Hypogonadism Research Articles

Abstract 101: A case of CYP11A1 enzyme deficiency with unambiguity

We hereby present a 20 years old boy who presented at 14 years of age with generalized hyperpigmentation, bilateral breast enlargement, loose stools and fever. He was born out of second-degree consanguinity with uneventful birth and childhood history. On examination he had generalized hyperpigmentation, gynecomastia, no genital ambiguity with normal sexual maturity ratings. Blood biochemistry was suggestive of primary adrenal insufficiency and primary testicular failure. The computerized tomography imaging showed normal adrenal glands. With involvement of both adrenal glands and gonads, differential diagnosis including autoimmune polyglandular syndrome, NR5A1 and NR0B1 mutations were considered. Clinical exome sequencing was done which showed a novel homozygous missense variation in exon 4 of the CYP11A1 gene (chr15:g.74343895G>C). A diagnosis of side chain cleavage enzyme (CYP11A1) deficiency unusually presenting with genital unambiguity was made.

Correction of Androgen Deficiency in Men with Type 2 Diabetes.

In men with low levels of testosterone in the blood, it is believed that the symptoms can be regarded as an association between testosterone deficiency syndrome and related comorbidities. To investigate the effectiveness of testosterone therapy in patients with type 2 diabetes (T2D) and androgen deficiency. Testosterone replacement therapy was carried out in 26 men with T2D and clinically or laboratory-confirmed androgen deficiency. The age of the subjects ranged from 35 to 69 years old. Laboratory studies included determinations of the concentration of the hormones estradiol, luteinizing hormone (LH), and prostate-specific antigen (PSA). The observation period was 9 months. The average level of total blood testosterone in the subjects before treatment was 9.4 mol/l and was likely lower than that of the control group (19.3 ± 1.6 nmol/l). The levels of total testosterone in the subjects ranged from 3.9 nmol/l to 10.7 nmol/l, and hormone levels measuring less than 8.0 nmol/l were observed in only 11 patients. After a course of testosterone replacement therapy, a stabilization in total testosterone levels at the level of reference values (as compared to the start of treatment) was observed in the blood of men with T2D after 9 months of observation and the administration of the fourth injection (16.83 ± 0.75 nmol/l). The use of long-acting injectable testosterone undecanoate leads to normalization of total testosterone levels in the blood of men with T2D and androgen deficiency, and LH levels in these patients are unlikely to change.

Chronic exposure to delta-9-tetrahydrocannabinol impacts testicular volume and male reproductive health in rhesus macaques

To determine the dose-dependent effect of delta-9-tetrahydrocannabinol (THC) exposure on male testes and reproductive health in a nonhuman primate model. Research animal study. Research institute. Adult male rhesus macaques 8-10 years of age (n = 6). Daily edible THC at medically and recreationally relevant doses. Testicular volume and epididymal head width, serum levels of inhibin B, albumin, total testosterone, prolactin, follicle-stimulating hormone, estradiol, and luteinizing hormone; semen volume; and sperm motility, morphology, and concentration. For each 1 mg/7 kg/day increase in THC dosing, there was a marked loss in total bilateral testicular volume of 11.8 cm3 (95% confidence interval [CI]: 8.3-15.4). In total, average bilateral testicular volume decreased by 58%. Significant dose-response decreases in mean total testosterone level by 1.49 ng/mL (95% CI: 0.83-2.15) and in estradiol level by 3.8 pg/mL (95% CI: 2.2-5.4) were observed, but significant increases in the levels of follicle-stimulating hormone by 0.06 ng/mL (95% CI: 0.02-0.10), luteinizing hormone by 0.16 ng/mL (95% CI: 0.08-0.25), and prolactin by 7.4 ng/mL (95% CI: 3.4-11.3) were observed. There were no statistically significant changes in semen parameters. In rhesus macaques, chronic exposure to THC resulted in significant dose-response testicular atrophy, increased serum gonadotropin levels, and decreased serum sex steroids, suggestive of primary testicular failure. Further studies are needed to determine if reversal of these observed adverse effects would occur if THC was discontinued and for validation of thefindings in a human cohort.

Endocrine aberrations of human nonobstructive azoospermia.

Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic–pituitary–testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.

Disorders of Sex Development of Adrenal Origin.

Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.

New and Consolidated Therapeutic Options for Pubertal Induction in Hypogonadism: In-depth Review of the Literature.

Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at "the child with delayed puberty of uncertain etiology" risk being misapplied to older adolescents likely to have permanent hypogonadism.

Ovarian reserve in nigerian women with sickle cell anaemia: a cross- sectional study

IntroductionSickle cell disease is the most common monogenetic disorder worldwide. There have been reports of endocrine dysfunction and gonadal failure among affected individuals, especially in males. The findings on ovarian reserve and failure in women with sickle anaemia have been inconsistent.Aim and objectiveThe aim of this study was to determine and compare the ovarian reserve of Nigerian women with and without sickle cell anaemia attending a University Teaching Hospital.Study DesignThis cross-sectional study was carried out at the Adult Sickle Cell Clinic and the Community Health Clinic of the Lagos University Teaching Hospital.MethodologyA total of 166 participants who met the selection criteria, were recruited for the study. The study population consisted of two groups of women matched for age: 83 women with HbSS and 83 women with HbAA. The haemoglobin phenotype of each participant was determined on alkaline electrophoresis (pH 8.4) before analysis. Serum Anti-Mullerian Hormone (AMH) was determined using Enzyme-linked immunosorbent assay (ELISA) method (Calbiotech Inc. USA, Catalog no AM448T).ResultsThe mean ± SD of serum AMH level in women with HbSS was 3.64 ± 0.65 ng/mL and was lower than that of women with HbAA 7.35 ±1.19 ng/mL (p < 0.001). Serum AMH negatively correlated with age in both study groups (HbAA and HbSS). Also, a significant negative correlation was found between serum AMH and BMI in women with HbAA.ConclusionThe study showed diminished ovarian reserve in women with HbSS when compared to age-matched women with HbAA.

Evaluating incidence, prevalence, and treatment trends in adult men with hypogonadism in the United States.

No extensive studies have investigated current diagnosis and treatment trends of hypogonadism (HG) in adult men in the United States. Using a comprehensive commercial insurance database, we surveyed current trends in incidence, prevalence, and treatment of hypogonadism in the United States. We analyzed insurance claims data from 2008-2017 using the IBM MarketScan™ Commercial Claims and Encounters database for men ≥18. Overall, we estimated annual incidence at 16.1 cases per 100,000 person-years, with the highest incidence seen among men 35-44 years at 21.5 cases per 100,000 person-years (IRR 1.83; 95% CI 1.63, 2.06, p < 0.001) and among those living in the Southern United States at 22.6 cases per 100,000 person-years(IRR 1.96; 95% CI 1.76, 2.18, p < 0.001). The prevalence of HG across the study period increased from 0.78% to 5.4%, while treatment rates decreased from 32.9% to 20.8%. These study findings provide a large-scale view of current diagnosis rates and treatment of hypogonadism in adult men in the United States. Despite the increase in prevalence of disease, there is an observed decline in treatment rates after diagnosis. Further investigations are needed to identify factors driving the observed decline in healthcare utilization among men with hypogonadism.

Clinical utility and prognostic implications of the novel 4S-AF scheme to characterize and evaluate patients with atrial fibrillation: a report from ESC-EHRA EORP-AF Long-Term General Registry.

The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60-25.9], (Sb) (aHR 1.21, 95% CI: 1.08-1.35), and (Su) (aHR 1.27, 95% CI: 1.14-1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45-2.06) and (Sy) (aHR 1.29, 95% CI: 1.00-1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55-0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16-1.56). Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

Impacts of polyclonal antibody preparations from avian origin as a feed additive to beef cattle: immune responses during the step-up transition diets.

