Reduced breast cancer incidence in women treated with subcutaneous testosterone,or testosterone with anastrozole: A prospective,observational study

Objectives

There is evidence that androgens are breast protective and that testosterone therapy treats many symptoms of hormone deficiency in both pre and postmenopausal patients. However, unlike estrogen and progestins, there is a paucity of data regarding the incidence of breast cancer in women treated with testosterone therapy. This study was designed to investigate the incidence of breast cancer in women treated with subcutaneous testosterone therapy in the absence of systemic estrogen therapy.

Study design

This is a 5-year interim analysis of a 10-year, prospective, observational, IRB approved study investigating the incidence of breast cancer in women presenting with symptoms of hormone deficiency treated with subcutaneous testosterone (T) implants or, T combined with the aromatase inhibitor anastrozole (A), i.e., T + A implants. Breast cancer incidence was compared with that of historical controls reported in the literature, age specific Surveillance Epidemiology and End Results (SEER) incidence rates, and a representative, similar age group of our patients used as a ‘control’ group. The effect of adherence to T therapy was also evaluated.

Results

Since March 2008, 1268 pre and post menopausal women have been enrolled in the study and eligible for analysis. As of March 2013, there have been 8 cases of invasive breast cancer diagnosed in 5642 person-years of follow up for an incidence of 142 cases per 100 000 person-years, substantially less than the age-specific SEER incidence rates (293/100 000), placebo arm of Women's Health Initiative Study (300/100 000), never users of hormone therapy from the Million Women Study (325/100 000) and our control group (390/100 000). Unlike adherence to estrogen therapy, adherence to T therapy further decreased the incidence of breast cancer (73/100 000).

Conclusion

T and/or T + A, delivered subcutaneously as a pellet implant, reduced the incidence of breast cancer in pre and postmenopausal women. Evidence supports that breast cancer is preventable by maintaining a T to estrogen ratio in favor of T and, in particular, by the use of continuous T or, when indicated, T + A. This hormone therapy should be further investigated for the prevention and treatment of breast cancer.     

Effects of tibolone and conventional HRT on the expression of estrogen and progesterone receptors in the breast

ObjectiveThere is evidence that long-term hormone replacement therapy (HRT) is associated with an increased breast cancer risk. The aim of this study was to assess the effects of tibolone on estrogen and progesterone receptors in comparison to the effects of conventional HRT in the breast of surgically postmenopausal macaques.MethodSixty macaques were bilaterally ovariectomized 3 months before hormonal treatment was initiated. The animals were randomized into four treatment groups, including tibolone (TIB), conjugated equine estrogens (CEE), conjugated equine estrogens + medroxyprogesterone acetate (CEE + MPA) and control animals (C). After 2 years treatment, breast tissues were collected, fixed and paraffin embedded. Immunohistochemistry assays with monoclonal antibodies for estrogen receptors (ERα and ERβ) and progesterone receptors (PRA and PRB) were performed.ResultsThe expression of ERα was markedly decreased in the CEE + MPA group as compared to C and TIB groups. The TIB group was not different from the C and CEE groups. No significant differences were found for ERβ immunostaining. The expression of PRA was strongly increased in the TIB group as compared to the C and CEE + MPA groups. Immunostaining of PRB was increased in the CEE and TIB treated animals as compared to both C and CEE + MPA groups.ConclusionsTibolone increased the expression of both PRA and PRB, without affecting ERα and ERβ expression in the macaque breast. These findings indicate that the effects of tibolone in breast tissue could be mediated via differential regulation of PRA and PRB isoforms and therefore distinct from those observed with conventional HRT.     

