Psychological impact of referral to an oncology hospital on patients with an ovarian mass.

OBJECTIVES: In patients with an ovarian mass, a risk of malignancy assessment is used to decide whether referral to an oncology hospital is indicated. Risk assessment strategies do not perform optimally, resulting in either referral of patients with a benign mass or patients with a malignant mass not being referred. This process may affect the psychological well-being of patients. We evaluated cancer-specific distress during work-up for an ovarian mass, and patients' perceptions during work-up, referral, and treatment. METHODS: Patients with an ovarian mass scheduled for surgery were enrolled. Using questionnaires we measured (1) cancer-specific distress using the cancer worry scale, (2) patients' preferences regarding referral (evaluated pre-operatively), and (3) patients' experiences with work-up and treatment (evaluated post-operatively). A cancer worry scale score of ≥14 was considered as clinically significant cancer-specific distress. RESULTS: A total of 417 patients were included, of whom 220 (53%) were treated at a general hospital and 197 (47%) at an oncology hospital. Overall, 57% had a cancer worry scale score of ≥14 and this was higher in referred patients (69%) than in patients treated at a general hospital (43%). 53% of the patients stated that the cancer risk should not be higher than 25% to undergo surgery at a general hospital. 96% of all patients were satisfied with the overall work-up and treatment. No difference in satisfaction was observed between patients correctly (not) referred and patients incorrectly (not) referred. CONCLUSIONS: Relatively many patients with an ovarian mass experienced high cancer-specific distress during work-up. Nevertheless, patients were satisfied with the treatment, regardless of the final diagnosis and the location of treatment. Moreover, patients preferred to be referred even if there was only a relatively low probability of having ovarian cancer. Patients' preferences should be taken into account when deciding on optimal cut-offs for risk assessment strategies.

Hemostatic markers in healthy postmenopausal women during intranasal and oral hormone therapy: a randomized trial.

OBJECTIVE: To study changes in the hemostatic balance during intranasal compared with oral administration of 17beta-estradiol (E2) and norethisterone (NET) or NET acetate in postmenopausal women. A wide range of markers of coagulation and fibrinolysis associated with coronary artery disease was tested. DESIGN: In a two-center, randomized, double-blind, comparative trial, 90 healthy postmenopausal women (aged 56.6 +/- 4.7 y) received daily continuous combined hormone therapy, either E2/NET 175 microg/275 mug intranasally as a spray (n = 47) or E2/NET acetate 1 mg/0.5 mg orally as a capsule (n = 43) for 1 year. Hemostatic markers were measured in blood samples taken at baseline and after 12, 24, and 52 weeks of treatment. RESULTS: After 52 weeks of treatment, changes in the intranasal group in markers of coagulation-fibrinogen (-1.3%), factor VII activity (-14.0%), and prothrombin fragment 1 + 2 (+5.8%)-were significantly less (P < 0.05) than the changes in the oral group for these parameters (-6.5%, -20.3%, and +19.0%, respectively). Changes in activated factor VII did not differ between the groups. Neither group showed significant changes in thrombin-antithrombin complex. In the intranasal group, decreases in markers of fibrinolysis-tissue-type plasminogen activator (-10.4%) and plasminogen activator inhibitor-1 antigen (-13.8%)-were significantly less (P < 0.05) than the decreases in the oral group (-17.8% and -38.0%, respectively). A decrease in plasminogen activator inhibitor-1 activity and increases in D-dimer and plasmin-alpha2-antiplasmin complex did not differ between the groups. No differences were found between the groups in homocysteine, which overall was unaltered in both groups. CONCLUSIONS: During intranasal E2/NET therapy, changes in the coagulatory and fibrinolytic markers were to some extent less than those observed during oral therapy.

Less effect of intranasal than oral hormone therapy on factors associated with venous thrombosis risk in healthy postmenopausal women.

