Imperial College London

Dr. Channa Jayasena MA PhD MRCP FRCPath

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Reader in Reproductive Endocrinology
 
 
 
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c.jayasena Website

 
 
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6N5CCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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194 results found

Hernández R, de Silva NL, Hudson J, Cruickshank M, Quinton R, Manson P, Dhillo WS, Bhattacharya S, Brazzelli M, Jayasena CNet al., 2024, Cost-effectiveness of testosterone treatment utilising individual patient data from randomised controlled trials in men with low testosterone levels., Andrology, Vol: 12, Pages: 477-486

BACKGROUND: Testosterone is safe and highly effective in men with organic hypogonadism, but worldwide testosterone prescribing has recently shifted towards middle-aged and older men, mostly with low testosterone related to age, diabetes and obesity, for whom there is less established evidence of clinical safety and benefit. The value of testosterone treatment in middle-aged and older men with low testosterone is yet to be determined. We therefore evaluated the cost-effectiveness of testosterone treatment in such men with low testosterone compared with no treatment. METHODS: A cost-utility analysis comparing testosterone with no treatment was conducted following best practices in decision modelling. A cohort Markov model incorporating relevant care pathways for individuals with hypogonadism was developed for a 10-year-time horizon. Clinical outcomes were obtained from an individual patient meta-analysis of placebo-controlled, double-blind randomised studies. Three starting age categories were defined: 40, 60 and 75 years. Cost utility (quality-adjusted life years) accrued and costs of testosterone treatment, monitoring and cardiovascular complications were compared to estimate incremental cost-effectiveness ratios and cost-effectiveness acceptability curves for selected scenarios. RESULTS: Ten-year excess treatment costs for testosterone compared with non-treatment ranged between £2306 and £3269 per patient. Quality-adjusted life years results depended on the instruments used to measure health utilities. Using Beck depression index-derived quality-adjusted life years data, testosterone was cost-effective (incremental cost-effectiveness ratio <£20,000) for men aged <75 years, regardless of morbidity and mortality sensitivity analyses. Testosterone was not cost-effective in men aged >75 years in models assuming increased morbidity and/or mortality. CONCLUSIONS AND FUTURE RESEARCH: Our data suggest that testosterone is cost-effective in men &l

Journal article

Mowla S, Farahani L, Tharakan T, Davies R, Correia G, Lee Y, Kundu S, Khanjani S, Sindi ERB, Rai R, Regan L, Khalifa D, Henkel R, Minhas S, Dhillo W, Nagi JB, Bennett P, MacIntyre D, Jayasena Cet al., 2024, Characterisation and comparison of semen microbiota and sperm function in men with infertility, recurrent miscarriage, or proven fertility, eLife, ISSN: 2050-084X

Journal article

Sharma A, Papanikolaou N, Abou Sherif S, Dimakopoulou A, Thaventhiran T, Go C, Holtermann Entwistle O, Brown A, Luo R, Jha R, Prakash A, Khalifa D, Lewis H, Ramaraju S, Leeds A, Chahal H, Purkayastha S, Henkel R, Minhas S, Frost G, Dhillo W, Jayasena Cet al., 2024, Improvements in sperm motility following low or high intensity dietary interventions in men with obesity, Journal of Clinical Endocrinology and Metabolism, Vol: 109, Pages: 449-460, ISSN: 0021-972X

Introduction:Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted.Methods:Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks’ observation. Semen parameters were compared at baseline and 16 weeks.Results:Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia.Conclusion:LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation.

