Publications
194 results found
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
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
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
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
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
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
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
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
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
Ho CLT, Vaughan-Constable DR, Ramsay J, et al., 2022, 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: 5
Bhasin S, Jayasena CN, 2022, Hypogonadism, Endocrinology and Metabolism Clinics of North America, Vol: 51, Pages: xv-xvi, ISSN: 0889-8529
Jayasena C, Anderson RA, Llahana S, et al., 2022, Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism, CLINICAL ENDOCRINOLOGY, Vol: 96, Pages: 200-219, ISSN: 0300-0664
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- Citations: 26
Sharma A, Ul-Haq Z, Sindi E, et al., 2022, Clinical characteristics and comorbidities associated with testosterone prescribing in men, CLINICAL ENDOCRINOLOGY, Vol: 96, Pages: 227-235, ISSN: 0300-0664
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- Citations: 1
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, Sperm quality evaluation and cryopreservation, Management of Infertility: A Practical Approach, Pages: 241-249, ISBN: 9780323899154
Semen quality evaluation forms an integral part of assessment of the infertile couple. The semen sample must be assessed using standardized and reproducible techniques and ranges to ensure integrity of both clinical care and research. There are a range of basic, extended, and advanced techniques to analyze semen used in various centers. The World Health Organization reference range for the basic assessment of semen remains contentious as it was derived from a fertile population. Furthermore, the evidence base for some of the extended and advanced techniques is still evolving. Cryopreservation describes the process of chemically preserving male gametes for subsequent use, typically prior to treatment for cancer or as part of assisted reproductive techniques.
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.
Tharakan T, Minhas S, Jayasena CN, 2022, Male Sexual and Reproductive Health, Comprehensive Pharmacology, Pages: 94-124, ISBN: 9780128204726
Infertility effects one in seven couples and in 50% of cases the cause will be attributable to an abnormality with the man’s sperm. We discuss the epidemiology, etiology and pathophysiology of male infertility and provide an evidence-based overview of the main therapeutic strategies. Moreover, we discuss the pathogenesis and management of both erectile dysfunction and late onset hypogonadism.
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.
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: 1743-4270
The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has taken a catastrophic toll on society, health-care systems and the economy. Notably, COVID-19 has been shown to be associated with a higher mortality rate in men than in women. This disparity is likely to be a consequence of a failure to invest in men’s health, as it has also been established that men have a lower life expectancy and poorer outcomes from non-communicable diseases than women. A variety of biological, social and economic factors have contributed to the sex disparities in mortality from COVID-19. A streamlined men’s health programme — with the urologist as the gatekeeper of men’s health — is needed to help prevent future tragedies of this nature.
Abbara A, Eng PC, Phylactou M, et al., 2021, 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: 8
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