The effect of testosterone alone and testosterone + estradiol therapy on bladder functions and smooth muscle/collagen content in surgically menopause induced rats

ObjectivesThe aim of the study was to investigate the effect of testosterone alone and testosterone + estradiol therapy on bladder functions and smooth muscle/collagen content in surgically menopause induced rat model.MethodsThe study included 34 female Sprague-Dawley rats, and the rats were divided into four groups. After bilateral oophorectomy, during a 60 days period, six rats received IM saline injection for one time, as a control group, and nine rats received testosterone undecanoate 100 mg/kg IM for one time, and nine rats received testosterone undecanoate 100 mg/kg IM for one time + daily 0.50 mg nasal spray of 17β estradiol. Ten rats were taken as sham group. Urodynamic studies were performed in all groups before and after the study. The rats were sacrificed after 60 days, and cystometric findings and smooth muscle/collagen ratio of the bladders were compared between the groups.ResultsIncrease in maximal bladder capacity and compliance were significantly higher in the testosterone treatment group and testosterone + estradiol treatment group than in the control group (p = 0.01 and p = 0.002, respectively for bladder capacity; p = 0.04 and p = 0.005, respectively for bladder compliance). Smooth muscle/collagen ratio of the bladders was significantly higher in the testosterone and testosterone + estradiol treatment groups than in the control group (p = 0.04 and p = 0.008, respectively).ConclusionsThis study shows that bladder functions may deteriorate in postmenopausal period. In addition to estrogen replacement therapy, testosterone has a significant role to increase bladder smooth muscle, leading to improvement in bladder functions in postmenopausal women with urogenital system dysfunction.     

Effect of a decision aid with patient narratives in reducing decisional conflict in choice for surgery among early-stage breast cancer patients: A three-arm randomized controlled trial

ObjectiveWe aimed to evaluate the effect of a decision aid (DA) with patient narratives on decisional conflict in surgery choice for Japanese women with early-stage breast cancer.MethodsTwo hundred ten women with early-stage breast cancer were randomly assigned to an intervention or control group. Groups 1 and 2 received standard information and a DA, with or without patient narratives, and Group 3 received standard information (control) before surgery choice. At baseline, post-intervention (Time 2), and 1 month after surgery (Time 3), we evaluated decisional conflict as the primary outcome using a decisional conflict scale (DCS). Sidak corrections for multiple comparisons in analysis of covariate were used to compare Time 2 and Time 3 DCS mean scores between each pair of groups.ResultsAt Time 3, decisional conflict was significantly reduced for Group 1 vs control (P = 0.021, Cohen’s d  = 0.26) and Group 2 vs control (P = 0.008, Cohen’s d = 0.40).ConclusionThe DAs with and without patient narratives are equivalently effective at reducing postoperative decisional conflict in Japanese women with early-stage breast cancer.Practice implicationsThe DAs with and without patient narratives can be used in clinical practice for women with early-stage breast cancer.     

Testosterone implants in women: Pharmacological dosing for a physiologic effect

ObjectivesThe objectives of this study were to determine therapeutic serum testosterone (T) levels/ranges and inter-individual variance in women treated with subcutaneous T implants.Study designIn study group 1, T levels were measured at two separate time intervals in pre- and post-menopausal women treated with subcutaneous T for symptoms of androgen deficiency: (i) four weeks after pellet insertion, and (ii) when symptoms of androgen deficiency returned.In a separate pharmacokinetic study (study group 2), 12 previously untreated postmenopausal women each received a 100 mg T implant. Serum T levels were measured at baseline, 4 weeks and 16 weeks following T pellet implantation.In study ‘group’ 3, serial T levels were measured throughout a 26 h period in a treated patient.ResultsIn study group 1, serum T levels measured at ‘week 4’ (299.36 ± 107.34 ng/dl, n = 154), and when symptoms returned (171.43 ± 73.01 ng/dl, n = 261), were several-fold higher compared to levels of endogenous T. There was significant inter-individual variance in T levels at ‘week 4’ (CV 35.9%) and when symptoms returned (CV 42.6%). Even with identical dosing (study group 2), there was significant inter-individual variance in T levels at ‘week 4’ (CV 41.9%) and ‘week 16’ (CV 41.6%). In addition, there was significant intra-individual circadian variation (CV 25%).ConclusionsPharmacologic dosing of subcutaneous T, as evidenced by serum levels on therapy, is needed to produce a physiologic effect in female patients. Safety, tolerability and clinical response should guide therapy rather than a single T measurement, which is extremely variable and inherently unreliable.     

