Reproductive factors and breast arterial calcification: a systematic review and meta-analysis.

BACKGROUND: Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). METHODS: MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. RESULTS: Nineteen observational studies (n = 47,249; three cohort studies, seven case-control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50-4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68-3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40-0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. CONCLUSIONS: BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO: CRD42020141644.

Celiac disease and bone health: is there a gap in the management of postmenopausal osteoporosis?

Malabsorption due to celiac disease (CD) may contribute to postmenopausal osteoporosis. This study aimed to survey participants with CD regarding their bone density, fractures, and bone-preserving medications; to compare tolerance of bone-preserving medications in participants with and without CD; and to review the evidence for CD screening and osteoporosis therapies in the setting of CD. We recruited 131 participants with CD and 102 participants without CD. Of those with CD, 87% were diagnosed in adulthood and 40% had no recognized gastrointestinal symptoms. In 21% CD was diagnosed after the diagnosis of osteoporosis and in 9% after a fracture. No difference was found in the tolerability of bone medications between participants with CD and those without. Review of the literature found that, although monitoring of bone health is recommended for patients with CD, screening for CD is not generally accepted for patients with osteoporosis, although studies of the prevalence of CD in osteoporosis had incomplete ascertainment methods. There is a lack of well-conducted studies and therefore insufficient data for the efficacy and tolerability of bone medication in CD. In conclusion, both CD and menopause lead to bone loss. Identifying CD in postmenopausal women should lead to modification of osteoporosis management.

An unusual hazard of menopause in the workplace: a case report.

Untreated vasomotor symptoms of the menopause can have a major impact on women at work. Recent recommendations advocate modification of the working environment, including adequate air-conditioning, to help relieve these symptoms. However, this may cause discomfort for work colleagues. We report the case of a 40-year-old woman with cold urticaria. Cold urticaria is a serious, potentially life-threatening condition. Our patient's symptoms were exacerbated when her postmenopausal work colleagues turned the air-conditioner temperature down to relieve their vasomotor symptoms.

Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial.

AIM: To assess the efficacy, safety and tolerability of beloranib treatment for obesity. METHODS: This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4 mg) or placebo, administered subcutaneously, for 12 weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered. RESULTS: At week 12, beloranib resulted in dose-dependent progressive weight loss of -5.5 ± 0.5, -6.9 ± 0.6 and -10.9 ± 1.1 kg for the 0.6, 1.2 and 2.4 mg beloranib doses, respectively, compared with -0.4 ± 0.4 kg with placebo (all p < 0.0001 vs placebo). Weight loss with beloranib was associated with corresponding reductions in waist circumference and body fat mass, as well as improvements in lipids, high-sensitivity C-reactive protein and blood pressure. Sleep disturbance and gastrointestinal adverse events were more common with beloranib than with placebo; these were generally mild to moderate, transient and dose-related, and led to more early study withdrawals in participants in the group with the highest dose of beloranib. CONCLUSIONS: In this 12-week phase II study, beloranib produced clinically and statistically significant weight loss and corresponding improvements in cardiometabolic risk factors. Beloranib appeared safe, and the 0.6 and 1.2 mg doses were generally well tolerated. The 2.4 mg dose was associated with increased sleep latency and mild to moderate gastrointestinal adverse events over the first month of treatment. These findings represent a novel mechanism for producing clinically meaningful weight loss.

Low urinary iodine postpartum is associated with hypothyroid postpartum thyroid dysfunction and predicts long-term hypothyroidism.