OBJECTIVE: To compare the effects of intranasal and oral administration of 17beta-estradiol (E2) and norethisterone(acetate) [NET(A)] in healthy postmenopausal women on activated protein C (APC) resistance and other hemostatic parameters associated with venous thrombosis. METHODS AND RESULTS: In this 2-center, randomized, double-blind, 1-year trial, 90 postmenopausal women (56.6+/-4.7 years of age) received daily either an intranasal spray with 175 microg/275 microg E2/NET (n=47) or 1 mg/0.5 mg oral E2/NETA (n = 43). Normalized APC sensitivity ratios (nAPCsr) were determined with a thrombin generation-based APC resistance test. After 1 year, the increase in nAPCsr was smaller in the intranasal than in the oral group: 11% (95% CI, 1% to 22%) versus 53% (95% CI, 37% to 72%). Overall, the decrease in antithrombin and increase in prothrombin fragment 1+2 (F1+2) were smaller and the decrease in free protein S larger in the intranasal compared with the oral group after 1 year. In both groups, the decreases in protein C and prothrombin, and the increase in d-dimer were similar. CONCLUSIONS: Compared with oral E2/NETA therapy, intranasal administration of E2/NET had less effect on APC resistance and on a number of other parameters associated with venous thrombosis. This observation suggests the possibility of a lower venous thrombosis risk for intranasal E2/NET compared with oral therapy.

Effects of transdermal and oral postmenopausal hormone therapy on vascular function: a randomized, placebo-controlled study in healthy postmenopausal women.

OBJECTIVE: To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women. DESIGN: In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 microg of transdermal 17ss-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 microg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness). RESULTS: Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P < 0.01; oE2+ G, P < 0.001), sE-selectin (oE2 + G, P < 0.05), von Willebrand factor (tE2, P < 0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery. CONCLUSIONS: Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive.

Oral, more than transdermal, estrogen therapy improves lipids and lipoprotein(a) in postmenopausal women: a randomized, placebo-controlled study.

OBJECTIVE: To assess the effects of low-dose oral and transdermal estrogen therapy on the lipid profile and lipoprotein(a) [Lp(a)] levels in healthy, postmenopausal women and to study the additional influence of gestodene administration. DESIGN: In a multicenter, randomized, double-blind, placebo-controlled study, 152 healthy, hysterectomized, postmenopausal women received daily either placebo (n = 49), 50 microg transdermal 17beta-estradiol (tE2, n = 33), 1 mg oral 17beta-estradiol (oE2, n = 37), or 1 mg oE2 combined with 25 microg gestodene (oE2 + G, n = 33) for 13 cycles of 28 days, followed by 4 cycles of placebo in each group. Fasting serum concentrations of total, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, triglycerides, and Lp(a) were measured at baseline and in cycles 4, 13, and 17. RESULTS: In cycle 13, a significant mean percentage decrease from baseline was found in all treatment groups compared with placebo in total cholesterol (tE2, -4.7%; oE2, -6.9%; oE2 + G, -10.5%) and LDL cholesterol (tE2, -5.8%; oE2, -12.6%; oE2 + G, -13.6%). For both oral groups, the reductions were already significant in cycle 4. None of the treatment groups showed a significant change in HDL cholesterol or triglycerides. In cycle 13, Lp(a) was decreased compared with placebo in the oE2 group (-6.6%) and the oE2 + G group (-8.2%). After washout, all observed changes had returned to baseline level, except for the decreases in total and LDL cholesterol in the oE2 + G group. CONCLUSIONS: Oral E2 and E2 + G, and to a lesser extent transdermal E2, decreased total and LDL cholesterol. Lp(a) was lowered only by the oral treatments.

Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review.

OBJECTIVE: To review the effects of non-oral administration of postmenopausal hormone therapy (HT) on risk markers for atherosclerotic and venous thromboembolic disease.Non-oral postmenopausal HT appears not to increase venous thromboembolic risk, whereas the effect on coronary heart disease risk is less clear. DESIGN: Systematic review of literature obtained from MEDLINE, EMBASE, and CENTRAL databases from 1980 until and including April 2006. Terms for "postmenopausal hormone therapy" and for "non-oral administration" were combined in the search. SETTING: Randomized clinical trials. PATIENT(S): Postmenopausal women, both healthy and with established cardiovascular disease or specified cardiovascular risk factors INTERVENTION(S): Non-oral HT (e.g., transdermal or intranasal) compared with oral HT or no treatment/placebo. MAIN OUTCOME MEASURE(S): Lipoprotein(a), homocysteine, C-reactive protein (CRP), cell adhesion molecules, markers of endothelial dysfunction, coagulation, and fibrinolysis. RESULT(S): Seventy-two studies investigating either transdermal or intranasal administration were included. For non-oral HT, decreases in lipoprotein(a), cell adhesion molecules, and factor VII generally were significant, resistance to activated protein C (APCr) was slightly increased, and other markers including CRP and homocysteine did not change. Compared with oral HT, changes in CRP and APCr were smaller, changes in cell adhesion molecules and some fibrinolytic parameters tended to be smaller, whereas changes in other factors including lipoprotein(a) and homocysteine did not differ. CONCLUSION(S): Potentially unfavorable changes seen with oral HT on two important markers, CRP and APCr, are substantially smaller with non-oral HT. Non-oral HT has minor effects on the other cardiovascular risk markers studied. Therefore, compared with oral HT, non-oral HT appears be safer with respect to atherosclerotic and venous thromboembolic disease risk.

