Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: A retrospective observational study.

OBJECTIVES: Functional hypothalamic amenorrhoea (FHA) is a common cause of amenorrhoea, but diagnosis can be challenging. The aim of this study was to investigate the clinical and biochemical features of FHA, compared to that of polycystic ovarian syndrome (PCOS) and assess the diagnostic performance of the different parameters for differentiating the two conditions. DESIGN AND PATIENTS: This was a retrospective observational study. We analysed clinical and biochemical parameters of women diagnosed with FHA and PCOS following specialist assessment at the reproductive endocrine gynaecology clinic, St Mary's Hospital. RESULTS: Compared with PCOS, women with FHA had significantly lower body mass index (BMI; 20.1 ± 2.9 vs. 31.1 ± 7.8 kg/m2 ; p< .0001) and a thinner endometrium (3.75 ± 2.23 vs. 6.82 ± 3.32 mm; p< .0001). Women with FHA had significantly lower luteinising hormone (LH; 3.46 ± 7.31 vs. 8.79 ± 4.98 IU/L; p< .0001), and lower LH to follicle-stimulating hormone (FSH) ratio, estradiol, thyroid-stimulating hormone, free thyroxine and prolactin levels; there was no significant difference in FSH levels. BMI had the greatest predictive performance for FHA (area under the curve [AUC]: 0.93; p< .001), followed by estradiol (AUC: 0.89; p< .001), LH (AUC: 0.88; p< .001) and LH:FSH ratio (AUC: 0.86; p< .001). CONCLUSIONS: Our data provides quantification for diagnostic accuracy of clinical parameters to differentiate FHA from PCOS, namely low BMI, estradiol, LH and LH:FSH ratio. These data could help clinicians more reliably diagnose FHA in women with secondary amenorrhoea.

Reduced Testicular Steroidogenesis and Increased Semen Oxidative Stress in Male Partners as Novel Markers of Recurrent Miscarriage.

BACKGROUND: Recurrent pregnancy loss, (RPL) affecting 1%-2% of couples, is defined as ≥3 consecutive pregnancy losses before 20-week' gestation. Women with RPL are routinely screened for etiological factors, but routine screening of male partners is not currently recommended. Recently it has been suggested that sperm quality is reduced in male partners of women with RPL, but the reasons underlying this lower quality are unclear. We hypothesized that these men may have underlying impairments of reproductive endocrine and metabolic function that cause reductions in sperm quality. METHODS: After ethical approval, reproductive parameters were compared between healthy controls and male partners of women with RPL. Semen reactive oxygen species (ROS) were measured with a validated inhouse chemiluminescent assay. DNA fragmentation was measured with the validated Halosperm method. RESULTS: Total sperm motility, progressive sperm motility, and normal morphology were all reduced in the RPL group vs controls. Mean ±SE morning serum testosterone (nmol/L) was 15% lower in RPL than in controls (controls, 19.0 ± 1.0; RPL, 16.0 ± 0.8; P < 0.05). Mean ±SE serum estradiol (pmol/L) was 16% lower in RPL than in controls (controls, 103.1 ± 5.7; RPL, 86.5 ± 3.4; P < 0.01). Serum luteinizing hormone and follicle-stimulating hormone were similar between groups. Mean ±SE ROS (RLU/sec/106 sperm) were 4-fold higher in RPL than in controls (controls, 2.0 ± 0.6; RPL, 9.1 ± 4.1; P < 0.01). Mean ±SE sperm DNA fragmentation (%) was 2-fold higher in RPL than in controls (controls, 7.3 ± 1.0; RPL, 16.4 ± 1.5; P < 0.0001). CONCLUSIONS: Our data suggest that male partners of women with RPL have impaired reproductive endocrine function, increased levels of semen ROS, and sperm DNA fragmentation. Routine reproductive assessment of the male partners may be beneficial in RPL.

