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Biomedical subjects

M Savvas

Publications and source records attributed to M Savvas.

At least 19 recordsLinked to original sources

Prospective evaluation of logistic regression models for the diagnosis of ovarian cancer.

OBJECTIVE: To test the accuracy of three logistic regression models in diagnosing malignancy in women with adnexal masses. METHODS: This was a prospective collaborative study. Women were recruited from three hospitals and all assessments were performed at the Gynaecology Ultrasound Unit, King's College Hospital. One hundred women with known adnexal masses were examined preoperatively. The demographic, biochemical, and sonographic data recorded for each patient included age, menopausal status, CA 125 levels, ultrasound morphology, and Doppler blood flow analysis. The diagnosis of malignancy was made for each woman using three logistic regression models previously described by Alcazar et al, Tailor et al, and Timmerman et al. Variables used in these models were then combined to form a new model. The results were compared with the final histopathologic diagnosis. RESULTS: Sixty-seven women had benign tumors and 33 had ovarian cancer. Women with malignant tumors were older than those with benign masses. There were significant differences in CA 125 levels, presence of papillary proliferations, and ascites between the two groups. The sensitivities and specificities achieved respectively by the models were as follows: 45% and 93% with Tailor et al's model, 9% and 99% with Alcazar et al's model, and 73% and 91% with Timmerman et al's model. There was no significant improvement over the performance of Timmerman et al's model and the new combined model. CONCLUSION: All models performed less well than originally reported. Combining the models did not lead to a significant improvement in performance. Larger sample sizes that incorporate all types of ovarian tumors are necessary to design more accurate diagnostic models.

Adult↗

A comparison of 25 mg and 50 mg oestradiol implants in the control of climacteric symptoms following hysterectomy and bilateral salpingo-oophorectomy.

OBJECTIVES: 1. To compare the effects of 25 mg and 50 mg oestradiol implants on serum follicle stimulating hormone and oestradiol levels; and 2. to assess the relationship of the dose of oestradiol implant and serum oestradiol on the effectiveness and duration of climacteric symptom control. DESIGN: Randomised, double-blind investigation. PARTICIPANTS: Forty-four women, who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy. METHODS: The women were randomised to receive either 25 mg (n = 20) or 50 mg (n = 24) oestradiol implants. Follow up consisted of prospective symptom enquiry and hormone assays. MAIN OUTCOME MEASURES: Primary: climacteric symptom control: duration and effectiveness; secondary: serum oestradiol and follicle stimulating hormone levels. RESULTS: Serum oestradiol was significantly higher and serum follicle stimulating hormone significantly lower after the fourth month of treatment in women receiving 50 mg implants. No significant difference in symptom control was noted in the two groups. The mean duration of symptom control was similar in the two groups: 5.9 months (SD 2.4) in those receiving 50 mg oestradiol and 5.6 months (SD 2.3) in those receiving 25 mg. CONCLUSION: The higher level, 50 mg oestradiol implants does not result in better control of symptoms nor in longer periods of symptom control compared with 25 mg oestradiol implants. In order to maximise compliance, 25 mg oestradiol implants should therefore be the treatment of choice for women with normal bone density seeking relief of climacteric symptoms.

Climacteric↗

Prospective evaluation of three different models for the pre-operative diagnosis of ovarian cancer.

OBJECTIVE: To test the accuracy of the risk of malignancy index, the revised risk of malignancy index and Tailor's regression model to diagnose malignancy in women with known adnexal masses. DESIGN: Prospective collaborative study. SETTING: Gynaecology Assessment Unit, Department of Obstetrics and Gynaecology, King's College Hospital, London. SAMPLE: Sixty-one women with known adnexal masses were examined pre-operatively. Women were recruited from three South London hospitals. METHODS: The demographic, biochemical and sonographic data recorded for each patient included: age; menopausal status; CA125 levels; tumour volume; ultrasound characteristics; and Doppler blood flow analysis (peak and mean blood velocities, the pulsatility and resistance indices). The diagnosis of malignancy was made for each woman using all three models and the results compared with the final histopathological diagnosis. RESULTS: Thirty-eight women had benign tumours and 23 had ovarian cancer. Women with malignant tumours were significantly older than those with benign masses. There were also significant differences in CA125 levels, locularity, presence of papillary proliferations and ascites between the two groups. Tailor's regression model achieved a 43% sensitivity and 92% specificity in the diagnosis of malignancy. This compared with a 74% sensitivity and 92% specificity with the risk of malignancy model, and a 74% sensitivity and 89% specificity with the revised risk of malignancy model. CONCLUSION: When applied prospectively all three diagnostic models performed less accurately than originally reported, despite clinical signs of malignancy being present in many cases. It is likely that their accuracy would be even less in a population of women in whom there was a substantial clinical uncertainty. Intra-tumoral blood velocity and CA125 levels were the best individual parameters for discrimination between benign and malignant tumours.

