Hormone-related Symptoms Research Articles

O-35: Evaluation of the effects on serum hormone levels of supplementation with 10 micrograms ethinyl estradiol daily during the typical hormone-free interval of a combined oral contraceptive

During the 7-day placebo or hormone-free interval (HFI) of a traditional 28-day oral contraceptive regimen, ethinyl estradiol (EE) is rapidly cleared from the circulation, allowing several hormone-free days in which recovery of the hypothalamic-pituitary-ovarian axis occurs and hormone levels approach those seen in normal ovulatory menstrual cycles. It has been suggested that this recovery increases the risk of follicular development and escape ovulation and may contribute to the occurrence of hormone-related symptoms.

Psychometric properties of a tool for measuring hormone-related symptoms in breast cancer survivors

Hormone-related symptoms are common in breast cancer survivors and many aspects of these symptoms are currently under study. Reliable and valid assessment tools are needed to successfully study hormone-related symptoms in breast cancer survivors; however, no gold standard currently exists for measuring these symptoms. This study evaluated the psychometric properties of a shortened version of the Breast Cancer Prevention Trial (BCPT) symptom checklist in a sample of 803 breast cancer survivors. Principal factor analysis with Promax oblique rotation revealed a five-factor structure, identifying five separate hormone-related symptoms scales: vasomotor symptoms, urinary incontinence, cognitive/mood changes, vaginal symptoms, and weight gain/appearance concern. Hormone-related symptom scale scores differed by demographic and clinical characteristics according to expectations, suggesting that these five scales from the shortened BCPT checklist are reasonably reliable and valid. Symptom scale scores were only weakly correlated with health-related quality of life scores; however, the pattern of results generally supported the validity of the symptom scales. This study adds to the evidence that breast cancer survivors experience a significant number of hormone-related symptoms. Future clinical trials and quality of life and symptom management intervention studies would benefit from accurate assessment of hormone-related symptoms with the five scales from the shortened BCPT checklist.

Radiofrequency ablation of neuroendocrine liver metastases—the Middlesex experience

Current treatment options for neuroendocrine liver metastases are not widely applicable or not that effective. Image-guided thermal ablation offers the possibility of a minimally invasive, albeit palliative, treatment that decreases tumor volume, preserves most of the normal liver, and can be repeated several times. We report our experience with image-guided thermal ablation in 25 patients with unresectable liver metastases. Since 1990 we have treated 189 tumors at 66 treatment sessions in 25 patients (12 female, 13 male; median age, 56 years; age range, 26--78 years). Thirty treatments were performed with a solid-state laser, and 36 treatments were performed with radiofrequency ablation. All but one treatment was performed percutaneously under image guidance. Sixteen patients had metastases from carcinoid primaries, three from gastrinoma, two from insulinoma, and four from miscellaneous causes. Fourteen of 25 had symptoms from hormone secretion. Imaging follow-up was available in 19 patients at a median of 21 months (range, 4--75 months). There was a complete response in six patients, a partial response in seven, and stable disease in one; hence, tumor load was controlled in 14 of 19 patients (74%). Relief of hormone-related symptoms was achieved in nine of 14 patients (69%). The median survival period from the diagnosis of liver metastases was 53 months. One patient with end-stage cardiac disease died after a carcinoid crisis. There were eight (12%) complications: five local and three distant, four major and four minor. As a minimally invasive, readily repeatable procedure that can be used to ablate small tumors, preferably before patients become severely symptomatic, radiofrequency ablation can provide effective control of liver tumor volume in most patients over many years.

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients.

Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.

Carcinoid Heart Disease: an Update

Background : Carcinoid tumours are a poorly defined collection of lesions, histopathologically indistinguishable from gastroentero-pancreatic neuroendocrine tumours. In this report, we discuss epidemiology and survival, clinical presentation, carcinoid valvular heart disease (CVHD), histopathological considerations and treatment options. Methods : Review and update of the literature. Results : The term carcinoid suggests a disease entity, but with increasing knowledge it becomes progressively confusing. To avoid further confusion, it is advisable to define these tumours using differentiation, stage, primary site, known tumour products and an associated clinical syndrome. Incidence varies between 0.8 and 1.9/100,000 population. About 20% present with metastases, with a 5-year survival varying between 15% and 35%. Metastatic disease frequently accompanies the carcinoid syndrome (flushing, diarrhoea, wheezing and CVHD). CVHD incidence is about 50%, and seems unrelated to disease duration and tumour mass. An aetiological relation of CVHD with urinary 5-HIAA remains to be confirmed. Resection is the only curative option. Surgery can also offer prolonged palliation and is needed to restore bowel transit in obstructive/ischaemic bowel problems. Adequate palliation of hormone-related symptoms can also be achieved by somatostatin analogues, meta-iodo-benzyl-guanidine preparations and interferon- α formulations, all with a 70% response rate. Embolization of liver metastases has led to objective responses in about 50% of patients, but is accompanied by significant side effects. Conclusions : Most patients are cured by surgery. Symptom relief is the main target in metastatic disease and can be achieved by a range of equally potent biologically active medications, debulking surgery and hepatic embolization.