BACKGROUND: Postpartum thyroid dysfunction (PPTD) is characterized by an early hyperthyroid phase followed, with peak prevalence at 6 months, by a hypothyroid phase which carries a risk of long-term hypothyroidism. Iodine has a major effect on thyroid function. Western Australia has previously been shown to be iodine replete. OBJECTIVE: To examine the iodine status of women with and without PPTD and the relationship of iodine status postpartum with long-term hypothyroidism. DESIGN: Case-control with follow-up. PATIENTS: A total of 149 women at 6 months postpartum (74 PPTD, 75 controls) with 98 (46 PPTD, 52 controls) followed up at 12 years. MEASUREMENTS: Urinary iodine concentration (UIC) and thyroid function at 6 months postpartum; thyroid function at 12-year follow-up. RESULTS: At 6 months postpartum, median UIC (quartiles) for observed TSH ranges were: for TSH < 0·4 mU/l 130·0 µg/l (82·0, 170·0); for TSH 0·4-4·0 mU/l 123·0 µg/l (80·5, 168·0); for TSH > 4·0 mU/l 85·0 µg/l (40·0, 141·5), P = 0·018. The odds ratio (OR) of hypothyroid PPTD with each unit of decreasing log iodine was 2·54, (95%CI: 1·47, 4·35), and with UIC < 50 µg/l, OR 4·22, (95%CI: 1·54, 11·55). In the long term, decreased log UIC significantly predicted hypothyroidism at 12-year follow-up (P = 0·002); as did UIC < 100 µg/l (P = 0·03) and UIC < 50 µg/l (P = 0·02). The association was independent of antibody status. CONCLUSION: Low UIC measured at 6 months postpartum is associated with hypothyroid PPTD and independently predicts long-term hypothyroidism. We believe that it results from more severe preceding destructive thyroiditis, with discharge of thyroidal iodine, and thereby predicts a greater risk of long-term hypothyroidism.

The effect of fenofibrate on HDL cholesterol and HDL particle concentration in postmenopausal women on tibolone therapy.

BACKGROUND: Low high-density lipoprotein (HDL) cholesterol and particle concentration are risk factors for coronary heart disease in women. Tibolone lowers HDL cholesterol and HDL particle concentration, an effect that could be reversed by the peroxisome proliferator-activator receptor-α agonist fenofibrate. OBJECTIVE: To assess the effects of fenofibrate on plasma HDL particles in postmenopausal women taking tibolone therapy. DESIGN AND PARTICIPANTS: Randomized crossover study conducted in a women's health clinic. Fourteen postmenopausal women taking tibolone 2.5 mg daily for menopausal symptoms were randomized to either fenofibrate 160 mg daily or no treatment for 8 weeks, followed by a 3-week wash-out for fenofibrate and then crossed over to alternate therapy for another 8 weeks. The main outcome measure was changes in plasma HDL cholesterol concentration, apoA-I and apoA-II, LpA-I and LpA-I-A-II. RESULTS: After 8 weeks of fenofibrate therapy, there was no change in HDL cholesterol, 1.13 ± 0.06 v 1.16 ± 0.06 mmol/l (P = 0.47) or apoA-I, 1.19 ± 0.05 v 1.20 ± 0.05 g/l (P = 0.23). LpA-I fell significantly 0.35 ± 0.03 v 0.29 ± 0.02 (P = 0.02) but there was a rise in apoA-II, 0.35 ± 0.01 v 0.39 ± 0.01 g/l (P = 0.01). There was a significant fall in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apoB. CONCLUSION: In women taking tibolone, fenofibrate increases plasma apoA-II concentration and effects a redistribution of HDL subfractions but does not correct tibolone-induced changes in HDL cholesterol or HDL particle concentration. The mechanism and significance of this require further investigation.

Postpartum thyroid dysfunction and the long-term risk of hypothyroidism: results from a 12-year follow-up study of women with and without postpartum thyroid dysfunction.

BACKGROUND: The long-term risk of hypothyroidism following postpartum thyroid dysfunction (PPTD) is uncertain. Most previous studies have been small, short-term or have lacked a control group. OBJECTIVE: To ascertain the long-term risk of hypothyroidism in women following PPTD. Design and participants A 12-year longitudinal study of 409 women (including 71 with PPTD) who previously participated in a PPTD prevalence study. MEASUREMENTS: The primary outcome measure was hypothyroidism (defined as TSH greater than 4 mU/l or on thyroxine replacement) at follow-up. Outcomes in women with and without PPTD were compared by logistic regression. Receiver operating characteristic analysis was used to determine the optimal cut-off for baseline TSH as a predictor of hypothyroidism in the cohort. RESULTS: At follow-up, hypothyroidism was present in 27 of 71 women who had PPTD at baseline (38%) and 14 of 338 women without PPTD (4%). From multivariate analysis, odds ratios (with 95% confidence intervals) for hypothyroidism were - 4.8 (1.6, 14.1) for PPTD; 8.2 (2.8, 24.6) for positive thyroid peroxidase antibodies (TPOAb); 9.7 (2.6, 37.0) for the hypothyroid phase of PPTD and 51.4 (19.2, 137.5) for hypothyroid PPTD with positive TPOAb. A baseline TSH above 2.6 mU/l was the optimal cut-off for predicting hypothyroidism (sensitivity 76%, specificity 86%). CONCLUSIONS: PPTD is a strong predictor of hypothyroidism in the long-term. Women who present with postpartum hypothyroidism or have positive TPOAb are at particularly high risk, suggesting that close long-term follow-up is advisable if thyroxine replacement is not instituted at an early stage.

