Decline In Testosterone Research Articles

Abstract 3227: Getting rid of obesity in middle-to-late adulthood relates to lower prostate cancer risk: Another piece of evidence supporting the “rapid testosterone reduction theory”

Abstract Background: Previously we demonstrated that a smoothed age-related decline in testosterone was associated with decreased risk of prostate cancer (PCa) (“rapid testosterone reduction theory”). Obesity relates to low testosterone, so body weight pattern reflecting smoothed testosterone decline should be related to lower PCa risk. This study aimed to validate the “rapid testosterone reduction theory” from the perspective of body mass index (BMI) pattern and risk of PCa. Methods: We conducted a nested case-control study in a retrospective hospital cohort with median follow-up of 5.0 years from a tertiary-level hospital in the Southeastern US. Electronic medical records of 18168 patients with prostate-related disease diagnosed between November 4, 1995 and January 10, 2016 were screened. The outcome was newly diagnosed PCa. Only patients with BMI measured at ≥3 differing calendar years before PCa diagnosis or the latest follow-up (for non-PCa patients) were included, resulting in a sample of 1571, among which 128 were PCa patients. BMI was analyzed in cross-section value, change, and developmental trajectories in relation to PCa risk. Results: Participant ages spanned a range of 40 to 90 years, with mean age at baseline was 57 years (standard deviation = 9.6). Baseline BMI was inversely associated with PCa risk (adjusted odds ratio [AOR], 0.76; 95% confidence interval [CI], 0.63-0.91 for every 5-unite increase in BMI). When analyzed in change between baseline and the latest follow-up, BMI increment was associated with increased PCa risk (AOR, 1.26; 95% CI, 1.05-1.51 for every 5-unite increase in BMI change). When analyzed in latent-class trajectory, a downward BMI trajectory of being obese in the 4th, 5th, and 6th decade then progressing to be non-obese since the 7th decade of age was associated with decreased PCa risk (AOR, 0.66; 95% CI, 0.45-0.98), compared to those with consistently normal BMI. When analyzed by strata of PCa diagnosis age, the same associations were more evident for PCa diagnosed after age 65. Conclusions: Weight loss and getting rid of obesity during middle-to-late adulthood is related to a decreased PCa risk, supporting the “rapid testosterone reduction theory” in explaining PCa risk. If this finding can be verified with more rigorous study, provision of testosterone replacement therapy as a weight control measure for men in middle-to-later adulthood has potentials in PCa prevention. Citation Format: Kai Wang, Xinguang Chen, Travis A. Gerke, Victoria Y. Bird, Mattia Prosperi. Getting rid of obesity in middle-to-late adulthood relates to lower prostate cancer risk: Another piece of evidence supporting the “rapid testosterone reduction theory” [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3227.

What is the andropause and how can it be managed in aesthetic practice?

Just as women experience hormonal changes during the menopause, men are affected by a gradual decline in testosterone. Beverley Ashton reflects on common symptoms of the andropause and its long-term health implications. She explains why the use of biochemical blood analysis to diagnose low testosterone has been questioned and says a validated questionnaire must be used during assessment

Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells.

Testosterone is indispensable for sexual development and maintaining male characteristics, and deficiency of this hormone results in primary or late-onset hypogonadism (LOH). Testosterone is primarily produced in Leydig cells, where autophagy has been reported to be extremely active. However, the functional role of autophagy in testosterone synthesis remains unknown. In this study, we show that steroidogenic cell-specific disruption of autophagy influenced the sexual behavior of aging male mice because of a reduction in serum testosterone, which is similar to the symptoms of LOH. The decline in testosterone was caused mainly by a defect in cholesterol uptake in autophagy-deficient Leydig cells. Further studies revealed that once autophagic flux was disrupted, Na+/H+ exchanger regulatory factor 2 (NHERF2) accumulated in Leydig cells, resulting in the down-regulation of scavenger receptor class B, type I (SR-BI) and eventually leading to insufficient cholesterol supply. Collectively, these results reveal that autophagy promotes cholesterol uptake into Leydig cells by eliminating NHERF2, suggesting that dysfunction of autophagy might be causal in the loss of testosterone production in some patients.

