Publications
178 results found
Grossmann M, Jayasena CN, Anawalt BD, 2023, Approach to the patient: the evaluation and management of men ≥ 50 years with a low serum testosterone concentration, Journal of Clinical Endocrinology and Metabolism, Pages: 1-14, ISSN: 0021-972X
Although testosterone replacement in men with classic hypogonadism due to an identified pathology of the hypothalamic-pituitary-testicular axis is uncontroversial, the role of testosterone treatment for men with age-related declines in circulating testosterone is unclear. This is due to the lack of large, long-term testosterone therapy trials assessing definitive clinical endpoints. However, men >50 years, particularly those who have a body mass index >25 kg/m2 and multiple co-morbidities, commonly present with clinical features of androgen deficiency and low serum testosterone concentrations. Clinicians are faced with the question whether to initiate testosterone therapy, a difficult dilemma that entails a benefit-risk analysis with limited evidence from clinical trials. Using a case scenario, we present a practical approach to the clinical assessment and management of such men.
Davies R, Jayasena CN, Rai R, et al., 2023, The role of seminal oxidative stress in recurrent pregnancy loss, Antioxidants, Vol: 12, Pages: 1-12, ISSN: 2076-3921
Recurrent pregnancy loss is a distressing condition affecting 1-2% of couples. Traditionally investigations have focused on the female, however more recently researchers have started to explore the potential contribution of the male partner. Seminal reactive oxygen species have a physiological function in male reproduction but in excess are suspected to generate structural and functional damage to the sperm. Evidence is mounting to support an association between elevated seminal reaction oxygen species and recurrent pregnancy loss. Studies suggest that the rates of sperm DNA damage are higher in the male partners of women affected by recurrent pregnancy loss compared with unaffected men. However, the available pool of data is conflicting, and interpretation is limited by the recent change in nomenclature and the heterogeneity of study methodologies. Furthermore, investigation into the effects of oxidative stress on the epigenome show promise. The value of antioxidant therapy in the management of recurrent pregnancy loss currently remains unclear.
Desai A, Chen R, Cayetano A, et al., 2023, Understanding and treating ejaculatory dysfunction in men with Diabetes mellitus, Andrology, Vol: 11, Pages: 379-398, ISSN: 2047-2919
INTRODUCTION: Diabetes mellitus (DM) is a rapidly rising metabolic disorder with important systemic complications. Global figures have demonstrated the prevalence of DM has almost quadrupled from 108 million in 1980 to 422 million in 2014, with a current prevalence of over 525 million. Of the male sexual dysfunction resulting from DM, significant focus is afforded to erectile dysfunction (ED). Nevertheless, ejaculatory dysfunction (EjD) constitutes important sexual sequelae in diabetic men, with up to 35-50% of men with DM suffering from EjD. Despite this, aspects of its pathophysiology and treatment are less well understood than ED. The main disorders of ejaculation include premature ejaculation (PE), delayed ejaculation (DE), anejaculation (AE) and retrograde ejaculation (RE). BACKGROUND: Although EjD in DM can have complex multifactorial aetiology, understanding the pathophysiological mechanisms caused by DM has facilitated the development of therapies in the management of EjD. Most of our understanding of its pathophysiology is derived from diabetic animal models, however observational studies in humans have also provided useful information in elucidating important associative factors potentially contributing to EjD in diabetic men. These have provided the potential for more tailored treatment regimens in patients depending on the ejaculatory disorder, other co-existing sequelae of DM, specific metabolic factors as well as the need for fertility treatment. However, the evidence for treatment of EjD, especially DE and RE, is based on low-level evidence comprising small sample-size series and retrospective or cross-sectional studies. Whilst promising findings from large randomised controlled trials (RCTs) have provided strong evidence for the licensed treatment of PE, similar robust studies are needed to accurately elucidate factors predicting EjD in DM, as well as for the development of pharmacotherapies for DE and RE. Similarly, more contemporary robust data is
Grant B, Pradeep A, Minhas S, et al., 2023, Survey of endocrinologists managing recovery from anabolic androgenic steroid induced hypogonadism, Reproduction and Fertility, Vol: 4, Pages: 1-3, ISSN: 2633-8386
Anabolic steroids (also known as ‘steroids’) are banned drugs like testosterone, which make muscles bigger in men. These drugs are dangerous because they stop the testes from making natural testosterone and can cause heart attacks. Men stopping steroids have very low testosterone, which makes them feel weak, depressed, suicidal, infertile, and unable to have erections. We surveyed over 100 doctors to find out how they treat men giving up steroids. We report that doctors differ widely in the way they treat these men. Most doctors simply advise men to wait for the natural recovery of testosterone levels to happen. But 20% of doctors give men drugs to boost testosterone and make men feel better. Unfortunately, many patients had not recovered by the time of our survey. In summary, our survey highlights differences and limitations in the treatment of men giving up steroids. The use of steroids is increasing rapidly among young men, so we recommend further work to improve the treatment of men who are motivated to give up steroids.
