Publications
149 results found
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., Hum Reprod Update
BACKGROUND: The 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 RATIONALE: The 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 METHODS: A 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. OUTCOMES: A 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 ex
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
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
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
Bhasin S, Jayasena CN, 2022, Hypogonadism, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: xv-xvi, ISSN: 0889-8529
Holtermann Entwistle O, Sharma A, Jayasena CN, 2022, What must be considered when prescribing hormonal pharmacotherapy for male infertility?, Expert Opinion on Pharmacotherapy, Pages: 1-6, ISSN: 1465-6566
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.
Dimakopoulou A, Millar OD, Moschonas D, et al., 2022, The role of androgens in transgender medicine., Best Practice and Research: Clinical Endocrinology and Metabolism, Pages: 101617-101617, 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.
Kaur V, Dimitriadis G, Perez-Pevida B, et al., 2021, Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome, Metabolism: clinical and experimental, Vol: 125, Pages: 1-8, ISSN: 0026-0495
BackgroundDuodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans.MethodsThirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention.ResultsA small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion.ConclusionsThese findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
Ho CLT, Vaughan-Constable DR, Ramsay J, et al., 2021, The relationship between genitourinary microorganisms and oxidative stress, sperm DNA fragmentation and semen parameters in infertile men, ANDROLOGIA, Vol: 54, ISSN: 0303-4569
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- Citations: 2
Sharma A, Ul-Haq Z, Sindi E, et al., 2021, Clinical characteristics and comorbidities associated with testosterone prescribing in men, CLINICAL ENDOCRINOLOGY, Vol: 96, Pages: 227-235, ISSN: 0300-0664
Jayasena C, Anderson RA, Llahana S, et al., 2021, Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism, CLINICAL ENDOCRINOLOGY, Vol: 96, Pages: 200-219, ISSN: 0300-0664
Tharakan T, Khoo CC, Giwercman A, et al., 2021, Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?, NATURE REVIEWS UROLOGY, Vol: 19, Pages: 47-63, ISSN: 1759-4812
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- Citations: 2
Johnson H, Piggin M, Abbara A, et al., 2021, Insight Report: Metabolic medicine and endocrinology online public involvement session on weight and fertility
Summary report on the views of members of the public on the proposed research on weight and fertility by the Metabolic Medicine and Endocrinology Theme of the Imperial Biomedical Research Centre.
Wernig F, Jayasena CN, Dhillo WS, 2021, Carcinoid syndrome and neuroendocrine tumours, Medicine (United Kingdom), Vol: 49, Pages: 544-547, ISSN: 1357-3039
Neuroendocrine tumours (NETs) arise from neuroendocrine cells of the gastrointestinal tract, pancreas, bronchi or other rare primary sites and comprise a variety of different tumour types. NETs can be associated with a variety of clinical syndromes. For instance, classic symptoms of carcinoid syndrome, such as flushing and diarrhoea, occur because of the release of hormones, including serotonin, tachykinins and peptide hormones. However, most NETs are non-secretory in nature and are detected incidentally or through compression of surrounding structures. Liver metastasis has usually already occurred at the time of diagnosis. Surgery can be curative if disease is entirely localized. Injections of somatostatin analogues are the mainstay of non-surgical treatment for well-differentiated NETs. Surgical debulking and embolization techniques are useful to reduce tumour bulk in patients who remain symptomatic despite medical treatment. Peptide receptor radionucleotide therapy using radiolabelled somatostatin analogues has recently been shown to prolong progression-free survival. Furthermore, several novel agents, such as everolimus or sunitinib, have emerged in the treatment of patients with metastatic disease. This article aims to summarize the pathophysiology and clinical features of NETs, with a focus on carcinoid syndrome. It also discusses recent advances in clinical management of NETs.