This study investigated the effects of feeding an avian-derived polyclonal antibody preparation (PAP; CAMAS, Inc.) against Streptococcus bovis, Fusobacterium necrophorum, and lipopolysaccharides (LPS; 40%, 35%, and 25% of the preparation, respectively) on immune responses (haptoglobin [Hp], serum amyloid A [SAA], rectal temperature [RT], leukocyte counts, and expression of cell adhesion molecules cluster of differentiation [CD] CD11b, CD14, and CD62L) of beef steers during a 21-d step-up adaptation to a high-grain diet. Eight ruminally cannulated Angus crossbred beef steers (658 ± 79 kg of BW) were assigned in a cross-over design and transitioned from a diet containing bermudagrass hay (Cynodon dactylon (L.) Pers.) ad libitum plus 0.45 kg/d of molasses with 0 (CON) or 3 g of PAP to a high-grain diet. Transition consisted of three 7-d steps of increased inclusion of cracked corn (35%, 60%, and 82% of the diet dry matter for STEP1, STEP2, and STEP3, respectively). On each transition day and 7 d after STEP3 (STEP3-7d), RT was obtained every 3 h for a total of 24 h, whereas blood was collected on days 0, 1, and 3, relative to diet transition. There were no effects of PAP inclusion in any of the blood parameters (P > 0.11). However, a tendency for day effect (P = 0.10) was observed for concentrations of Hp, which were greater on days 3 and 7 vs. day 0 relative to the second diet transition (STEP2). Plasma concentrations of SAA were greater on days 1, 3, and 7 compared to day 0 during STEP1 (P = 0.01), while during STEP2 and STEP3, SAA concentrations increased (P < 0.01) from day 0 to 3. During STEP2, PAP steers tended to have lower (P = 0.08) RT than CON steers. Neutrophil and monocyte counts were the least during STEP3 (P < 0.01), whereas expression of CD11b and CD62L was the least through forage feeding (P < 0.01). Concentration of starch in the diet was correlated to all the variables tested (P ≤ 0.01), except for the percentage of B cells (P = 0.22). Yet only ruminal pH, RT, monocyte, and neutrophil counts presented strong correlation coefficients. In conclusion, the step-up transition from forage to high-grain diets triggered systemic inflammation in beef steers as observed by increased plasma concentrations of Hp, SAA, and expression on adhesion molecules in leukocytes. However, feeding polyclonal antibody preparations against S. bovis, F. necrophorum, and LPS did not provide benefits to mitigate inflammation.

Generation of Primordial Germ Cell-like Cells from iPSCs Derived from Turner Syndrome Patients

Turner syndrome (TS) is a genetic disorder in females with X Chromosome monosomy associated with highly variable clinical features, including premature primary gonadal failure leading to ovarian dysfunction and infertility. The mechanism of development of primordial germ cells (PGCs) and their connection with ovarian failure in TS is poorly understood. An in vitro model of PGCs from TS would be beneficial for investigating genetic and epigenetic factors that influence germ cell specification. Here we investigated the potential of reprogramming peripheral mononuclear blood cells from TS women (PBMCs-TS) into iPSCs following in vitro differentiation in hPGCLCs. All hiPSCs-TS lines demonstrated pluripotency state and were capable of differentiation into three embryonic layers (ectoderm, endoderm, and mesoderm). The PGCLCs-TS recapitulated the initial germline development period regarding transcripts and protein marks, including the epigenetic profile. Overall, our results highlighted the feasibility of producing in vitro models to help the understanding of the mechanisms associated with germ cell formation in TS.

Impact of Andropause on Multiple Sclerosis.

Andropause results from the natural decrease in testosterone levels that occurs with age. In contrast to menopause, which is a universal, well-characterized process associated with absolute gonadal failure, andropause ensues after gradual decline of both hypothalamic-pituitary-gonadal axis activity, as well as of testicular function, a process which usually develops over a period of many years. Increasing evidence on greater risk of Multiple sclerosis (MS) associated with lower testosterone levels is being reported. Likewise, epidemiological studies have shown a later age of onset of MS in men, relative to women, which could perhaps respond to the decline in protective testosterone levels. In this review, we will discuss the role of androgens in the development and function of the innate and adaptive immune response, as well as in neuroprotective mechanisms relevant to MS. Testosterone effects observed in different animal models and in epidemiological studies in humans will be discussed, as well as their correlation with physical disability and cognitive function levels. Finally, published and ongoing clinical trials exploring the role of androgens, particularly at key stages of sexual maturation, will be reviewed.

