Use of hormone replacement therapy for correction of high turnover bone disease in hypogonadal ß-Thalassemia major patients presenting with osteoporosis: comparison with idiopathic premature ovarian failure.

Osteopenia-osteoporosis syndrome (OOS) causes considerable morbidity in 60-80% ß-thalassemia major (ß-TM) patients. We evaluated the effect of sex hormone replacement therapy (HRT) in ß-TM patients with hypogonadism presenting with OOS using premature ovarian failure (POF) for comparative purposes. We undertook a 10-year prospective study of in 50 ß-TM and 375 patients with POF and OOS. All were treated with HRT for 2-5 years. We used dual X-ray absorptiometry (DEXA), and plasma type 1-collagen markers of bone turnover for monitoring of response to therapy. Our results suggest that prior to HRT, both groups had comparable degrees of OOS. Both groups had significant improvement but the POF group had normalization of spinal T scores following HRT in contrast to the ß-TM patients. Femoral T scores did not normalize in both groups. These data indicate for the first time from comparative POF control studies that hypogonadism is not the only cause of OOS in ß-TM.

Abnormal seminal parameters in patients with thalassemia intermedia and low serum folate levels.

Seminal parameters were evaluated in 16 fully mature patients with thalassemia intermedia. Their ages ranged from 19 to 54 years (mean age 27 yrs) and serum ferritin levels varied from 205 to 3400 ng/ml. Eleven patients (68.7 %) had normal seminal parameters, 1 (1.6 %) had oligospermia, 3 (18.7 %) had asthenospermia and 1 (1.6 %) had oligoasthenospermia. A significant positive correlation was observed between the serum ferritin and ALT and serum ferritin and ?-GT (r: 0.636, p: 0.007; r: 0.497, p: 0.048, respectively), ALT and ?-GT (r: 0.749, p: 0.001) and total sperm concentration and serum folate (r: 0.572, p: 0.02). Despite some limitations, our study has useful clinical implications for the treatment of patients with thalassemia intermedia.

Spermatozoal DNA damage in patients with B thalassaemia syndromes.

OBJECTIVE: to determine whether sperm DNA damage is increased in patients with beta-thalassaemia syndromes. DESIGN: prospective comparative assessment of sperm genomic integrity in thalassaemia patients and donor controls and correlation of sperm DNA damage with other measures of semen quality, reproductive hormones, ferritin, zinc and vitamin E levels. SETTING: Thalassaemia Centre of Paediatric and Adolescent Unit, Ferrara, Italy and Academic Research Institutions in the UK. SUBJECTS: twenty-eight thalassaemia major and thalassaemia intermedia patients attending the clinic for regular treatment. INTERVENTIONS: assessment of the degree of spermatozoa undergoing apoptosis by terminal deoxynucleotidyl transferase mediated assay (TUNEL) and measurement of the degree of those with compromised structural integrity as measured by the sperm chromatin structure assay (SCSA) using flow cytometry. MAIN OUTCOME MEASURES: the degree of spermatozoal DNA damage by TUNEL and SCSA and the correlation between these measures and sperm motility, concentration, morphology and serum FSH, LH, sex hormone binding globulin, free and total testosterone, ferritin, zinc and vitamin E using regression analysis and Student t-test. RESULTS: comparative analysis showed that beta-thalassaemia patients had significantly more sperm DNA damage (mean TUNEL=18.5%, SCSA=0.28) than controls (mean TUNEL=11.4%, mean SCSA=0.18) (p<0.001). Among thalassaemia patients there was a negative correlation between itchromatin structure damage and sperm concentration (r2=0.3, p<0.006). There was a significant negative correlation between serum ferritin levels and abnormal sperm morphology (r2=0.2, p<0.05). CONCLUSIONS: compared to controls there was a higher degree of DNA damage in spermatozoa of beta-thalassaemia patients. Thalassaemic patients with low sperm concentrations were more likely to have a higher degree of defective chromatin packaging. The negative association between ferritin levels and abnormal sperm morphology suggests a possible detrimental effect on spermatogenesis by the iron chelator desferrioxamine, which is used to reduce iron overload. Thalassaemic patients especially those being considered for assisted conception procedures should be counselled accordingly.

