Hormone and genetic study in male to female transsexual patients.

BACKGROUND: Data of the literature demonstrated controversial results of a correlation between transsexualism and genetic mutations. AIM: To evaluate the hormone and gene profile of male-female (M-F) transsexual. SUBJECTS AND METHODS: Thirty M-F transsexuals aged 24-39. Seventeen had already undergone sex reassignment surgery, 13 were awaiting. All subjects had been undergoing estrogen and antiandrogen therapy. We studied hormones of the hypothalamus- pituitary-testicular axis, thyroid and adrenal profile, GH basal and after GHRH stimulation, IGF-I. The gene study analyzed SRY, AR, DAX1, SOX9, AZF region of the Y chromosome. RESULTS: Pre-surgery subjects had elevated PRL, reduced testosterone and gonadotropins. Post-surgery subjects showed reduced androgens, a marked increase in LH and FSH and normal PRL. Cortisol and ACTH were similar to reference values in pre- and post-surgery patients. There was a marked increase in the baseline and post-stimulation GH values in 6 of the 13 pre-surgery patients, peaking at T15. IGF-I was similar to reference values in both groups except for one post-surgery patient, whose level was below the normal range. There were no polymorphisms in the amplified gene region for SOX9, and a single nucleotide synonimous polymorphism for DAX1. No statistically significant differences were seen in the mean of CAG repeats between controls and transsexual subjects. SRY gene was present in all subjects. Qualitative analysis of the AZFa, AZFb, and AZFc regions did not reveal any microdeletions in any subject. CONCLUSIONS: This gender disorder does not seem to be associated with any molecular mutations of some of the main genes involved in sexual differentiation.

Impact of chronic viral diseases on semen parameters.

The aim of this study was to assess the effect of human immunodeficiency virus (HIV), hepatitis C (HCV) and B (HBV) virus infection on semen parameters. Semen samples were obtained from 27 HCV, 34 HIV, 30 HBV and 41 HCV-HIV-seropositive patients and compared with those of a control population of healthy seronegative subjects. Tests for detection of HIV, HCV and HBV were performed on seminal samples. The sperm concentration was significantly decreased in HCV- and HBV-seropositive males compared to that of controls (P < 0.001). The mean sperm motility (a + b) was significantly decreased in HCV- and HBV-seropositive (P < 0.001) and in HCV-HIV-seropositive subjects (P < 0.05) compared to that of controls. The sperm viability was significantly lower in HCV- and HBV-seropositive men than in controls (P < 0.001). The normal morphology was significantly reduced in HCV-seropositive and HBV-seropositive men (P < 0.05) with respect to that of controls (P < 0.05). The sperm concentration after sperm wash was significantly higher in controls than in HCV-, HIV-, HBV- and HIV-HCV-seropositive men (P < 0.001). We can conclude that HBV- and HCV-infected men have a significantly impaired sperm quality compared with that of controls. The reason for the better sperm quality in our series of HIV- and HCV-HIV-infected men is still under debate. Further investigations in a larger case series are warranted.

Androgen receptor polymorphisms and testicular cancer risk.

Testicular cancer (TC) is currently the most common malignant solid tumour in Caucasian males aged 15-39 years. Epidemiological evidence suggests that its onset may be due to an imbalance in the action of steroidal sex hormones and their receptors. A faulty androgen receptor signalling pathway can, in fact, cause various male reproductive disorders. The androgen receptor (AR) gene has two polymorphic segments consisting of CAG and GGC repeats. The length of CAG repeats has been shown to affect the regulation of AR activity. In our study, we used fragment analysis to evaluate the AR gene repeats of 302 TC patients and 322 controls, to establish if there is any association between repeat number and TC. This study of the largest Italian caseload investigated to date highlighted three particularly significant aspects. First, a CAG repeat number of ≥25 may be considered a risk factor for the onset of TC, given its greater frequency in patients in comparison with controls. This difference became significant for the non-seminoma group. Second, men with CAG repeats below 21 or above 24 were found to have a, respectively, 50 and 76% higher risk of TC than those with CAG 21-24, suggesting that these too can be considered a risk factor for TC. Finally, stage II patients were more likely to have a CAG repeat number <21 or >24 than stage I patients.

Suicide in two patients with a diagnosis of probable Alzheimer disease.

Two patients meeting the criteria for probable Alzheimer disease (AD) who were participating in a phase 3 clinical program with eptastigmine, a cholinesterase inhibitor, committed suicide. The first patient committed suicide by a self-inflicted gunshot wound to the head. The second patient committed suicide by jumping from a 19th story window. These two patients shared several clinical features with those found in the literature: being at the early stages of the disease, having a high level education, with preserved insight, having access to firearms, and being aware of not responding to pharmacological treatment.