometrial hyperplasia. CONCLUSION: Adjuvant therapy with anastrozole may be beneficial in resolving endometrial hyperplasia in patients with breast cancer.     

Histopathologic behavior of endometrial hyperplasia during tamoxifen therapy for breast cancer

OBJECTIVE: The purpose of the present study is to prospectively evaluate the effects of tamoxifen on the pathological behavior of endometrial hyperplasias without atypia, diagnosed before the start of adjuvant endocrine therapy, in menopausal patients suffering from breast cancer. METHODS: Twenty-six patients suffering from estrogen-receptor positive breast cancer and candidate to receive adjuvant tamoxifen, were found to be affected by endometrial hyperplasias before the start of endocrine therapy. All women showed a baseline endometrial stripe, measured by transvaginal ultrasonography, thicker than 4 mm and the diagnosis of endometrial hyperplasia was made by hysteroscopy and endometrial biopsy. Two patients showing complex atypical hyperplasia underwent vaginal hysterectomy, whereas the remaining 24 patients, suffering from endometrial hyperplasia without atypia, were followed on a yearly basis during the period of tamoxifen intake, by hysteroscopy and endometrial biopsy. RESULTS: Baseline histopathology showed simple and complex hyperplasia in 20 and in 4 patients, respectively. The median follow-up period was 38 months; in particular, all patients underwent endometrial assessment after 12 months, while 22, 16, 10 and 4 patients were followed-up after 24, 36, 48 and 60 months of tamoxifen therapy, respectively. Progression from complex hyperplasia to complex atypical hyperplasia (1 patient) and from complex and simple hyperplasia to adenocarcinomas (2 patients) was found within 24 months of tamoxifen intake in 3 patients (12.5%). In 2 patients (8.3%), a progression from simple to complex hyperplasia was detected within 36 months of tamoxifen treatment. In 13 patients (54.1%), stable histology of simple or complex hyperplasia was found, whereas 6 patients (25.0%), with focal hyperplasia harbored in an endometrial polyp, showed a normalization of endometrial histology after polyp resection. CONCLUSIONS: Endometrial hyperplasias without atypia diagnosed before endocrine therapy for breast cancer in menopausal patients show an early and high progression-rate to atypical lesions under tamoxifen influence.     

Endometrial hyperplasia and the risk of carcinoma

Recent reports suggest that atypical endometrial hyperplasia diagnosed by biopsy or curettage is accompanied by a higher than expected risk of coexistent invasive cancer. In order to test this hypothesis we reviewed the pathology and clinical history of all patients at our institution who underwent hysterectomy for endometrial hyperplasia with or without cytologic atypia. We found 24 patients of 45 with a preoperative diagnosis of hyperplasia with cytologic atypia, and 21 with simple or complex hyperplasia without atypia. No cancers were found at surgery in the latter group nor were any significant historical differences found between the two groups. Of the patients with atypia, 12/24 (50%) had an endometrial carcinoma and nine patients (37.5%) were stage IB or greater. This is a significantly greater risk than previously reported in the literature. Endometrial hyperplasia with cytologic atypia may carry a higher risk of coexistent invasive endometrial carcinoma than previously believed. Methods to identify those patients at highest risk should be determined.     

Atypical endometrial hyperplasia in an 18-year-old woman

The natural history and the factors that lead to the acquisition of atypia in endometrial hyperplasias in young aged women, especially under the age of 20, have not been fully elucidated. In such cases, although there exists a considerable risk of progression to carcinoma, a conservative antiestrogenic treatment is primarily indicated, in attempt to preserve the reproductive ability of the young woman. We report of a 18-year-old girl with atypical hyperplasia of the endometrium, a diagnosis confirmed by reviewing of the histologic material by specialized gynecopathologists. The patient has been treated with gonadotropin releasing hormone agonist (leuprolide acetate) and tibolone for 1 year, which led to endometrial atrophy and amenorrhea, without hypoestrogenic side effects. Six months after cessation of the therapy the endometrial hyperplasia relapsed (this time without atypia), but in about 2 years of follow-up and after short courses of treatment with clomiphene citrate and progestins the biopsy of the endometrium revealed a functional endometrium and the patient presents with an almost regular menstrual cycle.