Bilateral Gonadoblastoma in a 6-Year-old Girl With Frasier Syndrome: Need for Early Preventive Gonadectomy.

Frasier syndrome (FS) is a rare condition, caused by splice-site mutations of intron 9 in the Wilms' tumor suppressor gene 1 (WT1 gene). The WT1 protein is essential for urogenital development and patients with 46XY karyotype present with female (FS type 1) or male phenotype, gonadal dysgenesis, progressive glomerulopathy, and high risk of gonadoblastoma. We describe a female patient with an IVS9+4C>T donor splice-site mutation, who underwent a preventive gonadectomy at the age of 6 years due to imaging findings of dysplastic gonads. The biopsy revealed bilateral gonadoblastoma, emphasizing the need for early gonadectomy in 46XY FS patients.

Castration Complications: A Review of Castration Techniques and How to Manage Complications.

Castration is one of the most common surgical procedures performed in equine practice. Open, closed, and semiclosed techniques are described for castration of horses, and the procedure may be performed in a standing, sedated animal or in a recumbent animal under general anesthesia. Although a relatively routine procedure, complications can occur, with reported complication rates ranging from 10.2% to 60%. Most complications are mild and resolve rapidly with appropriate treatment, but more serious or life-threatening complications can also occur. A thorough knowledge of male reproductive anatomy combined with good surgical technique is imperative to help reduce the rate of complications.

The Link between Estradiol and Neuroplasticity in Transgender Women after Gender-Affirming Surgery: A Bimodal Hypothesis.

For transgender individuals, gender-affirming surgery (GAS) and cross-sex hormone therapy (CSHT) are part of the gender transition process. Scientific evidence supporting the maintenance of CSHT after GAS-related gonadectomy is accumulating. However, few data are available on the impact of CSHT on the brain structure following hypogonadism. Thus, we aimed to investigate links between estradiol and brain cortical thickness (CTh) and cognition in 18 post-gonadectomy transgender women using a longitudinal design. For this purpose, the participants underwent a voluntary period of CSHT washout of at least 30 days, followed by estradiol re-institution for 60 days. High-resolution T1-weighted brain images, hormonal measures, working and verbal memory were collected at 2 time points: on the last day of the washout (t1) and on the last day of the 2-month CSHT period (t2). Between these 2 time points, CTh increased within the left precentral gyrus and right precuneus but decreased within the right lateral occipital cortex. However, these findings did not survive corrections of multiple comparisons. Nevertheless, there was a significant negative correlation between changes in estradiol levels and changes in CTh. This effect was evident in the left superior frontal gyrus, the left middle temporal gyrus, the right precuneus, the right superior temporal gyrus, and the right pars opercularis. Although there was an improvement in verbal memory following hypogonadism correction, we did not observe a significant relationship between changes in memory scores and CTh. Altogether, these findings suggest that there is a link between estradiol and CTh.

Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment.

INTRODUCTION: Establishing the influence of long-term, gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender individuals is important to improve the therapeutic guidelines for these individuals. AIM: To examine the effect of long-term HT and gonadectomy on BMD in transgender individuals. METHODS: 68 transwomen and 43 transmen treated with HT who had undergone gonadectomy participated in this study. Dual-energy x-ray absorptiometry (DXA) scans were performed to measure BMD at the lumbar spine and total hip. Laboratory values related to sex hormones were collected within 3 months of performing the DXA scan and analyzed. MAIN OUTCOME MEASURE: BMD and levels of sex hormones in transwomen and transmen. RESULTS: In transwomen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 0.99 ± 0.15 g/cm2 (n = 68) and 0.94 ± 0.28 g/cm2 (n = 65). In transmen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 1.08 ± 0.16 g/cm2 (n = 43) and 1.01 ± 0.18 g/cm2 (n = 43). A significant decrease in total hip BMD was found in both transwomen and transmen after 15 years of HT compared with 10 years of HT (P = .02). CONCLUSION: In both transwomen and transmen, a decrease was observed in total hip bone mineral density after 15 years of HT compared to the first 10 years of HT. Dobrolinska M, van der Tuuk K, Vink P, et al. Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment. J Sex Med 2019; 16:1469-1477.

Clinical development of novel therapeutics for castration-resistant prostate cancer: historic challenges and recent successes.