Associations between the number of natural teeth in postmenopausal women and hormone replacement therapy

ObjectivesIncreasing research suggests that periodontal status is associated with hormone replacement therapy in postmenopausal women. This study was performed to assess the relationship between the number of natural teeth and ever use of hormone replacement therapy in postmenopausal women using nationally representative Korean data.MethodsData from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to a total of 4869 respondents over 19 years old who had gone through menopause and who had no missing data for the reproductive factors and outcome variables in that study. The total number of natural teeth was then calculated after excluding third molars. The time of day when tooth brushing was done was recorded as representative oral health behavior. Multiple logistic regression analyses were used to assess association between the number of natural teeth and the use of hormone replacement therapy.ResultsAmong participants who had ever used hormone replacement therapy, the proportions (percentage and standard error) with no teeth, 1–9 teeth, 10–19 teeth, 20–27 teeth, and 28 teeth were 5.0 ± 2.4%, 6.7 ± 1.4%, 12.5 ± 1.7%, 18.9 ± 1.0%, and 20.7 ± 1.6%, respectively (P < 0.05). The adjusted odds ratio and 95% confidence interval for having fewer than 20 teeth <20 was 0.624 [0.464–0.840] for the individuals using hormone replacement therapy, after adjustments.ConclusionsThe analysis revealed that the use of hormone replacement therapy by postmenopausal women showed positive effects for retention of natural teeth. Lack of hormone replacement therapy may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women.     

Predictors of adherence to follow-up recommendations after an abnormal Pap smear among underserved inner-city women

ObjectivesThis study aimed to identify cognitive-affective predictors of adherence to initial diagnostic colposcopy and 6-month follow-up recommendations among underserved women.MethodsA secondary data analysis was completed of a randomized clinical trial assessing tailored telephone counseling for colposcopy adherence after an abnormal screening Pap smear among 210 underserved inner-city women.ResultsAdherence to initial diagnostic colposcopy was significantly associated with greater self-efficacy (OR = 1.504, 95% CI 1.021–2.216). Women with lower monitoring attentional style had significantly greater adherence to 6-month follow-up recommendations compared to women with higher monitoring scores (OR = 0.785, 95% CI 0.659–0.935).ConclusionIncreasing cervical cancer-related self-efficacy and tailoring cervical cancer risk communication to monitoring attentional style may help improve adherence to follow-up recommendations after an abnormal Pap smear test result.Practice implicationsFuture research is needed to develop and implement psychosocial approaches to improving adherence to diagnostic colposcopy and follow-up recommendations adherence among underserved women.     

Bioidentical compounded hormones: A pharmacokinetic evaluation in a randomized clinical trial

ObjectiveBioidentical compounded hormone therapy is popular among patients, but providers do not have pharmacokinetic information or dosing guidelines for these preparations. Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice.MethodsWe conducted a randomized, blinded, four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream (Bi-est (80:20); 2.0, 2.5, or 3.0 mg) + compounded oral progesterone 100 mg, or to a conventional estradiol patch (Vivelle-Dot? 0.05 mg) + Prometrium? 100 mg. Serum levels of estrone, estradiol, estriol, and progesterone were obtained at multiple time intervals during the first 24-h, and at steady-state.ResultsResults were analyzable for 37/40 women. Study medications were well tolerated. The AUC at 24 h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch. The difference was statistically significant for Bi-est 2.0 mg (AUC-estradiol = 181 vs. 956; p < 0.001) and 2.5 mg (AUC-estradiol = 286 vs. 917; p < 0.001). Estriol levels remained low in all study arms. Serum progesterone levels were comparable in conventional vs. compounded groups.ConclusionsThis pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the standard-dose estradiol patch. To find comparable doses, further studies are needed. This successfully conducted randomized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial.     

