Safety and efficacy of low-dose esterified estrogens and methyltestosterone, alone or combined, for the treatment of hot flashes in menopausal women: a randomized, double-blind, placebo-controlled study.

This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.30-mg methyltestosterone combination was the lowest effective dose, and our results are consistent with the known safety profile of estrogen and androgen combination products.

Validation of a Women's Sexual Interest Diagnostic Interview--Short Form (WSID-SF) and a Daily Log of Sexual Activities (DLSA) in postmenopausal women with hypoactive sexual desire disorder.

INTRODUCTION: Currently, there is no clear standard assessment tool for the diagnosis and daily monitoring of hypoactive sexual desire disorder (HSDD) in postmenopausal women. AIM: The aim of the study was to validate (i) the Women's Sexual Interest Diagnostic Interview-Short Form (WSID-SF) which is a structured tool to identify HSDD; and (ii) the Daily Log of Sexual Activities (DLSA) which is a diary to monitor daily HSDD status in postmenopausal women. Both assessments were collected as self-reports by an interactive voice response system (IVRS). METHODS: At the initial study visit, 629 postmenopausal women, age 39-66, were evaluated for HSDD by the WSID-SF. In addition, in a subgroup of 175 subjects at five study sites, HSDD was assessed by physicians who were blinded to the WSID-SF diagnosis. During the 58-day study period, patients completed the DLSA daily through self-reported IVRS. All women also completed the Female Sexual Function Index (FSFI), Menopause Sexual Interest Questionnaire (MSIQ), Female Sexual Distress Scale (FSDS), Dyadic Adjustment Scale (DAS), and Kellner Symptom Questionnaire (KSQ) at both the initial study visit and at the end of the study. The WSID-SF-based identifications were compared with clinical diagnoses made based on physicians' clinical experience. Construct validity of the WSID-SF and DLSA were assessed based on comparisons with questionnaire results. Internal consistency and test-retest reliability of the DLSA were also evaluated. MAIN OUTCOME MEASURES: Main outcome measures include the agreement between WSID-SF diagnosis and clinician diagnosis, convergent and divergent validity of the WSID-SF and DLSA, and reliability of the DLSA. Results. Enrolled subjects were classified into HSDD (N = 468) and non-HSDD (N = 161) groups by WSID-SF. When compared with physician's diagnosis, WSID-SF-based diagnosis had a specificity of 89% and a sensitivity of 70% (kappa = 0.46, P < 0.001). WSID-SF showed significant correlation with each domain of the FSFI, MSIQ, and FSDS (all P < 0.001). As anticipated, WSID-SF had low or nonsignificant correlations with all domains of the DAS and the KSQ. Four different algorithms were piloted to calculate DLSA scores. Data on the detailed analysis conducted to evaluate the four scoring strategies is on file (not presented in this article). Ultimately, the weekly DLSA total score calculated by algorithm #4 was selected to validate the DLSA. In the test-retest reliability evaluation, the intraclass correlation coefficient was 0.80 for women with HSDD and 0.84 for women without HSDD (P < 0.001 for all analysis). In the known-group validity comparison, the weekly DLSA total score was significantly different (P < 0.001) among the HSDD and the no HSDD groups, with an effect size of 0.89-0.92 based on Cohen's d. The DLSA also showed convergent validity with moderate to high correlations with each domain of the FSFI, MSIQ, and FSDS (P < 0.001 for all correlations). As anticipated, the DLSA had weak correlations with the DAS and KSQ demonstrating divergent validity. CONCLUSIONS: The WSID-SF had good specificity and sensitivity (i.e., discriminative validity) in identifying HSDD in postmenopausal women. In addition, the DLSA is a reliable and valid patient-reported outcomes tool that can be utilized to assess effectiveness of treatments in postmenopausal women with HSDD. Further, the WSID-SF and DLSA both demonstrated good convergent and divergent validity.

Development and evaluation of the Women's Sexual Interest Diagnostic Interview (WSID): a structured interview to diagnose hypoactive sexual desire disorder (HSDD) in standardized patients.

