The adolescent brain and age-related behavioral manifestations

High resolution two-dimensional electrophoresis of basic as well as acidic proteins

Pathology and genetics of tumours of the urinary system and male genital organs

WHO laboratory manual for the examination and processing of human semen

Objective: Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testos...

/pdf/testosterone-therapy-in-men-with-androgen-deficiency-5gq7m38esq.pdf

Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline.

Peroxidative Breakdown of Phospholipids in Human Spermatozoa, Spermicidal Properties of Fatty Acid Peroxides, and Protective Action of Seminal Plasma

Danazol, an androgen derivative, was evaluated for its effectiveness in preventing attacks of hereditary angioedema in a double-blind study with nine patients. Of 47 placebo courses, 44 ended with attacks, but during 46 danazol courses only one attack occurred. Side effects were minimal, and virilization was not observed in the women studied. C1 esterase inhibitor levels increased three to four times, and levels of the fourth component of complement (C4) increased 15 times. These changes began during the first day of therapy and were maximal by one to two weeks. After therapy was stopped, C1 esterase inhibitor and C4 levels rapidly decreased. Danazol effectively prevents attacks in hereditary angioedema and acts to correct the underlying biochemical abnormality. (N Engl J Med 295:1444–1448, 1976)

Treatment of Hereditary Angioedema with Danazol

CHARGE syndrome and Kallmann syndrome (KS) are two distinct developmental disorders sharing overlapping features of impaired olfaction and hypogonadism. KS is a genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia, and is most commonly due to KAL1 or FGFR1 mutations. CHARGE syndrome, a multisystem autosomal-dominant disorder, is caused by CHD7 mutations. We hypothesized that CHD7 would be involved in the pathogenesis of IHH and KS (IHH/KS) without the CHARGE phenotype and that IHH/KS represents a milder allelic variant of CHARGE syndrome. Mutation screening of the 37 protein-coding exons of CHD7 was performed in 101 IHH/KS patients without a CHARGE phenotype. In an additional 96 IHH/KS patients, exons 6–10, encoding the conserved chromodomains, were sequenced. RT-PCR, SIFT, protein-structure analysis, and in situ hybridization were performed for additional supportive evidence. Seven heterozygous mutations, two splice and five missense, which were absent in ≥ 180 controls, were identified in three sporadic KS and four sporadic normosmic IHH patients. Three mutations affect chromodomains critical for proper CHD7 function in chromatin remodeling and transcriptional regulation, whereas the other four affect conserved residues, suggesting that they are deleterious. CHD7's role is further corroborated by specific expression in IHH/KS-relevant tissues and appropriate developmental expression. Sporadic CHD7 mutations occur in 6% of IHH/KS patients. CHD7 represents the first identified chromatin-remodeling protein with a role in human puberty and the second gene to cause both normosmic IHH and KS in humans. Our findings indicate that both normosmic IHH and KS are mild allelic variants of CHARGE syndrome and are caused by CHD7 mutations.

https://www.cell.com/ajhg/pdf/S0002-9297(08)00492-8.pdf

Mutations in CHD7, Encoding a Chromatin-Remodeling Protein, Cause Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome

Since the introduction of antineoplastic chemotherapy, lasting clinical remissions have been obtained for many patients with acute lymphoblastic leukemia, Hodgkin's disease, gestational trophoblastic tumors, and other malignancies. With this therapeutic success there have been concerns about persistent or delayed toxicities of cancer chemotherapy that may become clinically significant for long-term survivors. Gonadal toxicity and infertility occur in many men, women, and children treated with antineoplastic drugs. In this paper we review the clinical syndromes of chemotherapy-related gonadal toxicity and discuss how particular drug classes, doses, or combinations correlate with the degree of gonadal injury and with the potential for recovery of function. Further, we examine how drug effects on germ cell production and endocrine function vary with the age of the patient at the time of treatment. Finally, we comment on the need for long-term prospective studies of fertility, teratogenesis, and mutagenesis in patients receiving cancer chemotherapy.

Gonadal dysfunction in patients receiving chemotherapy for cancer.

This study describes sexual activity, nocturnal penile erections, and mood states as a function of serum levels of androgens in previously untreated hypogonadal men before and during hormone replacement, selected infertile men (elevated serum follicle-stimulating hormone levels), and normal men. Nocturnal penile tumescence and rigidity were measured with a portable monitor, and sexual activity and mood were assessed by prospective, self-reported written forms. Nocturnal erections were absent or of very low amplitude and duration in the untreated hypogonadal men compared to the infertile and normal men. Nocturnal erections increased steadily during hormone replacement and were in the normal range within 6 to 12 months of treatment. In contrast, serum testosterone concentration rapidly reached the upper range of normal. During treatment, the hypogonadal men reported increases in several aspects of sexual activity, including sexual interest and the number of spontaneous erections. On mood inventories, the untreated hypogonadal men scored significantly higher in ratings of depression, anger, fatigue, and confusion than did infertile and normal men. During hormonal replacement therapy these scores decreased, although the hypogonadal men continued to score higher in "depression" than did infertile and normal men. In most instances, the men with infertility and the normal men were statistically indistinguishable in nocturnal penile tumescence and rigidity parameters, self-reported sexual activity, and mood state. These data support the hypothesis that androgen treatment increases nocturnal and spontaneous erections, and sexual interest, and has some capacity to improve mood.

Richard J. Sherins

Papers

Peroxidative Breakdown of Phospholipids in Human Spermatozoa, Spermicidal Properties of Fatty Acid Peroxides, and Protective Action of Seminal Plasma

Treatment of Hereditary Angioedema with Danazol

Mutations in CHD7, Encoding a Chromatin-Remodeling Protein, Cause Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome

Gonadal dysfunction in patients receiving chemotherapy for cancer.

A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men.