Breast cancer in systemic sclerosis: Results of a cross-linkage of an Italian Rheumatologic Center and a population-based Cancer Registry and review of the literature

ObjectiveIncreased frequency of few types of cancer in systemic sclerosis (SSc) has been reported in the literature; in particular, breast carcinoma has been proposed as one of the most frequent malignancy in SSc patients, even though data are not univocal. The aim of the present study was to retrospectively evaluate the prevalence of breast cancer in our SSc series, compared with sex-/age-matched general population of the same geographical area, and the possible correlations with SSc features, including X-ray exposure for clinical investigations. A review of the world literature about this topic was also done.MethodsClinical records of 318 consecutive SSc patients, 31 M and 287 F, age 51.5 ± 14.5 SD years, disease duration 10 ± 6.5 SD years, referred to our Rheumatology Unit between January 2002 and December 2012 were evaluated.ResultsTwelve (3.8%) cases of breast cancer were recorded, including 11/287 females (3.8%) and 1/31 (3.2%) male patients. Considering the subgroup of 202 SSc patients resident in the Province of Modena compared with data of the local Tumor Registry, the incidence of breast cancer observed in our SSc series is significantly higher than expected (SIR 2.1; 95% interval of confidence: 1.13–3.90; p < 0.01). On the whole, the comparison between SSc patients with cancer and those without did not show any significant differences with regard to SSc clinical features, including the X-ray exposure. Of note is the relatively shorter disease duration at the time of breast cancer detection (median 2.5 years, range 1–21; disease duration of mean 10 ± 6.5 SD years in the entire cohort).The review of the literature revealed that the observed incidence of breast cancer in our case series is comparable to the few studies reporting the highest percentages of this malignancy.ConclusionsA significant increase of breast cancer incidence compared to sex–age-matched general population from the same geographic area was observed. Moreover, a close temporal relationship between SSc and breast cancer onset was found, independently from clinical, serological, and instrumental features of SSc. The possible pathogenetic link between this systemic autoimmune disease and complicating breast cancer, as well as the results of previous studies, are discussed.     

Patient knowledge and information-seeking about personalized cancer therapy

BackgroundUnderstanding patients’ knowledge and prior information-seeking regarding personalized cancer therapy (PCT) may inform future patient information systems, consent for molecular testing and PCT protocols. We evaluated breast cancer patients’ knowledge and information-seeking behaviors regarding PCT.MethodsNewly registered female breast cancer patients (n = 100) at a comprehensive cancer center completed a self-administered questionnaire prior to their first clinic visit.ResultsKnowledge regarding cancer genetics and PCT was moderate (mean 8.7 ± 3.8 questions correct out of 16). A minority of patients (27%) indicated that they had sought information regarding PCT. Higher education (p = 0.009) and income levels (p = 0.04) were associated with higher knowledge scores and with seeking PCT information (p = 0.04). Knowledge was not associated with willingness to participate in PCT research.ConclusionEducational background and financial status impact patient knowledge as well as information-seeking behavior. For most patients, clinicians are likely to be patients’ initial source of information about PCT. Understanding patients’ knowledge deficits at presentation may help inform patient education efforts.     

Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy

OBJECTIVE: There is now convincing evidence that usual hormone therapy for ovarian failure increases the risk for breast cancer. We have previously shown that ovarian androgens normally protect mammary epithelial cells from excessive estrogenic stimulation, and therefore we hypothesized that the addition of testosterone to usual hormone therapy might protect women from breast cancer. DESIGN: This was a retrospective, observational study that followed 508 postmenopausal women receiving testosterone in addition to usual hormone therapy in South Australia. Breast cancer status was ascertained by mammography at the initiation of testosterone treatment and biannually thereafter. The average age at the start of follow-up was 56.4 years, and the mean duration of follow-up was 5.8 years. Breast cancer incidence in this group was compared with that of untreated women and women using usual hormone therapy reported in the medical literature and to age-specific local population rates. RESULTS: There were seven cases of invasive breast cancer in this population of testosterone users, for an incidence of 238 per 100,000 woman-years. The rate for estrogen/progestin and testosterone users was 293 per 100,000 woman-years--substantially less than women receiving estrogen/pro-gestin in the Women's Health Initiative study (380 per 100,000 woman-years) or in the "Million Women" Study (521 per 100,000 woman-years). The breast cancer rate in our testosterone users was closest to that reported for hormone therapy never-users in the latter study (283 per 100,000 woman-years), and their age-standardized rate was the same as for the general population in South Australia. CONCLUSIONS: These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population.     

