Monitoring of Testosterone Replacement Therapy to Optimize the Benefit-to-Risk Ratio.

For hypogonadal men treated with testosterone, the goal is to ensure that benefits are optimized, risks are minimized, and any adverse effects are identified early and managed appropriately. This can best be achieved by careful patient selection, excluding men with contraindications and addressing any modifiable risk factors in those at increased risk. A standardized plan should be used for monitoring that includes evaluation of symptoms, side effects, adherence, and measurement of testosterone and hematocrit.

Further Delineation of Liver Involvement in Girls and Women with Turner Syndrome: Case Report of a 2-Year-Old with Liver Dysfunction and Review of Patients Followed in the MassGeneral Hospital Turner Syndrome Clinic.

Background: Liver function test (LFT) abnormalities, which may reflect underlying pathophysiology, are a well-known feature of Turner syndrome. Less frequently, liver findings may include vascular changes and, rarely, severe liver disease. Although previous studies on children and adolescents suggest a frequency of LFT abnormalities of up to 60%, less is known about the age at onset and natural history.

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years.

Turner syndrome is recognized now as a syndrome familiar not only to pediatricians and pediatric specialists, medical geneticists, adult endocrinologists, and cardiologists, but also increasingly to primary care providers, internal medicine specialists, obstetricians, and reproductive medicine specialists. In addition, the care of women with Turner syndrome may involve social services, and various educational and neuropsychologic therapies. This article focuses on the recognition and management of Turner syndrome from adolescents in transition, through adulthood, and into another transition as older women.

Klinefelter Syndrome and Diabetes.

Purpose Of Review: Klinefelter syndrome (KS) is associated with increased insulin resistance and high rates of type 2 diabetes (T2DM). Our aim was to review what is known about the prevalence of diabetes in men with KS, potential mechanisms underlying the observed metabolic phenotype, and the data that are available to guide treatment decisions.

Recent Findings: The increased prevalence of T2DM seen in men with KS appears to be the result of multiple mechanisms including increased truncal adiposity and socioeconomic disadvantages, but it is likely not a direct consequence of hypogonadism alone.

Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History.

Context: After completion of puberty a subset of men experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men.

Objective: To investigate the neuroendocrine mechanisms, genetics, and natural history underlying FHH.

Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.

Objective: To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010.

Participants: The participants include an Endocrine Society-appointed task force of 10 medical content experts and a clinical practice guideline methodologist.

Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence.

Turner syndrome: update on biology and management across the life span.

Purpose Of Review: We review recent understanding of the pathophysiology, molecular biology, and management of Turner syndrome.

Recent Findings: Sophisticated genetic techniques are able to detect mosaicism in one-third of individuals previously thought to have monosomy X. Prenatal detection using maternal blood should permit noninvasive detection of most fetuses with an X chromosome abnormality.

Reversal and relapse of hypogonadotropic hypogonadism: resilience and fragility of the reproductive neuroendocrine system.

Context: A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal.

Objective: The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes.

Design, Setting, And Subjects: This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center.

Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism.

Context And Objective: The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method.

Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism.

Objective: This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT).

Design: Cross-sectional study.

Patients And Methods: 74 men (19-74 years, mean 51·4 ± 1·4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min.

Long-term outcome of idiopathic hypogonadotropic hypogonadism.

Purpose Of Review: This review focuses on the presentation, treatment and long-term outcomes of men with idiopathic hypogonadotropic hypogonadism (IHH).

Recent Findings: The traditional view that IHH is a simple monogenic disorder has now been revised, with some cases having an oliogenic basis involving mutations in more than one locus in each affected individual. The majority of IHH men respond well to induction of spermatogenesis with gonadotropins or pulsatile gonadotropin-releasing hormone.

The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism.

Context And Objective: Adult-onset idiopathic hypogonadotropic hypogonadism (AHH) is a rare disorder characterized by an isolated failure of gonadotropin secretion occurring after an otherwise normal sexual maturation in men. This study aims to examine the etiology and long-term natural history of this disorder.

Design And Setting: Long-term follow up, including detailed clinical, biochemical, and genetic examinations, were performed and compared with those at diagnosis.

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

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.

Congenital idiopathic hypogonadotropic hypogonadism: evidence of defects in the hypothalamus, pituitary, and testes.

Context: Idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH) or anosmia (Kallmann syndrome) is associated with defects in the production or action of GnRH. Accordingly, most IHH patients respond to physiological pulsatile GnRH replacement by normalizing serum LH, FSH, and testosterone (T) levels and achieving gametogenesis; some patients, however, show atypical responses. Interestingly, several IHH-associated genes are expressed in multiple compartments of the hypothalamic-pituitary-gonadal axis.

Role of seminiferous tubular development in determining the FSH versus LH responsiveness to GnRH in early sexual maturation.

Background: The onset of sexual maturation at puberty is a unique developmental period from a neuroendocrine perspective in that it is characterized by enhanced FSH secretion and FSH responsiveness to exogenous GnRH (vs. LH) from the gonadotrope, yet the mechanism of these dynamics remains unclear. This study aimed to elucidate this phenomenon using a human disease model of GnRH deficiency (idiopathic hypogonadotropic hypogonadism, IHH) in which GnRH input can be experimentally controlled.

Impaired fibroblast growth factor receptor 1 signaling as a cause of normosmic idiopathic hypogonadotropic hypogonadism.

Context: FGFR1 mutations have been identified in about 10% of patients with Kallmann syndrome. Recently cases of idiopathic hypogonadotropic hypogonadism (IHH) with a normal sense of smell (nIHH) have been reported.

Aims: The objective of the study was to define the frequency of FGFR1 mutations in a large cohort of nIHH, delineate the spectrum of reproductive phenotypes, assess functionality of the FGFR1 mutant alleles in vitro, and investigate genotype-phenotype relationships.

Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine.

Objective: To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.

Methods: Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy.

Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum.

Context: Mice deficient in prokineticin 2(PROK2) and prokineticin receptor2 (PROKR2) exhibit variable olfactory bulb dysgenesis and GnRH neuronal migration defects reminiscent of human GnRH deficiency.

Objectives: We aimed to screen a large cohort of patients with Kallmann syndrome (KS) and normosmic idiopathic hypogonadotropic hypogonadism (IHH) for mutations in PROK2/PROKR2, evaluate their prevalence, define the genotype/phenotype relationship, and assess the functionality of these mutant alleles in vitro.

Design: Sequencing of the PROK2 and PROKR2 genes was performed in 170 KS patients and 154 nIHH.

Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups.

Context: Low sex hormone levels have been associated with the metabolic syndrome (MetS).

Objectives: Our objective was to determine whether the association between sex hormone levels and MetS varies by race/ethnicity among men and to investigate the relationship of sex hormones and individual components of MetS.

Design: We conducted a population-based observational survey.