Effectiveness of mesenchymal stem cells cultured under hypoxia to increase the fertility rate in rats (Rattus norvegicus).

Background and Aim:Mesenchymal stem cells (MSCs) transplanted into the testes of rats with testicular failure can help rescue fertility. However, the low viability of transplanted MSCs limits the success of this treatment. This study aimed to determine the effectiveness of MSCs cultured under hypoxia to increase the fertility rate in rats (Rattus norvegicus).Materials and Methods:Bone marrow-derived MSCs (200 million cells/rat) were transplanted into male rat models with induced infertility (10 rats/treatment group) after 4 days of culture in 21% O2 (normoxia) and 1% O2 (hypoxia). Ten fertile and 10 untreated infertile rats served as controls. In the infertile male rats that had been fasted from food for 5 days, the fasting condition induced malnutrition and then resulted in testicular failure.Results:The results indicated that the MSCs cultured under hypoxic conditions were more effective than those cultured in normoxic conditions as a treatment for testicular failure in infertile male rats based on the increased number of cells expressing p63 as a quiescent cell marker and ETV5 as a transcription factor expressed in Sertoli and germ cells. Furthermore, the structure of the seminiferous tubules, which contain spermatogonia, primary and secondary spermatocytes, and spermatid, Sertoli, and Leydig cells, was improved in infertile male rats treated with the MSCs cultured under hypoxic conditions.Conclusion:The testicular transplantation of MSCs cultured under hypoxic conditions was an effective treatment for testicular failure in rats.

Effect of superhydrophobicity on the wake of a pitching foil across various Strouhal numbers

Particle image velocimetry-based measurements have been performed to study the flow over a pitching superhydrophobic NACA—National Advisory Committee for Aeronautics—0012 foil (SphNACA0012 foil) and to compare the same with NACA0012 foil. This is perhaps the first experimental study on a pitching SphNACA0012 foil. The objective is to understand the effects of superhydrophobicity on NACA0012 foil pitching about its leading edge at various Strouhal numbers, St = 0.08–0.65, with a constant pitching amplitude, θ0 = 4°, and Reynolds number, Re = 2400. Superhydrophobicity is found to significantly affect three different flow regimes: 2S von-Ka´rma´n wake, symmetric wake, and asymmetric wake regimes at smaller, intermediate, and larger values of St. In the 2S von-Ka´rma´n wake regime, although the wake structures of both the foils are quite comparable, a reduction in the shear layer strength and early rolling-up of vortices are observed for SphNACA0012 foil due to a partial slip effect. With a further increase in St, a transition to the symmetric wake regime is observed for both the foils and another transition that leads to a symmetry breaking of the vortex street is found to be earlier for SphNACA0012 foil, which results in the onset of lift generation at lower St than that of NACA0012 foil. The shear layer strength is weaker for the SphNACA0012 foil except at St = 0.24, which is a critical St for the jet deflection point and results in a 13% larger thrust coefficient for SphNACA0012 foils as compared to NACA0012 foils. These results on the larger lift as well as thrust coefficient at low St suggest improved maneuverability with high propulsive efficiency when superhydrophobicity is employed on the propulsor of underwater vehicles.

Cryopreservation of Gametes and Embryos and Their Molecular Changes.

The process of freezing cells or tissues and depositing them in liquid nitrogen at –196 °C is called cryopreservation. Sub-zero temperature is not a physiological condition for cells and water ice crystals represent the main problem since they induce cell death, principally in large cells like oocytes, which have a meiotic spindle that degenerates during this process. Significantly, cryopreservation represents an option for fertility preservation in patients who develop gonadal failure for any condition and those who want to freeze their germ cells for later use. The possibility of freezing sperm, oocytes, and embryos has been available for a long time, and in 1983 the first birth with thawed oocytes was achieved. From the mid-2000s forward, the use of egg vitrification through intracytoplasmic sperm injection has improved pregnancy rates. Births using assisted reproductive technologies (ART) have some adverse conditions and events. These risks could be associated with ART procedures or related to infertility. Cryopreservation generates changes in the epigenome of gametes and embryos, given that ART occurs when the epigenome is most vulnerable. Furthermore, cryoprotective agents induce alterations in the integrity of germ cells and embryos. Notably, cryopreservation extensively affects cell viability, generates proteomic profile changes, compromises crucial cellular functions, and alters sperm motility. This technique has been widely employed since the 1980s and there is a lack of knowledge about molecular changes. The emerging view is that molecular changes are associated with cryopreservation, affecting metabolism, cytoarchitecture, calcium homeostasis, epigenetic state, and cell survival, which compromise the fertilization in ART.

