David Muram

Medication adherence and treatment patterns for hypogonadal patients treated with topical testosterone therapy: a retrospective medical claims analysis.

INTRODUCTION There is limited information on adherence to topical testosterone replacement therapy (TRT) among hypogonadal men. AIM To determine adherence rates among men treated with topical testosterone gels and to examine factors that may influence adherence, including age, presence of a specific diagnosis, and index dose. METHODS Included were 15,435 hypogonadal men, from the Thomson Reuters MarketScan Database, who had an initial topical testosterone prescription in 2009 and who were followed for 12 months. MAIN OUTCOME MEASURES Adherence to testosterone was measured by medication possession ratio (MPR), with high adherence defined as ≥0.8. Persistence was defined as the duration of therapy from the index date to the earliest of the following events: end date of the last prescription, date of the first gap of >30 days between prescriptions, or end of the study period (12 months). RESULTS Adherence to topical TRT was low. By 6 months, only 34.7% of patients had continued on medication; at 12 months, only 15.4%. Adherence rates were numerically similar among men who received AndroGel or Testim topical gels and did not differ among men of different age groups. Approximately 80% of patients initiated at the recommended dose of 50 mg/day. Over time, an increased proportion of men used a higher dose. This change was the result of dose escalation, rather than of greater adherence among men initiating therapy at a high dose. Dose escalation was seen as early as 1 month into therapy. Approximately 50% of men who discontinued treatment resumed therapy; most men used the same medication and dose. CONCLUSIONS Discontinuation rates are high among hypogonadal men treated with testosterone gels, irrespective of their age, diagnosis, and index dose. Further study, evaluating other measurable factors associated with low adherence among patients receiving topical TRT, may lead to interventions designed to improve adherence with therapy.

Validation of a Two-item Quantitative Questionnaire for the Triage of Women With Urinary Incontinence

OBJECTIVE: To evaluate the reproducibility, construct validity, and preferences for the 2-item Stress/Urge Incontinence Questionnaire. METHODS: The questionnaire asks a patient to recall the number of stress urinary incontinence and urge urinary incontinence episodes she experienced during the preceding week. The 4-week prospective study included 3 office visits and enrolled women with stress, urge, or mixed urinary incontinence symptoms. The test–retest reproducibility was assessed after 3 days, and the construct validity of the questionnaire was evaluated against a diary and other measures of incontinence severity and effect. The bother associated with completing (patients) or analyzing (physicians) the diary was assessed. Both groups also reported their time requirements and preferences for the questionnaire or diary. RESULTS: Reproducibility for the classification of symptoms was moderately strong (&kgr; = .536). Test–retest agreement was good (64–80%) for all but balanced mixed incontinence (38%). Intraclass correlations revealed good reproducibility for the number of stress (.694), urge (.703), and total (.726) incontinence episodes. Significant (P < .01) correlations with other measures of incontinence established construct validity. Patients and physicians reported it took less time to complete the questionnaire than the diary, but the majority said the completion or analysis of the diary was of little or no bother and preferred the diary. CONCLUSION: The Stress/Urge Incontinence Questionnaire is a valid tool that can be used in clinical practice to differentiate between symptoms of stress and urge urinary incontinence to make an initial diagnosis, especially in primary care where incontinence is not a focus of the practice. LEVEL OF EVIDENCE: III

Long‐Term Treatment Patterns of Testosterone Replacement Medications

INTRODUCTION Testosterone replacement therapy (TRT) is prescribed to men diagnosed with hypogonadism to alleviate symptoms, improve quality of life, and improve overall health. However, most men use TRT for only a short duration. AIM To evaluate the long-term treatment patterns in hypogonadal men using topical TRT or short-lasting TRT injections. METHODS Using the Truven MarketScan(®) Database, 15,435 men who received their first (index) topical TRT prescription and 517 men who received their short-lasting TRT injection index prescription in 2009 were followed from 12 to 30 months after treatment initiation. Treatment interruption was defined as a medication gap of >30 days. Patients who remained off treatment were classified as having discontinued treatment. Patients who restarted therapy after 30 days were classified as cyclic users. Patients were required to have continuous insurance coverage during 1 year prior to treatment initiation and at least 1 year afterward. MAIN OUTCOME MEASURES Main outcome measures were length of therapy, discontinuation, and restarts of topical TRT or short-lasting TRT injections. RESULTS The patient characteristics were similar for patients who received topical TRT or short-lasting TRT injections. Of the patients who discontinued therapy during the follow-up period, the percentages of patients who were still on therapy after 3 months were 52% and 31% for topical TRT and short-lasting TRT users, respectively. For cyclic users, there was an attrition rate of approximately 40% to 50% of patients in each cycle. For both topical TRT and short-lasting TRT injections, the gap between stopping and restarting therapy tended to decrease over time. CONCLUSIONS In this analysis, high discontinuation rates were observed. The treatment pattern of TRT may be related to the disease state rather than dosing, daily use, or mode of administration.

Skin reactions in a phase 3 study of a testosterone topical solution applied to the axilla in hypogonadal men.

