Ann Danoff

Health Care Utilization, Barriers to Care, and Hormone Usage Among Male-to-Female Transgender Persons in New York City

OBJECTIVES We investigated health care utilization, barriers to care, and hormone use among male-to-female transgender persons residing in New York City to determine whether current care is in accord with the World Professional Association for Transgender Health and the goals of Healthy People 2010. METHODS We conducted interviews with 101 male-to-female transgender persons from 3 community health centers in 2007. RESULTS Most participants reported having health insurance (77%; n = 78) and seeing a general practitioner in the past year (81%; n = 82). Over 25% of participants perceived the cost of medical care, access to specialists, and a paucity of transgender-friendly and transgender-knowledgeable providers as barriers to care. Being under a physicians care was associated with high-risk behavior reduction, including smoking cessation (P = .004) and obtaining needles from a licensed physician (P = .002). Male-to-female transgender persons under a physicians care were more likely to obtain hormone therapies from a licensed physician (P < .001). CONCLUSIONS Utilization of health care providers by male-to-female transgender persons is associated with their reduction of some high-risk behaviors, but it does not result in adherence to standard of care recommendations for transgender individuals.

Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women

Objective: To assess the association between protease inhibitor (PI) use and the incidence of diabetes mellitus (DM) among participants in the Womens Interagency HIV Study. Design: Prospective multicenter cohort study. The diagnosis of DM was based on self‐report at semiannual interviews conducted from 1994 to 1998. Setting: Six inner‐city clinical sites in the United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San Francisco, CA; and Los Angeles, CA). Participants: A total of 1785 nonpregnant women who had no history of prior DM. The women made up four groups: 1) PI users (n = 609, person‐years [PY] at risk = 707); 2) reverse transcriptase inhibitor (RTI)‐only users (n = 932, PY = 1486); 3) HIV‐infected women reporting no antiretroviral therapy (ART) ever (n = 816, PY = 1480): and 4) HIV‐uninfected women (n = 350, PY = 905). Main Outcomes: Incidence of DM and median body mass index (BMI) from 1995 to 1998 were compared among the four groups. Results: Sixty‐nine incident cases of DM occurred among 1785 women (1.5 cases per 100 PY; 95% CI: 1.2‐1.9). The incidence of DM among PI users was 2.8 cases per 100 PY (2.8%) versus 1.2% among both RTI users and women on no ART (95% CI: 1.6‐4.1 [PI]; 0.7‐1.8 [RTI and no ART]; P = 0.01 for comparison of the PI group with the RTI group) and 1.4% among HIV‐uninfected women (95% CI: 0.7‐2.2, P = 0.06 for comparison with PI group). Weight gain was not associated with either PI or RTI use. Multivariate models identified PI use (hazard ratio [HR] = 2.90 [95% CI: 1.50‐5.60]; P = 0.002), age (HR = 1.75 per 10 years [95% CI: 1.31‐2.34]; P = 0.0002) and BMI as independent risk factors for DM. Conclusions: PI use was associated with a threefold increase in the risk of reporting incident DM. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is advisable.

Tumors, IGF-2, and Hypoglycemia: Insights From the Clinic, the Laboratory, and the Historical Archive

Tumors of mesenchymal and epithelial origin produce IGF-2, which activates pathways in the tumors. In a minority of patients, the tumors (hepatomas, fibromas, and fibrosarcomas are the most common among many) release into the circulation enough IGF-2-related peptides to mimic the fasting hypoglycemia characteristic of patients with insulin-producing islet-cell tumors. Rarely, markedly elevated IGF-2 levels produce somatic changes suggestive of acromegaly. Typically, the elevated IGF-2 levels are associated with suppressed plasma levels of insulin, IGF-1, and GH. Complicating the pathophysiology are the IGF binding proteins (IGFBPs) that can bind IGF-2 and IGF-1, modifying hormone metabolism and action. IGFBP concentrations are often altered in the presence of these tumors. At the cellular level, the 3 hormone-related ligands, IGF-2, IGF-1, and insulin, all bind to 4 (or more) types of IGF-1 receptor (IGF-1R) and insulin receptor (IR). Each receptor has its own characteristic affinity for each ligand, a tyrosine kinase, and overlapping profiles of action in the target cells. The IGF-2R, in addition to binding mannose-6-phosphate-containing proteins, provides an IGF-2 degradation pathway. Recent evidence suggests IGF-2R involvement also in signal transduction. Surgery, the treatment of choice, can produce a cure. For patients not cured by surgery, multiple therapies exist, for the tumor and for hypoglycemia. Potential future therapeutic approaches are sketched. From 1910 to 1930, hypoglycemia, insulin, insulinomas, and non-islet-cell tumors were recognized. The latter third of the century witnessed the emergence of the immunoassay for insulin; the IGFs, their binding proteins, and assays to measure them; and receptors for the insulin-related peptides as well as the intracellular pathways beyond the receptor. In closing, we replace non-islet-cell tumor hypoglycemia, an outdated and misleading label, with IGF-2-oma, self-explanatory and consistent with names of other hormone-secreting tumors.