There have been more drugs approved by the US Food and Drug Administration for the treatment of castration-resistant prostate cancer in the past 3 years than in the prior 3 decades, with additional drugs on the verge of approval based on the results of recently reported randomized trials. While an improvement in the understanding of the pathogenesis of castration-resistant prostate cancer has undeniably accelerated the transition of novel approaches from "bench to bedside," the recent successes in the treatment of prostate cancer are also a result of the efforts of clinical investigators to redefine the framework in which drugs for castration-resistant disease are evaluated. This review will explore the shifting paradigm in drug development for castration-resistant prostate cancer over the past several decades, and highlight how new definitions, trial designs, and endpoints have facilitated the emergence of new therapies for this challenging disease.

Jiedu Huoxue decoction improves inflammation in rat type III prostatitis: The importance of the NF-κB signalling pathway.

This study aimed to investigate the mechanism of Jiedu Huoxue decoction (JDHXD) in type III prostatitis based on the NF-κB signalling pathway. Twenty-six Sprague-Dawley male rats were divided into blank control, model, positive (Prostate Plus), low-dose JDHXD, medium-dose JDHXD and high-dose JDHXD groups. Type III prostatitis rat model was established and confirmed with HE staining. NF-кB P50 and NF-κB P65 expression was detected with immunohistochemistry. NF-κB mRNA expression was detected with qRT-PCR. Protein expression of NF-κB and its inhibitor Iκ-Bα was detected with Western blot. Compared to the model group, a decrease in glandular hyperplasia and inflammation, and in NF-кB P50 and NF-κB P65 expression in the medium- and high-dose JDHXD groups was observed. NF-κB mRNA expression was significantly increased in the model group compared to control (p < 0.05), and significantly decreased in the JDHXD treatment groups compared to model group (p < 0.05). Protein expression of NF-κB was significantly increased in the model and low-dose JDHXD groups compared to control(p < 0.05), and significantly decreased in the medium- and high-dose JDHXD groups compared to model group (p < 0.05). Protein expression of Iκ-Bα was vice versa. JDHXD could be a potential treatment for type III prostatitis via its regulation of NF-κB and Iκ-Bα expression.

Castration Induces Down-Regulation of A-Type K+ Channel in Rat Vas Deferens Smooth Muscle.

A-type K+ channels contribute to regulating the propagation and frequency of action potentials in smooth muscle cells (SMCs). The present study (i) identified the molecular components of A-type K+ channels in rat vas deferens SMs (VDSMs) and (ii) showed the long-term, genomic effects of testosterone on their expression in VDSMs. Transcripts of the A-type K+ channel α subunit, Kv4.3L and its regulatory ß subunits, KChIP3, NCS1, and DPP6-S were predominantly expressed in rat VDSMs over the other related subtypes (Kv4.2, KChIP1, KChIP2, KChIP4, and DPP10). A-type K+ current (IA) density in VDSM cells (VDSMCs) was decreased by castration without changes in IA kinetics, and decreased IA density was compensated for by an oral treatment with 17α-methyltestosterone (MET). Correspondingly, in the VDSMs of castrated rats, Kv4.3L and KChIP3 were down-regulated at both the transcript and protein expression levels. Changes in Kv4.3L and KChIP3 expression levels were compensated for by the treatment with MET. These results suggest that testosterone level changes in testosterone disorders and growth processes control the functional expression of A-type K+ channels in VDSMCs.

Complications associated with closed castration using the Henderson equine castration instrument in 300 standing equids.