Jasuja R, Pencina KM, Spencer DJ, et al., 2023, Reference intervals for free testosterone in adult men measured using a standardized equilibrium dialysis procedure., Andrology, Vol: 11, Pages: 125-133
BACKGROUND: Free testosterone (FT) determination may be helpful in evaluating men suspected of testosterone deficiency especially in conditions with altered binding-protein concentrations. However, methods for measuring FT by equilibrium dialysis and reference intervals vary among laboratories. OBJECTIVE: To determine reference intervals for FT in healthy, nonobese men by age groups as well as in healthy young men, 19-39 years, using a standardized equilibrium dialysis procedure METHODS: We measured FT in 145 healthy, nonobese men, 19 years or older, using a standardized equilibrium dialysis method performed for 16-h at 37°C using undiluted serum and dialysis buffer that mimicked the ionic composition of human plasma. FT in dialysate was measured using a CDC-certified liquid chromatography tandem mass spectrometry assay. RESULTS: In healthy nonobese men, the 2.5th, 10th, 50th, 90th, and 97.5th percentile values for FT were 66, 91, 141, 240, and 309 pg/ml, respectively; corresponding values for men, 19-39 years, were 120, 128, 190, 274, and 368 pg/ml, respectively. FT levels by age groups exhibit the expected age-related decline. FT levels were negatively associated with body mass index, age, and sex hormone-binding globulin (SHBG) levels. Percent FT was lower in middle-aged and older men than young men adjusting for SHBG level. DISCUSSION: Further studies are needed to determine how these reference intervals apply to the diagnosis of androgen deficiency in clinical populations and in men of different races and ethnicities in different geographic regions. CONCLUSION: Reference intervals for free FT levels (normative range 66-309 pg/ml [229-1072 pmol/L] in all men and 120-368 pg/ml [415-1274 pmol/L] in men, 19-39 years), measured using a standardized equilibrium dialysis method in healthy nonobese men, provide a rational basis for categorizing FT levels. These intervals require further validation in other populations, in relation to outcomes, and in randomized tri
Foran D, Chen R, Jayasena CN, et al., 2022, The use of hormone stimulation in male infertility, Current Opinion in Pharmacology, Vol: 68, Pages: 1-21, ISSN: 1471-4892
Infertility affects 15% of couples worldwide and in approximately 50% of cases the cause is secondary to an abnormality of the sperm. However, treatment options for male infertility are limited and empirical use of hormone stimulation has been utilised. We review the contemporary data regarding the application of hormone stimulation to treat male infertility. There is strong evidence supporting the use of hormone stimulation in hypogonadotropic hypogonadism but there is inadequate evidence for all other indications.