Journal article

Li M, Chen L, Yan J, Jayasena CN, Liu Z, Li J, Li A, Zhu J, Wang R, Li J, Zhang C, Guo J, Zhao Y, Feng C, Tang M, Zheng Yet al., 2024, Super-resolution ultrasound localization microscopy for the non-invasive imaging of human testicular microcirculation and its differential diagnosis role in male infertility, VIEW, ISSN: 2688-3988

Testicular microcirculation is closely related to spermatogenic function and seminiferous tubular function. The diagnosis and monitoring of testicular diseases can be associated with testicular microcirculation; however, there are currently no effective non-invasive methods for super-resolution imaging of testicular microcirculation. In this study, we introduced state-of-the-art graph-based tracking with the Kalman motion model algorithm to non-invasively image human testicular microcirculation for the first time with a regular frame-rate clinical ultrasound imaging system (37 Hz). Two distinct testicular vessels with an 81 µm separation were resolved in the testicular vasculature, surpassing all other imaging modalities. In a retrospective study, we performed contrast-enhanced ultrasound examinations(CEUS) and ultrasound localization microscopy (ULM) processing on the included 76 infertile patients and 15 healthy controls from August 2021 to May 2023 and obtained super-resolution images of testicular microcirculation with sub-diffraction resolution. Through the results of one-way analysis of variance tests and receiver operating characteristic analyses, we found that the ULM-based parameters hold promise as clinical guidance for differentiating between non-obstructive and obstructive male infertility. The mean vessel diameter achieved an area under the curve (AUC) of 0.920 (95% confidence interval [CI]: 0.847–0.994, p <.001) with a cut-off value of 170.9 µm in oligoasthenospermia, and an AUC of 0.952 (95% CI: 0.875–1.000, p <.001) with a cut-off value of 169.9 µm in azoospermia patients, respectively, addressing a significant clinical challenge.

Journal article

Davies R, Minhas S, Jayasena CN, 2023, Next-Generation Sequencing to Elucidate the Semen Microbiome in Male Reproductive Disorders., Medicina (Kaunas), Vol: 60

Mean sperm counts are declining at an accelerated rate and infertility is increasingly becoming a public health concern. It is now understood that human semen, previously considered to be sterile, harbours its own specific microbiome. Via activated leucocytes and the generation of reactive oxygen species, bacteria have the capability of evoking an immune response which may lead to sperm damage. Men with infertility have higher rates of both reactive oxygen species and sperm DNA damage. Due to the lack of sensitivity of routine culture and PCR-based methods, next-generation sequencing technology is being employed to characterise the seminal microbiome. There is a mounting body of studies that share a number of similarities but also a great range of conflicting findings. A lack of stringent decontamination procedures, small sample sizes and heterogeneity in other aspects of methodology makes it difficult to draw firm conclusions from these studies. However, various themes have emerged and evidence of highly conserved clusters of common bacteria can be seen. Depletion or over-representation of specific bacteria may be associated with aberrations in traditional and functional seminal parameters. Currently, the evidence is too limited to inform clinical practice and larger studies are needed.

Journal article

Grant B, Campbell J, Pradeep A, Burns AD, Bassett P, Abbara A, Saket P, Minhas S, Dhillo WS, McVeigh J, Bhasin S, Jayasena CNet al., 2023, Factors predicting normalization of reproductive hormones after cessation of anabolic-androgenic steroids in men: a single center retrospective study., Eur J Endocrinol, Vol: 189, Pages: 601-610

OBJECTIVE: Symptomatic hypogonadism discourages men from stopping anabolic-androgenic steroids (AAS). Some men illicitly take drugs temporarily stimulating endogenous testosterone following AAS cessation (post-cycle therapy; PCT) to lessen hypogonadal symptoms. We investigated whether prior PCT use was associated with the normalization of reproductive hormones following AAS cessation. METHODS: Retrospective analysis of 641 men attending a clinic between 2015-2022 for a single, nonfasting, random blood test <36 months following AAS cessation, with or without PCT. Normalized reproductive hormones (ie, a combination of reference range serum luteinizing hormone, follicle-stimulating hormone, and total testosterone levels) were the surrogate marker of biochemical recovery. RESULTS: Normalization of reproductive hormones was achieved in 48.2% of men. PCT use was associated with faster biochemical recovery (13.0 (IQR8.0-19.0) weeks, PCT; 26.0 (IQR10.5-52) weeks, no-PCT; P < .001). Odds of biochemical recovery during multivariable analysis were: (1) higher with PCT (OR3.80) vs no-PCT (P = .001), in men stopping AAS ≤3 months previously; (2) reduced when 2 (OR0.55), 3 (OR0.46), or 4 (OR0.25) AAS were administered vs 1 drug (P = .009); (3) lower with AAS >6 vs ≤3 months previously (OR0.34, P = .01); (4) higher with last reported AAS >3 months (OR 5.68) vs ≤3 months (P = .001). PCT use was not associated with biochemical recovery in men stopping AAS >3 months previously. CONCLUSION: Without evidence-based withdrawal protocols, men commonly try avoiding post-AAS hypogonadism with PCT, which is illicit, ill-defined, and not recommended. Only half of men had complete biochemical testicular recovery after stopping AAS. The surprising association of self-reported PCT use with short-term biochemical recovery from AAS-induced hypogonadism warrants further investigation.

