Introduction: Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and ...therapeutic considerations for male hypogonadism and identifies key questions for future research.
Main recommendations: Key points and recommendations are:
Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment. Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk.
Testosterone is the native hormone that should be replaced in men being treated for pathological hypogonadism. Convenient and cost‐effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations).
Monitoring of testosterone therapy is recommended for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.
Treatment aims to relieve an individual's symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men.
Evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of similar age. Nevertheless, when there is a reasonable possibility of substantive pre‐existing prostate disease, digital rectal examination and prostate‐specific antigen testing should be performed before commencing testosterone treatment.
Changes in management as result of the position statement: Treatment aims to relieve symptoms and signs of androgen deficiency, using convenient and effective formulations of testosterone. Therapy should be monitored for efficacy and safety.
Abstract Objective To determine the effect of testosterone vs placebo treatment on health-related quality of life (HR-QOL) and psychosocial function in men without pathologic hypogonadism in the ...context of a lifestyle intervention. Design, Setting, Participants Secondary analysis of a 2-year randomized controlled testosterone therapy trial for prevention or reversal of newly diagnosed type 2 diabetes, enrolling men ≥ 50 years at high risk for type 2 diabetes from 6 Australian centers. Interventions Injectable testosterone undecanoate or matching placebo on the background of a community-based lifestyle program. Main Outcomes Self-reported measures of HR-QOL/psychosocial function. Results Of 1007 participants randomized into the Testosterone for Type 2 Diabetes Mellitus (T4DM) trial, 648 (64%) had complete data available for all HR-QOL/psychosocial function assessments at baseline and 2 years. Over 24 months, while most measures were not different between treatment arms, testosterone treatment, compared with placebo, improved subjective social status and sense of coherence. Baseline HR-QOL/psychosocial function measures did not predict the effect of testosterone treatment on glycemic outcomes, primary endpoints of T4DM. Irrespective of treatment allocation, larger decreases in body weight were associated with improved mental quality of life, mastery, and subjective social status. Men with better baseline physical function, greater sense of coherence, and fewer depressive symptoms experienced greater associated decreases in body weight, with similar effects on waist circumference. Conclusion In this diabetes prevention trial, weight loss induced by a lifestyle intervention improved HR-QOL and psychosocial function in more domains than testosterone treatment. The magnitude of weight and waist circumference reduction were predicted by baseline physical function, depressive symptomology, and sense of coherence.
Summary A 33-year-old man with Kallmann syndrome had received pulsatile GnRH as an infant for the treatment of cryptorchidism. As an adult, his treatment for fertility with gonadotrophins was ...unusually rapid compared with expectations, with a total sperm count of 25 million after only 12 months of gonadotrophin therapy. We propose that pulsatile GnRH treatment as an infant induced minipuberty and facilitated his successful, rapid response to therapy. We also propose that identification of the absence of minipuberty in infants with clinical signs suggesting congenital hypogonadotrophic hypogonadism (CHH) is an opportunity for intervention with pulsatile GnRH yielding benefits for fertility decades later. Learning points Absence of minipuberty in males with CHH results in low Sertoli cell numbers and delayed response to induction of spermatogenesis in adulthood. Presentation with 'red flags' for androgen deficiency including cryptorchidism at birth, with or without micropenis, should prompt screening for CHH and minipuberty by measurement of gonadotrophins and testosterone in the first 2 months after birth. Pulsatile GnRH therapy in patients with CHH, given prior to age of attainment of Sertoli cell maturation, can replicate the normal physiology of minipuberty, thereby priming the testis for future fertility.