OBJECTIVE: To describe a closed castration technique in standing equids, report associated complications, and identify potential risk factors. STUDY DESIGN: Prospective cohort study of 300 standing equids that were castrated with the Henderson Equine Castrating Instrument. METHODS: Thirteen participating veterinarians recorded intraoperative difficulties and postoperative complications. Descriptive statistics, univariate analyses with Fisher's exact tests, and logistic regressions were used to evaluate intraoperative difficulties and postoperative complications and to assess risk factors for postoperative complications. RESULTS: Data were collected on 300 equids (269 horses, 23 ponies, and 8 donkeys). Intraoperative difficulties were experienced in 39 of 300 (13%) procedures. Postoperative complications were reported in 69 of 300 (23%) equids, including excessive swelling (29, 9.67%), surgical site infection (SSI; 27, 9%), severe hemorrhage (3, 1%), and prolapse of the omentum (2, 0.64%). Donkeys were at increased risk of severe hemorrhage (2/8, 25%, P = .0019). Equids that were castrated in a hospital setting (83/300, 27.66%) more frequently developed excessive swelling (P = .0034, odds ratio [OR] = 3.20) and SSI (P = .0047, OR = 3.18) compared with equids that were castrated in a field setting (217/300, 72.33%). Prolonging antimicrobial prophylaxis or age of the equid at the time of castration had no effect on the prevalence of excessive swelling or SSI. CONCLUSION: The method of castration evaluated here resulted in a similar prevalence of postoperative complications to that previously reported for castrations in standing horses but fewer SSI. CLINICAL SIGNIFICANCE: The described method provides a viable option for castrating horses and ponies, but is not recommended in donkeys.

Medical Castration is a Rare but Possible Trigger of Torsade de Pointes and Ventricular Fibrillation.

Prostate cancer is the most common non-cutaneous malignancy in men and has been steadily rising in an aging society. Medical castration therapy is effective for metastatic prostate cancer, but the proarrhythmic properties have not been reported. We present a 71-year-old Japanese man with metastasis prostate cancer that, during medical castration therapy, had torsades de pointes (TdP) with a QT prolongation and ventricular fibrillation (VF). His QT interval diminished after discontinuing the medical castration, and he developed no further VF recurrences for 15 months. Medical castration is a rare but possible trigger of TdP with QT prolongation and VF.

Bone mineral density in complete androgen insensitivity syndrome and the timing of gonadectomy.

OBJECTIVE: Low bone mineral density (BMD) has been reported in complete androgen insensitivity syndrome (CAIS), but the impact of timing of gonadectomy is not known. We aimed to assess the relationship between age of gonadectomy and BMD in women with CAIS. DESIGN: Retrospective analysis of pre- and post-gonadectomy parameters in women with CAIS attending an adult Disorders of Sex Development (DSD) clinic in a tertiary centre. PATIENTS: One hundred and thirteen women with CAIS. MEASUREMENTS: Dual-energy X-ray absorptiometry (DXA) before and after gonadectomy; and pre-gonadectomy hormone profile. RESULTS: Mean BMD was reduced (95% confidence interval); T-score -1.34 (-1.55 to -1.13; P<.001) at the lumbar spine and -0.3 (-0.49 to -0.12; P=.001) at the hip. There was no relationship between age of gonadectomy and BMD. Thirty-two subjects had BMD measured before or within 2 years of gonadectomy, and mean BMD was reduced (95% CI) at the lumbar spine; T-score: -1.05 (-1.54 to -0.57; P<.001), but was normal at the hip; T-score -0.04 (-0.35 to 0.28; P=.8). There was no relationship between BMD and history of hernia, testosterone, oestradiol or follicle stimulating hormone levels. Twelve subjects had DXA both before and after gonadectomy, and after 4.3 (1.7-12.8) years, there was no change in BMD. CONCLUSIONS: We found reduced BMD at the spine and hip in subjects with CAIS. We found no relationship between age of gonadectomy and BMD, and we also found no drop in BMD in subjects followed up after gonadectomy.

Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats.

BACKGROUND: Testosterone is believed to mediate the penile erectile response by producing adequate nitric oxide; therefore, testosterone deficiency results in erectile dysfunction through decreased nitric oxide bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone deficiency remain unclear. AIM: To investigate the mechanism of endothelial dysfunction in a rat model of testosterone deficiency. METHODS: Rats were distributed into 3 groups: castrated (Cast), castrated and supplemented with testosterone (Cast + T), and sham (Sham). In the Cast + T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats received only the vehicle. OUTCOMES: Erectile function using intracavernosal pressure and mean arterial pressure measurements after electrical stimulation of the cavernous nerve, endothelial function using isometric tension, asymmetric dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and tandem mass spectrometry, and inflammatory biomarker expression were performed 4 weeks after the operation. RESULTS: In the Cast group, the ratio of intracavernosal pressure to mean arterial pressure significantly decreased, acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and inflammation biomarker levels were significantly increased (P < .01). Testosterone injection significantly improved each of these parameters (P < .01). CLINICAL TRANSLATION: The present results provide scientific evidence of the effect of testosterone deficiency on erectile function and the effect of testosterone replacement therapy. STRENGTHS AND LIMITATIONS: This study provides evidence of the influence of testosterone deficiency on endothelial function by investigating ADMA and oxidative stress. A major limitation of this study is the lack of a direct link of increased ADMA by oxidative stress to inflammation. CONCLUSION: Testosterone deficiency increased not only ADMA levels but also oxidative stress and inflammation in castrated rats, which can cause damage to the corpus cavernosum, resulting in erectile dysfunction. Kataoka T, Hotta Y, Maeda Y, Kimura K. Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats. J Sex Med 2017;14:1540-1548.

