Effect of denosumab on semen quality in infertile men selected by serum level of antimüllerian hormone: a randomized controlled trial.

Objective: To determine whether denosumab could improve sperm concentration in infertile men selected by serum antimüllerian hormone (AMH) ≥ 38 pmol/L. Mouse models, human testicular tissue models, and clinical intervention studies have suggested that the RANKL-inhibitor denosumab, normally used to treat osteoporosis, can improve semen quality in a sub-population of infertile men.

Design: A double-blinded, placebo-controlled, single-center, randomized clinical trial.

Determination of Androgen Bioactivity by an In Vitro Assay During Pubertal Transition in Healthy Boys.

Objective: To describe the bioactivity of circulating androgens during pubertal transition as determined by an in vitro bioassay assessing androgen receptor (AR) activation, and to compare these findings with circulating concentrations of total testosterone (total T) measured by LC-MS/MS.

Methods: This longitudinal study included ten healthy boys from the Copenhagen Puberty Study II conducted from 2006 to 2011.

Main Outcome Measure(s): Androgen bioactivity and serum concentrations of total T were measured by an in vitro bioassay and LC-MS/MS with limits of detection of 0.

Adolescent acne: association to sex, puberty, testosterone and dihydrotestosterone.

The manifestation of acne in adolescents coincides with the emergence of other androgen-dependent characteristics of puberty such as sweat odor and pubic hair. Yet, little is known about the associations with circulating levels of androgens. Thus, the objective was to study the prevalence of acne in healthy children and adolescents according to sex, age, pubertal stage and concentrations of testosterone and dihydrotestosterone (DHT) quantified by LC-MS/MS.

Targeted proteomics of serum IGF-I, -II, IGFBP-2, -3, -4, -5, -6 and ALS.

Objectives: The insulin-like growth factors (IGFs) regulate growth in humans. IGF-I and IGF binding protein (IGFBP)-3 are biomarkers in children with growth disorders. We investigate a targeted proteomics method for absolute quantitation of eight IGF protein family members in human serum, including the peptide hormones IGF-I and -II, and the six binding proteins IGFBP-2, -3, -4, -5, -6 and acid labile subunit (ALS).

Effect of testosterone treatment during puberty in boys with Klinefelter syndrome (The TIPY Study): protocol for a nationwide randomised, double-blinded, placebo-controlled study.

Introduction: Klinefelter syndrome (KS) is a genetic condition characterised by the presence of an extra X chromosome in males (47,XXY). KS is associated with various phenotypic characteristics in adult life, including infertility, hypogonadism and increased risk of type II diabetes, cardiovascular disease and osteoporosis. Additionally, individuals with KS often experience mental health challenges and functional impairments that significantly impact their quality of life.

New Horizons in Klinefelter Syndrome: Current Evidence, Gaps, and Research Priorities.

Klinefelter syndrome (KS) is caused by the presence of a supernumerary X chromosome (conferring the classical 47,XXY karyotype) and is the most common sex chromosome abnormality in men. The clinical features described in the early characterization of the syndrome include tall stature, small testes, hypogonadism, gynecomastia, and neurodevelopmental deficits. However, the syndrome presents a broad phenotypic spectrum that seems to be evolving, along with environmental and general health changes.

Hypophosphatemia is a frequent finding in infertile men and is associated with low motile sperm count.

Study Question: Is serum phosphate linked with semen quality and reproductive hormones in infertile men?

Summary Answer: Hypophosphatemia is a frequent finding in infertile men and is associated with lower number of motile sperm.

What Is Known Already: Phosphate is available in fluid from all segments of the male reproductive tract in concentrations manyfold higher than in serum. However, the role of phosphate in male fertility is largely unknown.

Testicular histopathology and its association with germ cell numbers, serum concentrations of reproductive hormones, and semen quality.

Background: It is well-established that spermatogenesis, semen quality, and reproductive hormones are interlinked. It is, however, less well-described how various specific testicular histopathologies are linked to reproductive hormones and semen quality.

Objectives: To describe the detailed relationship between specific testicular histopathologies and the serum concentrations of reproductive hormones and semen quality.

Sex- and age-specific reference intervals of 16 steroid metabolites quantified simultaneously by LC-MS/MS in sera from 2458 healthy subjects aged 0 to 77 years.

Background: Reference intervals covering the whole life span for all the metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing.

