leuprolide and Cardiovascular-Diseases

The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.. We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.. There is consistent but methodologically limited data to suggest that GnRH antagonists-a relatively new class of androgen deprivation therapy for prostate cancer-cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

Topics: Androgen Antagonists; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Prostatic Neoplasms

In the 1990s, estrogens were thought to protect the aging brain. Large randomized controlled studies, however, showed that estrogens did not treat dementia symptoms and even increased risk for dementia in older women. These findings contrast with earlier positive findings, including a wealth of cell culture and animal data all suggesting that estrogens could be a prophylactic treatment for dementia. Observational data had also suggested a significantly decreased risk for dementia in women who had been treated with estrogens for menopausal symptoms in midlife. This review discusses the "Critical Window", Healthy Cell Bias' and "Limited Duration" hypotheses, and forms of bias (healthy user, recall and survivor bias) and potential mediators (e.g., body mass, genetics) to attempt to explain the differences seen between the studies. On the basis of limited data, we conclude that estrogens only have limited positive effects on some tests for a number of months regardless of age. These effects were seen in recently menopausal women, but also in women with dementia, who are at least 15 years past the average age of menopause. In addition, after a longer period of time, treatment may confer risk, especially in older women. From this it would follow that longer term treatment with estrogens to maintain cognitive function is not indicated for older women. Whether there still is a case to treat surgical menopausal women with estrogens for a longer or shorter period of time remains to be tested.

Topics: Aged; Aged, 80 and over; Animals; Brain; Cardiovascular Diseases; Cognition Disorders; Comorbidity; Confounding Factors, Epidemiologic; Dementia; Estrogen Replacement Therapy; Female; Humans; Leuprolide; Male; Menopause; Menopause, Premature; Middle Aged; Models, Biological; Obesity; Prevalence; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors

Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Cell Division; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Utilization; Endometrial Neoplasms; Endometrium; Estrogen Replacement Therapy; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hyperplasia; Incidence; Leuprolide; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis; Ovarian Neoplasms; Pilot Projects; Premenopause; Progesterone; Progestins; Reproductive History; Risk Factors; Testosterone

Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.. In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.. A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).. In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Phenylurea Compounds; Prostatic Neoplasms; Pyrimidinones; Testosterone

Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease.. We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial.. A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors.. The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA.. Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death.. Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit.. We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.

Topics: Aged; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Follow-Up Studies; Goserelin; Humans; Incidence; Leuprolide; Male; Middle Aged; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Survival Rate; Time Factors

Androgen deprivation therapy (ADT) is an important component of modern prostate cancer treatment. Survival benefits from neo-adjuvant and adjuvant hormones may take years to manifest, and balancing this with potential morbidity of therapy can be challenging. This study aimed to assess whether education and short-term combined aerobic and resistance exercises could help to ameliorate the adverse side effects of ADT.. Eight hundred fifty-nine patients with relapsed or metastatic prostate cancer on leuprorelin acetate were allocated to three interventional streams based on patient preference and medical fitness: supervised group (Face-to-Face) exercise sessions, home-based (At Home) exercise or a support programme for those incapable of exercising (Support). Patients enrolled onto Face to Face underwent measurement of body composition and cardiorespiratory fitness variables at baseline and programme completion. Patients in the exercise streams were surveyed to determine the programme's impact on physical fitness and well-being.. Statistically significant improvements (p < 0.001) were seen in all measured cardiorespiratory fitness and strength variables. Programme attrition rates were low (75/859; 8.7%), the primary reason for withdrawal being discontinuation of hormones (70%). Programme satisfaction was high, with 98% of surveyed patients reporting a positive impact on fitness and 97% planning to continue exercising after programme completion. At 6 months, improved physical and emotional well-being was reported by 93 and 79% of patients, respectively.. A short-term structured exercise intervention results in high compliance and significant improvements in muscle strength and cardiorespiratory fitness in prostate cancer patients on ADT.

Topics: Aged; Androgen Antagonists; Australia; Cardiovascular Diseases; Causality; Combined Modality Therapy; Comorbidity; Exercise Therapy; Humans; Leuprolide; Male; Metabolic Diseases; Prevalence; Prospective Studies; Prostatic Neoplasms; Risk Factors; Treatment Outcome

We assessed the cardiovascular safety profile of degarelix, a new gonadotropin-releasing hormone antagonist.. This is the first report to our knowledge on cardiovascular safety data from a completed 1-year randomized controlled trial of leuprolide acetate vs degarelix. Outcomes considered in these analyses included the QT interval by central reading and analysis, and cardiovascular adverse events. On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated.. There were no significant differences between treatment groups for mean change in Fridericia's correction of QT during the trial. Markedly abnormal Fridericia's correction of QT values (500 milliseconds or greater) were observed in only a small number of subjects by treatment group, that is 2 (less than 1%) in the pooled degarelix group and 2 (1%) in the leuprolide group. Supraventricular arrhythmias were the most common type of arrhythmias, affecting 2% of subjects in the pooled degarelix group and 4% in the leuprolide group. Other arrhythmias occurred in 1% or less of subjects by treatment group. The most frequently reported cardiac disorder was ischemic heart disease, which occurred in 4% of subjects treated with degarelix and 10% of those on leuprolide. Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age (p=0.0459) and systolic blood pressure (p=0.0061).. In men with prostate cancer degarelix and leuprolide have similar cardiovascular safety profiles. These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prostatic Neoplasms; Time Factors