Adult↗

The diagnostic value of endometrial thickness and volume measurements by three-dimensional ultrasound in patients with postmenopausal bleeding.

We compared endometrial thickness and volume in patients with postmenopausal bleeding, and examined the value of each parameter in differentiating between benign and malignant endometrial pathology. A total of 103 patients with a history of postmenopausal bleeding were recruited into the study. Patients who were taking hormone replacements therapy or other hormonal preparations with a known effect on the endometrium were excluded. Each patient underwent three-dimensional ultrasonography for the measurement of endometrial thickness and volume. In 97 cases both of these measurements were obtained and the results were compared to the histological diagnosis after endometrial biopsy or dilatation and curettage. Endometrial cancer was diagnosed in 11 patients. The mean endometrial thickness was 29.5 mm (SD 12.59) and the mean volume was 39.0 ml (SD 34.16). In the remaining 86 patients there were eight cases with endometrial hyperplasia and seven with endometrial polyps. The endometrial thickness and volume in patients with benign pathology was 15.64 mm (SD 5.26) and 5.47 ml (SD 6.32), respectively. In 71 patients with atrophic or normal endometrium the mean thickness and volume was 5.29 mm (SD 3.97) and 0.91 ml (SD 1.71), respectively. Receiver operating characteristic curves showed endometrial volume to be superior to endometrial thickness for the diagnosis of endometrial cancer. The optimal cut-off value of endometrial thickness for the diagnosis of cancer was 15 mm, with the test sensitivity of 83.3% and positive predictive value of 54.5%. With the cut-off level of 13 ml for endometrial volume measurement the sensitivity was 100% and the positive predictive value 91.7%. Both the thickness and volume were higher in patients with advanced and less differentiated cancers. The measurements of endometrial volume was superior to that of endometrial thickness as a diagnostic test for the detection of endometrial cancer in symptomatic postmenopausal women.

Aged↗

Bone loss after hysterectomy with ovarian conservation.

OBJECTIVE: To examine the long-term effects of hysterectomy with conservation of the ovaries on bone density of the lumbar spine and proximal femur. METHODS: A cross-sectional study of the bone density of 40 postmenopausal women who had undergone hysterectomy with ovarian conservation before menopause compared with a matched group of 40 women who had not had hysterectomy. The 40 women who had undergone hysterectomy were also compared with a control population, using multiple linear regression analysis. Bone density of the femoral neck and lumbar spine was measured by quantitative digital radiography. RESULTS: Bone density in the hysterectomy group was significantly reduced at the spine (P < .05) and at the femoral neck (P < .05) compared with the matched group. Comparisons of the hysterectomy group with the reference group demonstrated that in addition to significant reductions in bone density at the spine (P < .05) and hip (P < .05), bone density at the femoral neck (P < .05), trochanter (P < .05), Ward's triangle (P < .05), and the second (P < .05) and fourth (P < .05) lumbar vertebrae was also significantly less in the hysterectomy group. CONCLUSION: Premenopausal women who have hysterectomy will have significantly lower bone density than controls, despite conservation of both ovaries at the time of surgery.

Aged↗

Type III collagen content in the skin of postmenopausal women receiving oestradiol and testosterone implants.

OBJECTIVE: To investigate the effect of subcutaneous oestradiol and testosterone on the proportion of type III collagen in the skin of postmenopausal women. DESIGN: A cross sectional comparison. SETTING: Dulwich Hospital menopause clinic. SUBJECTS: Fourteen untreated women and 11 women who had received subcutaneous oestradiol and testosterone for a median 8.0 years (range 3-14). Ten of the untreated women received subcutaneous hormone implants and the effect on skin collagen was studied prospectively. MEASUREMENTS: The proportion of type III collagen in skin biopsies taken from the lateral aspect of the thigh. RESULTS: The median type III collagen content in the skin of the women who had received hormone replacement therapy (25.4%, range 21.4-30.2) was significantly higher (P < 0.01) than in the untreated women (19.6%, range 18.2-28.8). The proportion of type III collagen in the skin of 10 untreated women increased significantly (P < 0.01) from a median of 19.9% (range 18.2-23.9) to 22.4% (range 20.5-31.5) following 6 months of treatment with hormone implants. CONCLUSION: This study indicates an increase in the proportion of type III collagen in women receiving hormone replacement therapy.

