Behaviour of some steroids in postmenopausal women with coelomic ovarian tumors

In order to study the hormonal pattern in ten postmenopausal women with coelomic ovarian tumors we measured Estrone, Androstenedione, DHEA-S and Testosterone plasmatic levels before and after surgery. Estrone and Androstenedione plasmatic levels were significantly higher in patients with coelomic ovarian tumors than in the control group and they showed a rapid and constant decrease after surgery. Nevertheless we didn't find any ovarian histological picture to explain the hormonal increase.     

Adrenal steroids, bone mineral content and endometrial pathology in postmenopausal women

In 19 postmenopausal women, basal serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone and unconjugated and total estrone were measured both before and during an ACTH test. A positive correlation was found both between basal levels of DHAS and the DHA response to ACTH, respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also observed between bone mineral content and precancerous/cancerous states of the uterine epithelium.     

Transvaginal ultrasonography and endometrial histology in peri- and postmenopausal women on hormone replacement therapy

Objective To determine the association between endometrial thickness and endometrial histology in a large sample of women using HRT.
Design Results from three multi-centre studies were combined.
Participants Five hundred and sixty-four climacteric women were treated with either sequential, continuous combined or long-cycle therapy.
Main outcome measures The women underwent 717 examinations with both transvaginal ultrasonography and histological examination of the endometrium. Endometrial thickness was measured and associated with the histological findings.
Results Eight cases of endometrial hyperplasia were diagnosed. All the hyperplasias were simple without atypia. Two cases had an endometrial thickness < 4 mm and two a thickness > 8 mm. The > 4 mm threshold for abnormal endometrium had a sensitivity of 75%, a specificity of 47%. a positive predictive value of 2% and a negative predictive value of 99%.
Conclusion No association could be found between the endometrial thickness measured by transvaginal ultrasonography and endometrial pathology. In six out of eight women with simple hyperplasia the endometrium measured > 4 mm.     

Transvaginal ultrasonography and endometrial histology in peri- and postmenopausal women on hormone replacement therapy.

OBJECTIVE: To determine the association between endometrial thickness and endometrial histology in a large sample of women using HRT. DESIGN: Results from three multi-centre studies were combined. PARTICIPANTS: Five hundred and sixty-four climacteric women were treated with either sequential, continuous combined or long-cycle therapy. MAIN OUTCOME MEASURES: The women underwent 717 examinations with both transvaginal ultrasonography and histological examination of the endometrium. Endometrial thickness was measured and associated with the histological findings. RESULTS: Eight cases of endometrial hyperplasia were diagnosed. All the hyperplasias were simple without atypia. Two cases had an endometrial thickness < 4 mm and two a thickness > 8 mm. The > 4 mm threshold for abnormal endometrium had a sensitivity of 75%, a specificity of 47%, a positive predictive value of 2% and a negative predictive value of 99%. CONCLUSION: No association could be found between the endometrial thickness measured by transvaginal ultrasonography and endometrial pathology. In six out of eight women with simple hyperplasia the endometrium measured > 4 mm.     

Plasma 20 alpha-OH-progesterone in women with malignant epithelial 'non-endocrine' ovarian tumors

The production of 20 alpha-OH-progesterone (20 alpha-OH-P) in women with malignant epithelial ovarian tumors was investigated. The study material comprised 51 postmenopausal and/or oophorectomized women with ovarian carcinoma, including the histological types Ic, IIc, IIIc and V and FIGO stages I-IV. Their tumor volumes were evaluated once a month using bimanual recto-vaginal palpation under anesthesia. Blood samples were drawn for 20 alpha-OH-P radio-immunoassay at monthly intervals for 3 months. The plasma levels were compared with those of a control group of postmenopausal women. The results show a relationship between tumor volume and plasma 20 alpha-OH-P level. Another finding is that endometrioid ovarian cancer (histologically IIIc) showed a significantly lower 20 alpha-OH-P production than the other types. The reason for this is discussed.     

