Late intracaval and intracardiac leiomyomatosis following hysterectomy for benign myomas treated by surgery and GnRH agonist

BACKGROUND: The aim of this study was to report an exceptional case of a patient presenting with intracaval and intracardiac leiomyomatosis treated by combined surgical and medical treatment. CASE: A 48-year-old presented with intracaval and intracardiac leiomyomatosis (IL) discovered 6 years following a total hysterectomy with ovarian conservation for myomas. Surgical resection of the pelvic myomas and intracaval leiomyomatosis was performed during the same surgical procedure. Given the presence of a small tumor residuum in the pelvic cavity, postoperative medical treatment based on a gonadotropin-releasing hormone (GnRH) agonist was delivered for 1 year. The patient was followed-up using clinical examination and systematic CT scan. Ten months following the end of medical treatment, she is still in good health and the pelvic residuum has stabilized. CONCLUSIONS: Patients with pelvic tumor combined with IL could be treated using a one-stage surgical procedure. In cases of incomplete surgical resection, medical treatment based on GnRH agonist could be successfully delivered.     

Body fat distribution and body composition during GnRH agonist therapy

OBJECTIVE: To identify the effects of GnRH agonist therapy on body composition (lean and fat mass components) and body fat distribution. METHODS: Fifteen women with uterine leiomyomas were given a GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Weight, height, and body mass index (BMI, weight/height) were recorded. Regional and total body composition, trunk-leg fat ratio, bone mineral density of the lumbar spine (L2-L4), and total body were assessed by whole-body scanning with dual-energy x-ray absorptiometry before and after treatment. Uterine volume was measured by transabdominal ultrasonography. RESULTS: The mean (+/- standard deviation [SD]) lean mass of total body, trunk, and leg decreased significantly (36.3 +/- 4.9 to 35.4 +/- 4.4 kg, P <.01; 18.8 +/- 2.8 to 18.1 +/- 2.8 kg, P <.05; and 11.4 +/- 1.8 to 11.1 +/- 1.6 kg, P <.05; respectively), whereas body fat mass, percentage of body fat, and trunk fat mass increased significantly (20.8 +/- 4.8 to 21.8 +/- 4.6 kg, P <.01; 34.9 +/- 5.9 to 36.5 +/- 5.2%, P <.01; and 8.6 +/- 3.0 to 9.3 +/- 3.0 kg, P <.01; respectively). Trunk-leg fat ratio increased significantly (1.03 +/- 0.32 to 1.12 +/- 0.33, P <.05). Weight, BMI, arm tissue composition (lean and fat mass components), and leg fat mass did not change during 4 months of GnRH agonist therapy. Bone mineral density and uterine volume decreased significantly. CONCLUSION: Hypogonadism by GnRH agonist therapy induces lean mass loss, increased adiposity overall, and upper body fat accumulation.     

Intravenous leiomyomatosis misdiagnosed with large thrombosis in inferior vena cava

ObjectiveThe aim of this report is to highlight the importance of a comprehensive preoperative evaluation in the case of intravenous leiomyomatosis.Case reportA 49-year-old women was presented with dyspnea and abdominal distension. Imaging studies revealed a large leiomyoma with intravenous leiomyomatosis from this mass to the right parauterine veins, right ovarian vein reaching the inferior vena cava. Complete resection was performed by a two-stage operation by a multidisciplinary team. Final pathology confirmed it to be intravenous leiomyomatosis and uterine leiomyomas.ConclusionIntravenous leiomyomatosis is a benign and rare disease that can be a fatal condition. Precise diagnosis and appropriate treatment are important for the best outcome. Gynecologists should consider this rare disease when a patient with a uterine tumor shows symptoms such as chest pain and dyspnea.     