Serum prokineticin-2 in prepubertal and adult Klinefelter individuals.

The prokineticin-2 (PROK2) is a small peptide belonging to the prokineticin family. In humans and rodents this chemokine is primarily involved in the control of central and peripheral reproductive processes. Klinefelter's syndrome (KS) is the first cause of male genetic infertility, due to an extra X chromosome, which may occur with a classical karyotype (47, XXY) or mosaic forms (46, XY/47, XXY). In affected subjects, pubertal maturation usually begins at an adequate chronological age, but when development is almost complete, they display a primary gonadal failure, with early spermatogenesis damage, and later onset of testosterone insufficiency. Thus, the main aim of the present study was to investigate the serum levels of PROK2 in prepubertal and adult KS patients, comparing them with healthy subjects. We showed for the first time the presence of PROK2 in the children serum but with significant changes in KS individuals. Indeed, compared with healthy subjects characterized by PROK2 serum elevation during the growth, KS individuals showed constant serum levels during the sexual maturation phase (higher during the prepubertal phase but lower during the adult age). In conclusion, these data indicate that in KS individuals PROK2 may be considered a biomarker for investigating the SK infertility process.

Health problems of postmenopausal women

Abstract: The postmenopausal period is the final stage of the transition from the procreative period to the senium period. It is also a time of many complex biological transformations. The changes that occur, associated with the gradual expiration of the endocrine function of the ovaries, can affect the appearance of many psychophysical ailments. Low estrogen values, which are physiologically observed in the postmenopausal period, result in the appearance of various health problems. Clinical signs are divided into early (short-term) and late (long-term). This work discusses the definition and course of postmenopause and the health problems and consequences of sex hormone deficiencies on a woman's body systems. Being aware of the changes taking place during this period of women's lives can help improve and/or create new prophylactic programs. This knowledge seems essential in the daily practice of health professionals, in particular gynaecologists and midwives.&#x0D; Key words: menopause, postmenopause, climacteric syndrome

Pregnancy and pregnancy outcomes after hematopoietic stem cell transplantation in childhood: a cross-sectional survey of the EBMT Pediatric Diseases Working Party.

What are the characteristics of patients with conceptions transplanted in childhood and adolescence? Insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence was possible, even after myeloablative conditioning regimes, although some patients required reproductive medicine support. Preparative regimens of HCT are highly gonadotoxic, which leads to gonadal failure and pubertal development disorders. There are few population-based studies assessing the risk of future infertility in children after HCT. We conducted a retrospective study to investigate natural or assisted conceptions and their outcomes in patients <18 years old before their first transplantation who received HCT between 1995 and 2016 and were in the European Society for Blood and Marrow Transplantation (EBMT) registry. Adoptions were excluded from the analysis. Detailed information concerning pregnancy occurrences and outcomes were obtained by a separate questionnaire. Quantitative variables were presented as medians with their interquartile range (IQR) or range, and categorical variables were presented as frequencies and percentages. In total, 62 988 pediatric patients received a first HCT in EBMT centers between 1995 and 2016. Pregnancy was reported in 406 patients in the database. The median age at transplantation was 15.7 (range: 0.7-18) years, and the median age at declared conception was 25.0 (range: 16.3-38.8) years. Details concerning the first pregnancy and pregnancy outcome were obtained from 99 patients (24%) from the returned questionnaires. The median age at delivery or pregnancy interruption of the females was 23.0 (IQR: 20.8-27) years, with a median time after transplant of 10.7 (IQR: 6.6-15.4) years. Compared with the mean age of healthy women at their first child's birth (29 years old), the transplanted women delivered 5 years earlier (mean: 24.3 years). In terms of conception modality, 13/25 (52%) females conditioned with total body irradiation (TBI) and 50/52 (96%) of those conditioned without TBI conceived naturally. All seven male patients who had been conditioned with TBI achieved fatherhood but required assisted fertilization or used their cryopreserved sperm. In the females, 63/70 (90%) of all conceptions resulted in a live birth, 49/63 (84.5%) were at term and 43/46 (93%) had normal birthweight. Cesarean delivery was performed in 9/61 (15%) especially in women who had received a myeloablative regimen. In the EBMT pediatric dataset, the age at last follow-up or death was <17 years for 75% of the patients, therefore a longer follow-up for all patients would be necessary to calculate the cumulative incidence of conception for patients transplanted during childhood and allow all patients to realize their reproductive willingness/potential. Reproductive health surveillance and fertility preservation counseling are important in younger transplanted patients. Our results showed that there is a window of opportunity to conceive naturally or with reproductive medicine support. Funding was provided by the 'Stiftung für krebskranke Kinder Regio Basiliensis', Basel, Switzerland. All authors have no conflicts of interest to declare. N/A.