Peripheral and ovarian venous concentrations of steroid and gonadotropin hormones in postmenopausal women with epithelial ovarian tumors

Peripheral serum concentrations of estrone (E1), estradiol (E2), testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), cortisol, prolactin, LH, and FSH were measured in 28 postmenopausal women with epithelial ovarian tumors (12 ovarian cancer, 5 borderline malignant, 11 benign neoplasms) and in 15 controls before bilateral salpingo-oophorectomy and 1 and 8 weeks postoperatively. The levels of these hormones were also measured in ovarian venous blood of 15 patients with ovarian tumors. E2 was significantly higher in the tumor group than in controls preoperatively and the levels of E1 and E2 decreased after radical operation. Hormone levels were similar in the benign and malignant tumor groups. Only DHEAS levels in peripheral serum were significantly lower in ovarian cancer patients than in the group with benign neoplasm. This was not the case in testosterone and androstenedione measurements. The measured levels of the hormones in ovarian venous blood were highest in mucinous ovarian tumors. E2 and testosterone levels were higher in mucinous ovarian tumors than in others. LH(hCG)-receptor levels were measured in 24 specimens and none of these showed detectable concentrations of LH(hCG) receptor. The results indicate that of all epithelial tumors mucinous ovarian tumors had hormonal activity most often, and malignancy had no effect on hormonal activity.     

Peripheral and ovarian venous concentrations of estradiol and progesterone in postmenopausal women with "non-endocrine" ovarian tumors

Estradiol (E2) and progesterone (P4) levels in peripheral venous blood were measured in 45 postmenopausal (more than 5 years after menopause) women with ovarian neoplasms. The E2 and P4 concentrations in ovarian venous blood were also measured in 26 of these 45 patients. The steroid levels were compared with the values in 10 postmenopausal women without ovarian tumors. In peripheral venous blood, relatively high E2 concentrations were found in 24 of the 45 (53%) postmenopausal patients with ovarian tumors, and relatively high P4 concentrations were noted 15 of 45 (33%) of the patients. In ovarian venous blood, relatively high values of E2 were found in 18 of 26 (69%) of the postmenopausal patients, and relatively high values of P4 were noted in 11 of these 26 (42%). No differences in the E2 and P4 levels in peripheral and ovarian venous blood were noted between the patients with benign tumors and those with malignant tumors. These results suggest that some of the epithelial ovarian tumors in postmenopausal women have steroid-producing activity.     

Estrogenization in women with postmenopausal ovarian hyperthecosis

The cases of two women who show postmenopausal bleeding and signs of endogenous estrogen production are presented. At laparotomy, ovarian hyperthecosis was found and confirmed histologically. Determination of 17 beta-estradiol concentrations in ovarian and peripheral veins suggested that these ovaries actively secreted excessive estrogens. Ovarian hyperthecosis is discussed as a cause of renewed endogenous estrogen activity in the postmenopausal women.     

Transvaginal power Doppler sonography can discriminate between benign and malignant endometrial conditions in women with postmenopausal bleeding

ObjectiveTo evaluate the role of transvaginal power Doppler sonography in differentiation between benign and malignant endometrial conditions in women with postmenopausal bleeding.SettingOB/GYN Dept., Suzan Mubarak University Hospital and Radiology Dept., Minia University Hospital, Minia University, Minia, Egypt.Study designProspective observational study.PatientsEighty patients with postmenopausal bleeding.Intervention(s)Grey scale transvaginal sonography, power Doppler study of the endometrium and endometrial-myometrial interface, and office hysteroscopy and the final diagnosis by histopathological examination of hysteroscopic guided biopsy.ResultsEndometrial power Doppler signals were positive in 69 out of the eighty patients (86.25%): 8 cases showed multiple vessel pattern -A- (10%); 19 cases with single vessel pattern -B- (23.75%); 42 cases with scattered vessel pattern -C- (52.5%) while in the remaining 11 cases (13.75%), no power Doppler signals were detected. The hysteroscopic findings were endometrial polyp in 16 cases (20%), atrophic endometrium in 14 cases (17.5%), hyperplasic endometrium in 32 cases (40%), submucus fibroid in 6 cases (7.5%), cervical polyp in 3 cases (3.75%) and suspicious endometrium for malignancy in 8 cases (10%). Hysteroscopy was more accurate in cases with intra-cavitary masses (polyps and submucous fibroids) than power Doppler, but power Doppler had a more predictive value for malignant endometrium.ConclusionPower Doppler blood flow mapping of the endometrium in women with postmenopausal bleeding is useful to discriminate carcinoma from other endometrial pathologies.     