Low androgen levels in men are associated with increased cardiovascular risk, through unclear mechanisms. We measured arterial stiffness ('compliance') in 21 men receiving complete testosterone suppression therapy for prostate cancer, and in 25 controls. Systemic arterial compliance (SAC), which assesses proximal aortic stiffness, was calculated by simultaneous recording of aortic flow and carotid artery pressure (the 'area method'). Aorto-femoral (A-F), aorto-radial (A-R) and femoral-dorsalis pedis (F-DP) pulse-wave velocities (PWVs) were recorded using the 'Complior' system. SAC was significantly lower in the androgen-depleted men compared to controls (0.81 +/- 0.53 vs. 1.18 +/- 0.43 arbitrary compliance units, p = 0.01, mean +/- SD). Correspondingly, their A-F PWV was higher (14.1 (10.1-21.8) vs. 12.4 (9.6-17.4) m/s, p = 0.03, median (range)). Cases tended to be older (75 +/- 7 vs. 71 +/- 6 years, p = 0.07), and to have higher systolic blood pressure (148 +/- 22 vs. 143 +/- 17 mmHg, p = 0.40); however, SAC was still significantly lower (p = 0.03) after adjustment for age and stratification for central systolic pressure (< or = or > the median). Adjustment of A-F PWV for age and central systolic pressure reduced significance to p = 0.07. There was no significant difference in peripheral PWVs between groups. In conclusion, testosterone suppression is associated with increased aortic stiffness, only partly explained by age and blood pressure. Loss of androgens in men might therefore adversely affect cardiovascular risk.

Topics: Age Factors; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Arteries; Cardiovascular Diseases; Flutamide; Goserelin; Hemodynamics; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Vascular Patency

Unlike in other mouse models of atherogenesis, it has recently been suggested that orchiectomy plays a role in accelerating atherosclerosis and inhibiting the progression of cardiovascular disease in the ApoE. Male ApoE. Castration was achieved for all three modes of ADT. However, degarelix-treated mice gained significantly less weight, had lower serum leptin levels and systolic blood pressure compared to orchiectomy and leuprolide-treated mice. ADT improved dysglycemia and atherosclerotic burden. GnRH-antagonist significantly improved survival compared to GnRH-agonist but not compared to orchiectomy.. Further characterization of the ApoE

Topics: Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Disease Models, Animal; Hyperglycemia; Insulin; Leuprolide; Male; Metabolic Syndrome; Mice; Mice, Knockout, ApoE; Oligopeptides; Orchiectomy; Protective Factors

We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and those who receive GnRH antagonist therapy.. Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score-matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional-hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase-9 (MMP-9) expression and invasion ability in THP-1 differentiated macrophages.. GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90) than GnRHa therapy, with a mean follow-up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06-0.70) and all-cause mortality (HR, 0.77; 95% CI, 0.61-0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP-9 activity and the invasive ability of THP-1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively.. GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Follow-Up Studies; Gonadotropin-Releasing Hormone; Heart Disease Risk Factors; Humans; Leuprolide; Male; Matrix Metalloproteinase 9; Middle Aged; Oligopeptides; Prostatic Neoplasms; Taiwan; THP-1 Cells; Young Adult

Androgen deprivation therapy using gonadotropin-releasing hormone (GnRH) analogues is standard treatment for intermediate and advanced prostate cancer. GnRH agonist therapy results in an initial testosterone flare, and increased metabolic and cardiovascular risks. The GnRH antagonist relugolix is able to reduce serum testosterone levels in men with prostate cancer without inducing testosterone flare. In the HERO Phase III trial, relugolix was superior to leuprolide acetate at rapidly reducing testosterone and continuously suppressing testosterone, with faster post-treatment recovery of testosterone levels. Relugolix was associated with a 54% lower incidence of major adverse cardiovascular events than leuprolide acetate. As the first oral GnRH antagonist approved for the treatment of advanced prostate cancer, relugolix offers a new treatment option.. Lay abstract The male sex hormone testosterone promotes the growth of prostate cancer cells. Some drug treatments for prostate cancer, such as gonadotropin-releasing hormone (GnRH) receptor agonists and antagonists, work to reduce the production of testosterone. However, GnRH receptor agonists like leuprolide acetate can increase testosterone levels at first, before reducing it, and this temporary increase can cause side effects, such as bone pain. Drugs of this type have also been linked to a higher risk of heart attacks, strokes, and death. Relugolix works a different way; it is a GnRH receptor antagonist that reduces testosterone without an initial increase. A clinical study showed that relugolix reduced testosterone levels more quickly than leuprolide acetate, a commonly used injectable drug for the treatment of prostate cancer. After stopping treatment, levels of testosterone in the blood returned to normal faster in men who received relugolix than in men who received leuprolide acetate. Men who received relugolix had a lower incidence of heart attacks, strokes, and death compared with men who received leuprolide acetate. The US FDA approved relugolix as the first oral, once-daily GnRH receptor antagonist for the treatment of advanced prostate cancer, offering men a new treatment option.