Abstract Objective: Axiron (testosterone topical solution 2%) is an approved topical testosterone replacement therapy applied to the axilla. The axilla is a novel application site for testosterone replacement therapy, with differences in skin structure and exposure that could impact the type and/or severity of skin reactions observed with testosterone topical solution 2%. We therefore present a detailed description of data from a pivotal clinical trial regarding the incidence, time of onset, duration, and severity of patient-reported skin reactions as well as visual assessments made by investigators and rated using Draize scoring. *Axiron is a trademark of Eli Lilly and Company, Indianapolis, IN, USA. Methods: Data were analyzed from a multinational, open-label, clinical study in which a 2% testosterone topical solution was applied to the axilla in hypogonadal men. The primary study was for 120 days (N = 155) with a 60-day extension that evaluated skin safety (N = 71). At each visit investigators asked patients about adverse skin reactions (including those occurring between study visits); visually assessed the application site; and graded observed instances of erythema or edema using Draize scoring (rated from 0 to 4). Results: Application-site irritation following study drug application was the most commonly reported event (n = 12 patients) and was generally mild (n = 11; moderate, n = 1) in severity. Application-site irritation did not increase in severity over time and led to only one discontinuation. Erythema was the second most common patient-reported skin reaction (n = 10 patients) and was also generally mild (n = 9; moderate, n = 1). Draize scoring rated all directly observed cases of erythema as grade 1 (very slight, 6 patients) or grade 2 (well-defined, two patients), and identified two instances of erythema not reported by patients. Erythema was typically transient, and in most cases resolved without interruption of therapy. Three cases of edema were reported by patients, and two of these were also identified by visual inspection; all cases of edema occurred in conjunction with erythema. Two cases of acne (facial, shoulders) and one of folliculitis (scalp) were also reported. Conclusions: Skin reactions were observed in a minority of patients, were mild or at most moderate in severity, and seldom led to discontinuation.

Pattern recognition in pediatric and adolescent gynecology--a case for formal education.

Physicians, particularly gynecologists, pediatricians and family practitioners, are often called upon to perform a gynecologic evaluation of a child. The indications for such evaluations include various gynecologic complaints as well as allegations of sexual abuse. Yet, many physicians receive no formal training in the evaluation of the sexually abused child. Not surprisingly, many feel uneasy evaluating these young patients, and many clinicians do not incorporate genital inspection into the routine well-child examination. One survey of 129 pediatricians and family practitioners revealed that only 77% of these respondents examined the genitalia of prepubescent girls more than half the time, and only 59% of these respondents were able to correctly identify the hymen of a sixyear-old girl. Another study, using both gross and colposcopic images of the female genitalia, showed that physicians of all specialties and various levels of experience often failed to recognize the normal appearance of the genitalia of a prepubertal girl and misdiagnosed common gynecologic conditions. That study also demonstrated that residents who had a well defined program in pediatric gynecology scored significantly better than those who did not have such a program. Over the past decade, many residency programs instituted a more formal training in pediatric and adolescent gynecology. The purpose of the current study was to evaluate the impact of such educational opportunities in one institution on the ability of residents and faculty to recognize the normal appearance of the genitalia of prepubertal girls and to diagnose common gynecologic conditions. Materials and Methods

Use of Hormone Testing for the Diagnosis and Evaluation of Male Hypogonadism and Monitoring of Testosterone Therapy: Application of Hormone Testing Guideline Recommendations in Clinical Practice

INTRODUCTION Clinical practice guidelines recommend that testosterone (T) levels be measured on ≥2 occasions to confirm a diagnosis of hypogonadism, gonadotropins be measured to determine whether hypogonadism is primary or secondary, and T levels be measured to monitor the adequacy of T therapy. However, it is not known whether hormone testing as recommended by guidelines is routinely performed in real-world clinical practice. AIM The aim of this study was to assess the use of hormone testing for the diagnosis and evaluation of hypogonadism and monitoring of T therapy in clinical practice. METHODS In this retrospective cohort study of the Truven Health Marketscan(®) Commercial and Medicare Supplemental Insurance Databases during 2010-2012, 63,534 men over 18 years old who received T therapy and had continuous medical benefit enrollment for 1 year prior to and 6 months after T therapy initiation were included in this analysis. MAIN OUTCOME MEASURES Proportion of patients who received ≥2, 1, or no T-level determinations prior to or following T therapy initiation. RESULTS Seventy-one percent of hypogonadal men had T measured at least once and 40% had ≥ 2 tests, but only 12% of men had luteinizing hormone and/or follicle-stimulating hormone levels measured prior to T therapy initiation. Following T therapy initiation, 46% had ≥1 follow-up T measurements. CONCLUSIONS Appropriate use of T and gonadotropin levels in clinical practice as recommended by guidelines is suboptimal, increasing the possibility of overdiagnosis of male hypogonadism, underdiagnosis of secondary hypogonadism, and inappropriate T therapy use and management. Further investigation is needed into reasons for nonadherence to guidelines for appropriate hormone testing to inform future quality improvement efforts.