Journal article

Grant B, Minhas S, Jayasena CN, 2023, A review of recent evidence on androgen abuse from interviews with users., Curr Opin Endocrinol Diabetes Obes, Vol: 30, Pages: 285-290

PURPOSE OF REVIEW: Androgens (also known as anabolic-androgenic steroids; AAS) are increasingly being abused worldwide to enhance body physique or athletic performance. Qualitative studies including interviews provide a wider understanding of androgen abuse and focus specific support needs to this group. This narrative review summarizes recent studies (2021-2023) using interviews with individuals abusing androgens. RECENT FINDINGS: Motivations for androgen abuse in men include desires to achieve certain physicality, enhance self-confidence and improve libido. The risks of androgen abuse are justified to achieve these outcomes and men may use other illicit substances as postcycle-therapy to lessen the risks. Some adverse effects may be more pronounced with certain substances. The therapeutic relationship with healthcare professionals is often described negatively by androgen abusers due to stigma and a perceived lack of knowledge. Both healthcare professionals and androgen abusers agree that development of guidelines are needed. Androgen abuse in women is rare however body dissatisfaction and desires for improve appearance and strength are motivators. SUMMARY: Recent qualitative studies have helped further our understanding of men and women who abuse androgens, however the small number of recently published studies confirms there is still a paucity of evidence in the literature. Further research is needed to develop specific harm minimization strategies in those abusing androgens.

Journal article

Grant B, Kean J, Vali N, Campbell J, Maden L, Prun B, Dhillo W, McVeigh J, Quinton R, Jayasena Cet al., 2023, The use of post-cycle therapy is associated with reduced withdrawal symptoms from anabolic-androgenic steroid use: a survey of 470 users, Substance Abuse Treatment, Prevention, and Policy, Vol: 18, ISSN: 1747-597X

Background: Anabolic-androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms. Methods: An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support. Results: The majority of respondents were white, aged 18-30 years old, and working in skilled manual work. 51.7% (n=243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n=306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community. Conclu

Journal article

de Silva NL, Dissanayake H, Kalra S, Meeran K, Somasundaram NP, Jayasena CNet al., 2023, Global barriers to accessing off-patent endocrine therapies: a renaissance of the orphan disease?, J Clin Endocrinol Metab

CONTEXT: Clinical endocrinology encompasses many diseases requiring long-term drug therapy. Prohibitive pricing of some endocrine drugs classified as essential by the World Health Organisation has created sub-optimal care of patients with endocrine disorders. EVIDENCE ACQUISITION: This review is based on evidence obtained from several databases and search engines including PubMed, Google and Google Scholar, reference searches, manual searching for web pages of international regulatory bodies and the authors' experience from different healthcare settings. EVIDENCE SYNTHESIS: After the expiry of a patent, generic versions with the opportunity for increased availability and a price reduction are expected. There are access barriers worldwide for many off-patent endocrine drugs. The high price is the main issue for several medicines including insulin, hydrocortisone, testosterone, and gonadotropins. This is contributed to by several factors including the market monopoly due to the lack of registered generics or suppliers limiting the benefit of competition and a complex supply chain. Additionally, the lack of some medicines had been concerning due to market factors such as the relatively small number of patients making it less attractive for the manufacturers. Commissioning of non-profit manufacturers and state manufacturing as well as strict price control measures could alleviate this situation. CONCLUSIONS: Lack of availability and disproportionate price inflation affecting essential off-patent endocrine therapies is common due to several interrelated factors. Global collaboration among healthcare organisations with the support of policy-making bodies might be needed to mitigate this.