Adult↗

Increase in bone mass after one year of percutaneous oestradiol and testosterone implants in post-menopausal women who have previously received long-term oral oestrogens.

OBJECTIVE: To determine the effect on the bone density of the skeleton after changing from oral oestrogen to subcutaneous oestradiol and testosterone replacement. DESIGN: Prospective non-randomized single centre study. SUBJECTS: Twenty women who were receiving long-term oral oestrogen replacement. Ten changed to oestradiol and testosterone implants; the remaining ten continued with oral oestrogens. MAIN OUTCOME MEASURES: Bone density was measured using dual photon absorptiometry at the lumbar spine and neck of femur at the start of the study and after one year. RESULTS: The bone density increased significantly by 5.7% at the spine and by 5.2% at the neck of femur in those women who changed to implant therapy but remained unchanged in those women who continued with oral therapy. CONCLUSION: Subcutaneous oestradiol and testosterone implants will result in an increase in bone mass even after many years of oral oestrogen replacement therapy.

Administration, Cutaneous↗

The effects of plasma estradiol levels on increases in vertebral and femoral bone density following therapy with estradiol and estradiol with testosterone implants.

Percutaneous estradiol (E2) implants effectively preserve bone density in postmenopausal women. However, these implants are often given with testosterone, which may itself have an anabolic effect on bone. To determine whether testosterone confers any additional bone-sparing effect, we studied 50 postmenopausal women randomly allocated to receive E2 (75 mg) alone or with testosterone (100 mg) every 6 months for 1 year. Women with an intact uterus received cyclic norethindrone (5 mg) for 10 days of each calendar month. Twenty-five untreated women were recruited to act as a reference group. Bone density was measured at the lumbar spine and proximal femur by dual x-ray densitometry. By 1 year, bone density at the lumbar spine had fallen by 1.8% in the reference group. In the women treated with E2 alone, it increased significantly by 7.8% (P less than .0001) and in those receiving E2 with testosterone, it increased by 6.3% (P less than .0001). At the femoral neck, bone density decreased by 3% in the controls and increased by approximately 4% in both treated groups (P less than .0001). The increase in bone density at these sites was unrelated to the woman's chronological age, menopausal age, or initial bone density. However, it correlated significantly with the serum E2 levels attained after 1 year of therapy. In no treated patients did bone density decrease significantly. These data show that testosterone confers no additional bone-sparing effect in postmenopausal women.

Bone Density↗

Endometrial histology and bleeding patterns after 8 years of continuous combined estrogen and progestogen therapy in postmenopausal women.

Continuous combined estrogen and progestogen preparations enable the postmenopausal woman to enjoy the benefits of estrogen replacement without the inconvenience of regular progestogen-induced withdrawal bleeding. The endometrium appears to be adequately protected in the short term, but no published data are available on the bleeding patterns or endometrial response after more than 18 months of therapy. Therefore, we reviewed 41 patients who continued on such preparations for up to 10 years (mean duration of use 8.0 years). Six women had experienced episodes of breakthrough bleeding after achieving amenorrhea, two of whom had benign endometrial polyps and two with adenocarcinoma of the endometrium. The remaining 35 women each had prolonged amenorrhea and were found to have an atrophic inactive endometrium. It is too early to comment on the long-term endometrial effects of these preparations because the numbers are too small; however, any breakthrough bleeding occurring after a period of prolonged amenorrhea must be investigated by means of endometrial biopsy.

Drug Therapy, Combination↗

A cross-sectional study of the effects of long-term percutaneous hormone replacement therapy on bone density.

The effect of hormone implants on the bone density of postmenopausal women was studied in 110 patients (mean age 54.7 years; mean menopausal age 8.6 years, range 2-30) who had received hormone replacement in the form of estradiol (50-75 mg) and testosterone (100 mg) pellets at 6-month intervals for 2-24 years (mean 5.2). They were compared with 254 untreated women (mean age 55.0 years; mean menopausal age 6.8 years, range 1-37). The bone density at the spine, measured by quantitative digital radiography, was 1.123 grams hydroxyapatite (gHa)/cm2 in the treated group and 0.951 gHa/cm2 in the controls (P less than .0001). The total bone density at the proximal femur was 1.002 gHa/cm2 in the treated group, compared with 0.914 gHa/cm2 in the controls (P less than .0001). There were significant differences in the density of the trochanteric, intertrochanteric, and neck areas of the proximal femur as well as the Ward triangle (all P less than .0001). These differences became significant from the age of 55 at the neck of the femur, Ward triangle, and lumbar spine, and from age 60 for all other values. Subcutaneous estradiol and testosterone prevent postmenopausal osteoporosis and maintain normal bone density for as long as treatment is continued.