Complications and risk factors of castration with primary wound closure: Retrospective study in 159 horses.

Castration with primary wound closure reportedly has lower complication rates and shorter recovery periods compared to castration with second intention healing. However, little is known about risk factors associated with complications using primary wound closure. Medical records of 159 horses castrated and having primary wound closure were reviewed. Main short-term complications were: scrotal hematoma in 12 horses (7.6%), signs of colic in 6 horses (3.8%), fever in 4 horses (2.5%), and peri-incisional edema in 3 horses (1.9%). As for long-term complications, 24 out of 105 (23%) horses sustained some form of edema. One horse was euthanized because of a suspected inguinal abscess. Among tested parameters, horses aged 3 to 6 years old and French trotters appeared to be more at risk of developing complications. Intraoperative ligation of the cremaster muscle and use of electrocautery prevented complications. Overall, client satisfaction was excellent (98%).

Complications et facteurs de risque de la castration avec fermeture des plaies par première intention : étude rétrospective chez 159 chevaux. La castration avec fermeture des plaies par première intention a un taux de complications plus faible et une période de convalescence plus courte que la castration avec cicatrisation par seconde intention. Cependant, on en sait peu sur les facteurs de risque associés aux complications en utilisant la technique de fermeture des plaies par première intention. Les dossiers médicaux de 159 chevaux castrés de cette façon ont été examinés. Les complications à court terme sont les suivantes: hématome scrotal chez 12 chevaux (7,6 %), signes de coliques chez 6 chevaux (3,8 %), fièvre chez 4 chevaux (2,5 %) et de l'œdème péri-incisionel chez 3 chevaux (1,9 %). En ce qui concerne les complications à long terme, 24 sur 105 (23 %) chevaux ont présenté un certain degré d'œdème. Un cheval a été euthanasié à cause d'un probable abcès inguinal. Parmi les paramètres testés, les chevaux âgés de 3 à 6 ans et les Trotteurs Français semblent être plus à risque de développer des complications. En outre, la ligature peropératoire du muscle crémaster et l'utilisation du bistouri électrique semblent prévenir les complications. Dans l'ensemble, la satisfaction des clients était excellente (98 %).(Traduit par les auteurs).

Admissions to hospital due to fracture in England in patients with prostate cancer treated with androgen-deprivation therapy - do we have to worry about the hormones?

OBJECTIVE: To investigate the association between androgen-deprivation therapy (ADT) and fracture risk in men with prostate cancer in England. PATIENTS AND METHODS: Using the Hospital Episodes Statistics database, which contains all the information about National Health Service (NHS) and NHS-funded hospital admissions in England, for the years 2004-2008, 8 902 patients were found to have had prostate cancer and an admission to hospital with a fracture. Of these patients, 3 372 (37.8%) were identified as being treated with ADT, whilst 5 530 (62.2%) were not. There was a total of 228 852 admissions in the background population. RESULTS: The risk of a fracture requiring hospitalisation increased from 1.12 to 1.41 per 100 person-years in a man with prostate cancer treated with ADT compared with those without ADT, an absolute increase of only 0.29 per 100 person-years. When compared with the background population, there was an increase from 0.58 to 1.41 per 100 person-years, a relative rate ratio increase of 2.4 (P < 0.01) with an absolute increase of 0.83 per 100 person-years. CONCLUSION: In England there was a small but statistically significant increased risk of fracture in men who had been treated with ADT. Men with prostate cancer, with or without ADT, were at an increased risk of fracture compared with the background population. We therefore suggest that if bone health is to be taken seriously in men with prostate cancer that all these men should be risk assessed (FRAX(®) or Qfracture(®) tools, as National Institute for Health and Care Excellence advised), as all men with prostate cancer have an increased risk of fracture, with those on ADT having slightly higher risk.