INTRODUCTION: Female sexual dysfunction (FSD) is a common disorder in postmenopausal women. Currently, there is no clear "gold standard" for the diagnosis of FSD. AIM: The aim of this study was to evaluate the interrater reliability of the Women's Sexual Interest Diagnostic Interview (WSID), a new structured clinical interview designed to diagnose hypoactive sexual desire disorder (HSDD). The reliability of additional interview questions focused on the diagnosis of other types of FSD was also evaluated. MAIN OUTCOME MEASURES: The main outcome measure was the level of agreement in the diagnosis of FSD among clinical experts, between clinical experts and study coordinators, and between clinical experts and patients' self-reported interactive voice response system (IVRS) version of the WSID. METHODS: Two versions of WSID were developed based on current diagnostic criteria: a clinician-administered version using a structured interview guide, and a patient self-report version using an IVRS. Three sexual medicine experts developed 20 clinical scenarios portraying cases and noncases of HSDD and other FSD diagnostic subtypes. Ten actresses with experience in standardized patient interviewing rehearsed these scenarios and performed the scripted patient roles in a standardized clinical interview with clinical experts (not the author of the script) and study coordinators, on a one-on-one basis, using the WSID interview format. In addition, all actresses completed the IVRS version of the WSID. Interviews were videotaped and viewed by the expert panel. In each instance, the diagnosis that the interview was scripted to portray was considered as the "gold standard." Kappa (kappa) coefficients were utilized to assess the level of agreement among experts, between study coordinators and the "gold standard", and between the IVRS version of the WSID and the "gold standard". RESULTS: All experts agreed with the gold standard diagnosis provided by the author of the script (kappa=1.0). Similarly, there was perfect agreement among the experts on the presence of depressive symptomatology (kappa=1.0). On the related diagnoses of arousal disorder, orgasmic disorder, and sexual pain disorder, kappas of 0.894, 0.966, and 0.946 were observed (P<0.0001 for all comparisons). When study coordinator's WSID diagnoses were compared with the "gold standard," kappa for HSDD was 0.851; sensitivity was 0.864, and specificity and positive predictive value (PPV) were 1.00 (P<0.001 for all comparisons). When diagnoses obtained via IVRS interviews were compared with the "gold standard", kappa for HSDD was 0.802, sensitivity was 0.818, and specificity and PPV were 1.00 (P<0.001 for all comparisons). CONCLUSION: Agreement as estimated by kappa coefficients was consistently high in both clinician-administered and patient self-reported IVRS versions in the diagnosis of HSDD.

Hypomagnesemia associated with chemotherapy in patients treated for acute lymphoblastic leukemia: possible mechanisms.

Body weight, height and lumbar spine bone mineral density (BMD) were measured in 40 children (27 male, 13 female, aged 0.3-17.0 years) with acute lymphoblastic leukemia (ALL) at diagnosis and 6 months after initiation of chemotherapy, and in 40 age- and sex-matched local healthy children. Serum and urinary biochemical indices of mineral metabolism were measured in the children with ALL at both time points. From diagnosis to 6 months, a reduction in the fractional excretion of magnesium was found. Serum osteocalcin was low at diagnosis and increased during chemotherapy, whereas 24-h urinary type I collagen cross-linked N-telopeptide was unchanged. The Z-scores for lumbar spine BMD increased and were correlated with the serum osteocalcin at 6 months. The change in serum magnesium was correlated negatively with the change in lumbar spine BMD, and with the lumbar spine BMD Z-score at 6 months. After initiation of treatment for ALL, rapid recovery in bone formation, which results in the movement of extracellular magnesium into the skeleton through bone formation, may be an important contributor to hypomagnesemia.

Osteopenia in survivors of Wilms tumor.

Diminished bone mass (osteopenia) is recognized increasingly as a consequence of therapy in survivors of cancer in childhood. It has been reported in two small series of survivors of Wilms tumor. The objectives of this study were to explore, in a larger sample of such subjects, the prevalence of osteopenia and a possible relationship between osteopenia of the lumbar spine and abdominal irradiation. All survivors of Wilms tumor (n=49) in a single institution were considered eligible for study. Thirty-one agreed to participate; the non-participants were not notably different in their demographic characteristics and diseases/treatment experience. Information was obtained about prior treatment, and usual diet, sun exposure and physical activity. Bone mineral content was measured by dual energy X-ray absorptiometry, and biochemical markers of bone turnover, calciotropic hormones and minerals were assessed in a single blood sample. By Z-scores of whole body bone mineral content, 8 subjects were osteopenic. This was unrelated to milk intake or sun exposure and was not more common in the lumbar spine of those who had been irradiated (15/31 subjects). Physical activity correlated positively with bone mineral density Z-scores (p<0.005). Normal bone formation was reflected in normal blood levels of osteocalcin. C-telopeptide levels, reflecting bone resorption, were high but approximately correlated inversely with maturity. Low serum magnesium and parathyroid hormone levels were detected in a minority of subjects. Osteopenia is present in a large minority (27%) of survivors of Wilms tumor, and an imbalance of bone turnover (with excessive resorption) may be common. Irradiation does not appear to play a causal role. It is possible that a subtle renal tubular defect exists in these individuals; a prospect worthy of further exploration.