Objective To examine the prevalence of a history of polycystic ovary syndrome (PCOS) in women with type 2 diabetes (DM2) and to compare metabolic and reproductive outcomes between women with and ...without PCOS. Design Cross-sectional study. Setting Tertiary hospital. Patient(s) Female inpatients age 18–75 years with DM2. Intervention(s) A face-to-face questionnaire was administered. Main Outcome Measure(s) Age at diagnosis of diabetes, history of gestational diabetes, family history of diabetes, and reproductive history, fertility history, number of miscarriages, and morbidity in pregnancy. Result(s) One hundred seventy-one inpatients with DM2 participated. The prevalence of a history of PCOS was 37%. Women with PCOS had an earlier mean age of diagnosis of DM2 (44.2 vs. 48.8 years), higher recalled peak body mass index (BMI; 43.1 kg/m2 vs. 36.8 kg/m2 ), higher rate of gestational diabetes (28% vs. 18%), and higher rate of hypertension in pregnancy (40% vs. 22%). Women with PCOS were less likely to have a family history of DM2 than those without PCOS (45% vs. 67%). Conclusion(s) A history of PCOS in women with DM2 is associated with earlier onset of DM2, higher BMI, and a more severe phenotype. Since PCOS subjects were less likely to have a family history of DM2, lack of a family history of DM2 in women with PCOS is not reassuring for DM2 risk. We recommend identifying PCOS in early life and intervening to reduce the risk of diabetes and its comorbidities and suboptimal reproductive outcomes.
Context: In patients with primary hypothyroidism, anecdotal evidence suggests that well-being is optimized by fine adjustment of T4 dosage, aiming for a serum TSH concentration in the lower reference ...range. This has not been tested in a clinical trial.
Objective: Our objective was to test whether adjustment of T4 dosage aiming for a serum TSH concentration less than 2 mU/liter improves well-being compared with a serum TSH concentration in the upper reference range.
Design: We conducted a double-blind, randomized clinical trial with a crossover design.
Participants: Fifty-six subjects (52 females) with primary hypothyroidism taking T4 (≥100 μg/d) with baseline serum TSH 0.1–4.8 mU/liter participated.
Interventions: Each subject received three T4 doses (low, middle, and high in 25-μg increments) in random order.
Outcome Measures: Outcome measures included visual analog scales assessing well-being (the primary endpoint) and hypothyroid symptoms, quality of life instruments (General Health Questionnaire 28, Short Form 36, and Thyroid Symptom Questionnaire), cognitive function tests, and treatment preference.
Results: Mean (± sem) serum TSH concentrations were 2.8 ± 0.4, 1.0 ± 0.2, and 0.3 ± 0.1 mU/liter for the three treatments. There were no significant treatment effects on any of the instruments assessing well-being, symptoms, quality of life, or cognitive function and no significant treatment preference.
Conclusions: Small changes in T4 dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH and markers of thyroid hormone action. These data do not support the suggestion that the target TSH range for the treatment of primary hypothyroidism should differ from the general laboratory range.
The new millennium has brought intense focus of interest on the risk of cardiovascular disease in women. The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women characterised by ...hyperandrogenism and oligomenorrhoea. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Echocardiography, imaging of coronary and carotid arteries, and assessments of both endothelial function and arterial stiffness have recently been employed to address this question. These studies have collectively demonstrated both structural and functional abnormalities of the cardiovascular system in PCOS. These alterations, however, appear to be related to the presence of individual cardiovascular risk factors, particularly insulin resistance, rather than to the presence of PCOS and hyperandrogenaemia per se. However, given the inferential nature of the evidence to date, more rigorous cohort studies of long-term cardiovascular outcomes and clinical trials of risk factor modification are required in women with PCOS.
OBJECTIVE:--To investigate the effects of fenofibrate and coenzyme Q₁₀ (CoQ) on diastolic function, ambulatory blood pressure (ABP), and heart rate (HR) in type 2 diabetic subjects with left ...ventricular diastolic dysfunction (LVDD). RESEARCH DESIGN AND METHODS--We randomized, double-blind, 74 subjects to fenofibrate 160 mg daily, CoQ 200 mg daily, fenofibrate 160 mg plus CoQ 200 mg daily, or matching placebo for 6 months. Echocardiography (including tissue Doppler imaging) and 24-h ABP and HR monitoring were performed pre- and postintervention. RESULTS:--Neither fenofibrate nor CoQ, alone or in combination, altered early diastolic mitral annular myocardial relaxation velocity (E'), early-to-late mitral inflow velocity ratio (E/A), deceleration time, isovolumic relaxation time, or the ratio of early mitral flow velocity to early diastolic mitral annular myocardial relaxation velocity (E/E') compared with placebo (P > 0.05). Fenofibrate and CoQ interactively (P = 0.001) lowered 24-h systolic blood pressure (-3.4 ± 0.09 mmHg, P = 0.010), with a prominent nocturnal effect (-5.7 ± 1.5 mmHg, P = 0.006). Fenofibrate (-1.3 ± 0.5 mmHg, P = 0.013) and CoQ (-2.2 ± 0.5 mmHg, P < 0.001) independently lowered 24-h diastolic blood pressure. Fenofibrate reduced 24-h HR (-3.3 ± 0.5 beats/min, P < 0.001), but CoQ had no effect on HR. CONCLUSIONS:--In type 2 diabetic subjects with LVDD, neither fenofibrate nor CoQ, alone or in combination, improved diastolic function significantly. However, fenofibrate and CoQ independently and interactively lowered 24-h blood pressure, and fenofibrate alone reduced 24-h HR.