Abbara A, Patel B, Parekh I, et al., 2022, Ovarian Hyperstimulation Syndrome (OHSS) requiring Intensive Care Unit (ICU) admission between 1996-2020 in England, Wales, and Northern Ireland, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Introduction: Ovarian Hyperstimulation Syndrome (OHSS) is a life-threatening iatrogenic complication of In vitro fertilisation (IVF). This study aimed to quantify rates of Ovarian Hyperstimulation Syndrome (OHSS) requiring intensive care unit (ICU) admission and assess whether trends have changed between 1996-2020 commensurate with the introduction of safer IVF practices.Methods: Data regarding Intensive Care Unit (ICU) admission across England, Wales and Northern Ireland was gathered retrospectively from the Intensive Care National Audit and Research Centre (ICNARC) database. 38,957 female patients aged between 18-55 years were admitted to ICU for OHSS or related conditions between 1996-2020. The primary outcome was the rate of OHSS requiring ICU admission expressed as a proportion of the number of fresh IVF cycles conducted in that year according to Human Fertility and Embryology Authority (HFEA) records. Baseline characteristics (for example, age, ethnicity, BMI), biochemical parameters (such as renal function, serum electrolytes), length of ICU stay and duration and need for organ support, were also compared between ICU patients with ‘confirmed OHSS’ and those ‘without OHSS’.Results: There were 238 cases of ‘confirmed OHSS’ requiring ICU admission recorded between 1996-2020. Rates of OHSS requiring ICU admission declined over the study period (P=0.006); the annual rate of severe OHSS requiring intensive care admission halved when comparing those occurring between 1996-2007 and 2008-2020 (OR=0.37, 95% CI 0.37-0.45; P<0.0001). Patients spent a mean of 3.5 days in the ICU, with 86.3% of patients with ‘confirmed OHSS’ requiring at least 2 days of higher level (i.e., level 2 or 3) care. Patients with ‘confirmed OHSS’ required a shorter duration of renal, advanced cardiovascular, and advanced respiratory support than patients ‘without OHSS’ (P<0.0001 for all comparisons). There was no signif
Sharma A, Davies R, Kapoor A, et al., 2022, The effect of hormone replacement therapy on cognition and mood, Clinical Endocrinology, Vol: 98, Pages: 285-295, ISSN: 0300-0664
ObjectivesTo summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women.BackgroundComplaints of impaired cognition and mood are common in the peri-menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon.DesignA literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included.PatientsPerimenopausal and menopausal women.ResultsDue to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a ‘critical window’ for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri-menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear.ConclusionsFurther study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence-based conclusions can be drawn.
Abbara A, Koysombat K, Phylactou M, et al., 2022, Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Background: Delayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH.Materials and methods: Retrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured.Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB.Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54.Results: Median INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating
Hamoda H, Mukherjee A, Morris E, et al., 2022, Authors reply: 'Response to the British Menopause society, Royal College of Obstetricians and Gynaecologists and Society for Endocrinology position statement - Best practice recommendations for the care of women experiencing the menopause'., Post Reproductive Health, Vol: 28, Pages: 1-5, ISSN: 2053-3705
Dimakopoulou A, Clarke SA, Jayasena CN, 2022, Screening for adverse metabolic consequences in women with idiopathic hirsutism-is it relevant?, Journal of Clinical Endocrinology and Metabolism, Vol: 108, Pages: e38-e39, ISSN: 0021-972X
Wyrwoll MJ, Gaasbeek CM, Golubickaite I, et al., 2022, The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans, American Journal of Human Genetics, Vol: 109, Pages: 1850-1866, ISSN: 0002-9297
Infertility affects around 7% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with SPGF and detected rare bi-allelic loss-of-function variants in FKBP6 in five additional persons. All six individuals had no or extremely few sperm in the ejaculate, which were not suitable for medically assisted reproduction. Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining. In mice, Fkbp6 is essential for spermatogenesis and has been described as being involved in piRNA biogenesis and formation of the synaptonemal complex (SC). We did not detect FKBP6 as part of the SC in normal human spermatocytes, but small RNA sequencing revealed that loss of FKBP6 severely impacted piRNA levels, supporting a role for FKBP6 in piRNA biogenesis in humans. In contrast to findings in piRNA-pathway mouse models, we did not detect an increase in LINE-1 expression in men with pathogenic FKBP6 variants. Based on our findings, FKBP6 reaches a "strong" level of evidence for being associated with male infertility according to the ClinGen criteria, making it directly applicable for clinical diagnostics. This will improve patient care by providing a causal diagnosis and will help to predict chances for successful surgical sperm retrieval.
Dimakopoulou A, Millar OD, Moschonas D, et al., 2022, The role of androgens in transgender medicine, Best Practice and Research: Clinical Endocrinology and Metabolism, Vol: 36, ISSN: 1521-690X
Androgen therapy is the mainstay of treatment in female to male (FtM) transgender persons to increase testosterone levels, suppress oestrogens and treat gender dysphoria. Testosterone is widely used for male hypogonadism, but is comparatively under-investigated in FtM transgender persons. The aim of our study was to identify treatment and safety outcomes associated with testosterone use in transgender medicine. Androgens in FtM transgender persons are effective to lower voice frequency, increase facial hair-growth, and increase hematocrit and hemoglobin levels to adult male reference ranges. A 1.2-fold-3.7-fold higher rate of myocardial infarction has been reported retrospectively, compared to cisgender women. Blood pressure, glycaemic control and body mass index remained unchanged in FtM transgender persons. Androgens in FtM transgender persons have important cardio-metabolic implications. Randomised control trials, longer follow-up periods and studies involving older persons may further improve the management of FtM transgender persons.
