Publications
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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.
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
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- Citations: 2
Jayasena CN, Sironen A, 2021, Diagnostics and management of male infertility in primary ciliary dyskinesia, Diagnostics, Vol: 11, Pages: 1-15, ISSN: 2075-4418
Primary ciliary dyskinesia (PCD), a disease caused by the malfunction of motile cilia, manifests mainly with chronic recurrent respiratory infections. In men, PCD is also often associated with infertility due to immotile sperm. Since causative mutations for PCD were identified in over 50 genes, the role of these genes in sperm development should be investigated in order to understand the effect of PCD mutations on male fertility. Previous studies showed that different dynein arm heavy chains are present in respiratory cilia and sperm flagellum, which may partially explain the variable effects of mutations on airways and fertility. Furthermore, recent studies showed that male reproductive tract motile cilia may play an important part in sperm maturation and transport. In some PCD patients, extremely low sperm counts were reported, which may be due to motile cilia dysfunction in the reproductive tract rather than problems with sperm development. However, the exact roles of PCD genes in male fertility require additional studies, as do the treatment options. In this review, we discuss the diagnostic and treatment options for men with PCD based on the current knowledge.
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
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- Citations: 1
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
Wernig F, Jayasena CN, Dhillo WS, 2021, Carcinoid syndrome and neuroendocrine tumours, Medicine, 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.
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
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.
Tharakan T, Luo R, Jayasena CN, et al., 2021, Non-obstructive azoospermia: current and future perspectives., Faculty Reviews, Vol: 10, Pages: 1-12, ISSN: 2732-432X
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.
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: 28
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, 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: 13
Abbara A, Eng P, Phylactou M, et al., 2020, Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders., Journal of Clinical Investigation, Vol: 130, Pages: 6739-6753, ISSN: 0021-9738
BACKGROUND. Kisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders.METHODS. We conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signaling in cell lines and on action potential firing of GnRH neurons in brain slices.RESULTS. In healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU∙h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012).CONCLUSION. Taken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders.TRIAL REGISTRATION. International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316.FUNDING. National Institute for Health Research and NIH.
Pasvol T, Teh J, Balfoussia D, et al., 2020, Fertility evaluation in adults with perinatally acquired HIV-1 infection: a cross-sectional observational study, Publisher: WILEY, Pages: 38-38, ISSN: 1464-2662
Jayasena CN, Sharma A, Abbara A, et al., 2020, Burdens and awareness of adverse self-reported lifestyle factors in men with sub-fertility: a cross-sectional study in 1149 men., Clinical Endocrinology, Vol: 93, Pages: 312-321, ISSN: 0300-0664
BACKGROUND: There are no current pharmacological therapies to improve sperm quality in men with sub-fertility. Reducing the exposure to lifestyle risk factor (LSF) is currently the only intervention for improving sperm quality in men with sub-fertility. No previous study has investigated what proportion of men with sub-fertility are exposed to adverse lifestyle factors. Furthermore, it is not known to what extent men with sub-fertility are aware of lifestyle factors potentially adversely impacting their fertility. METHODS: A cross-sectional anonymous questionnaire-based study on self-reported exposure and awareness of LSF was conducted in 1149 male partners of couples investigated for sub-fertility in a tertiary andrology centre in London, UK. RESULTS: Seventy-percent of men investigated for sub-fertility had ≥1 LSF, and twenty-nine-percent had ≥2 LSF. Excessive alcohol consumption was the most common LSF (40% respondents). Seventeen-percent of respondents used recreational drugs (RD) regularly, but only 32% of RD users believed RD impair male fertility. Twenty-five-percent of respondents were smokers, which is higher than the UK average (20%). Twenty-seven percent of respondents had a waist circumference (WC) >36inches (91cm), and 4% had WC >40inches (102cm). Seventy-nine-percent of respondents wanted further lifestyle education to improve their fertility. CONCLUSIONS: Our data suggest that men with sub-fertility are: (1) exposed to one or more LSF; (2) have incomplete education about how LSF may cause male sub-fertility; (3) want more education about reducing LSF. Further studies are needed to investigate the potential of enhanced education of men about LSF to treat couples with sub-fertility.
Roberts RE, Farahani L, Webber L, et al., 2020, Current understanding of hypothalamic amenorrhoea, Therapeutic Advances in Endocrinology and Metabolism, Vol: 11, Pages: 1-12, ISSN: 2042-0188
Hypothalamic amenorrhoea (HA) accounts for approximately 30% of cases of secondary amenorrhoea in women of reproductive age. It is caused by deficient secretion of hypothalamic gonadotrophin-releasing hormone, which in turn leads to failure of pituitary gonadotrophin and gonadal steroid release. Functional HA (FHA) is defined as HA occurring in the absence of a structural lesion and is predominantly caused by significant weight loss, intense exercise or stress. Treatment of FHA is crucial in avoiding the long-term health consequences on fertility and bone health, in addition to reducing psychological morbidity. This article summarises our understanding of the mechanisms underlying FHA, the evidence base for its clinical management and emerging therapies.