Treatment of Paget's disease of bone: a survey of clinical practice in Australia.

Consensus guidelines for the treatment of Paget's disease of bone have been published, but it is not known how closely these reflect clinical practice. We conducted a multi-centre, stratified, retrospective review of case notes of 531 subjects treated for Paget's disease of bone between 2000 and 2005 in 29 Australian centres. The subjects received 1072 courses of bisphosphonate treatment (pamidronate 363, alendronate 324, risedronate 208, tiludronate 103, zoledronic acid 69, and etidronate 5). The most recent treatment received was oral therapy in 57% of patients (alendronate 29%, risedronate 24%, and tiludronate 4%) and intravenous in 43% (pamidronate 33%, and zoledronic acid 10%). For oral bisphosphonates, the percentages of courses which were at the recommended dosage and duration were: alendronate 33%, risedronate 60% and tiludronate 29%. Pamidronate was administered in a wide range of dosing schedules, most commonly 60 mg every 3 months (18%), 6 months (17%) or annually (12%), whereas zoledronic acid was mainly given as a 4 mg infusion (98%) as a single dose (52%) or annually (19%). Most clinicians reported taking into account symptoms, plasma alkaline phosphatase activity and anatomical location of disease in determining the need for treatment. Patient preference, intolerance of oral therapy and compliance were ranked highest in determining the choice between oral and intravenous therapy. We conclude that oral and intravenous bisphosphonate dosing regimens are both commonly used to treat Paget's disease of bone in Australia. Only a minority of courses of oral bisphosphonate treatment are at the recommended dosage and duration, and there is a lack of consensus on regimens for intravenous treatment.

Quality of life and psychological morbidity in women with polycystic ovary syndrome: body mass index, age and the provision of patient information are significant modifiers.

OBJECTIVE: Polycystic ovary syndrome (PCOS) has clinical features and implications for long-term health that may lead to decreased quality of life (QoL) and psychological morbidity. We studied QoL in women with PCOS, compared the findings with population norms and assessed whether they correlated with reported quality of patient information received. DESIGN: Cross-sectional study. PATIENTS: Women with PCOS by National Institutes of Health (NIH) criteria, diagnosis confirmed by one endocrinologist. MEASUREMENTS: Four questionnaires were mailed: the Short Form-36 (SF-36), the Quality-of-Life Questionnaire for Women with Polycystic Ovary Syndrome (PCOSQ), the General Health Questionnaire-28 (GHQ-28) and an assessment of information quality and sources, the Patient Information Questionnaire (PIQ). RESULTS: Questionnaires were sent to 443 women with PCOS from one endocrinologist's database; 203 women aged 15-65 years agreed to participate. To compare with Australian population norms, data from those women aged 18-44 years (n = 173) were used. Of these, 64% were obese, 18% overweight and 18% of normal weight. The demographics, socioeconomic status and untreated biochemistry of the responders and the total patient group were not significantly different. SF-36 scores were significantly lower than the age- and sex-matched Australian population (P < 0.01), including the overweight subset (P < 0.01). Health-related QoL by PCOSQ was similar to other published studies. GHQ-28 identified psychological morbidity in 62.4%, compared with 26.4% in a matched Australian population (P < 0.0001). Body mass index (BMI) was negatively correlated with QoL (P < 0.01). There was a positive association between the psychological domain of QoL and the subjective assessment of the quality of health-related information in general (P < 0.001), for hirsutism (P < 0.01) and for menstrual irregularity (P < 0.05). CONCLUSIONS: We have shown impaired QoL and increased prevalence of psychological morbidity in PCOS compared with population norms. The perception of inadequate information about the condition correlated with poorer QoL scores. Improved information delivery may lead to an improvement in QoL and needs to be tested with an intervention study.