Vitamin D supplementation does not prevent the testosterone decline in males with advanced heart failure: the EVITA trial.

Observational studies indicate a positive association between circulating 25-hydroxyvitamin D (25OHD) and testosterone (T) concentrations. Because low 25OHD concentrations and T deficiency are considered to be a generalized phenomenon in patients with advanced heart failure (HF), we aimed to investigate whether vitamin D supplementation has beneficial effects on T indices in these patients. In a pre-specified secondary analysis of the EVITA (effect of vitamin D on mortality in heart failure) randomized controlled trial, we analyzed in male subjects with 25OHD concentrations < 75nmol/L the effect of a daily vitamin D3 supplement of 4000IU for 3years (n = 71) vs. placebo (n = 62) on total T (TT), sex hormone-binding globulin (SHBG), free T (fT), and bioactive T (BAT). We assessed changes from baseline until study termination and between-group differences at study termination. 25OHD increased in the placebo group from 36.6nmol/L by 9.2nmol/L (95% CI 3.2-15.1nmol/L; P = 0.003) and in the vitamin D group from 36.5nmol/L by 63.9nmol/L (95% CI 52.6-75.3nmol/L; P < 0.001), with a significant between-group difference at study termination (P < 0.001). TT and SHBG concentrations did not change significantly, neither in the placebo group nor in the vitamin D group (P = 0.845-0.082), but concentrations of fT and BAT declined significantly in both groups (P = 0.025-0.008). At study termination, there were no between-group differences in TT (P = 0.612), SHBG (P = 0.393), fT (P = 0.861), or BAT (P = 0.960). In male patients with advanced HF and low 25OHD concentrations, a daily vitamin D3 supplement of 4000IU for 3years did not prevent the decline in testosterone indices.

Does a change in sleep timing increase testosterone in young adult men?

Men are more evening oriented than women. These sex difference might be a result of gonadal hormones, especially of testosterone. Here, we tested for a causal relationship by shifting the sleep timing of young men to one hour later and assessed the influence on saliva testosterone. 50 men participated in our study (31 experimental, 19 control group). Sleep timing was measured with actigraphy. One week served as baseline and afterwards, participants were randomly assigned to either the control or the experimental group. In the experimental group, men were asked to go to bed about one hour later and to sleep one hour longer in the morning. Participants in the control group experienced no significant changes in sleep timing. In the experimental group, participants went to bed later and woke up later; therefore, mid-point of sleep was shifted to a later time and sleep duration decreased, because he men went to bed about one hour later but woke up only about 30 min later. The control group experienced a decline in testosterone, but the experimental group not. Changes in mid-point of sleep between baseline week and experimental week were correlated with the change in testosterone (r = 0.285).

Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age.

Inflammation, both acute and chronic, is associated with testosterone deficiency, raising the possibility of a direct causal link. One potential trigger for inflammation in obese men is the passage of intestinal bacteria into the circulation due to a breakdown in mucosal barrier integrity. Recently, we hypothesized that this endotoxin exposure may cause androgen deficiency in obese men. To test this hypothesis, we analyzed the relationship between serum levels of lipopolysaccharide-binding protein (LBP), an indirect measure of endotoxin exposure, against male reproductive hormones, inflammatory markers (C-reactive protein, IL-1β, IL-6, TNF-α), and adiposity in 75 men. Adiposity was positively correlated with endotoxin exposure (LBP) and inflammation (C-reactive protein, IL-6) and negatively correlated with testosterone. Furthermore, endotoxemia (LBP) was negatively correlated with serum testosterone but positively correlated with IL-6. Multivariate analysis revealed a significant, negative correlation between serum IL-6 and free testosterone. In a second interventional study, low-dose endotoxin challenge in lean men produced a transient inflammatory response that was followed by a decline in serum testosterone, without changes in LH or FSH, providing further evidence that endotoxin-driven inflammation may result in impaired Leydig cell function.