Summary
Objective Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk but it is not clear if this is independent of obesity and insulin resistance. This study therefore ...investigates endothelial function and arterial stiffness in nonobese, noninsulin resistant women with PCOS.
Design This is cross‐sectional case–control study.
Patients A total of 19 young women with PCOS, with body mass index (BMI) <30 kg/m2, and 19 healthy controls matched for age and BMI were included in the study.
Measurements Endothelial function was assessed with flow mediated dilatation (FMD) of the brachial artery, while arterial stiffness was assessed with pulse wave velocity (PWV) and augmentation index (AI).
Results There were no significant differences between PCOS and control subjects when assessing the following clinical and biochemical variables: blood pressure, homeostasis model assessment insulin‐resistance index, lipids and oestradiol. Women with PCOS had higher free androgen index scores (5·14 ± 3·47 vs. 3·25 ± 1·42, P = 0·036). The PCOS subjects had significantly lower FMD of the brachial artery compared with the controls (6·5 ± 2·9%vs. 10·5 ± 4·0%, P < 0·01). There were no significant differences in markers of arterial stiffness (PWV 5·8 ± 1·1 vs. 6·0 ± 1·0, P = 0·58, AI 16·5 ± 10·2 vs. 20·3 ± 10·2, P = 0·25).
Conclusions Women with polycystic ovary syndrome who are young, nonobese, and have no biochemical evidence of insulin resistance, have abnormal vascular function, but normal arterial stiffness, when compared with age and weight matched control subjects. Whether this leads to a greater risk of cardiovascular disease requires further investigation.
Abstract Aims To determine whether idiopathic erectile dysfunction, in the absence of overt cardiovascular disease or cardiovascular risk factors, is associated with vascular or autonomic ...dysfunction. Methods We studied 49 men with ED (without known cardiovascular risk factors or disease) and 50 age-matched controls, aged 40–70 years. Macrovascular endothelial function was examined by brachial artery ultrasonography and microvascular function by venous occlusion plethysmography. Blood pressure measurement and electrocardiography were performed lying and standing, and the 30:15 RR ratio calculated. Results Body mass index, testosterone, fasting lipids and glucose did not differ significantly between groups. Standing pulse pressure was higher (50 ± 1 mm Hg versus 43 ± 2 mm Hg, p < 0.004) and 30:15 RR ratio lower (0.97 ± 0.01 versus 1.01 ± 0.01, p < 0.02) in the ED group. Flow-mediated dilatation of the brachial artery was not significantly different between groups. Flow debt repayment during forearm reactive hyperaemia was lower in the ED group (7.2 ± 0.7 ml versus 9.5 ± 0.8 ml per 100 ml, p < 0.02) than in controls. Conclusions Men with idiopathic ED have evidence of endothelial dysfunction in forearm resistance vessels, increased pulse pressure and impaired heart rate variability. This supports the concept that erectile dysfunction is a predictor of cardiovascular dysfunction and a precursor of clinical cardiovascular disease.
Highlights • Estrapel is an oestradiol implant that provides a non-oral treatment option for menopausal hormone therapy. • Its prolonged action makes patient selection important, as the implants ...cannot easily be removed. • In women with an intact uterus, the continuation of progestin therapy after cessation of implant therapy is imperative.
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