Al-Sharefi A, Wilkes S, Jayasena CN, et al., 2020, How to manage low testosterone level in men: a guide for primary care, British Journal of General Practice, Vol: 70, Pages: 364-365, ISSN: 0960-1643
Sharma A, Thaventhiran T, Minhas S, et al., 2020, Kisspeptin and testicular function-is it necessary?, International Journal of Molecular Sciences, Vol: 21, Pages: 1-14, ISSN: 1422-0067
The role of kisspeptin in stimulating hypothalamic GnRH is undisputed. However, the role of kisspeptin signaling in testicular function is less clear. The testes are essential for male reproduction through their functions of spermatogenesis and steroidogenesis. Our review focused on the current literature investigating the distribution, regulation and effects of kisspeptin and its receptor (KISS1/KISS1R) within the testes of species studied to date. There is substantial evidence of localised KISS1/KISS1R expression and peptide distribution in the testes. However, variability is observed in the testicular cell types expressing KISS1/KISS1R. Evidence is presented for modulation of steroidogenesis and sperm function by kisspeptin signaling. However, the physiological importance of such effects, and whether these are paracrine or endocrine manifestations, remain unclear.
Sharma A, Mollier J, Brocklesby RWK, et al., 2020, Endocrine-disrupting chemicals and male reproductive health, Reproductive Medicine and Biology, Vol: 19, Pages: 243-253, ISSN: 1445-5781
BackgroundA number of different types of endocrine‐disrupting chemicals (EDCs) including bisphenol A, phthalates, pesticides, and other environmental chemicals have been shown to adversely impact upon male reproductive health. Understanding the potential effects of EDCs on male reproductive health may enable the development of novel treatments and early prevention of the effects of EDCs on male infertility and their potential long‐term sequelae. This review critically evaluates the research performed in this area and explores potential harmful effects of EDCs in animals and humans, including the possibility of trans‐generational transmission.MethodsA literature review was conducted using electronic databases using the following terms: ‘endocrine disrupt*’ OR ‘endocrine disruptors’ OR ‘endocrine disruptor chemicals’ OR ‘EDC’ AND ‘sperm*’ OR ‘spermatozoa’ OR ‘spermatozoon’ OR ‘male reproductive health’ OR’ male fertility’.Main findingsSeveral studies have shown that EDCs have a variety of pathophysiological effects. These include failure of spermatogenesis, embryonic development, the association with testicular cancer, and long‐term metabolic effects.ConclusionsSeveral studies observe correlations between chemical doses and at least one sperm parameter; however, such correlations are sometimes inconsistent between different studies. Mechanisms through which EDCs exert their pathophysiological effects have not yet been fully elucidated in human studies.
Tharakan T, Jayasena C, Minhas S, 2020, Men's health clinics: a real need or a marketing strategy, International Journal of Impotence Research, Vol: 32, Pages: 565-568, ISSN: 0955-9930
Globally, the life expectancy for men is 5.1 years less than for women. This gender gap in mortality is intrinsically linked to a higher proportion of premature male mortality and is a significant economic, social and healthcare issue. We explore the main causes for premature male death and also discuss the need for a dedicated men’s health clinic, especially in the context of potential commercial exploitation.
Dimakopoulou A, Foran D, Jayasena CN, et al., 2020, Stimulation of Leydig and Sertoli cellular secretory function by anti-oestrogens: Tamoxifen, Current Pharmaceutical Design, Vol: 26, ISSN: 1381-6128
Tamoxifen is a selective oestrogen receptor modulator (SERM). SERMs act on oestrogen receptors to inhibit oestradiol mediated negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, thereby upregulating gonadotrophin secretion and release from the pituitary. Hence, Tamoxifen is used to upregulate activation of the HPG axis in the treatment of male-factor infertility. However, due to a lack of robust evidence, Tamoxifen has not been FDA approved for use in male-factor infertility and so its use is currently off-label. In this study, we performed a literature search of the OVID medline database and identified 37 studies describing the effects of tamoxifen which we then reviewed. Evidence suggests Tamoxifen effectively increases androgen levels and sperm concentrations in males with idiopathic oligozoospermia. Evidence for increased motility and pregnancy rates in these patients is less conclusive. Further randomised control trials are needed to elucidate the safety of Tamoxifen combination therapies and their efficacy in improving pregnancy rates.