Journal article

Hudson J, Cruickshank M, Quinton R, Aucott L, Wu F, Grossmann M, Bhasin S, Snyder PJ, Ellenberg SS, Travison TG, Brock GB, Gianatti EJ, van der Schouw YT, Emmelot-Vonk MH, Giltay EJ, Hackett G, Ramachandran S, Svartberg J, Hildreth KL, Antonic KG, Tenover JL, Tan HM, Ho Chee Kong C, Tan WS, Marks LS, Ross RJ, Schwartz RS, Manson P, Roberts SA, Skovsager Andersen M, Velling Magnussen L, Aceves-Martins M, Gillies K, Hernández R, Oliver N, Dhillo WS, Bhattacharya S, Brazzelli M, Jayasena CNet al., 2023, Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis., Lancet Healthy Longev, Vol: 4, Pages: e561-e572

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; m

Journal article

Khoo CC, Cayetano-Alcaraz AA, Rashid R, Tharakan T, Yap T, Sofikitis N, Salonia A, Corona G, Giwercman A, Jayasena CN, Minhas Set al., 2023, Does Testicular Sperm Improve Intracytoplasmic Sperm Injection Outcomes for Nonazoospermic Infertile Men with Elevated Sperm DNA Fragmentation? A Systematic Review and Meta-analysis., Eur Urol Focus

CONTEXT: For nonazoospermic infertile men with elevated sperm DNA fragmentation (SDF), it is unclear whether the use of testicular sperm for intracytoplasmic sperm injection (ICSI) may offer advantages over ejaculated sperm. OBJECTIVE: To determine whether ICSI outcomes (fertilisation rate, pregnancy rate, miscarriage rate, and live birth rate) are better with testicular sperm than with ejaculated sperm for men with elevated SDF. EVIDENCE ACQUISITION: We searched the Cochrane Central, EMBASE, MEDLINE, Web of Science, and Scopus databases (1946-2023) in February 2023 for relevant human comparative studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: Out of 2032 records, nine studies (more than 536 participants, mean age range 33-40.5 yr for males and 30.1-37.9 yr for females) were included in the systematic review and meta-analysis. Pooled estimates demonstrated that the pregnancy rate was significantly higher with testicular than with ejaculated sperm according to a sperm chromatin structure assay (SCSA)/sperm chromatin integrity test (SCIT) (odds ratio [OR] 2.51; p = 0.001) and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assays (OR 3.65; p = 0.005). The live birth rate was significantly higher according to SCSA/SCIT (OR 2.59; p = 0.005). There were no significant differences in the fertilisation rate or miscarriage rate. CONCLUSIONS: Although significant improvements in pregnancy and live birth rates were observed with testicular sperm, the strength of findings is limited by availability and quality of evidence, both of which undermine recommendations for clinical practice. Standardised randomised controlled trials are needed to definitively determine whether the use of testicular sperm improves ISCI outcomes for men with high SDF. Until such evidence exists, ICSI after testicular sperm extraction or aspiration should not be routine

Journal article

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, Vol: 108, Pages: e871-e884, 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.