Perspective on prescribing conjugated estrogens/bazedoxifene for estrogen-deficiency symptoms of menopause: A practical guide

Current guidelines recommend that hormone therapy (HT) in postmenopausal women with a uterus include a progestin to protect against endometrial hyperplasia. However, many concerns relating to HT use appear to be related to the progestin component, including cardiovascular risk, breast stimulation, and irregular vaginal bleeding. Conjugated estrogens (CE) combined with the selective estrogen receptor modulator bazedoxifene (BZA) is a new progestin-free HT option for alleviating estrogen deficiency symptoms in postmenopausal women with a uterus for whom treatment with progestin-containing therapy is not appropriate. Five double-blind, randomized, placebo-controlled, phase 3 studies, known as the Selective estrogens, Menopause, And Response to Therapy (SMART) trials have investigated the efficacy of CE/BZA for relieving vasomotor symptoms (VMS), and effect on bone mass, as well as endometrial and breast safety in postmenopausal women. In a 12-week study, CE 0.45 mg/BZA 20 mg significantly reduced the number and severity of hot flushes compared with placebo at weeks 4 and 12. Unlike estrogen-progestin therapy (EPT), CE 0.45 mg/BZA 20 mg did not increase breast density compared with placebo. In clinical trials up to 2 years, CE/BZA had a favorable tolerability profile, demonstrated by amenorrhea rates similar to placebo. Vascular disorders including venous thromboembolic events (pulmonary embolism, retinal vein thrombosis, deep vein thrombosis, and thrombophlebitis) were rare events, occurring in less than 1 per 1000 patients. CE/BZA was associated with significantly higher incidences of amenorrhea and lower incidences of bleeding compared with CE/medroxyprogesterone acetate in 2 comparative trials. Therefore, CE 0.45 mg/BZA 20 mg provides an effective, well-tolerated, progestin-free alternative to EPT for postmenopausal women with a uterus.     

An informed decision?: Breast cancer patients and their knowledge about treatment

ObjectiveAlthough involving women in breast cancer treatment decisions is advocated, there is little understanding of whether women have the information they need to make informed decisions. The objective of the current study was to evaluate women's knowledge of survival and recurrence rates for mastectomy and breast conserving surgery (BCS) and the factors associated with this knowledge.MethodsWe used a population-based sample of women diagnosed with breast cancer in metropolitan Los Angeles and Detroit between December 2001 and January 2003. All women with ductal carcinoma in situ and a random sample of women with invasive disease were selected (N = 2382), of which 1844 participated (77.4%). All participants were mailed surveys. The main outcome measures were knowledge of survival and recurrence rates by surgical treatment type.ResultsOnly 16% of women knew that recurrence rates were different for mastectomy and BCS, and 48% knew that the survival rates were equivalent across treatment. Knowledge about survival and recurrence was improved by exposure to the Internet and health pamphlets (p < 0.01). Women who had a female (versus male) surgeon, and/or a surgeon who explained both treatments (rather than just one treatment) demonstrated higher survival knowledge (p < 0.01). The majority of women had inadequate knowledge with which to make informed decisions about breast cancer surgical treatment.ConclusionPrevious explanations for poor knowledge, such as irrelevance of knowledge to decision making and lack of access to information, were not shown to be plausible explanations for the low levels of knowledge observed in this sample.Practice implicationsThese results suggest a need for fundamental changes in patient education to ensure that women are able to make informed decisions about their breast cancer treatment. These changes may include an increase in the use of decision aids and in decreasing the speed at which treatment decisions are made.     

Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: A double-blind,randomised study

ObjectiveThis study compared the effects of a continuous-combined regimen of low-dose hormone therapy (LD-HT) versus tibolone and supplemental calcium/vitamin D3 (control) on quality of life (QoL) in symptomatic postmenopausal women.DesignThis study was a prospective, randomised, double-blind, comparative trial with a control group.SettingThe study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora, Brazil.PopulationA total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited. These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy.InterventionsThe patients were randomised into three groups: (1) daily treatment with 2.5 mg tibolone (n = 64), (2) 50 mg calcium carbonate + 200 IU vitamin D3 (Ca/Vit D3, n = 54) or (3) 1 mg oestradiol + 0.5 mg norethindrone acetate (E2/NETA, n = 56) for 12 weeks.Primary outcome measuresThe primary outcome was the evaluation of QoL using the Women's Health Questionnaire (WHQ) in all subjects at baseline and after 4, 8 and 12 weeks of treatment.ResultsA total of 130 women in the following groups completed the study: tibolone (n = 42), Ca/Vit D3 (n = 44) and E2/NETA (n = 44). An improved QoL based on the WHQ was observed at T0 (80.12 ± 14.04, 77.73 ± 15.3, 77.45 ± 15.4) and T12 (57.0 ± 15.5, 55.7 ± 16.7, 58.4 ± 12.6) for the tibolone, E2 + NETA and Ca/Vit D3 groups, respectively (p values <0.05). The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms. The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups (4.2 ± 26, 5.6 ± 2.8, 5.4 ± 2.8, respectively, p values <0.05). LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms (3.2 ± 1.5, 4.0 ± 1.8, 4.3 ± 2.0, respectively, p values <0.05). Adverse effects were few and mild.ConclusionsAn improved QoL was observed in the three study groups. Tibolone primarily improved sexual function, and E2/NETA exhibited a superior response for vasomotor symptoms.     

Testostérone libre ou biodisponible : dosages ou calculs. Comparaison critique de différents modes d'approche

The aim of the study is to find the most reliable practical approach to the estimation of free or bioavailable serum testosterone. We compare assayed values of bioavailable testosterone (T Bio), Free testosterone DPC (Free T DPC), total testosterone (Ttot) and calculated Free Androgen Index FAI = [Ttot/SHBG] × 100, calculated Free Testosterone using the equation derived from the law of mass action for the model: two binding proteins (SHBG, Albumin) and two ligands (T,E₂) (FTc_II Södergaard) or one ligand (T) (Ftc_I Kaufman and Fiers). Serum SHBG, Albumin, E₂ are determined exprimentally in every sample. The bioavailable (or non-SHBG bound) T correlates well with Free T by ultrafiltration (r = 0.96; P < 0.01), is easy to perform, reliable and sensitive if a particular care is ensured in the purification of the tracer. Assayed women values of T Bio agreed well with calculated values for FTc _II or FTc _I (r = 0.93; P < 0.01) using the laws of mass action. In contrast, the ratios of FTc _II/T Bio and FTc _I/T Bio (which should be constant if indexes reflect T Bio) remain negatively SHBG dependent for women and positively SHBG dependent for men confirming that the assumptions of the model are too simplified and the association constants Ka values too approximative. Calculated FTc is an acceptable substitute for an estimation of bioavailable T if we presume women with standard SHBG binding conditions and sera free of significant amounts of substances or steroids that could occupy the binding sites in the SHBG moiety and invalidate the calculation. Although showing a good correlation (r = 0.89; P < 0.01) with T Bio, FAI is not a useful index: the FAI/T Bio ratio is negatively correlated (r = –0.86 P < 0.001) with SHBG and overestimate strongly the SHBG binding capacity contribution for a reliable quantification of the non-SHBG bound T. The Free T DPC is inaccurate, not sufficiently sensitive, not free of proteins effects and less correlated with T Bio (r = 0.49; P < 0.05) than Ttot (r = 0.64; P < 0.01) for women!     

Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions

BackgroundHuman papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis.ObjectiveOur study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis.Study designWomen with normal cervix who were high-risk HPV-negative (N = 104) and HPV-positive (N = 105); women with CIN 1 (N = 106) and CIN 2/CIN 3 (N = 62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N = 106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women.ResultHPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp.ConclusionThe higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix.     