Objective: To develop a state-of-the-art LC-MS/MS method for simultaneous quantification of multiple steroid metabolites and to establish detailed sex- and age-specific reference intervals for 16 steroid metabolites.

Materials And Method: An isotope diluted LC-MS/MS method was developed for simultaneous quantitation of 16 steroid hormones.

Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life.

Objective: To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development.

Methods: Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs).

X‑chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome.

Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome.

Reduced serum concentrations of biomarkers reflecting Leydig and Sertoli cell function in male patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a recessive condition that affects the adrenal glands. Despite life-long replacement therapy with glucocorticoids and mineralocorticoids, adult patients with CAH often experience impaired gonadal function. In pubertal boys and in men with CAH, circulating testosterone is produced by the adrenal glands as well as the testicular, steroidogenic cells.

Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome.

Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

Introduction: Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors.

Patients And Methods: This was a single-center, double-blind, randomized, controlled trial.

Microdissection Testicular Sperm Extraction Versus Multiple Needle-pass Percutaneous Testicular Sperm Aspiration in Men with Nonobstructive Azoospermia: A Randomized Clinical Trial.

Background: Surgical extraction of testicular spermatozoa is needed in men with nonobstructive azoospermia (NOA) who wish to become biological fathers. Based on available uncontrolled studies with unspecific patient selection, microdissection testicular sperm extraction (mTESE), having a sperm retrieval rate (SRR) of 50%, is considered the most efficient sperm retrieval procedure. However, no randomized clinical trials for comparison of different sperm retrieval procedures exist.

Optimized detection of germ cell neoplasia in situ in contralateral biopsy reduces the risk of second testis cancer.

Objective: To evaluate whether optimized and standardized diagnostic procedures would improve detection of germ cell neoplasia in situ (GCNIS) in the contralateral testis of patients with testicular germ cell tumour (TGCT) and decrease the rate of metachronous tumours, which in a nationwide Danish study was estimated to be 1.9%.

Patients And Methods: This was a retrospective analysis of outcomes in 655 patients with TGCT who underwent contralateral biopsies (1996-2007) compared with those in 459 non-biopsied TGCT controls (1984-1988).

Prepubertal and pubertal gonadal morphology, expression of cell lineage markers and hormonal evaluation in two 46,XY siblings with 17β-hydroxysteroid dehydrogenase 3 deficiency.

Objectives: 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiency results in insufficient biosynthesis of testosterone and consequently dihydrotestosterone. This is important for the fetal development of male genitalia. Thus, most 46,XY patients with 17β-HSD3 deficiency have a female appearance at birth and present with virilization at puberty.

Long-term testosterone undecanoate treatment in the elderly testosterone deficient male: An observational cohort study.

Background: Quarterly intramuscular injections with long-acting testosterone undecanoate (TU) provide stable serum testosterone concentrations over time and are therefore preferred by many testosterone-deficient patients. However, the use of long-acting TU in elderly patients is limited due to lack of safety and feasibility studies.

Objective: To investigate long-acting TU pharmacokinetics and assess differences in treatment regimens and risk of adverse outcomes in younger versus elderly testosterone-deficient patients.

Serum Concentrations and Gonadal Expression of INSL3 in Eighteen Males With 45,X/46,XY Mosaicism.

Objective: Insulin-like factor 3 (INSL3) is produced in the testes and has been proposed as a circulating biomarker of Leydig cell capacity, but remains undescribed in 45,X/46,XY mosaicism. The aim was to examine serum concentrations and gonadal expression of INSL3 in 45,X/46,XY mosaicism.

Methods: Retrospectively collected data from medical records, gonadal tissue samples, and prospectively analyzed serum samples from eighteen male patients with 45,X/46,XY mosaicism (one prepubertal, four testosterone-treated, 13 untreated) were included.

The LH/FSH ratio is not a sex-dimorphic marker after infancy: data from 6417 healthy individuals and 125 patients with Differences of Sex Development.

Study Question: What is the course of the LH/FSH ratio from infancy into adulthood in healthy individuals and in patients with Differences of Sex Development (DSD)?

Summary Answer: The LH/FSH ratio had a marked overlap between the sexes after infancy and onwards throughout adulthood in healthy individuals and it was not a marker of hypogonadism in DSD patients.

What Is Known Already: The LH/FSH ratio is a distinct marker of sex during minipuberty. No study has evaluated the LH/FSH ratio from infancy into adulthood.