Sexual dysfunction is highly prevalent among men with chronic hepatitis C virus infection and negatively impacts health-related quality of life.

OBJECTIVES:Although sexual dysfunction has been reported in patients with hepatitis C virus (HCV) infection, little is known about this association. The aims of this study were to determine the prevalence of sexual dysfunction among men with chronic HCV infection and to evaluate the impact of sexual dysfunction on health-related quality of life (HRQOL).METHODS:We prospectively enrolled 112 HCV positive men and 239 HCV negative controls, and all patients completed validated questionnaires to assess sexual function (Brief Male Sexual Function Inventory [BMSFI]), depression (Beck Depression Inventory), and HRQOL (Medical Outcomes Study Short Form-36). The BMSFI assessed sexual drive, erection, ejaculation, sexual problem assessment, and overall sexual satisfaction.RESULTS:HCV positive men had significantly more sexual dysfunction than control subjects across all five domains of the BMFSI. In addition, HCV-infected men were significantly more likely than controls to not be sexually satisfied (53.6% vs 28.9%, p < 0.001) and this remained statistically significant after adjusting for age, race, and other potential confounding variables (OR = 3.36; 95% CI, 1.59–7.13). In the 241 individuals without depression, HCV positive men were significantly more likely to not be sexually satisfied as compared with control subjects (47.5% vs 11.0%, p < 0.001). HCV-infected men who were not sexually satisfied scored significantly worse in six of eight domains of HRQOL as compared with HCV-infected men who were sexually satisfied.CONCLUSIONS:Sexual dysfunction is highly prevalent in men with chronic HCV infection, is independent of depression, and is associated with a marked reduction in HRQOL.

What is a normal thyroid-stimulating hormone (TSH) level? Effects of stricter TSH thresholds on pregnancy outcomes after in vitro fertilization

Using a thyroid-stimulating hormone (TSH) cutoff of 2.5 mIU/L or 4.5 mIU/L, no differences in the rates of clinical pregnancy, delivery, or miscarriage were observed in this large, retrospective cohort study of first-cycle IVF patients from 2005 through 2008, after controlling for age. Although lowering the TSH threshold to 2.5 mIU/L would result in a nearly fivefold increase in the number of women being classified as hypothyroid, the lack of differences in maternal clinical outcomes must be considered in the current controversy regarding the relative merits of lowering the upper limit of normal of TSH.

GH peak response to GHRH-arginine : relationship to insulin resistance and other cardiovascular risk factors in a population of adults aged 50-90

Objective  To assess the GH response to GHRH‐arginine in apparently healthy adults in relation to cardiovascular risk factors.

Glycated haemoglobin in diabetic women with and without HIV infection: data from the Women's Interagency HIV Study

BACKGROUND Limited data suggest that glycated haemoglobin (haemoglobin A1c; A1C) values might not reflect glycaemic control accurately in HIV-infected individuals with diabetes. METHODS We evaluated repeated measures of paired fasting glucose and A1C values in 315 HIV-infected and 109 HIV-uninfected diabetic participants in the Womens Interagency HIV Study. Generalized estimating equations used log A1C as the outcome variable, with adjustment for log fasting glucose concentration in all models. RESULTS An HIV-infected woman on average had 0.9868 times as much A1C (that is, 1.32% lower; 95% confidence interval 0.9734-0.9904) as an HIV-uninfected woman with the same log fasting glucose concentration. In multivariate analyses, HIV serostatus was not associated, but White, other non-Black race, and higher red blood cell mean corpuscular volume (MCV) were statistically associated with lower A1C values. Use of diabetic medication was associated with higher A1C values. In multivariate analyses restricted to HIV-infected women, White and other race, higher MCV, and HCV viraemia were associated with lower A1C values, whereas older age, use of diabetic medications and higher CD4(+) T-cell count were associated with higher A1C values. Use of combination antiretroviral therapy, protease inhibitors, zidovudine, stavudine or abacavir was not associated with A1C values. CONCLUSIONS A1C values were modestly lower in HIV-infected diabetic women relative to HIV-uninfected diabetic women after adjustment for fasting glucose concentration. The difference was abrogated by adjustment for MCV, race and diabetic medication use. Our data suggest that in clinical practice A1C gives a reasonably accurate refection of glycaemic control in HIV-infected diabetic women.