Adult↗

The relationship between plasma estradiol and the increase in bone density in postmenopausal women after treatment with subcutaneous hormone implants.

Twenty-three postmenopausal women with a median of 2 years past menopause (range, 1 to 12 years) and a median age of 52 years (range, 39 to 62 years) were recruited to participate in a longitudinal study designed to investigate the factors that influence the increase in bone density with subcutaneous estradiol and testosterone implants. All women received 75 mg of estradiol with 100 mg testosterone subcutaneously. Bone density was measured at the spine and hip by dual-photon absorptiometry before therapy and after 1 year of subcutaneous hormonal therapy. The mean pretreatment bone density at the lumber vertebrae and neck of the femur was 0.84 grams of hydroxyapatite per square centimeter (SD, 0.11) and 0.73 grams of hydroxyapatite per square centimeter (SD, 0.10), respectively. The bone density at both sites increased with values of 0.91 grams of hydroxyapatite per square centimeter (SD, 0.11) and 0.75 grams of hydroxyapatite per square centimeter (SD, 0.11), respectively. These values represent an increase of 8.3% (p less than 0.0001) at the spine and 2.8% (p less than 0.01) at the neck of the femur. The plasma estradiol level increased from a median of 80.5 pmol/L to 453 pmol/L (p less than 0.001). The percentage increase of vertebral bone density was not related to age, number of years past the menopause, pretreatment bone density, or serum testosterone levels, but a significant correlation was found between the percentage increase in bone density at the spine and the serum estradiol level (p less than 0.02, r = 0.45).

Adult↗

Hormone implants and tachyphylaxis.

The serum oestradiol levels of 1388 women treated with hormone implants at a menopause clinic were reviewed in 1988. Thirty-eight (3%) were found to be above 1750 pmol/l. Of these 38 women with supraphysiological oestradiol levels 23 had started therapy for menopausal symptoms and 15 for the premenstrual syndrome (PMS). Of the 23 women treated for menopausal symptoms 11 had a history of psychiatric referral for depression and nine had undergone a surgical menopause. Nine of the 15 women with PMS had a history of psychiatric referral for depressive symptoms. We conclude that the women who attain supraphysiological levels of oestradiol on implant therapy have a high frequency of psychopathology or surgical menopause and may require higher oestradiol levels for adequate control of symptoms.

Adult↗

The long-term effects of estradiol implant therapy for the treatment of premenstrual syndrome.

Fifty patients receiving estradiol implants for long-term treatment of premenstrual syndrome were studied over 5.6 years (range 2-8 years). There was a continued beneficial response to treatment in all symptoms, varying between 74% for bloating and 96% for depression. Menstrual cycle control improved in 31 patients and periods were less painful in 30 patients. Cyclical progestogenic symptoms occurred in 58% of patients. These were partially relieved by alterations in dose, type and duration of progestogen treatment but in 7 patients the symptoms remained severe. Eight patients had a hysterectomy during treatment; 5 for continuing progestogenic symptoms, 1 for prolapse and 2 for prolonged menstrual bleeding despite adequate progestogen therapy. Attempts to reduce the dose of progestogen led to cystic hyperplasia in 4 patients. This was treated by hysterectomy in 2 patients and corrected with two 21-day courses of progestogen in the other 2. Uterine enlargement with a mean weight of 133 g (125-145 g) associated with myometrial hypertrophy occurred in all 8 hysterectomy patients. There were no complications form venous thrombosis, pulmonary embolus, breast disease or atypical endometrial hyperplasia.

Adult↗

Treatment of severe premenstrual syndrome with oestradiol patches and cyclical oral norethisterone.

40 patients with premenstrual symptoms were randomly allocated to receive placebo patches or active treatment with transdermal oestradiol patches (2 x 100 micrograms) to suppress ovulation. Norethisterone 5 mg was given in each group from day 19-26 of the cycle to ensure a regular withdrawal bleed. Treatment was for 6 months with crossover at 3 months. Patients completed the Moos menstrual distress questionnaire (MDQ) and the premenstrual distress questionnaire (PDQ) daily throughout the study. 5 patients withdrew, 4 because of skin reactions and 1 because of considerable improvement with initial (active) treatment. After 3 months, both groups showed improvement in MDQ and PDQ scores. In general, between 3 and 6 months, patients who switched from active treatment to placebo had deteriorating scores while patients who switched from placebo to active treatment maintained or improved upon their initial gains. Significant improvements occurred after changing to active treatment in five of six negative MDQ symptom clusters and in six of ten PDQ symptoms.

Administration, Cutaneous↗