Prague J, Abbara A, Comninos A, et al., 2020, Neurokinin 3 receptor antagonists do not increase FSH or estradiol secretion in menopausal women, Journal of the Endocrine Society, Vol: 4, ISSN: 2472-1972
Background: Neurokinin 3 receptor (NK3R) antagonism is a promising novel treatment for menopausal flashes. However, to avoid adverse hormonal effects it is clinically important to first confirm whether gonadotropin and estradiol concentrations change as a result of their administration. Methods: Single-center, randomized, double-blind, placebo-controlled, crossover trial of an oral NK3R antagonist (MLE4901) in 28 women aged 40-62yrs, experiencing >7 hot flashes/24h; some bothersome or severe (Clinicaltrials.gov NCT02668185). Weekly serum gonadotropins and estradiol levels were measured using commercially available automated immunoassays a priori. Serum estradiol was also measured post hoc using a highly sensitive direct assay by liquid chromatography tandem mass spectrometry. Hormone levels were compared by the paired sample t-tests or by the Wilcoxon matched-pairs signed rank test, as appropriate for the distribution of the data. Results: Mean (SD) serum FSH concentration was not significantly increased when taking MLE4901 (72.07 ±19.81iU/L) compared to placebo (70.03 ±19.56iU/L), p=0.26. Serumestradiol was also not significantly altered, irrespective of which assay method was used (median IQR of serum estradiol by immunoassay: placebo 36 ±3pmol/L, MLE4901 36 ± 1pmol/L, p=0.21; median serum highly sensitive estradiol: placebo 12 ± 16pmol/L, MLE4901 5 13 ± 15pmol/L, p=0.70). However, mean (SD) serum LH concentration significantly decreased with MLE4901 (27.63 ± 9.76iU/L) compared to placebo (30.26 ± 9.75iU/L), p=0.0024. Implication: NK3R antagonists do not increase serum estradiol or FSH despite their reduction in hot flashes. This is clinically significant; and highly reassuring for women who have a contraindication to conventional hormone therapy such as prior/existing breast cancer and/or thromboembolism.
Al-Sharefi A, Mohammed A, Abdalaziz A, et al., 2019, Androgens and anaemia: current trends and future prospects, Frontiers in Endocrinology, Vol: 10, ISSN: 1664-2392
Sharma A, Jayasena CN, 2019, Male infertility linked to risk of prostate cancer, BMJ: British Medical Journal, Vol: 366, ISSN: 0959-535X
Dimakopoulou A, Jayasena CN, Radia UK, et al., 2019, Animal models of diabetes-related male hypogonadism, Frontiers in Endocrinology, Vol: 10, ISSN: 1664-2392
Hypogonadism is the clinical syndrome associated with low testosterone secretion in men. Hypogonadism affects ~37–57% men with diabetes mellitus (1). Male reproduction is orchestrated by the hypothalamo-pituitary-gonadal (HPG) axis, which regulates the biosynthesis of testosterone from the testes. Diabetes may cause hypogonadism through multiple mechanisms including suppression of hypothalamic gonadotrophin-releasing hormone (GnRH) secretion, or direct disruption of spermatogenesis (2). Clinical stigmata of hypogonadism include reduced libido, erectile dysfunction (ED) and reduced physical strength. This article will summarize the evidence from animal models including how diabetes affects male reproductive endocrine function and predisposes to hypogonadism.
Prague J, voliotis M, Clarke S, et al., 2019, Determining the relationship between hot flushes and LH pulses in menopausal women using mathematical modelling, Journal of Clinical Endocrinology and Metabolism, Vol: 104, Pages: 3628-3636, ISSN: 0021-972X
BackgroundHypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurones regulate LH pulsatility. It is widely accepted that the menopausal hot flush (HF) consistently synchronises with the LH pulse. This suggests that the hypothalamic KNDy neurones are implicated in generating LH pulsatility and HF. Using a modern immunoassay and mathematical modelling we investigated if the HF and LH pulse was consistently synchronised in menopausal women.MethodsEleven menopausal women (51-62yrs experiencing ≥7 HF/24hrs) attended for an 8 hour study where they self-reported HF and underwent peripheral blood sampling every 10 mins. LH pulsatility was determined using two mathematical models: blinded deconvolution analysis and Bayesian spectrum analysis. The probability that the LH pulse and HF event intervals matched was estimated using the interval distributions observed in our data.ResultsNinety-six HF were self-reported, and 82 LH pulses were identified by blinded deconvolution analysis. Using both models, the probability that the two event intervals matched was low in the majority of participants (mean P=0.24 (P=1 reflects perfect association)).InterpretationOur data challenges the widely accepted dogma that HF consistently synchronise with an LH pulse, and so has clinically important therapeutic and mechanistic implications.
Agarwal A, Parekh N, Panner Selvam MK, et al., 2019, Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility, World Journal of Mens Health, Vol: 37, ISSN: 2287-4208
Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
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