Publications
172 results found
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, ISSN: 1664-2392
Sharma A, Davies R, Kapoor A, et al., 2022, The effect of hormone replacement therapy on cognition and mood, CLINICAL ENDOCRINOLOGY, ISSN: 0300-0664
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, ISSN: 1664-2392
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, Pages: 20533691221141132-20533691221141132, 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 & METABOLISM, 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, WORLD JOURNAL OF MENS HEALTH, ISSN: 2287-4208
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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
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
Huhtaniemi I, Jayasena C, 2022, Androgens part 2: Emerging areas, BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 36, ISSN: 1521-690X
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
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.
Desai A, Chen R, Cayetano A, et al., 2022, Understanding and treating ejaculatory dysfunction in men with Diabetes mellitus, Andrology, 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
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
Papanikolaou N, Jayasena CN, 2022, Fertility considerations in hypogonadal men, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: 133-148, ISSN: 0889-8529
Bhasin S, Jayasena CN, 2022, Hypogonadism, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: xv-xvi, ISSN: 0889-8529
Mowla S, Tharakan T, Farahani L, et al., 2022, Associations between seminal microbiota composition and ROS in men with fertility disorders, Publisher: ELSEVIER, Pages: S1187-S1187, ISSN: 0302-2838
Aceves-Martins M, Quinton R, Brazzelli M, et al., 2022, Identifying the outcomes important to men with hypogonadism: A qualitative evidence synthesis, Andrology, Vol: 10, ISSN: 2047-2919
OBJECTIVE: Men with male hypogonadism (MH) experience sexual dysfunction, which improves with testosterone replacement therapy (TRT). However, randomised controlled trials provide little consensus on functional and behavioural symptoms in hypogonadal men; these are often better captured by qualitative information from individual patient experience. METHODS: We systematically searched major electronic databases to identify qualitative data from men with hypogonadism, with or without TRT. Two independent authors performed the selection, extraction, and thematic analysis of data. Quality of eligible studies was assessed using the Critical Appraisals Skills Programme and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tools. RESULTS: We analysed data from five studies published in nine reports that assessed a total of 284 participants. Published data were only available within North America, with no ethnic minority or other underserved groups included. In addition to sexual dysfunction, men with MH experienced adverse changes in physical strength, perceptions of masculinity, cognitive function, and quality of life. The experience of MH appeared dependent on the source(s) of educational material. DISCUSSION: We propose a patient-centred approach to clinician interactions rather than focusing on discreet MH symptoms. Current evidence about the experience of MH is limited to North America and predominantly white ethnicity, which may not be broadly applicable to other geographic regions. Broadening our understanding of the MH experience may improve the targeting of information to patients. In addition, a multidisciplinary approach may better address symptoms neither attributable to MH nor alleviated by TRT.
Davies R, Jayasena CN, Minhas S, 2022, Hormonal and nonhormonal treatment of male infertility, Management of Infertility: A Practical Approach, Pages: 145-154, ISBN: 9780323899154
The causes and management of male infertility can be broadly classified by the position of the defect in the hypothalamo-pituitary-gonadal axis. However a significant portion of male infertility is unexplained and thus termed idiopathic infertility. Hormonal replacement is an established treatment for infertility associated with hypothalamo-pituitary dysfunction. The management of testicular failure involves surgical sperm removal and assisted reproductive technology. In specialist centers, hormonal stimulation is used to increase the success rate of surgical sperm retrieval; the evidence for this is conflicting. Idiopathic male infertility poses a clinical challenge. It is being increasingly understood that reactive oxygen species may play an important role in the etiology of idiopathic infertility. As such lifestyle modification and antioxidant therapy show promise.
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