Jayasena CN, Sironen A, 2021, Diagnostics and Management of Male Infertility in Primary Ciliary Dyskinesia, DIAGNOSTICS, Vol: 11
Shrimplin V, Jayasena CN, 2021, Was Henry VIII Infertile? Miscarriages and Male Infertility in Tudor England, JOURNAL OF INTERDISCIPLINARY HISTORY, Vol: 52, Pages: 155-176, ISSN: 0022-1953
Abou Sherif S, Newman R, Haboosh S, et al., 2021, Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: A retrospective observational study, CLINICAL ENDOCRINOLOGY, Vol: 95, Pages: 618-627, ISSN: 0300-0664
Phylactou M, Clarke S, Patel B, et al., 2021, Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS), Clinical Endocrinology, Vol: 95, Pages: 239-252, ISSN: 0300-0664
BackgroundSecondary oligo/amenorrhoea occurs in 3%–5% of women of reproductive age. The two most common causes are polycystic ovary syndrome (PCOS) (2%–13%) and functional hypothalamic amenorrhoea (FHA) (1%–2%). Whilst both conditions have distinct pathophysiology and their diagnosis is supported by guidelines, in practice, differentiating these two common causes of menstrual disturbance is challenging. Moreover, both diagnoses are qualified by the need to first exclude other causes of menstrual disturbance.AimTo review clinical, biochemical and radiological parameters that could aid the clinician in distinguishing PCOS and FHA as a cause of menstrual disturbance.ResultsFHA is uncommon in women with BMI > 24 kg/m2, whereas both PCOS and FHA can occur in women with lower BMIs. AMH levels are markedly elevated in PCOS; however, milder increases may also be observed in FHA. Likewise, polycystic ovarian morphology (PCOM) is more frequently observed in FHA than in healthy women. Features that are differentially altered between PCOS and FHA include LH, androgen, insulin, AMH and SHBG levels, endometrial thickness and cortisol response to CRH. Other promising diagnostic tests with the potential to distinguish these two conditions pending further study include assessment of 5‐alpha‐reductase activity, leptin, INSL3, kisspeptin and inhibin B levels.ConclusionFurther data directly comparing the discriminatory potential of these markers to differentiate PCOS and FHA in women with secondary amenorrhoea would be of value in defining an objective probability for PCOS or FHA diagnosis.
Chen R, Tharakan T, Jayasena CN, et al., 2021, Does intracytoplasmic morphologically selected sperm injection improve live birth rates compared to ICSI in men with infertility and raised sperm DNA fragmentation?, Publisher: ELSEVIER, Pages: S699-S700, ISSN: 0302-2838
Jayasena CN, Quinton R, 2021, Male hypogonadism and general practitioners in the UK. How to increase case recognition, without compromising diagnostic accuracy?, CLINICAL ENDOCRINOLOGY, Vol: 95, Pages: 412-413, ISSN: 0300-0664
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- Citations: 1
Sharma A, Thaventhiran T, Braggins S, et al., 2021, Fatal epidural abscess from diabetic foot disease, Endocrinology, Diabetes and Metabolism Case Reports, Vol: 2021, Pages: 1-5, ISSN: 2052-0573
SummaryInfection is a common complication of advanced diabetic foot disease, increasing the risk of acute admission and amputation. It is less well-known that foot ulceration and osteomyelitis may cause bacteraemia-associated hematogenous seeding and subsequent epidural abscess formation. Here we describe the case of a 57-year-old woman with known diabetic foot ulcer with underlying osteomyelitis admitted with backpain in the absence of trauma. Her condition deteriorated secondary to overwhelming sepsis. MRI of the spine confirmed spondylodiscitis and posterior epidural collection, not amenable to surgical intervention due to patient’s comorbidities and high surgical risk. Despite prolonged antibiotic therapy, the patient died following a hospital admission lasting 2.5 months. This case highlights the importance of regular contact with diabetes foot service for optimisation and prompt treatment of diabetic foot disease, which can be an underestimated potential source of remote site invasive systemic infection. Secondly, high clinical suspicion in admitting clinicians is imperative in ensuring timely diagnosis and early intervention to minimise fatal consequences.
Pasvol TJ, Teh J, Balfoussia D, et al., 2021, Outcomes of fertility investigations in a cohort of adults with perinatally acquired HIV-1 infection: a UK cross-sectional observational study., AIDS, Vol: 35, Pages: 343-345, ISSN: 0269-9370
There are no published studies of fertility measurements in people living with perinatally acquired HIV (PaHIV). We performed fertility investigations in 25 adults with PaHIV. Seven (78%) men had sperm morphology normal forms (%) below the fifth centile for the general population with four (44%) having no normal forms. Mean (SD) serum anti-Müllerian hormone level was 19.4 (9.5) pmol/l; lower than expected for this age group. A larger study is needed to verify our findings.