Comparison of symptoms and presentation of women with benign, low malignant potential and invasive ovarian tumors

OBJECTIVES: To describe symptoms, delay in presentation and reasons for non-presentation among women diagnosed with benign, low malignant potential and malignant ovarian tumors. METHODS: Study participants included 457 women who underwent surgery for an ovarian tumor in Queensland, Australia, between July 1999 and February 2002 (244 with invasive cancer, 62 with low malignant potential tumors, and 151 with benign ovarian tumors). Women were contacted a minimum of three months post-diagnosis. Information concerning symptoms and presentation history was obtained via interview. RESULTS: Overall, only 8% of the women were asymptomatic at the time of their diagnosis. Women with invasive cancer reported a greater number of symptoms (3.1 and 3.6 for Stages I-II and III-IV, respectively) than women with benign or low malignant potential tumors (2.8 and 2.2 respectively; p < 0.0001). Women with invasive disease were more likely to experience weight loss or gain, general malaise, chest/respiratory pain, abdominal swelling and bowel symptoms than women with benign ovarian tumors, however the symptom pattern for early- and late-stage invasive ovarian cancer could not be clearly differentiated. There was no suggestion that women with advanced stage disease had delayed longer before presenting to their doctor. The most common reasons given for not telling their doctor about specific symptoms were the woman's perception that the symptom was not serious enough, it was mild or intermittent, or was related to normal physical changes associated with age or menopause. CONCLUSIONS: We found only marginal differences in the symptom patterns of early and advanced stage invasive cancer. Delay in presentation was not associated with more advanced disease suggesting that earlier diagnosis may not increase the proportion of cancers diagnosed at an early stage.     

Long-term survival and patterns of care in women with ovarian tumors of low malignant potential

OBJECTIVES: The objectives of this study were to ascertain long-term survival and patterns of care among women diagnosed with ovarian tumors of low malignant potential (LMP) in a population-based data set. METHODS: Using the NCI's Surveillance, Epidemiology, and End Results (SEER) database, we identified 2818 women diagnosed with ovarian tumors of low malignant potential between 1988 and 1997. RESULTS: By FIGO stage, 10-year relative survival was as follows: stage I, 99%; stage II, 98%; stage III, 96%; and stage IV 77%. One-quarter of women with stage I disease underwent partial or unilateral oophorectomy only, while women with more advanced disease commonly underwent omentectomy, unilateral or bilateral oophorectomy, and hysterectomy. Adjuvant chemotherapy was given to about 30% of women with stage III and IV disease. Radiation therapy was rarely used. We observed no significant changes in primary surgery or adjuvant treatment over time. CONCLUSIONS: The diagnosis of an ovarian tumor of LMP conveys a relatively benign prognosis. Conservative surgery should be considered in younger women with early-stage disease. There are insufficient data to support a role for adjuvant chemotherapy for women with advanced disease.     

Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors

Objective

Epithelial ovarian carcinoma (OvCa) is rarely detected early, and it is also difficult to determine whether an adnexal mass is benign or malignant. Previously, we noted differences in methylation patterns of cell-free plasma DNA (cfpDNA) in women without disease compared to patients with OvCa. In this work, we investigated whether methylation patterns of cfpDNA can differentiate between benign and malignant tumors.

Methods

Methylation patterns in cfpDNA were determined in three cohorts (30 samples each) using a microarray-based assay (MethDet 56). Principal component analysis, supervised clustering, linear discrimination analysis, and 25 rounds of 5-fold cross-validation were used to determine informative genes and assess the sensitivity and specificity of differentiating between OvCa vs. healthy control (HC), benign ovarian disease (mostly serous cystadenoma, BOD) vs. HC, and OvCa vs. BOD samples.