Oral glucose tolerance and insulin sensitivity are unaffected by HIV infection or antiretroviral therapy in overweight women

Objective:To assess the frequency of diabetes, prediabetes, and insulin resistance among a subset of participants in the Womens Interagency HIV Study (WIHS). Design:Cross-sectional substudy nested within a prospective multicenter cohort study. Women underwent 75 g oral glucose tolerance testing. Diagnoses of diabetes and prediabetes were made according to the American Diabetes Association criteria, and insulin resistance was determined by area under the curve insulin and homeostasis model assessment values. Setting:Six urban clinical sites in the United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San Francisco, CA; Los Angeles, CA) participate in the entire WIHS. The Bronx, NY, and San Franscisco, CA, WIHS sites participated in this substudy. Participants:A total of 258 women, 88 HIV negative, 74 HIV positive not on highly active antiretroviral therapy (HAART), and 96 HIV positive taking HAART were enrolled in the study. Main Outcomes:Prevalence of diabetes, prediabetes, and insulin resistance was compared among the HIV-uninfected and HIV-infected women. Results:The frequency of diabetes, prediabetes, or insulin resistance was unrelated to HIV status or antiretroviral treatment. Increasing body mass index was the only characteristic associated with the combined endpoints of diabetes and prediabetes (odds ratio = 1.104, P = 0.0002). Conclusions:Routine oral glucose tolerance testing of HIV-infected women is not supported by these findings. Elucidation of putative perturbations from HIV or antiretroviral medications requires direct studies of insulin resistance and β-cell function.

Insulin-like growth factor-I inhibition with pasireotide decreases cell proliferation and increases apoptosis in pre-malignant lesions of the breast: a phase 1 proof of principle trial

IntroductionEstrogen inhibition is effective in preventing breast cancer in only up to 50% of women with precancerous lesions and many experience side effects that are poorly tolerated. As insulin-like growth factor I (IGF-I) underlies both estrogen and progesterone actions and has other direct effects on mammary development and carcinogenesis, we hypothesized that IGF-I inhibition might provide a novel approach for breast cancer chemoprevention.MethodsIn total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH) were treated for 10 days with pasireotide, a somatostatin analog which uniquely inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12 patients also had proliferative lesions and one a ductal carcinoma in situ (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed. Core and excision biopsies from 14 untreated patients served as non-blinded controls. Hyperglycemia and other side effects were carefully monitored.ResultsPasireotide decreased proliferation and increased apoptosis in all AH (from 3.6 ± 2.6% to 1.3 ± 1.2% and from 0.3 ± 0.2% to 1.5 ± 1.6%, respectively) and proliferative lesions (from 3.8 ± 2.5% to 1.8 ± 1.8% and from 0.3 ± 0.2% to 1.3 ± 0.6%, respectively). The DCIS responded similarly. ER and PR were not affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased significantly. In contrast, tissue from untreated controls showed no change in cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate hyperglycemia associated with reduced insulin levels was found. Glucose fell into the normal range after discontinuing treatment. Pasireotide was well tolerated and did not cause symptoms of estrogen deprivation.ConclusionsIGF-I inhibition by pasireotide, acting through the IGF-1R, was associated with decreased proliferation and increased apoptosis in pre-malignant breast lesions and one DCIS. Assuming hyperglycemia can be controlled, these data suggest that inhibiting the IGF-I pathway may prove an effective alternative for breast cancer chemoprevention.Trial registrationNCT01372644 Trial date: July 1, 2007.

Can 'personalized diagnostics' promote earlier intervention for dysglycaemia? Hypothesis ready for testing

The risk associated with progression to diabetes as well as for cardiovascular complications increases along a continuum, rather than being threshold‐dependent. How can we identify those with glucose levels in the upper reaches of normal who are most in need of a preventive intervention? With present criteria, we are likely excluding many individuals who have heightened risk. We introduce here the possibility of using a “personalized” glucose profile to encourage early intervention in subjects in whom glucose metabolism is deteriorating (on an individual level) but not yet abnormal on a population‐based norm. We further suggest that “personalized profiles” of hemoglobin A1c and basal plasma insulin may also help encourage appropriately early intervention. That the first line therapies are so effective, safe and simple make these more sensitive approaches very attractive. Copyright