Sharma A, Minhas S, Dhillo WS, et al., 2021, Male infertility due to testicular disorders, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 106, Pages: E442-E459, ISSN: 0021-972X
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- Citations: 3
Vessey W, Saifi S, Sharma A, et al., 2021, Baseline levels of seminal reactive oxygen species predict improvements in sperm function following antioxidant therapy in men with infertility, Clinical Endocrinology, Vol: 94, Pages: 102-110, ISSN: 0300-0664
BACKGROUND: Poor sperm function is a major cause of infertility. There is no drug therapy to improve sperm function. Semen oxidative stress is a recently identified pathway for sperm damage. Commercial antioxidants such as L-carnitine and acetyl-L-carnitine (LAL) are commonly self-administered by infertile men. However, concerns have been raised whether inappropriate LAL therapy causes reductive stress-mediated sperm damage. It is imperative to investigate whether: (1) LAL improves sperm function by reducing reactive oxidative species (ROS); (2) LAL has differential effects on sperm function between men with normal and elevated ROS. METHODS: A prospective cohort study of routine clinical practice was performed in infertile men with abnormal sperm quality. Changes in sperm function and semen ROS levels following three months of oral LAL therapy were compared between participants with baseline seminal normal ROS (≤10RLU/SEC/106 sperm; n = 29) and High ROS (>10 RLU/SEC/106 sperm; n = 15) levels measured using an established colorimetric-luminol method. RESULTS: In normal ROS group, sperm function did not change following LAL therapy. In high ROS group, LAL therapy reduced semen ROS fivefold, increased sperm count by 50% (mean count in mill/ml: 21.5 + 7.2, baseline; 32.6 + 9.5, post-treatment, P = .0005), and total and progressive sperm motility each by 30% (mean total sperm motility in % 29.8 + 5.0, baseline: 39.4 + 6.2, post-treatment, P = .004; mean progressive sperm motility in % 23.1 + 4.6, baseline: 30.0 + 5.5, post-treatment, P = .014 vs. baseline). CONCLUSIONS: We report for the first time that LAL only improves sperm quality in infertile men who have baseline high-ROS levels prior to treatment. These data have important potential implications for couples with male infertility and their clinicians.
Farahani L, Tharakan T, Yap T, et al., 2021, The semen microbiome and its impact on sperm function and male fertility: a systematic review and meta-analysis, Andrology, Vol: 9, Pages: 115-144, ISSN: 2047-2919
BACKGROUND: Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting. MATERIALS AND METHODS: A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction. RESULTS: The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology. DISCUSSION AND CON
Tharakan T, Luo R, Jayasena CN, et al., 2021, Non-obstructive azoospermia: current and future perspectives., Fac Rev, Vol: 10
Infertility affects 1 in 6 couples, and male factor infertility has been implicated as a cause in 50% of cases. Azoospermia is defined as the absence of spermatozoa in the ejaculate and is considered the most extreme form of male factor infertility. Historically, these men were considered sterile but, with the advent of testicular sperm extraction and assisted reproductive technologies, men with azoospermia are able to biologically father their own children. Non-obstructive azoospermia (NOA) occurs when there is an impairment to spermatogenesis. This review describes the contemporary management of NOA and discusses the role of hormone stimulation therapy, surgical and embryological factors, and novel technologies such as proteomics, genomics, and artificial intelligence systems in the diagnosis and treatment of men with NOA. Moreover, we highlight that men with NOA represent a vulnerable population with an increased risk of developing cancer and cardiovascular comorbodities.
Tharakan T, Salonia A, Corona G, et al., 2020, The Role of Hormone Stimulation in Men With Nonobstructive Azoospermia Undergoing Surgical Sperm Retrieval, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 105, ISSN: 0021-972X
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- Citations: 6
Abbara A, Eng PC, Phylactou M, et al., 2020, Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism, NEUROENDOCRINOLOGY, Vol: 111, Pages: 1176-1186, ISSN: 0028-3835
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- Citations: 2
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