Polymorphism of the follistatin gene in polycystic ovary syndrome.

Follistatin has been reported as a candidate gene for polycystic ovary syndrome (PCOS) from linkage and association studies. Acting to regulate the development of ovarian follicles and as an antagonist to aromatase activity, alterations in follistatin function or expression may result in key features of PCOS such as reduced serum FSH, impaired ovarian follicle development and augmented ovarian androgen production. We investigated polymorphisms in the FST gene to determine if genetic variation is associated with susceptibility to PCOS or key phenotypic features of PCOS patients in a case-control association study. One hundred and seventy-three PCOS patients of Caucasian descent (mean age 30.0 +/- 4.8 years), conforming to the NIH diagnostic criteria, were recruited from a clinical practice database and 107 normal ovulating women (mean age 38.8 +/- 13.4 years) were recruited from the general community as control subjects. Morphometric data, biochemistry and genomic DNA were collected from study subjects and genotyping was performed on seven Single nucleotide polymorphisms (SNPs) in the FST gene region. Allele frequencies of the SNPs were rs1423560 G/C (0.99/0.01), rs3797297 C/A (0.80/0.20), rs11745088 C/G (0.98/0.02), rs3203788 A/T (0.98/0.02) and rs1062809 G/C (1.00/-), rs1127760 A/T (0.98/0.02) and rs1127761 A/T (0.98/0.02), and these were not significantly different between the PCOS and control groups (P < 0.05). Statistical analysis revealed significant associations between the SNP rs3797297 and sex hormone-binding globulin (P = 0.04) and free androgen index (FAI) (P < 0.01). We conclude that FST is not a susceptibility locus for PCOS; however, the SNP rs3797297 from FST gene was associated with androgenic markers for PCOS and may be of importance in the hyperandrogenaemia of the disease.

Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

OBJECTIVE: We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus. PATIENTS AND MEASUREMENTS: Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism. RESULTS: Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements. CONCLUSIONS: In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.

A 6-month study of the efficacy and safety of tadalafil in the treatment of erectile dysfunction: a randomised, double-blind, parallel-group, placebo-controlled study in Australian men.

The efficacy and safety of tadalafil for the treatment of erectile dysfunction (ED) were assessed in a 6-month, randomised, double-blind, placebo-controlled study. Australian men with mild, moderate or severe ED of organic, psychogenic or mixed aetiology were randomised to tadalafil 20 mg as needed (n = 93) or placebo (n = 47). Efficacy assessments included the international index of erectile function (IIEF) and the sexual encounter profile (SEP) diary. Tadalafil significantly improved erectile function compared with placebo (p < 0.001, all measures). At the end of the study, the mean per-patient proportion of successful sexual intercourse attempts (SEP question three) was 73.5% for patients treated with tadalafil and 26.8% for placebo-treated patients. Improved erections were reported by 78% of tadalafil-treated patients compared to 12.8% of placebo-treated patients. The most common treatment-emergent adverse events--headache and dyspepsia--were generally mild or moderate. Tadalafil was effective and well tolerated in Australian men with mild to severe ED.

Oestrogen replacement therapy may improve memory functioning in the absence of APOE epsilon4.

There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an epsilon4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 +/- 6.34); ERT non-users (n = 80, mean age 67.03 +/- 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2-5; P < 0.05) and memory (e.g. total number of items recalled; P < 0.05) performance was observed in women taking ERT who were not carriers of the APOE epsilon4 allele. APOEepsilon4 carriers receiving ERT performed no better on episodic memory testing than APOE epsilon4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE epsilon4 allele.

A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of bone.