Castration induces Parkinson disease pathologies in young male mice via inducible nitric-oxide synthase.

Although Parkinson disease (PD) is a progressive neurodegenerative disorder, available animal models do not exhibit irreversible neurodegeneration, and this is a major obstacle in finding out an effective drug against this disease. Here we delineate a new irreversible model to study PD pathogenesis. The model is based on simple castration of young male mice. Levels of inducible nitric-oxide synthase (iNOS), glial markers (glial fibrillary acidic protein and CD11b), and α-synuclein were higher in nigra of castrated male mice than normal male mice. On the other hand, after castration, the level of glial-derived neurotrophic factor (GDNF) markedly decreased in the nigra of male mice. Accordingly, castration also induced the loss of tyrosine hydroxylase-positive neurons in the nigra and decrease in tyrosine hydroxylase-positive fibers and neurotransmitters in the striatum. Reversal of nigrostriatal pathologies in castrated male mice by subcutaneous implantation of 5α-dihydrotestosterone pellets validates an important role of male sex hormone in castration-induced nigrostriatal pathology. Interestingly, castration was unable to cause glial activation, decrease nigral GDNF, augment the death of nigral dopaminergic neurons, induce the loss of striatal fibers, and impair neurotransmitters in iNOS(-/-) male mice. Furthermore, we demonstrate that iNOS-derived NO is responsible for decreased expression of GDNF in activated astrocytes. Together, our results suggest that castration induces nigrostriatal pathologies via iNOS-mediated decrease in GDNF. These results are important because castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study PD-related nigrostriatal pathologies, paving the way for easy drug screening against PD.

Gonadectomy prior to puberty decreases normal parental behavior in adult mice.

Sex steroid hormones secreted by gonads influence development and expression of many behaviors including parental behaviors. The capacity to display many behaviors develops under the influence of sex steroid hormones; it begins with gonadal differentiation and lasts through puberty. The timing of gonadectomy may have important and long lasting effects on the organization and activation of neural circuits regulating the expression of different behaviors. The present study investigated the importance of exposure to endogenous gonadal steroid hormones during pubertal period/adolescence on parental behavior in adult mice. Male and female WT mice were gonadectomized either before puberty (25 days of age) or after puberty (60 days of age) and tested for parental behavior with and without estradiol benzoate (EB) replacement in adulthood. Additional groups of mice were gonadectomized at P25 and supplemented with estradiol (females) or testosterone (males) during puberty. Female mice gonadectomized after puberty or gonadectomized before puberty and supplemented with estradiol during puberty, displayed better pup directed parental behaviors in comparison to mice gonadectomized at 25 days of age regardless of treatment with estradiol in adulthood. However, mice treated with EB in adulthood displayed better non-pup directed nest building behavior than when they were tested without EB treatment regardless of sex and time of gonadectomy. To examine whether the sensitivity to sex steroid hormones was altered due to differences in time without gonads prior to the testing, mice were also tested for female sex behavior and there were no differences between mice gonadectomized at P25 or P60, although this could not completely rule out the possibility that parental behavior is more sensitive to prolonged absence of steroid hormones than female sex behavior. These results suggest that the absence of gonads and thereby the absence of appropriate gonadal steroid hormones during puberty/adolescence may have a profound effect on pup directed parental behaviors in adult mice.

Testosterone ameliorates streptozotocin-induced memory impairment in male rats.