The effects of raloxifene on mammographic breast density: a review of clinical trials.

Objective: Breast density is an independent risk factor for the development of invasive breast cancer (BC). It has been hypothesized that because raloxifene (RLX) has been shown to reduce BC risk, its use will result in reduced breast density. Methods: This article provides a review of seven clinical studies that examined the effects of RLX on breast density. Results: Overall, RLX did not increase or decrease mammographic breast density. This article provides a review of the various methods used to determine breast density in these RLX studies and offers a potential explanation as to why the studies failed to show an effect on mammographic density. Conclusions: Presently, no clinical recommendations can be made with regard to RLX and its effects on breast density. To determine the effect of RLX on breast density, larger studies need to be conducted in postmenopausal women with high breast density at baseline who are at high risk for BC, with a standardized method of breast density measurement.

The Medical Evaluation of Sexually Abused Children

Participants: Astrid Heger, MD 1 , Martin A. Finkel, DO 2, Karen J. Simmons, MD 3 , and J.M. Whitworth, MD 4 1 LAC & USC VIP, LaCanada, California, USA, 2 UMDNJ Center for Children Support, Stratford, New Jersey, USA, 3 Department of Obstetrics and Gynecology, University of Miami, Miami, Florida, USA, and 4 Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA

Gynecologic effects of arzoxifene in postmenopausal women with osteoporosis or low bone mass

ObjectiveThe aim of this study was to report the gynecologic safety findings from the Generations trial, a phase 3 study of the selective estrogen receptor modulator (SERM), arzoxifene. MethodsA predefined objective of the trial was to evaluate the effects of arzoxifene on the genital tract. Gynecologic examinations were performed yearly, and further gynecologic assessment, including endometrial biopsy, was performed in a predefined subset of women and in those who developed vaginal bleeding. ResultsOverall, 9,354 women were randomized (4,678 to placebo, 4,676 to arzoxifene 20 mg/d). There were 13 adjudicated cases of endometrial cancer (placebo, 4 cases; arzoxifene, 9 cases: P = 0.165) and 6 cases of endometrial hyperplasia (placebo, 2 cases; arzoxifene, 4 cases). Endometrial thickness, assessed at 24- and 36-month transvaginal ultrasounds in a subset of women, increased slightly in women assigned to arzoxifene compared with baseline and women in placebo. At the last measurement, 3 (1.7%) women assigned to placebo and 21 (10.2%) assigned to arzoxifene had an endometrial thickness greater than 5 mm (P < 0.001 for difference between treatment groups). Endometrial polyps were more common in women treated with arzoxifene (n = 37) than in women treated with placebo (n = 18; P < 0.05). Vulvular and vaginal inflammation, including mycotic infections, and vaginal discharge were reported more frequently in women treated with arzoxifene than in women treated with placebo, as were urinary tract infections. ConclusionsGynecologic events were generally more common in women treated with arzoxifene than in women treated with placebo. The gynecologic effects of arzoxifene seem to differ from those of raloxifene, although both SERMs have a benzothiophene structure. Although all SERMs influence cells through the estrogen receptor, they need to be evaluated independently in terms of their effects on various tissues, including the genital tract.

Duloxetine in the treatment of women with stress urinary incontinence: results from DESIRE (Duloxetine Efficacy and Safety for Incontinence in Racial and Ethnic populations)

ABSTRACT Objective: To evaluate the effectiveness and safety of duloxetine for the treatment of African– American and Hispanic women with stress urinary incontinence. Research design and methods: The 10‐week (a 2‐week lead in period followed by 8 weeks of active treatment), open-label, multicenter study of duloxetine 40 mg twice daily included women with stress urinary incontinence or stress predominant mixed incontinence. Efficacy was measured by the median percent change from baseline to endpoint of weekly incontinence episode frequency. The primary objective assessed the treatment response in a pre-specified group of women (n = 2960; 2321 Caucasian, 271 African–American, and 368 Hispanic) with similar baseline incontinence and comorbidity characteristics as the subjects enrolled in the placebo-controlled trials of duloxetine for the treatment of stress urinary incontinence. The efficacy in African–American and Hispanic women was compared with Caucasians using a predefined non-inferiority subpopulation analysis. Safety measures included adverse events, laboratory test results, and vital signs. Results: All three subgroups reported significant (all p < 0.001) median percent decreases in weekly incontinence episode frequency: –65.7% (African–American), –73.0% (Hispanic), and –75.0% (Caucasian). Non-inferior efficacy was demonstrated for African–American and Hispanic women compared to the Caucasian women. Common adverse events included nausea (21.8%, 28.0%, 25.3%), dry mouth (7.7%, 11.4%, 11.9%), and fatigue (9.2%, 5.7%, 11.6%) for the African–American, Hispanic, and Caucasian groups, respectively. Conclusion: Duloxetine was efficacious and well tolerated for the treatment of African–American, Hispanic, and Caucasian women with stress urinary incontinence. The trial design was successful in enrolling a diverse population of patients. The most important limitations include the lack of placebo control, the short study duration, and the exclusion of patients with less than seven incontinence episodes per week.