THE SURGICAL MANAGEMENT OF PANCREATIC NEUROENDOCRINE TUMORS

NETs of pancreas are rare and may or may not be associated with symptoms of hormone overproduction. Treatment is required for control of tumor growth and for relief of symptoms associated with excess hormone. With advances in the nonsurgical management of many hormone-related symptoms (e.g., proton pump inhibitors or somatostatin analogues), care for many of these patients has shifted toward the control of tumor progression. Complete surgical resection is the only curative treatment for these tumors. With improvements in the preoperative imaging and intraoperative localization techniques, it is hoped that these tumors will be identified and resected for cure with increased frequency. For patients with hepatic metastasis, initial expectant observation and medical management of symptoms is appropriate in view of the long and indolent course of the disease. Hepatic arterial embolization is the preferred mode of palliation for pain and hormonal symptoms. A curative hepatic resection may be possible in selected patients.

Hormone withdrawal symptoms in oral contraceptive users

Objective: To measure the timing, frequency, and severity of hormone-related symptoms in oral contraceptive (OC) users, specifically to compare active-pill with hormone-free intervals. Methods: Using daily diaries, women recorded pelvic pain, bleeding, headaches, analgesic use, nausea or vomiting, bloating or swelling, and breast tenderness during active-pill intervals and hormone-free intervals. Participants either had no prior OC use, had taken OCs and were restarting, or had been taking OCs continuously for 12 months or longer. Results: Two hundred sixty-two women, 26 with no previous OC use, 43 prior users, and 193 current users, provided daily records of hormone-related symptoms. Subjects with no prior OC use and prior users restarting were similar in no recent OC use, and because of the small sample, they were pooled for analysis as new-start OC users. Current users had patterns of symptoms that were more frequent during hormone-free intervals than during the three active-pill weeks. These included pelvic pain (70% versus 21%, P < .001), headaches (70% versus 53%, P < .001), use of pain medication (69% versus 43%, P < .001), bloating or swelling (58% versus 19%, P < .001), and breast tenderness (38% versus 16%, P < .001). Similar patterns were seen in new-start OC users after the first cycle. Among new-start OC users, menstrual flow patterns, headache, bloating or swelling, and breast-tenderness symptoms decreased during the three cycles to approach those levels of current users. Conclusion: Almost all symptoms assessed were significantly worse during the 7-day hormone-free interval than during the 21 days of hormone-containing pills.

Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients.

Patients with neuroendocrine carcinoma often present with liver metastases not amenable to hepatic resection. For them, liver transplantation has been considered a viable treatment option, especially if hormonal symptoms and pain cannot be controlled medically. Still, little is known regarding potential prognostic factors and long-term survival after liver transplantation for neuroendocrine tumors. A search of English, French, and German literature identified patients with liver transplantation for extensive metastases from neuroendocrine carcinoma for whom follow-up data were available. Overall, 2-year and 5-year survival for all 103 patients was 60% and 47%, respectively, but recurrence-free 5-year survival did not exceed 24%. Univariate analysis identified age less than 50 years, primary tumor location in lung or bowel, and pretransplant somatostatin therapy as favorable prognostic factors, whereas extended operations combining liver transplantation with upper abdominal exenteration or Whipple's procedure were associated with poor prognosis. Multivariate analysis identified age greater than 50 years (P<0.03) and transplantation combined with upper abdominal exenteration or Whipple's operation (P<0.001) as adverse prognostic factors. Liver transplantation may be justified in selected patients to provide immediate relief of otherwise intractable pain or hormone-related symptoms. Transplantation with curative intent appears worthwhile in young patients with only hepatic disease. In older patients with extrahepatic disease requiring extended operations, long-term results are discouraging, and the small benefit achieved by liver transplantation must be weighed against medical treatment options and the natural course of often slowly progressing disease.

Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicentric report.

The purpose of this study was to assess the value and timing of orthotopic liver transplantation (OLT) in the treatment of metastatic neuroendocrine tumors (NET). Liver metastasis from NET seems less invasive than other secondary tumors. This observation suggests that OLT may be indicated when other therapies become ineffective. However, the potential benefit of this highly aggressive procedure is difficult to assess due to the scarcity and heterogeneity of NET. A retrospective multicentric study was carried out, including all cases of OLT for NET performed in France between 1989 and 1994. There were 15 cases of metastatic carcinoid tumor and 16 cases of islet cell carcinomas. Hormone-related symptoms were present in 16 cases (55%). Only 5 patients (16%) had no previous surgical or medical therapy before OLT. Median delay from diagnosis of liver metastasis and OLT was 19 months (range, 2 to 120). The primary tumor was removed at the time of OLT in 11 cases, by upper abdominal exenteration in 7 cases and the Whipple resection in 3. Actuarial survival rate after OLT was 59% at 1 year, 47% at 3 years, and 36% at 5 years. Survival rates were significantly higher for metastatic carcinoid tumors (69% at 5 years) than for noncarcinoid apudomas (8% at 4 years), because of higher tumor- and non-tumor-related mortality rates for the latter. OLT can achieve control of hormonal symptoms and prolong survival in selected patients with liver metastasis of carcinoid tumors. It does not seem indicated for other NET.