Perceptions of care coordination in a population-based sample of diverse breast cancer patients

ObjectiveTo identify factors associated with perceptions of care coordination in a diverse sample of breast cancer patients.MethodsBreast cancer patients reported to the metropolitan SEER registries of Detroit or Los Angeles from 6/05 to 2/07 were surveyed after diagnosis (N = 2268, RR = 72.4%). Outcomes were two dichotomous measures reflecting patient appraisal of care coordination during their treatment experience. Primary independent variables were race/ethnicity (white, African American, Latina-high acculturated, Latina-low acculturated) and health literacy (low, moderate, high). Logistic regression was used to evaluate factors associated with both measures of care coordination.Results2148 subjects were included in the analytic dataset. 16.4% of women perceived low care coordination and 12.5% reported low satisfaction. Race/ethnicity was not significantly associated with care coordination. Women with low subjective health literacy were 3–4 times as likely as those with high health literacy to perceive low care coordination and low satisfaction with care coordination (OR = 3.88; 95% CI: 2.78–5.41; OR = 3.19 95% CI: 2.25–4.52, respectively).ConclusionsMany breast cancer patients positively appraised their care coordination, but patients with low health literacy perceived low care coordination.Practice implicationsProviders should be aware of the health literacy deficits that may contribute to their patients’ attitudes towards their breast cancer care coordination.     

Détermination de la testostérone biodisponible dans le diagnostic de l'hyperandrogénisme féminin

The aim of the study is to find the parameter, which may give the best accurate assessment of hyperandrogenic state in women. We compare: bioavailable testosterone (T Bio), total testosterone (Ttot), Δ⁴ androstenedione (Δ4A), 5α-androstane 3α17β-diol glucuronide (Adiol), DHEA sulfate (DHEA-s), free androgen index FAI =(Ttot/SHBG) × 100, calculated free testosterone using the equation derived from the law of mass action for the model: two binding proteins (SHBG, Albumin) and two ligands (T, E₂) (FTc _II Södergard) or one ligand (T) (FTc _I Kaufman et Fiers) while serum SHBG, albumin, E₂ are determined experimentally in every sample. Subjects were healthy (N =25) or hirsute women (N =66) with acne (N =15), obesity (N =20), polycystic ovarian syndrome (N =12), excess hair growth (N =66), some receiving estrogen (N =12). Congenital adrenal hyperplasia, Cushing syndrome, ovarian neoplasms were not observed. ROC curves were constructed to determine the sensitivity and specificity of each assay or calculated method. The maximal area under curve reflects maximal sensitivity and specificity for the assay. For a requirement of 100% sensitivity, the specificity is 96% for TBio, 88% for calculated FTc _II, 72% for Ttot and 68% for FAI. Calculated FTc _II is an acceptable substitute for measurement of bioavailable T if you exclude the fact that high concentrations of free fatty acids, endogenous or analog steroids may compete for binding sites on SHBG. The utility of FAI is questioned since less specific that Ttot. The T Bio is very sensitive and useful to evaluate the response to treatments.     

Trends in the Incidence of Colorectal Cancer in Relation to County-Level Poverty among Blacks and Whites

Objective:The overall incidence of colorectal cancer has been decreasing rapidly in the United States since 1998. The extent to which the recent accelerated decline varies by socioeconomic status has not been examined. We analyzed trends in colorectal cancer incidence rates from 1992-2004 by area socioeconomic status, race, gender and stage at diagnosis.Methods:Incidence data from 13 Surveillance, Epidemiology and End Results reporting areas were used to examine temporal trends in age-standardized colorectal cancer incidence rates from 1992-2004 by race, gender, stage at diagnosis and 3 levels of county poverty (counties with < 10%, 10% to < 20% and ≥ 20% of residents living below the poverty level).Results:Among whites, colorectal cancer incidence rates decreased in both men and women residing in low- and moderate-poverty areas. The decrease involved both early- and late-stage disease in men and late-stage disease in women.In contrast, among those residing in high-poverty areas incidence rates increased for early-stage disease in men; rates were stable for late-stage disease in men and for both categories of stage in women. Among blacks, incidence rates decreased only in men residing in low-poverty areas.Conclusions:The recent decrease in colorectal cancer incidence has not yet benefited persons residing in high-poverty areas. Additional effort is needed to extend prevention and early detection measures to all segments of the population.