Results

Differential methylation of three promoters (RASSF1A, CALCA, and EP300) differentiated between OvCa vs. HC with a sensitivity of 90.0% and a specificity of 86.7%. Three different promoters (BRCA1, CALCA, and CDKN1C) were informative for differentiating between BOD vs. HC, with a sensitivity of 90.0% and a specificity of 76.7%. Finally, two promoters (RASSF1A and PGR-PROX) were informative for differentiating between OvCa vs. BOD, with a sensitivity of 80.0% and a specificity of 73.3%.

Conclusions

This proof-of-principle data show that differential methylation of promoters in cfpDNA may be a useful biomarker to differentiate between certain benign and malignant ovarian tumors.

Research Highlights

? Methylation patterns in cell-free DNA from blood can detect ovarian tumors ? These patterns are different in patients with benign and malignant tumors ? Methylation of blood DNA can be used for differential diagnosis of ovarian cancer     

Tamoxifen-induced endometrial changes in postmenopausal women with breast carcinoma.

OBJECTIVES: To assess the effects of tamoxifen (TAM) on the endometrium in postmenopausal women. METHODS: A case control study of postmenopausal women with breast carcinoma, who were undergoing treatment in the Department of Radiotherapy and Surgery at the Christian Medical College Hospital, Vellore, India was done. Thirty-five women who were on tamoxifen (20 mg/day) for a period of at least 6 months formed the study group. Thirty-three women who were not receiving tamoxifen, formed the control group. Subjects in both groups had a pelvic examination and transvaginal sonogram followed by endometrial biopsy. RESULTS: There was a statistically significant difference in the mean endometrial thickness between the study group and control group (7.8+/-6.4 mm vs. 4.0+/-2.0 mm, respectively) More women in the tamoxifen group had an endometrial thickness of >5 mm but the number of women with polyps or hyperplasia of the endometrium did not differ significantly between the two groups. There were no women with endometrial carcinoma in either group. CONCLUSION: All patients on tamoxifen need to be evaluated by clinical examination annually. A transvaginal sonogram and endometrial biopsy/hysteroscopy may be performed on patients with abnormal vaginal bleeding, bloody discharge, staining or spotting.     

Serum inhibin, activin and follistatin in postmenopausal women with epithelial ovarian carcinoma

Objective To investigate the role of serum inhibin A, inhibin pro-αC immunoreactivity, activin A, and follistatin in postmenopausal women with epithelial ovarian cancer.
Design Case-control study.
Sample Serum samples from 27 postmenopausal women with epithelial ovarian cancer and 54 controls from the general population participating in an ovarian cancer screening trial.
Results Women with epithelial ovarian cancer had significantly higher serum levels of pro-αC immunoreactivity (   P = 0.03  ), activin A (   P = 0.004  ) and follistatin (   P = 0.04  ), but not inhibin A (   P = 0.13  ). Using the 90th centile in the control group as the cut off, pro-αC levels were elevated in 41% of women with epithelial ovarian cancer, while inhibin A was elevated in only 15%. Using the 95th centile as the cut off, serum pro-αC was elevated in only 11% of women with epithelial ovarian cancer (3/27), while activin A was elevated in 48% (11/23). Follicle stimulating hormone levels were significantly lower in women with epithelial ovarian cancer (   P = 0.01  ). Although, inhibin-related peptides can modulate follicle stimulating hormone levels, there was no correlation between inhibin A, pro-αC immunoreactivity, activin A or follistatin and follicle stimulating hormone.
Conclusion These data demonstrate that though there is preferential secretion of precursor forms of the α subunit rather than dimeric inhibin A by epithelial ovarian cancer, pro-αC is unlikely to be a useful tumour marker. Activin A is more commonly elevated in postmenopausal women with epithelial ovarian cancer and its role as a tumour marker in the diagnosis and screening of epithelial ovarian cancer warrants further evaluation.