Prevalence of abnormal semen analysis and levels of adherence with fertility preservation in men undergoing therapy for newly diagnosed cancer: A retrospective study in 2906 patients.

BACKGROUND: Sperm cryopreservation (freezing) should be offered to all men with cancer due to risk of infertility. However, many men with cancer already have impaired spermatogenesis prior to sperm cryopreservation. Furthermore, physical ill-health may hinder attendance of freeze visits. Investigating both the distribution of sperm functions and freeze attendance rates in men with newly diagnosed cancer, may identify patients benefiting from targeted reproductive fertility support. METHODS: We performed a retrospective study of 2906 male patients undergoing sperm cryopreservation prior to cancer therapy at a single UK tertiary centre between 1989 and 2013; all patients were asked to attend three hospital semen collection visits prior to cancer therapy. RESULTS: Fifteen per cent (433/2906) of men with newly diagnosed cancer had severely impaired semen quality (i.e., sperm total motile count, TMC < 1 million) during the first semen collection visit. However, patients with severely impaired semen quality had the poorest attendance of subsequent semen collection visits despite being requested to do so (non-attendance in TMC < 1 million: 43.4%; TMC < 1-30 million: 35.7%, P < 0.05 vs. <1 million; TMC > 30 million: 33.2%, P < 0.01 vs. <1 million). CONCLUSIONS: This study expands understanding of the semen quality of men with newly diagnosed cancer, and their ability to adhere to fertility preservation recommendations. Our data suggest that patients with the poorest semen quality paradoxically suffer the poorest attendance rates of sperm cryopreservation appointments prior to commencing cancer therapy. We suggest that additional support may be of clinical benefit to men with newly diagnosed cancer and TMC < 1 million sperm.

Metabolic and cardiovascular risks of hormone treatment for transgender individuals.

Identifying metabolic and cardiovascular risks of gender-affirming hormone therapy (GAHT) is challenging due to other confounding variables that affect patient outcomes and the diversity of treatment regimes. Masculinising hormone therapy produces atherogenic lipid profiles, while effects on other metabolic parameters are not consistent. There is insufficient evidence to conclude if cardiovascular disease risk among transmen is increased. The effects of feminising hormone therapy on metabolic parameters do not demonstrate a consistent pattern in the available literature. However, the risk of venous thromboembolism is greater in transwomen than in cis-gender men and women with a possible increase in cardiovascular disease risk. It is recommended to discuss the potential effects of GAHT on cardiovascular health and encourage patients seeking GAHT to adopt a healthy lifestyle. Performing baseline and periodic assessments of cardiovascular risk factors would enable early identification and interventions. In high-risk individuals, the cardiovascular effects of hormonal regimes might impact the treatment decision.

The role of androgens in transgender medicine.

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.

Stimulation of Leydig and Sertoli Cellular Secretory Function by Anti-Oestrogens: Tamoxifen.

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.

Stress cardiomyopathy (Takotsubo) following radioactive iodine therapy

Summary: A 55-year-old female patient presented to the endocrine clinic with Grave's disease. She was initially treated with carbimazole. After an early relapse, a decision was made to proceed with radioactive iodine therapy. Four days after radioiodine administration, she presented to the emergency department with chest tightness and dyspnea due to heart failure. Biochemistry revealed thyrotoxicosis and significantly elevated Troponin-T. There was ST segment elevation on electrocardiography. However, coronary angiography was normal. Ventricular function was fully restored after 6 weeks of supportive medical management. A diagnosis of stress cardiomyopathy following radioactive iodine therapy was made. This is the second case reported in the literature so far to the best of our knowledge. Learning Points: Stress cardiomyopathy in the context of radiation thyroiditis is a rare complication following radioiodine therapy. A degree of awareness is essential because the approach is multidisciplinary. Management is mainly supportive and cardiac dysfunction is completely reversible in most cases. The pathogenesis of this condition remains unclear. Post-menopausal women and susceptible individuals appear to be pre-disposed.