Topics: Cardiovascular Diseases; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Gonadotropin-Releasing Hormone; Humans; Incidence; Leuprolide; Male; Phenylurea Compounds; Prostatic Neoplasms; Pyrimidinones; Randomized Controlled Trials as Topic; Testosterone; Treatment Outcome

To determine the effect of leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice.. We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008-2017. We used Kaplan-Meier survival estimates to compare the GnRH-a-treated patients and those not treated with GnRH-a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy.. After a mean follow-up of 41 months, POF developed in one of the 16 GnRH-a-treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH-a-treated group (P = 0.030). The hazard model analysis showed that treatment with GnRH-a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio = 0.12, 95% CI 0.01-0.67, P = 0.013) but not incidences of cardiovascular events, strokes or osteoporosis.. The combined use of GnRH-a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH-a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy.

Topics: Administration, Intravenous; Adult; Cardiovascular Diseases; Case-Control Studies; Cyclophosphamide; Female; Fertility Agents, Female; Fertility Preservation; Humans; Immunosuppressive Agents; Incidence; Infertility, Female; Kaplan-Meier Estimate; Leuprolide; Lupus Erythematosus, Systemic; Multivariate Analysis; Osteoporosis; Ovary; Premenopause; Primary Ovarian Insufficiency; Proportional Hazards Models; Stroke; Time Factors; Treatment Outcome; Young Adult

Recent studies suggest that androgen deprivation therapy (ADT) is associated with increased cardiovascular (CV) risk for patients with hormone-sensitive prostate cancer (PCa) and pre-existing CV disease. This risk seems to be different for the gonadotropin-releasing hormone (GnRH) agonists leuprolide and goserelin and GnRH antagonists, whereas the slightly more expensive GnRH antagonist shows a beneficial risk profile. The present study assesses the cost effectiveness of degarelix compared to leuprolide for PCa patients with increased CV risk.. This analysis is based on a pooled analysis of six phase III, randomized, controlled trials comparing the GnRH agonists leuprolide and goserelin with the GnRH antagonist degarelix. For the combined endpoint of CV events or death a superiority of degarelix was determined with a Number-Needed-to-Treat of 12. From the perspective of German statutory health insurance, this evaluation estimates and compares the additional drug costs of degarelix treatment to the cost of one (avoided) CV event. The CV event costs were estimated via emergency treatment and transportation, inpatient treatment, and rehabilitation. The difference of these two cost pools divided by 12 yields the average saving per patient and year.. For every 12 PCa patients with CV history that are treated with GnRH antagonists to prevent one CV event, there will be additional drug costs in comparison with leuprolide treatment of € 3111 per year. Costs of € 8447 per year are prevented. Therefore, each patient with a history of CV who is treated with degarelix instead of a leuprolide generates savings of € 445 per patient and year.. Compared to leuprolide, degarelix is cost effective for patients with increased CV risk.

Topics: Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Cost-Benefit Analysis; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Meta-Analysis as Topic; Oligopeptides; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors

As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD).. We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998-2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors.. Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD.. In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Arrhythmias, Cardiac; California; Cardiovascular Diseases; Cohort Studies; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Heart Failure; Humans; Imidazolidines; Leuprolide; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Nitriles; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Risk Factors; Tosyl Compounds

The most frequent cause of virilization in postmenopausal women is excessive androgen production of ovarian origin. Bilateral oophorectomy is usually performed, even in cases of benign tumors or hyperthecosis. This is the first report of a case series of long-term GnRH-agonist treatment of hyperandrogenism in postmenopausal women.. We present three women with postmenopausal hyperandrogenism of ovarian origin who were treated with GnRH agonists.. We describe three cases of postmenopausal women with virilization and hyperandrogenism of presumed ovarian origin, all with slight enlargement of the ovaries but without visualization of a tumor, who had long-term treatment with GnRH agonists. No histological diagnosis was available, and therefore all patients received careful follow-up, including periodic testing of androgen levels and ovarian imaging by computed tomography scans. The three patients responded in different ways to treatment with GnRH agonists.. Long-term GnRH agonist treatment is an acceptable choice for treatment of postmenopausal hyperandrogenism in patients where ovarian origin of androgen excess is ascertained, and especially in those patients who have an increased risk for surgery due to comorbidities or who are unwilling to undergo bilateral oophorectomy.

Topics: Aged; Alopecia; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Hyperandrogenism; Hypertension; Leuprolide; Liver Cirrhosis, Alcoholic; Magnetic Resonance Imaging; Middle Aged; Obesity; Ovary; Postmenopause; Tomography, X-Ray Computed