Pulmonary endometriosis in a patient with unicornuate uterus and noncommunicating rudimentary horn

OBJECTIVE: To report a rare case of a patient with catamenial hemoptysis, secondary infertility, and endometriosis associated with a unicornuate uterus and noncommunicating rudimentary horn. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 29-year-old woman who developed progressive catamenial hemoptysis and secondary infertility was evaluated at the University Hospital of Crete. INTERVENTION(S): The complete history, laboratory data, laparoscopic findings, and chest magnetic resonance image of this patient were analyzed. A GnRH agonist, leuprolide acetate, was successfully administered. MAIN OUTCOME MEASURE(S): Diagnosis and appropriate treatment of pulmonary endometriosis in a patient with rudimentary uterine horn. RESULT(S): Treatment with a GnRH agonist achieved suppression of both menstruation and hemoptysis. After 6 months of normal menstrual activity, the symptoms reappeared. The patient was again treated with leuprolide acetate (3.75 mg/mo IM) for 6 months and remained asymptomatic. In fact, the patient became pregnant after cessation of therapy. Finally, the patient was treated successfully with removal of the rudimentary uterine horn during cesarean section. Three-year follow-up showed disappearance of the chest symptoms. CONCLUSION(S): Pulmonary endometriosis and unicornuate uteri are rare. To our knowledge, this is the first case of catamenial hemoptysis with a congenital müllerian anomaly. We describe successful management using a combination of GnRH agonist and surgical resection of the rudimentary uterine horn.     

Effects of gonadotropin-releasing hormone agonists on uterine volume and vasculature and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) in uterine leiomyomas.

We investigated the effect of the GnRH agonist (GnRH-a) on the uterine volume and on the immunohistochemical expression of basic fibroblast growth factor (bFGF) and the vasculature of leiomyomas. Twenty-five women were treated with leuprorelin acetate for 3 months; 46 untreated patients were enrolled as a control group. The uterine volume was measured by ultrasonography. After myomectomy or hysterectomy, the immunoexpression of bFGF and the endothelial marker, CD34, was studied and compared in treated and untreated leiomyomas. Uterine volume decreased after therapy. The number of cells expressing bFGF and the vascularity were diminished in treated leiomyomas. Reduction in the blood supply might be responsible, in part, for uterine-volume shrinkage after GnRH-a therapy.     

Comparison of the effects of leuprorelin acetate and danazol treatments on serum CA-125 levels in women with endometriosis

OBJECTIVE: To investigate the effects of danazol and leuprorelin acetate on CA-125 levels during treatment for endometriosis. PATIENTS AND METHODS: Fifty women with laparoscopically diagnosed and treated endometriosis, and 50 women without pelvic disease as a control group. Following surgical treatment, 35 women with endometriosis were divided into two groups. The first group (20 women) received 200 mg danazol three times daily for 6 months; the second group (15 women) received 3.75 mg leuprorelin acetate depot every 28 days for 6 months. Serum CA-125 levels were measured before medical treatment, during the last 15 days of the 6-month treatment course, and 3 months after treatment. RESULTS: Serum CA-125 levels were significantly higher in women with endometriosis than in women in the control group. Before treatment, CA-125 levels in patients with stage III/IV endometriosis were significantly higher than those in stage I/II endometriosis. Six months of danazol or leuprorelin acetate depot treatment decreased serum CA-125 levels. Three months after stopping danazol, CA-125 levels remained significantly lower than pretreatment levels. On the other hand, 3 months after stopping leuprorelin acetate, CA-125 levels returned to pretreatment levels. CONCLUSIONS: (a) Danazol and leuprorelin acetate are equally effective in the treatment of endometriosis. (b) Moreover, the results support the view that the determination of CA-125 levels may assist in evaluating progress of endometriosis treatment.     