Чоловічий гіпогонадизм (частина 2)

У другій частині лекції наведені сучасні дані щодо методів діагностики різних форм гіпогонадизму, описано лікування найбільш поширених форм цієї патології.

MP31-08 EXOGENOUS TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME NEGATIVELY IMPACTS SPERM RETRIEVAL

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-08 EXOGENOUS TESTOSTERONE THERAPY IN MEN WITH KLINEFELTER SYNDROME NEGATIVELY IMPACTS SPERM RETRIEVAL Caroline Kang, Nahid Punjani, and Peter N. Schlegel Caroline KangCaroline Kang More articles by this author , Nahid PunjaniNahid Punjani More articles by this author , and Peter N. SchlegelPeter N. Schlegel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002035.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men with Klinefelter syndrome (KS) classically have testicular failure and are at risk for both testosterone (T) deficiency and infertility. T replacement therapy (TRT) often is initiated in adolescence for its potential neurodevelopmental benefits. Unfortunately, exogenous T has a defined adverse effect on spermatogenesis. We sought to examine the effect of exogenous T on sperm retrieval in men with KS. METHODS: All men with KS undergoing sperm retrieval by microdissection testicular sperm extraction (mTESE) performed by a single surgeon between 1995-2020 were reviewed. Demographic data and hormone-modifying agents, such as human chorionic gonadotropin (hCG) and aromatase inhibitors (AI), administered prior to mTESE were obtained. History or current use of exogenous T was recorded and categorized based on formulation into either short- (gel or foam) or long-acting (pellets or injection) groups. Descriptive statistics and SRR are reported. Patients with incomplete data on hormone therapy as well as repeat procedures on the same patient were excluded. RESULTS: A total of 290 sperm retrievals were performed on KS men during the study period. Fourteen men had a history of exogenous TRT or were currently using T at time of mTESE (Table 1). Median age was 34 years (interquartile range (IQR) 31–36), and median testis size was 1.3 mL (IQR 1.0–1.5). Five men had a remote history of TRT up to 2 years prior to mTESE, and received hCG and AI hormone therapy prior to retrieval. Of these, all five (100%) had successful sperm retrieval. In five men receiving topical testosterone and concurrent AI and/or hCG at time of mTESE, only two (40%) had successful sperm retrieval. No men receiving continuous delivery of exogenous testosterone (e.g., injectable or pellet) with concurrent hCG had sperm identified during mTESE. CONCLUSIONS: Exogenous TRT is common in KS patients. Long-acting (e.g. injectable or implantable T) therapy suppresses gonadotropin production and sperm production, predisposing men to failed sperm retrieval. However, T monotherapy with short-acting (e.g. topical) formulations together with AIs can maintain endogenous gonadotropin production and spermatogenesis; such therapy is consistent with sperm retrieval in KS men. Additional prospective trials are needed to elucidate the effects of T on sperm retrieval in KS patients. Source of Funding: CK and NP are supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e557-e558 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Caroline Kang More articles by this author Nahid Punjani More articles by this author Peter N. Schlegel More articles by this author Expand All Advertisement Loading ...