Agarwal A, Cannarella R, Saleh R, et al., 2022, Impact of antioxidant therapy on natural pregnancy outcomes and semen parameters in infertile men: a systematic review and meta-analysis of randomized controlled trials, The World Journal of Men's Health, Vol: 41, Pages: 14-48, ISSN: 2287-4208
Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy ofantioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases.Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients.We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies.A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphologywas found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels oftotal antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patientsthan controls. These results did not change after exclusion of studies performed following varicocele repair.Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertilityto improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increasein live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOXon live-birth rate. Therefore, further RCTs assessing the
Huhtaniemi I, Jayasena C, 2022, Androgens part 2: Emerging areas, Best Practice and Research: Clinical Endocrinology and Metabolism, Vol: 36, Pages: 1-2, ISSN: 1521-690X
Holtermann Entwistle O, Sharma A, Jayasena CN, 2022, What must be considered when prescribing hormonal pharmacotherapy for male infertility?, Expert Opinion on Pharmacotherapy, Vol: 23, Pages: 1003-1008, ISSN: 1465-6566
Hamoda H, Mukherjee A, Morris E, et al., 2022, Joint position statement by the British Menopause Society, Royal College of Obstetricians and Gynaecologists and Society for Endocrinology on best practice recommendations for the care of women experiencing the menopause, Post Reproductive Health, Vol: 28, ISSN: 2053-3705
Tharakan T, Corona G, Foran D, et al., 2022, Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis, Human Reproduction Update, Vol: 28, Pages: 609-628, ISSN: 1355-4786
BACKGROUNDThe beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40–60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.OBJECTIVE AND RATIONALEThe primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.SEARCH METHODSA literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.OUTCOMESA total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08–3.56, P = 0.03) and this trend persisted when e
Sharma A, Grant B, Islam H, et al., 2022, Common symptoms associated with usage and cessation of anabolic androgenic steroids in men., Best Practice and Research: Clinical Endocrinology and Metabolism, Vol: 36, Pages: 1-10, ISSN: 1521-690X
Anabolic-androgenic steroid (AAS) have widespread and growing illicit use as image and performance enhancing drugs (IPED), predominantly in young men. Users trying to stop AAS are prone to distressing withdrawal symptoms which may trigger relapse in use. It is important to develop therapies to support AAS withdrawal. The illicit nature of AAS use has impeded the robust characterisation of its clinical withdrawal syndrome within any single study. Therefore, we conducted a systematic review summarising the available clinical studies describing symptoms associated with non-medically indicated AAS use, and AAS withdrawal. Reported clinical features of AAS withdrawal include headache, fatigue, myalgia, restlessness, insomnia, low mood and libido, anorexia, suicidal ideation, body image dissatisfaction, and steroid cravings; novel therapies for AAS withdrawal would need evaluation against these symptoms.
Hamoda H, Mukherjee A, Morris E, et al., 2022, Optimising the menopause transition: joint position statement by the British Menopause Society, Royal College of Obstetricians and Gynaecologists and Society for Endocrinology on best practice recommendations for the care of women experiencing the menopause., Post Reproductive Health, Vol: 28, Pages: 121-122, ISSN: 2053-3705
Huhtaniemi I, Jayasena C, 2022, Androgens part 1: State-of-the-art, Best Practice & Research Clinical Endocrinology & Metabolism, Pages: 1-2, ISSN: 1521-690X
Shah R, Agarwal A, Kavoussi P, et al., 2022, Consensus and diversity in the management of varicocele for male infertility: results of a global practice survey and comparison with guidelines and recommendations, World Journal of Mens Health, Vol: 40, ISSN: 2287-4208
PurposeVaricocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility.Materials and MethodsSixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field.ResultsThe questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available.ConclusionsThis study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3
Mohamed RS, Balfoussia DT, Jayasena CN, 2022, Infertility in men: assessment and treatment, Pharmaceutical Journal, Vol: 309, ISSN: 0031-6873
Desai A, Yassin M, Cayetano A, et al., 2022, Understanding and managing the suppression of spermatogenesis caused by testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS), Therapeutic Advances in Urology, Vol: 14, Pages: 17562872221105017-17562872221105017, ISSN: 1756-2872