Medical (fluoxetine) and psychological (cognitive-behavioural therapy) treatment for premenstrual dysphoric disorder: a study of treatment processes.

OBJECTIVES: To investigate (i) the differential changes in premenstrual symptoms, mood, cognitions, and coping strategies during two treatments [cognitive-behavioural therapy (CBT) and fluoxetine] for premenstrual dysphoric disorder (PMDD) and (ii) the characteristics of those with good vs. poor outcome post treatment and at 1 year follow-up. METHODS: Premenstrual symptoms, mood (Hospital Anxiety and Depression Scale, HADS), causal attributions, and use of cognitive and behavioural coping strategies were examined during 6 months of both treatments. The two treatment groups were then combined and divided on the basis of good vs. poor outcome posttreatment and at 1 year follow-up. Baseline measures were used to predict posttreatment outcome, and baseline and posttreatment measures were examined when attempting to predict outcome at 1 year follow-up. RESULTS: Both treatments were equally effective at the end of 6 months (prospective daily diary measure). Fluoxetine treatment had a more rapid effect and greater impact upon anxiety symptoms, while CBT was associated with increased use of cognitive and behavioural coping strategies and a shift from a biomedical to a biopsychosocial causal attribution of premenstrual symptoms. Depressed mood at baseline assessment was associated with poorer response to both treatments, and learning active behavioural coping strategies was associated with a good outcome at 1 year follow-up. CONCLUSION: These results provide evidence of differential treatment effects of fluoxetine and CBT for PMDD and offer information that will enhance clinical decision-making.

Sperm DNA damage in potentially fertile homozygous beta-thalassaemia patients with iron overload.

BACKGROUND: To test the hypothesis that human sperm DNA could sustain iron-induced oxidative damage and reduce its fertilizing ability, we studied patients with homozygous beta-thalassaemia major (HbTh) as a model of iron overload. METHODS: Sperm from six thalassaemic patients and five age-matched controls were assessed by the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. Semen parameters, endocrine markers of testicular function, iron profiles and the presence of organ dysfunction were also determined. RESULTS: All patients with HbTh were iron overloaded (median ferritin: 2251 microg/l) and had evidence of spontaneous spermatogenesis. Thalassaemic patients had more sperm DNA damage than the controls (P < 0.01). The sperm DNA damage by SCSA and TUNEL were positively correlated (P < 0.05). Sperm motility and TUNEL results were negatively correlated (P < 0.05), while the age of onset of chelation and sperm DNA damage were positively associated with both SCSA (R(2) = 0.80, P = 0.016) and TUNEL data (R(2) = 0.67, P < 0.044). No other biochemical or clinical data were associated with sperm DNA damage. CONCLUSIONS: The increase in sperm DNA damage and the negative correlation between sperm motility and DNA damage suggest that iron overload in HbTh predisposes sperm to oxidative injury. This finding has important implications in assisted reproductive procedures such as ICSI where there is increased risk of transmitting defective DNA to the offspring.

Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy

Basal LH, FSH, 17 beta-oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty-four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration. The mean basal testosterone and 17 beta-oestradiol values in the lepromatous group were significantly lower than those of the tuberculoid and control groups. The abnormal gonadotrophin and sex steroid values in the lepromatous group are in keeping with the testicular atrophy and gynaecomastia accompanying this form of leprosy. However, the lack of a significant correlation between basal FSH and testicular atrophy should be noted. In addition, no correlation between any of these hormonal values and gynaecomastia could be demonstrated. The patients with tuberculoid leprosy had essentially normal hormonal profiles (except for two who had raised 17 beta-oestradiol values). This is compatible with the lack of gonadal involvement in these patients.