Testosterone and Cardiovascular Diseases: Causes or Consequences: The Lesson from the Last 5 Years

The relationship between the age-dependent decline of testosterone (T) and cardiovascular (CV) risk in men is still a matter of intense debate. In particular, over the last 5 years, several scientific reports have shed a new negative light on the association between T treatment (TTh) and forthcoming CV diseases (CVD). Based on this evidence, the US Food and Drug Administration agency has recommended that all T supplementations carry a warning that they may increase the risk of heart attack and stroke. To better clarify the available data on this topic, we scrutinized and summarized, also by using meta-analytic methods, the data generated during the last 5 years, as derived from the analysis of observational (either longitudinal or pharmaco-epidemiological) studies and from randomized controlled trials (RCTs) on TTh and CVD risk. Our analysis shows that there is a clear association between baseline T deficiency and overall mortality and CVD-related mortality when longitudinal surveys were analyzed, although a specific pathogenetic link cannot be made. When interventional trials were studied, several but not all pharmaco-epidemiological studies reported a possible protective role of TTh on CV risk; however, data from RCTs and their meta-analysis, presented here, do not provide us with sufficient information on this point. Present data do not indicate an increased risk with TTh, but there is also insufficient definitive evidence that TTh is protective. Therefore, further and more specific trials are advisable to better clarify the possible relationship between low T, TTh, and CVD in aging men.

Testosterone, social status and parental care in a cooperatively breeding bird

The steroid hormone testosterone not only plays an important role in gamete production, but also influences social and aggressive behavior. Testosterone varies seasonally, peaking when competition for mates is high and declining during parental care. Surprisingly, little is known about how testosterone mediates social conflict and parental care behavior in highly social species like cooperative breeders, where group members compete for breeding opportunities and provide parental or alloparental care. We examined how testosterone differs across breeding roles in the tropical cooperatively breeding superb starling, Lamprotornis superbus. We determined whether testosterone was elevated in larger groups, and whether testosterone was negatively related to total levels of parental and alloparental care. We found that male breeders had higher testosterone than male helpers and female breeders and helpers during incubation. However, breeding males exhibited a significant decline in testosterone from incubation to chick rearing, and all individuals had similar levels during the chick rearing stage. Additionally, helpers—but not breeders—in large social groups had higher testosterone than those in small groups. Finally, testosterone was not correlated with nestling provisioning rates during chick rearing, suggesting that natural variation in the low levels of testosterone observed during periods of high parental care does not affect nestling provisioning. Together, these results offer insight into how testosterone is related to breeding roles, intra-group conflict, and parental care in a highly social species.

Individual testosterone decline and future mortality risk in men

Male aging is characterized by a decline in testosterone (TS) levels with a substantial variability between subjects. However, it is unclear whether differences in age-related changes in TS are associated with general health. We investigated associations between mortality and intra-individual changes in serum levels of total TS, SHBG, free TS and LH during a ten-year period with up to 18 years of registry follow-up. 1167 men aged 30-60 years participating in the Danish Monitoring Trends and Determinants of Cardiovascular Disease (MONICA1) study and who had a follow-up examination ten years later (MONICA10) were included. From MONICA10, the men were followed up to 18 years (mean: 15.2 years) based on the information from national mortality registries via their unique personal ID numbers. Cox proportional hazard models were used to investigate the association between intra-individual hormone changes and all-cause, CVD and cancer mortalities. A total of 421 men (36.1%) died during the follow-up period. Men with most pronounced decline in total TS (<10th percentile) had a higher all-cause mortality risk compared to men within the 10th to 90th percentile (hazard ratio (HR): 1.60; 95% confidence interval (CI): 1.08-2.36). No consistent associations were seen in cause-specific mortality analyses. Our study showed that higher mortality rates were seen among the men who had the most pronounced age-related decline in TS, independent of their baseline TS levels.