Pelvic leiomyomatosis with intracaval and intracardiac extension: a case report and review of the literature

BACKGROUND: Intravenous leiomyomatosis with intracaval and intracardiac extension has been rarely described in surgical, gynecological, and radiological literatures. Complete excision of the tumor is essential for a favorable outcome. Because of the uniqueness of this tumor having an absent or localized attachment site, its removal is feasible when assisted, prior to surgery, with appropriate imaging and planning. CASE: The case was a 46-year-old woman, with intravenous leiomyomatosis originating from the uterus and extending to the inferior vena cava and right atrium, with extensive intracaval attachment, diagnosed from the various preoperative studies and operated successfully through the single-stage approach using cardiopulmonary bypass. CONCLUSION: We present an unusual case of intravenous leiomyomatosis originating from the uterus and extending to the inferior vena cava and right atrium with extensive intracaval attachment. We include a brief review of the literatures.     

子宫静脉内平滑肌瘤临床病理分析

目的 探讨子宫静脉内平滑肌瘤的临床生物学特征及治疗手段对预后的影响。方法 对北京协和医院和江西省妇幼保健院1992年6月至2003年6月间收治并经手术及病理检查证实的子宫静脉内平滑肌瘤7例患者的临床和病理资料进行回顾性分析,全部病例均随访。结果 临床表现：7例患者均以盆腔包块为主诉,其中3例盆腔包块超过妊娠12周子宫大小,最大者妊娠16周大小;2例表现为经期延长、经量增多,1例表现为绝经后出血。超声检查：4例提示子宫肌瘤,1例提示子宫肉瘤,2例提示卵巢肿瘤,术前确诊率为0。术中冰冻检查：2例中1例确诊。手术治疗：4例行全子宫及双侧附件切除术,2例行全子宫及一侧附件切除术,1例仅行肌瘤剔除术;1例行子宫及一侧附件切除术患者术后2年复发,瘤栓沿下腔静脉转移至右心房及右心室再次手术治疗。结论 子宫静脉内平滑肌瘤具有特殊的不良生物学行为,提高术中确诊率与正确选择手术方式及术后密切随诊可以改善其预后。     

Regression of peritoneal leiomyomatosis after treatment with gonadotropin releasing hormone analogue

A case of a 42-year-old woman with peritoneal leiomyomatosis (PL) unrelated to pregnancy or any other obvious hormonal source is presented. After treatment with leuprolide acetate for six months, a second-look operation revealed that the majority of the nodules totally regressed. The few remaining ones were substantially reduced in size and exhibited histopathologic evidence of fibrotic change. This response to treatment is documented here for the first time. Since this case was not associated with initial abnormally raised hormonal levels, the regression was caused solely by the treatment and not by the removal of any hormonal stimulus. The usefulness of GnRH analogues in the treatment of PL is proposed.     

Fetus-in-Fetu: A Case of Ovarian Involvement and Residual Regrowth in a Teenager

Background: Fetus-in-fetu (FIF) is a rare, congenital soft tissue mass typically occurring retroperitoneally in neonates younger than 18 months. We present a 13-year-old girl with an ovarian FIF occurrence and subsequent residual regrowth after resection.Case: A 13-year-old girl presented with abdominal pain and was found to have a 19-cm, complex, right adnexal mass. Preoperative tumor markers were normal and risk assessment favored a benign process. She underwent open ovarian cystectomy with pathology showing FIF. Nine months later, she had a recurrence of her ovarian mass and underwent right oophorectomy, with FIF on pathology.Summary and Conclusion: In patients in whom FIF is discovered within the ovary, consider postoperative surveillance, because of the risk of recurrence or residual disease.     

Uterine intravenous leiomyomatosis. A case report

Uterine intravenous leiomyomatosis is a rare benign tumor. We report the case of a 41-year-old woman, with no history, who presented an abdominopelvic mass arising from the uterus. Histological examination revealed uterine intravenous leiomyomatosis. The specificity of this tumor is hormonodependency and potential vascular extension.     

Gonadal protection by a gonadotropin-releasing hormone agonist depot in young women with Hodgkin's disease undergoing chemotherapy.