Journal article

Davies R, Minhas S, Jayasena CNN, 2023, The role of seminal reactive oxygen species assessment in the setting of infertility and early pregnancy loss, WORLD JOURNAL OF UROLOGY, ISSN: 0724-4983

Journal article

Papanikolaou N, Millar O, Coulden A, Parker N, Sit L, Kelly C, Cox J, Dhillo WS, Meeran K, Al Memar M, Anderson R, Rees DA, Karavitaki N, Jayasena CNet al., 2023, Clinical characteristics of functioning gonadotroph adenoma in women presenting with ovarian hyperstimulation: Audit of UK pituitary centres, CLINICAL ENDOCRINOLOGY, ISSN: 0300-0664

Journal article

Jayasena CN, de Silva NL, O'Reilly MW, MacKenzie F, Marrington R, Jones H, Livingston M, Downie P, Hackett G, Ramachandran S, Tomlinson J, David J, Boot C, Patel M, Tarling J, Wu F, Quinton Ret al., 2023, Standardising the biochemical confirmation of adult male hypogonadism; a joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine., Ann Clin Biochem, Vol: 60, Pages: 223-227

Background: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilis eassay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain.Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems.

Journal article

Jayasena CN, de Silva NL, O'Reilly MW, MacKenzie F, Marrington R, Jones H, Livingston M, Downie P, Hackett G, Ramachandran S, Tomlinson J, David J, Boot C, Patel M, Tarling J, Wu F, Quinton Ret al., 2023, Standardising the biochemical confirmation of adult male hypogonadism; a joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine*, ANNALS OF CLINICAL BIOCHEMISTRY, Vol: 60, Pages: 223-227, ISSN: 0004-5632

Journal article

de Silva NL, Dissanayake H, Suarez C, Wickramarachchi RE, Ramasamy R, Dhillo WS, Minhas S, Corona G, Jayasena CNet al., 2023, Effect of oestrogen modulation on semen parameters in men with secondary hypogonadism: Systematic review and meta-analysis, ANDROLOGY, ISSN: 2047-2919

Journal article

Davies R, Jayasena CN, Rai R, Minhas Set 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.

Journal article

Tharakan T, Luo R, Foran D, Smith M, Jayasena CN, Minhas Set al., 2023, Strategies in infertile azoospermic patients with negative microdissection testicular sperm extraction surgery, UROLOGY RESEARCH AND PRACTICE, Vol: 49

Journal article

Desai A, Chen R, Cayetano A, Jayasena CN, Minhas Set 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

Journal article

Grant B, Pradeep A, Minhas S, Dhillo WS, Quinton R, Jayasena CNet 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.

Journal article

Jasuja R, Pencina KM, Spencer DJ, Peng L, Privat F, Dhillo W, Jayasena C, Hayes F, Yeap BB, Matsumoto AM, Bhasin Set al., 2023, Reference intervals for free testosterone in adult men measured using a standardized equilibrium dialysis procedure, ANDROLOGY, Vol: 11, Pages: 125-133, ISSN: 2047-2919

Journal article

Foran D, Chen R, Jayasena CN, Minhas S, Tharakan Tet 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.

Journal article

Abbara A, Patel B, Parekh I, Garg A, Jayasena C, Comninos A, Dhillo Wet 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

Journal article

Sharma A, Davies R, Kapoor A, Islam H, Webber L, Jayasena CNNet 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.

Journal article

Abbara A, Koysombat K, Phylactou M, Eng PC, Clarke S, Comninos AN, Yang L, Izzi-Engbeaya C, Hanassab S, Smith N, Jayasena C, Xu C, Quinton R, Pitteloud N, Binder G, Anand-Ivell R, Ivell R, Dhillo Wet 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

Journal article

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

Journal article

Wyrwoll MJ, Gaasbeek CM, Golubickaite I, Stakaitis R, Oud MS, Nagirnaja L, Dion C, Sindi EB, Leitch HG, Jayasena CN, Sironen A, Dicke A-K, Rotte N, Stallmeyer B, Kliesch S, Grangeiro CHP, Araujo TF, Lasko P, Genetics of Male Infertility Initiative GEMINI consortium, D'Hauwers K, Smits RM, Ramos L, Xavier MJ, Conrad DF, Almstrup K, Veltman JA, Tüttelmann F, van der Heijden GWet 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.

Journal article

Dimakopoulou A, Millar OD, Moschonas D, Jayasena CNet 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.

Journal article

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