Effects of intranasal versus oral hormone therapy on asymmetric dimethylarginine in healthy postmenopausal women: a randomized study.

OBJECTIVE: Oral estrogens reduce asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and an independent risk factor for cardiovascular disease. This study was conducted to compare the effect on ADMA between intranasal and oral 17beta-estradiol (E2) combined with norethisterone (acetate) (NET(A)) administration in postmenopausal women. METHODS: In a two-center, randomized, double-blind, comparative study 90 healthy postmenopausal women (age 56.6+/-4.7 years) received daily continuous combined intranasal E2/NET 175 microg/275 microg (n=47) or oral E2/NETA 1 mg/0.5 mg (n=43) for one year. At baseline, week 12 and 52, plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography. RESULTS: Oral E2/NETA reduced ADMA concentrations (-7.4%; 95% confidence interval (CI) -10.4 to -4.4%), while intranasal E2/NET had no effect (-0.8%; 95% CI -3.7 to 2.1%) after 52 weeks. In both groups, arginine was transiently decreased compared to baseline at week 12 (intranasal: -6.1%; 95% CI -9.1 to -3.0%; oral: -6.5%; 95% CI -10.9 to -2.1%). Only oral E2/NETA reduced SDMA concentrations. CONCLUSIONS: Oral administration of E2/NETA reduced ADMA and SDMA concentrations, whereas intranasal administration did not. Both treatments transiently reduced arginine. The decrease in ADMA by oral estrogens could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal hormone therapy.

Intranasal continuous combined 17 beta-estradiol/norethisterone therapy improves the lipid profile in healthy postmenopausal women.

OBJECTIVE: To compare the effects of continuous combined 17beta-estradiol (E2) plus norethisterone (acetate) [NET(A)] therapy by either intranasal or oral administration on the lipid profile in postmenopausal women. DESIGN: Randomized, double-blind, multicenter trial. SETTING: Gynecologic outpatient department. PATIENT(S): Two-hundred thirty-three healthy postmenopausal women. INTERVENTION(S): Women received continuous combined hormone therapy, either intranasal E2/NET (175 microg/275 microg) as a spray (n = 117) or oral E2/NETA (1 mg/0.5 mg) as a capsule (n = 116), for 1 year. MAIN OUTCOME MEASURE(S): Fasting plasma concentrations of lipids and (apo)lipoproteins; and atherogenic indices at baseline and after 12, 24, and 52 weeks of treatment. RESULT(S): We found a significant (P < .001) decrease from baseline in both treatment groups in total, low-density lipoprotein- (LDL), high-density lipoprotein- (HDL), and HDL2-cholesterol, in triglycerides, apolipoprotein B (apoB), and lipoprotein(a). Levels of HDL3-cholesterol and apolipoprotein A1 (apoA1) were transiently decreased in the intranasal group. In the oral group, compared with the intranasal group, the decrease was larger for ratio total and LDL-cholesterol and lipoprotein(a) and smaller for triglycerides and apoA1. In the oral group, the ratios total/HDL cholesterol and LDL/HDL cholesterol were lowered, and the ratio apoB/LDL was increased, more than in the intranasal group. CONCLUSION(S): Both intranasal and oral E2/NET(A) therapy improved the lipid profile of healthy postmenopausal women, with some effects being more pronounced after oral administration.