OBJECTIVE: To explore the effects of a gonadotropin-releasing hormone (GnRH) agonist depot (goserelin acetate) in women with Hodgkin's disease receiving chemotherapy while taking a continuous combined estrogen-progestin preparation as add-back on the prevention of premature ovarian failure (POF). METHODS: In a prospective pilot study, five premenopausal women with Hodgkin's disease received a GnRH agonist depot plus add-back until polychemotherapy was completed. Every 4 weeks during treatment and thereafter, a hormonal profile (follicle-stimulating hormone (FSH), luteinizing hormone, 17beta-estradiol, progesterone and inhibin B) was measured until resumption of menstruation or the development of a hypergonadotropic state (2 x FSH > 30 U/l). RESULTS: All patients reached prepubertal status during treatment. After discontinuation of goserelin acetate, one patient developed a hypergonadotropic state and four patients resumed menstruation. One of those patients became pregnant and delivered a healthy son. CONCLUSIONS: The effectiveness of GnRH agonist plus add-back on the prevention of POF during polychemotherapy in women with Hodgkin's disease needs further elucidation in randomized controlled trials. The results of our pilot study are promising.     

Long-term use of gonadotropin-releasing hormone analogs and hormone replacement therapy in the management of endometriosis: a randomized trial with a 6-year follow-up

OBJECTIVE: To identify the effects of long-term GnRH agonist use (6-24 months), with and without add-back therapy, and spontaneous reversibility of bone mass density (BMD) up to 6 years after treatment. DESIGN: A prospective, randomized, long-term follow-up study. SETTING: Obstetrics and gynecology department in a university hospital in the United Kingdom. PATIENT(S): Forty-nine symptomatic women with a laparoscopic diagnosis of endometriosis who had been identified for treatment with long-acting GnRH agonist and volunteered to participate in the study. INTERVENTION(S): Women were randomly allocated to receive hormone replacement therapy (HRT) as a daily oral dose of estradiol, 2 mg, and norethisterone acetate, 1 mg, or no treatment in addition to monthly subcutaneous implants of goserelin acetate for up to 2 years, until cessation of symptoms. Bone mineral density (BMD) at the lumbar spine (C2-C4) and hip (Ward triangle) was measured every 6 months. MAIN OUTCOME MEASURE(S): BMD changes in both groups. RESULT(S): 45 women were followed up for 6 years, at the end of which the groups did not differ significantly in the reduction in mean BMD at the lumbar spine or hip. CONCLUSION(S): BMD reduction occurs during long-term GnRH agonist use and is not fully recovered by up to 6 years after treatment. Use of HRT does not affect this process.     

Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients with ovarian endometriomas

OBJECTIVE: To determine whether serum interleukin (IL)-6 can be measured in patients with ovarian endometriomas and whether these measurements are useful in managing this disease. DESIGN: A controlled clinical study and an in vitro study. SETTING: Department of Obstetrics and Gynecology, Tottori University, Japan.Twenty-two patients with ovarian endometriomas. INTERVENTION(S): Laparoscopic cystectomy for ovarian endometriomas was performed. Gonadotropin-releasing hormone (GnRH) agonist was administered for 3 months in nine patients before laparoscopic surgery. Endometriotic stromal cells obtained from patients with endometriomas with or without GnRH agonist treatment were cultured. MAIN OUTCOME MEASURES(S): IL-6 concentrations in serum or supernatant of the cell culture were measured using ELISA. RESULTS: The serum concentration of IL-6 in patients with endometriomas was higher at the time of diagnosis than in those without endometriomas. Laparoscopic surgery significantly reduced serum levels of IL-6. Serum IL-6 concentrations also decreased after treatment with GnRH agonist. IL-6 production was attenuated in the endometriotic stromal cells obtained from patients with GnRH agonist treatment compared with patients without such treatment. CONCLUSION(S): GnRH agonist treatment may decrease IL-6 production in endometriotic cells. Measurement of serum IL-6 concentrations may be of value in managing patients with endometriomas.     