Second and third generation bisphosphonates are the treatment of choice for Paget's disease of bone. These drugs are more effective than calcitonin and etidronate, but there have been no head to head, randomized controlled trials comparing potent bisphosphonates. We conducted a 2-year, randomized, open-label trial comparing oral alendronate and intravenous pamidronate in 72 subjects with Paget's disease. Randomization was stratified according to baseline plasma total alkaline phosphatase (ALP) and previous bisphosphonate treatment (yes or no). All previously treated patients had received pamidronate but not alendronate. Assigned treatments were pamidronate (60 mg) every 3 months as a single infusion or alendronate (40 mg) daily in 3-month blocks, continued until biochemical remission (defined as both ALP and urine deoxypyridinoline (DPD)/creatinine ratio in the reference range) or a clear plateau effect was observed. At 1 year, nonresponders to pamidronate were crossed over to alendronate treatment. At 1 year, 31/36 (86%) subjects randomized to alendronate achieved biochemical remission compared with 21/36 (56%) for pamidronate (P = 0.017). There was a significantly greater reduction in ALP (P < 0.001) and DPD/creatinine ratio (P < 0.001) for alendronate compared with pamidronate treatment. In previously untreated patients, alendronate resulted in remission in 20/22 (91%) subjects compared with 19/22 (86%) of pamidronate-treated subjects, which was not significantly different; however, alendronate resulted in a significantly greater reduction in ALP (P = 0.014) and DPD/creatinine ratio (P < 0.001). In previously treated patients, alendronate resulted in remission in 11/14 (79%) subjects compared with 2/14 (14%) for pamidronate (P < 0.001), with a significantly (P < 0.001) greater reduction in both ALP and DPD/creatinine ratio. Of subjects crossed over from pamidronate to alendronate, 10/14 (71%) achieved remission, including 9/11 (82%) previously treated patients. We conclude that, in patients with previously untreated Paget's disease of bone, alendronate and pamidronate have similar efficacy in achieving biochemical remission. In patients previously treated with pamidronate, alendronate is more effective.

A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: benefit of the combination on total body and hip density.

We report a prospective, randomized, multicenter, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below - 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 - 1.25 mg/d +/- medroxyprogesterone acetate (MPA) 2.5 - 5 mg/d; group HRT/D received HRT plus calcitriol 0.25 microg bd. All with a baseline dietary calcium (Ca) of < 1 g/ d received Ca carbonate 0.6 g nocte. Final data were on 66 - 70 patients. On HRT/D, significant (P < 0.001) BMD increases from baseline by DXA were at total body - head, trochanter, Ward's, total hip, intertrochanter and femoral shaft (% group mean delta 4.2, 6.1, 9.3, 3.7, 3.3 and 3.3%, respectively). On HRT, at these 6 sites, significant deltaS were restricted to the trochanter and Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean delta at these sites were 1.3, 2.6 and 3.9%. At the following, both groups improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site - specific benefits of the combination associated with significant suppression of parathyroid hormone-suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BMD at the hip, the major site of osteoporotic fracture.

The incidence and management of priapism in Western Australia: a 16 year audit.

The objective of the study was to conduct a retrospective audit of patients who presented with priapism in Western Australia during the years 1985-2000. We searched the records of the teaching hospitals in metropolitan Perth and those of the Keogh Institute for Medical Research for the diagnostic code for priapism. A total of 82 episodes of priapism in 63 patients occurred over this 16 year period. In all, 62 episodes occurred after intracavernosal injections (ICI) and 20 were due to other causes. Treatment of priapism included simple aspiration of blood, intracavernosal injection of alpha-adrenergic agents and surgical shunt procedures. Priapism occurring outside the setting of ICI was more likely to require surgery; seven of 20 episodes. After ICI therapy, eight of 62 episodes required shunts. The use of prostaglandin E1 as the drug of choice in ICI therapy in 1989 led to a fall in the incidence of ICI-induced priapism. Priapism is a major side effect of ICI therapy and an uncommon, although important, side effect of other conditions. The incidence of priapism has fallen with the introduction of prostaglandin E1 monotherapy as the favoured drug for ICI therapy of erectile failure.

Clinical course of penile fibrosis in intracavernosal prostaglandin E1 injection therapy: a follow-up of 44 patients.

A study was undertaken of 44 patients who had developed fibrotic changes in the penis in the course of intracavernosal prostaglandin E1 (PGE1) injection therapy for erectile dysfunction. Of these patients, 75.0% (n=33) were followed up for more than 24 months, and 59.1% (n=26) for more than 36 months. Of the patients, 52.3% (n=23) had clinical improvement of the fibrotic changes without therapeutic intervention and despite most (91.3%) continuing intracavernosal PGE1 injection therapy. These included 25.0% (n=11) no longer having clinically detectable penile fibrosis (PF). The presence of penile curvature or pain did not significantly influence this outcome. The ages of men who showed improvement and the duration of their injection therapy were similar to those who did not improve. It would be prudent to defer therapeutic intervention for PF in the course of intracavernosal PGE1 injection therapy in anticipation of possible spontaneous improvement.

