Colposcopy telemedicine: live versus static swede score and accuracy in detecting CIN2+, a cross-sectional pilot study.

BACKGROUND: This cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or equal to grade 2 severity (CIN2+). METHODS: VIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation. RESULTS: 495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2-95.0%) and 84.6% (95% CI 54.6-98.1%), for live- and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7-98.1%) and 92.6% (95% CI 75.7-99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors. CONCLUSIONS: Swede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available. TRIAL REGISTRATION: Ethical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014). The trial was retrospectively registered in the Clinical Trails Registry of India CTRI/2018/03/012470 .

Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration.

OBJECTIVE: The aim of the study was to assess the risk of venous thromboembolism (VTE) associated with systemic hormone therapy according to type and to route of administration and the risk of VTE associated with locally administered estrogen. METHODS: In this case-control study, conducted in Sweden between 2003 and 2009, we included 838 cases of VTE and 891 controls with a mean age of 55 years. Controls were matched by age to the cases and randomly selected from the population. We used logistic regression to calculate odds ratios (ORs) with 95% CIs and adjusted for smoking, body mass index, and immobilization. RESULTS: Current use of any hormone therapy was associated with an increased risk of VTE (OR 1.72, 95% CI 1.34-2.20). For estrogen in combination with progestogen the OR was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78-2.21). In orally administered estrogen combined with progestogen, the OR was slightly, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR 2.55, 95% CI 1.50-3.40). Transdermal estrogen combined with progestogen was not associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16). For local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI 0.43-1.10). CONCLUSIONS: The risk of VTE risk is higher in users of systemic combined estrogen-progestogen treatment than in users of estrogen only. Furthermore, the risk of VTE was lower for women who used local estrogen than among those using oral estrogen only. Transdermal estrogen only treatment and estrogen for local effect seem not to be related to an increased risk of VTE.

Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.

Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 µg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders.

Cognitive function in association with sex hormones in postmenopausal women.

Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.

A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women.

OBJECTIVE: To test the causal relationship between sex hormones and cognitive skills in postmenopausal women. We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo. For estrogen, we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group trial. SETTING: Women's health clinical research unit at a university hospital. PATIENT(S): Two-hundred healthy, naturally postmenopausal women aged 50-65 years. INTERVENTION(S): Randomization to 4 weeks' treatment with testosterone (testosterone undecanoate, 40 mg/day), estrogen (oral E2 2 mg/day) or placebo. MAIN OUTCOME MEASURE(S): Comparisons in verbal fluency, verbal memory, and spatial ability between the three treatment groups. RESULT(S): We found no significant effects of testosterone or estrogen on verbal fluency, verbal memory, or spatial ability. CONCLUSION(S): Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency, verbal memory, or spatial ability in healthy postmenopausal women.

Testosterone addition to estrogen therapy - effects on inflammatory markers for cardiovascular disease.

OBJECTIVE: To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women. METHODS: Fifty surgically postmenopausal women were included in this double-blind, placebo-controlled and randomized study to receive daily oral treatment with estradiol valerate 2 mg + placebo (E/P) or estradiol valerate 2 mg + testosterone undecanoate 40 mg (E/T) for 24 weeks and then switched to the other regimen for another 24 weeks. Sex hormones, High sensitivity CRP (hsCRP), Interleukin-6 (IL-6), Tissue necrosis factor (TNF)-alpha, Insulin-like growth factor binding globulin (IGFBP-1), vascular cell adhesion molecule (VCAM)- 1, and homocysteine were analyzed at baseline and after 6 and 12 months. RESULTS: Estradiol and androgens increased as expected during the treatments. After 6 months of E/P, increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded, whereas IL-6, TNF-alpha, and homocysteine were unchanged. When testosterone was added to estrogen, the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone. However, testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6, TNF-alpha, and homocysteine. CONCLUSION: Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects. On the contrary, the estrogen-induced increase in hsCRP was suppressed.

A randomized trial of the effect of estrogen and testosterone on economic behavior.

Existing correlative evidence suggests that sex hormones may affect economic behavior such as risk taking and reciprocal fairness. To test this hypothesis we conducted a double-blind randomized study. Two-hundred healthy postmenopausal women aged 50-65 years were randomly allocated to 4 weeks of treatment with estrogen, testosterone, or placebo. At the end of the treatment period, the subjects participated in a series of economic experiments that measure altruism, reciprocal fairness, trust, trustworthiness, and risk attitudes. There was no significant effect of estrogen or testosterone on any of the studied behaviors.

Insulin-like growth factor binding protein-1 and interleukin-6 are markers of fetal stress during parturition at term gestation.

OBJECTIVE: Maintaining an adequate blood glucose level is essential for neuron integrity. The increased energy demand imposed on the fetus by the birth process in combination with a limited glucose production capacity therefore threatens brain function. It is logical to presume that mechanisms increasing glucose mobilization as well as decreasing peripheral glucose utilization has evolved to preserve brain function, even after complicated deliveries. DESIGN: We studied umbilical cord levels of hormones involved in acute glucose regulation as well as insulin-like growth factor-I (IGF-I), modulating factors insulin-like growth factor binding protein (IGFBP)-1 and -3 as well as interleukin-6 (IL-6) in 149 infants born after different degrees of birth stress. We measured glucose, insulin, IGF-I, IGFBP-1, IGFBP-3, glucagon, growth hormone (GH), prolactin, adrenocorticotropin (ACTH), cortisol and IL-6 in umbilical cord blood of infants born at term gestation after: A) elective Cesarean-section (n = 37), B) normal delivery (n = 87) or C) complicated delivery (n = 25). All infants were of normal birth weight for gestational age. Arterial pH and lactate as well as S-100B, a marker of neuronal damage, were used as stress variables. RESULTS: With increasing fetal stress, we found significant and generally progressive elevations in glucose, IGFBP-1, IL-6, ACTH, cortisol, glucagon, GH, prolactin and lactate. This was accompanied by significant decreases of IGF-I, insulin and arterial pH. S-100B and IGFBP-3 levels did not differ between groups. IGFBP-1 showed a significant positive correlation to IL-6 and lactate and a significant negative correlation to both IGF-I and arterial pH. CONCLUSIONS: Increasing stress and energy demands during birth are accompanied by increasing fetal levels of glucose-mobilizing hormones in combination with depressed levels of insulin and IGF-I, despite increasing blood glucose. Furthermore, IGFBP-1 and IL-6 increase steeply, presumably aimed at diminishing insulin-like activity of IGF-I, thereby reducing peripheral glucose utilization. We believe that IGFBP-1 and IL-6 deserve evaluation as potential intrapartum indicators of fetuses at risk for asphyxia.