Intravenous leiomyomatosis with cardiac extension

Intravenous leiomyomatosis with cardiac extension is an extremely rare uterine tumor. We report here a case of a patient with a uterine leiomyoma which extended into the right atrium through the left ovarian vein, progressing into the left renal vein along the inferior vena cava. Complete one-stage removal of the tumor was performed using cardiopulmonary bypass, and the patient has shown a favorable outcome. Successful therapy for intravenous leiomyomatosis is dependent on total surgical excision of the tumor, cessation of ovarian function and avoidance of postoperative estrogen replacement therapy.     

Long-term administration of tibolone plus gonadotropin-releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass, and lipid profiles

OBJECTIVE: To evaluate the effects of long-term administration of GnRH agonist (GnRH-a) plus tibolone for uterine leiomyomatosis. DESIGN: Prospective open clinical trial. SETTING: Department of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II", Naples, Italy. PATIENT(S): Twenty-five subjects with symptomatic uterine leiomyomas. INTERVENTION(S): Treatment for 2 years with leuprolide acetate (3.75 mg IM every 28 days) and tibolone (2.5 mg/d per os). MAIN OUTCOME MEASURE(S): Uterine and uterine leiomyoma sizes, endometrial thickness, lumbar spine bone mineral density (BMD), bone metabolism, lipid profile, myoma-related symptoms at baseline and every 6 months. Hot flashes and vaginal bleeding episodes recorded in a daily symptom diary. RESULT(S): After 6 months of treatment, a significant reduction was observed in uterine and leiomyoma volumes and myoma-related symptoms compared with baseline values. No significant change was observed in bone turnover, lumbar BMD, or serum total cholesterol, low-density lipoprotein cholesterol, or triglyceride levels. High-density lipoprotein cholesterol values were significantly lower than baseline values after 6 months of treatment but not after 18 months of therapy. A low mean number of hot flashes per day was observed. CONCLUSION(S): Long-term administration of GnRH-a plus tibolone reduces hot flashes and prevents bone loss without changing the lipid profile.     

Diagnosis and Localization of Testosterone-Producing Ovarian Tumors: Imaging or Biochemical Evaluation

OBJECTIVE: In the testosterone-secreting ovarian tumor (TSOT), the role of whole-body positron emission tomography (WBPET) with (fluorine-18)-2-deoxyglucose scanning (FDG) and/or [(11)C]acetate is unclear, although it presents a rationale that these functional tumors would be more active and have increased use of glucose and oxygen consumption than normal tissues. CASE: A 52-year-old woman had a history of steroid cell tumors of the right ovary (IIA) and she received staging surgery including total hysterectomy, salpingo-oophorectomy, and lymph node sampling. Reelevated serum levels of T (5.24 ng/ml) were noted 52 months later. The patient received serial preoperative examinations including WBPET with FDG and acetate, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) to evaluate her recurrence. A suspicious mass on the liver was found on ultrasound, CT, and MRI. The ultrasound-guided biopsy was performed three times, and each of them failed to provide any pathological confirmation. Functional imaging studies showed an abnormal uptake in WBPET using [(11)C]acetate but were negative using FDG. Because of the size of the tumor, the patient's hesitatancy toward an operation, and good previous response to gonadotropin-releasing hormone (GnRH) agonist treatment, the patient received a six-cycle GnRH agonist treatment. Serum T levels returned to normal limits after administration of the first dose of GnRH agonist. At follow-up, serum hormone levels were all within the normal ranges consistent with menopause, but the size of the metastatic tumor was constant. The tumor was then completely excised pathologically proven to be a metastatic TSOT. CONCLUSIONS: Recurrent TSOT might be successfully detected using WBPET with [(11)C]acetate. In addition, GnRH agonist could be tried in patients with TSOT if initial responses were excellent and surgical intervention could not be performed.     