AIM: To study the effects of testosterone on streptozotocin (STZ)-induced memory impairment in male rats. METHODS: Adult male Wistar rats were intracerebroventricularly (icv) infused with STZ (750 µg) on d 1 and d 3, and a passive avoidance task was assessed 2 weeks after the first injection of STZ. Castration surgery was performed in another group of rats, and the passive avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg·kg(-1)·d(-1), sc), the androgen receptor antagonist flutamide (10 mg·kg(-1)·d(-1), ip), the estrogen receptor antagonist tamoxifen (1 mg·kg(-1)·d(-1), ip) or the aromatase inhibitor letrozole (4 mg·kg(-1)·d(-1), ip) were administered for 6 d after the first injection of STZ. RESULTS: STZ administration and castration markedly decreased both STL1 (the short memory) and STL2 (the long memory) in passive avoidance tests. Testosterone replacement almost restored the STL1 and STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ-treated rats. Administration of flutamide, letrozole or tamoxifen significantly impaired the memory in intact rats, and significantly attenuated the testosterone replacement in improving STZ- and castration-induced memory impairment. CONCLUSION: Testosterone administration ameliorates STZ- and castration-induced memory impairment in male Wistar rats.

Necrosuppurative orchitis and scrotal necrotizing dermatitis following intratesticular administration of zinc gluconate neutralized with arginine (EsterilSol) in 2 mixed-breed dogs.

Intratesticular injection of EsterilSol (zinc gluconate neutralized with arginine) is a chemical sterilant for male dogs sometimes used in population control campaigns. Adverse reactions have been reported in 1% to 4% of treated dogs, but detailed histomorphologic descriptions are lacking. During a behavioral study conducted in the Chilean Patagonia in 2012, severe necrosuppurative orchitis and ulcerative dermatitis were observed in 2 of 36 (6%) dogs sterilized with EsterilSol according to the manufacturer's instructions. Reactions were noted on days 8 and 7 postinjection and required scrotal ablation on days 8 and 13, respectively; neither reaction was associated with the injection site. Although self-trauma following administration may have contributed, the cause of the adverse reactions is uncertain. EsterilSol is a relatively uncomplicated method to sterilize male dogs, but the occurrence of severe adverse reactions several days after administration emphasizes the need for the provision of long-term monitoring and veterinary care during sterilization campaigns using this product.

Activation of FGF2-FGFR signaling in the castrated mouse prostate stimulates the proliferation of basal epithelial cells.

The prostate gland is unique in that it undergoes rapid regression following castration but regenerates completely once androgens are replaced. Residual ductal components play an important role in the regeneration of a fully functional prostate. In this study, to examine how androgen status affects prostate structure and components, we conducted histopathological studies of the involuted and regenerated mouse dorsolateral prostate (DLP). In the castrated mouse DLP, the number of luminal epithelial cells decreased in a time-dependent manner. On Day 14 postandrogen replacement, the number of luminal epithelial cells was completely restored to the baseline level. In contrast, the number of basal epithelial cells gradually increased in the castrated mouse prostate. The Ki67-labeling index of prostate basal epithelial cells was significantly increased after castration. The number of basal epithelial cells decreased to baseline after androgen replacement. After castration, mRNA expression levels of specific growth factors, such as Fgf2, Fgf7, Hgf, Tgfa, and Tgfb, were relatively abundant in whole mouse DLPs. In organ culture experiments, basal epithelial proliferation was recapitulated in the absence of dihydrotestosterone (DHT). The proliferation of basal epithelial cells in the absence of DHT was suppressed by treatment with an FGF receptor inhibitor (PD173074). Moreover, FGF2 treatment directly stimulated the proliferation of basal epithelial cells. Taken together, these data indicated that the FGF2-FGF receptor signal cascade in the prostate gland may be one of the pathways stimulating the proliferation of basal epithelial cells in the absence of androgens.

Metabolic complications of androgen deprivation therapy for prostate cancer.

PURPOSE: Androgen deprivation therapy has a variety of well recognized adverse effects including vasomotor flushing, loss of libido, fatigue, gynecomastia, anemia and osteoporosis. This review focuses on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease. MATERIALS AND METHODS: We reviewed the medical literature using the PubMed® search terms prostate cancer, androgen deprivation therapy, gonadotropin-releasing hormone agonists, obesity, insulin resistance, lipids, diabetes, cardiovascular disease and myocardial infarction. We provide a focused review and our perspective on the relevant literature. RESULTS: Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol. CONCLUSIONS: Androgen deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms. Little is known about the optimal strategy to mitigate the adverse metabolic effects of androgen deprivation therapy. Thus, we recommend an emphasis on existing strategies for screening and treatment that have been documented to reduce the risk of diabetes and cardiovascular disease in the general population.