Use of testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS) has increased over the last 20 years, coinciding with an increase in men presenting with infertility and hypogonadism. Both agents have a detrimental effect on spermatogenesis and pose a clinical challenge in the setting of hypogonadism and infertility. Adding to this challenge is the paucity of data describing recovery of spermatogenesis on stopping such agents. The unwanted systemic side effects of these agents have driven the development of novel agents such as selective androgen receptor modulators (SARMs). Data showing natural recovery of spermatogenesis following cessation of TRT are limited to observational studies. Largely, these have shown spontaneous recovery of spermatogenesis after cessation. Contemporary literature suggests the time frame for this recovery is highly variable and dependent on several factors including baseline testicular function, duration of drug use and age at cessation. In some men, drug cessation alone may not achieve spontaneous recovery, necessitating hormonal stimulation with selective oestrogen receptor modulators (SERMs)/gonadotropin therapy or even the need for assisted reproductive techniques. However, there are limited prospective randomized data on the role of hormonal stimulation in this clinical setting. The use of hormonal stimulation with agents such as gonadotropins, SERMs, aromatase inhibitors and assisted reproductive techniques should form part of the counselling process in this cohort of hypogonadal infertile men. Moreover, counselling men regarding the detrimental effects of TRT/AAS on fertility is very important, as is the need for robust randomized studies assessing the long-term effects of novel agents such as SARMs and the true efficacy of gonadotropins in promoting recovery of spermatogenesis.
Mehmet B, Gillard S, Jayasena CN, et al., 2022, Association between domains of quality of life and patients with klinefelter syndrome: a systematic review., European Journal of Endocrinology, Vol: 187, Pages: S21-S34, ISSN: 0804-4643
Klinefelter syndrome (KS) is the second-most prevalent chromosomal disorder in men, though late diagnosis is very common and 50-75% of men remain undiagnosed. Evidence suggests that men with KS have impaired Quality of Life (QoL) but research on how the diagnosis of KS is associated with different QoL domains and what factors influence patients' QoL is limited. This study aimed to provide a systematic review of the published evidence on factors that influence QoL in men with KS. DESIGN: Systematic review and meta-analysis with narrative synthesis. METHODS: Medline, Cochrane, Embase, Psychinfo, CINAHL, BASE and relevant publication reference lists were searched in January 2021. Eligible studies included RCTs, cohort studies, cross-sectional studies and epidemiology studies on KS and its effect on QoL and all domains of WHOQOL-100. Clinical studies with no date restriction published in English were included. RESULTS: Thematic analysis was completed on thirteen studies, with a meta-analysis of intelligence quotient (IQ) completed on seven studies. Twelve out of 13 studies suggested that KS negatively affected QoL outcomes and KS was associated with impairments in physical, psychological, level independence and social relationship domains of WHOQOL-100. Meta-analysis suggested men with KS have significantly lower full-scale Intelligence Quotient versus controls (P <0.00001). CONCLUSIONS: This is the first evidence synthesis of QoL in men with KS. Current evidence suggests that combined physical and psychological impairments affect men with KS who also experience impairments in relationships and independence in society. Further research is needed to identify factors that influence QoL in men with KS.
Hamoda H, Mukherjee A, Morris E, et al., 2022, Optimizing the menopause transition: Joint position statement by the British Menopause Society, Royal College of Obstetricians and Gynaecologists and Society for Endocrinology on best practice recommendations for the care of women experiencing the menopause, Clinical Endocrinology, ISSN: 0300-0664
Hudson J, Cruickshank M, Quinton R, et al., 2022, Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis., The Lancet Healthy Longevity, Vol: 3, Pages: e381-e393, ISSN: 2666-7568
Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225
Jayasena CN, Dhillo WS, 2022, Secondary amplification of sperm DNA fragmentation for male infertility: hope for improved and affordable fertility testing in affected couples, Clinical Chemistry, Vol: 68, Pages: 489-490, ISSN: 0009-9147
Jayasena CN, Ho CLT, Bhasin S, 2022, The effects of testosterone treatment on cardiovascular health, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: 109-122, ISSN: 0889-8529
Sharma A, Jayasena CN, Dhillo WS, 2022, Regulation of the hypothalamic-pituitary-testicular axis: pathophysiology of hypogonadism, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: 29-45, ISSN: 0889-8529
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