Current approaches to optimizing the treatment of endometriosis in adolescents

Endometriosis can occur in adolescents and this patient group presents particular challenges in terms of differential diagnosis, variable presentation and symptoms, and choice of treatment. Early diagnosis is essential in order to decrease pain and hopefully prevent disease progression and preserve future fertility. Endometriosis surgery is generally cytoreductive rather than curative, and postoperative medical therapy should be initiated regardless of disease stage. Menstrual suppressive therapy with the use of continuous combination estrogen/progestin is the main treatment for most adolescents with endometriosis. For those with a persistence of pain on this therapy Gonadotropin-releasing hormone (GnRH) agonists (with add-back therapy) can be effective in relieving symptoms. GnRH agonist therapy requires special consideration in adolescents due to possible adverse effects on bone mineralization--an important consideration in adolescents who are at a critical age for accrual of bone mineral density (BMD). However, potential problems of bone loss may be avoided with the use of 'add back' therapy. A recent clinical study found that most adolescents with endometriosis receiving a GnRH agonist plus add-back therapy with norethindrone acetate (NA) or estrogen plus NA had normal BMD at the hip. Add-back therapy appears to be a promising adjunct to GnRH agonist therapy for the prevention of bone loss and may allow a longer duration of therapy than with a GnRH agonist alone. BMD should continue to be carefully monitored after the initial 6-8 month period of therapy and then approximately every two years in adolescent patients (over age 16) receiving long-term GnRH agonist with add-back therapy.     

Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism.

The objective of this prospective randomized study was to evaluate and compare the hormonal and clinical effects of long-acting gonadotropin-releasing hormone (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five hirsute women with PCOS, ranging in age from 19-27 years, were randomly divided into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12) treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist plus flutamide for 6 months. Before, at the end and 6 months after the end of treatment, blood samples were drawn from all women (in early follicular phase in those with menstrual cycles) to measure ovarian and adrenal androgens, gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estradiol and estrone plasma levels. The results showed that all three protocols had good therapeutic efficacy. A significant reduction in hirsutism was observed in all patients after 6 months of therapy, the Ferriman-Gallwey scores dropping to 9 +/- 3 in group A, 10 +/- 4 in group B and 11 +/- 5 in group C. Six months after the end of therapy, the hirsutism score continued to be significantly reduced in all groups. After 6 months of therapy, a reduction in plasma levels of LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this was more pronounced in group B and group C. These therapies may be the basis of future treatments that quickly reduce hirsutism and remove its causes by reducing the secretion of ovarian and adrenal androgens and by blocking androgen receptors.     

A randomised controlled trial comparing GnRH antagonist cetrorelix with GnRH agonist leuprorelin for endometrial thinning prior to transcervical resection of endometrium

Objectives  To compare the effectiveness of leuprorelin and cetrorelix, when used as preoperative endometrial thinning agents prior to transcervical resection of endometrium (TCRE).
Design  A prospective, double-blind randomised controlled trial.
Setting  Gynaecological department of a UK district general hospital.
Participants  A total of 106 premenopausal women with dysfunctional uterine bleeding, undergoing TCRE.
Interventions  Women were equally randomised to 3.75 mg of leuprorelin acetate (3–4 weeks) or 3 mg cetrorelix (4–7 days) prior to TCRE. About 1 ml saline was given as placebo in both arms.
Main outcome measures  Amenorrhoea rate at 6 months, endometrial thickness using transvaginal ultrasound on the day of operation.
Results  A total of 100 women completed the trial with no loss to follow up. Amenorrhoea rate at 6 months after surgery was high in both groups (80% cetrorelix and 84% leuprorelin) with no statistical significance. All endometrial outcome measures including endometrial thickness on ultrasound, histology and operative appearance were more favourable in leuprorelin group as compared with cetrorelix ( P values 0.013, <0.001 and 0.003 respectively). More women in leuprorelin group had hot flushes as compared with cetrorelix (15/50 versus 6/50; P  = 0.047). No significant differences were seen in other outcome measures.
Conclusions  In dosages used, leuprorelin produced more consistent thinning of the endometrium as compared with cetrorelix, although this did not make any significant difference to operative or menstrual outcomes. The endometrial thinning effect with cetrorelix does appear to be more favourable than that seen at postmenstrual phase in other studies. The optimum (possibly higher) dosage of cetrorelix for this purpose has not yet been established.