Vascular function of forearm microcirculation in postmenopausal women with type 2 diabetes: potential benefit of hormone replacement therapy?

OBJECTIVE: To study the potential effects of hormone replacement therapy (HRT) on vascular function of the peripheral circulation in postmenopausal women with type 2 diabetes. METHODS: Seventeen premenopausal women aged 47.4 +/- 4.4 years (PreM), 23 nondiabetic postmenopausal women aged 59.4 +/- 7.0 years (PM), 15 postmenopausal women with type 2 diabetes aged 60.3 +/- 7.2 years (PMD) and 12 postmenopausal women with type 2 diabetes using HRT aged 61.2 +/- 4.0 years (PMDHRT) were studied. Vascular function of the peripheral circulation was investigated by measuring hyperemic responses of the forearm microcirculation following an ischemic stimulus using venous occlusion, strain-gauge plethysmography. Fasting lipids, glucose and glycated hemoglobin (HbA1c) were also measured. RESULTS: Forearm vascular function was significantly impaired in the PMD group: maximal blood flow (ml/100 ml/min) was 15.23 +/- 8.19 vs. 28.21 +/- 12.30 (PreM), 23.62 +/- 6.62 (PM) and 23.37 +/- 5.78 (PMDHRT) (p = 0.004); flow debt (ml/100 ml) was 3.99 +/- 2.83 vs. 7.40 +/- 4.92 (PreM), 5.66 +/- 3.67 (PM) and 8.57 +/- 4.84 (PMDHRT) (p = 0.0018); vascular resistance (mmHg/ml/100 ml/min) was 11.90 +/- 9.02 vs. 5.04 +/- 2.41 (PreM), 5.55 +/- 2.69 (PM) and 5.96 +/- 1.88 (PMDHRT) (p = 0.003). Fasting lipids, HbA1c and body mass index were not significantly different between the two diabetic groups. CONCLUSIONS: Postmenopausal women with diabetes have abnormal vascular function of resistance arteries that may improve with HRT. HRT may therefore reduce cardiovascular risk in postmenopausal women with type 2 diabetes, and a clinical end-point trial is warranted to test this hypothesis.

Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus.

OBJECTIVES: The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B-48 and apoC-III concentrations in postmenopausal women with and without type 2 DM. PATIENTS: Twenty-four postmenopausal women without DM and 14 postmenopausal women with diet-controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state. METHODS: The fractional catabolic rate (FCR) of an intravenously injected chylomicron remnant-like emulsion was determined from the appearance of 13CO2 in the breath using isotope-ratio mass spectrometry and multicompartmental modelling. apoB-48, a marker of particle number of intestinal lipoproteins, was determined immunoelectrophoretically. apoC-III was measured by immunoturbidimetric assay. RESULTS: Compared with the nondiabetic women, the women with DM had significantly higher plasma apoB-48 concentration (16.40 +/- 1.18 mg/l vs. 13.0 +/- 0.9 mg/l; mean +/- standard error mean; P = 0.021), higher plasma apoC-III concentration (204.24 +/- 15.18 mg/l vs. 170.74 +/- 10.75 mg/l; P = 0.042) and lower FCR of the chylomicron remnant-like emulsion (0.06 +/- 0.05 pools/h vs. 0.12 +/- 0.02 pools/h; P < 0.001). In the diabetic patients, the FCR of the emulsion was correlated significantly with plasma apoB-48 levels (r = -0.641, P = 0.007) but not with apoC-III levels. CONCLUSIONS: In postmenopausal women, diabetes mellitus appears to decrease the catabolism of chylomicron remnants and result in an accumulation of these particles in plasma. This may chiefly be due to decreased clearance by hepatic receptors related to an effect of insulin resistance. Impairment in the catabolism of chylomicron remnants may contribute to increased risk of atherosclerosis in postmenopausal women with type 2 diabetes mellitus.