P462Age-related testosterone decline and cardiovascular remodeling in hypertensive men

P462Age-related testosterone decline and cardiovascular remodeling in hypertensive men

Erectile dysfunction in patients with chronic pain treated with opioids

Introduction and objectiveChronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal–pituitary–hypothalamic axis and the decline in testosterone levels.To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. Material and methodsProspective observational study lasting 3 years, where the intensity of pain (visual analog scale, 0–10cm), erectile function (IIEF-EF, range 1–30 points), quality of life (EQ-VAS, 0–100mm), quality of sexual life (MSLQ-QOL, 0–100 points), anxiety/depression (HAD, 0–21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. ResultsED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. ConclusionsErectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the significant emotional impact posed to the patient, the impact on their overall quality of life and its good clinical response to an interdisciplinary treatment.

Functional significance of men's testosterone reactivity to social stimuli.

Rapid testosterone fluctuations in response to social stimuli are observed across a wide range of species, and the highly conserved nature of these fluctuations suggests an adaptive function. This paper reviews the current literature on testosterone reactivity, primarily in human males, and illustrates how life-history theory provides an adequate theoretical framework to interpret findings. The review is structured around supporting evidence suggesting that situations implicated in mating effort either directly (e.g., interactions with a mate) or indirectly (e.g., intrasexual competition) are generally associated with a brief elevation of testosterone, while situations implicated in parenting effort (e.g., nurturant interactions with offspring) are generally associated with a decline in testosterone. Further, we discuss how these fluctuations in testosterone have been linked to future behaviors, and how situational, motivational, and physiological variables moderate the interplay between social stimuli, testosterone reactivity, and behavior. Supporting the notion that testosterone can play a causal role in modulating behavior in response to social stimuli, we also summarize recent single administration studies examining the effects of testosterone on physiology, neurobiology, and behavior. A conceptual model provides links between supported findings, and hypothesized pathways requiring future testing.

Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer

ABSTRACTIntroduction: Androgen deprivation therapy (ADT) is the mainstay for advanced, hormone-sensitive prostate cancer, and options include surgical castration, luteinizing hormone-releasing hormone (LHRH) agonist, and more recently, gonadotropin releasing hormone (GnRH) antagonist therapy. Our understanding of the mechanisms and adverse effects of ADT has increased substantially, including the class-specific adverse effects of ADT.Areas covered: This review will summarize the pharmacodynamic and pharmacokinetic properties of the GnRH antagonist degarelix and its role in the management of advanced prostate cancer, the clinical evidence supporting its regulatory approval, as well as potential benefits and disadvantages over traditional LHRH agonist therapy.Expert opinion: Degarelix represents a newer class of ADT that results in a rapid and reliable decline in serum testosterone, a quality that makes it particularly advantageous in men presenting with symptomatic, hormone-sensitive prostate cancer. Due to differences in mechanism of action, there is observational data suggesting a potential cardiovascular and even oncologic benefit over traditional LHRH agonist therapy. Further research is ongoing to more clearly define this potential benefit.

CHARACTERISTICS OF STEROID METABOLISM IN MALE RATS AT STAGES OF EXPERIMENTAL LIVER METASTASIS

The aim of the study was to reveal characteristics of steroid metabolism in tumor, metastases, adrenal glands (AG) and blood serum (BS) in male rats in the course of liver metastasis, as well as diagnostic signs of metastases. Material and methods. The study included 44 white male rats weighing 180-250 g. S-45 sarcoma was transplanted intrasplenically. Estrone, estradiol, free testosterone, 17-OHP, cholesterol, cortisol (in tissues and BS), DHEAS (in tissues), DHEA and ACTH (in BS) were studied by the using standard test kits for ELISA and RIA. Results. We found that the pituitary gland does not participate in liver metastatic process (low ACTH in BS). AG are assumed to play a regulatory role of steroidogenesis in tissues. Characteristics of liver metastases that not re-metastasize - non-active metastases (NAM) are: decreased cortisol in the perifocal zone (PZ) and the less estrone increase in metastases. Characteristics of metastases that re-matastasize to lungs - active metastases (AM) are: increased cortisol in PZ and the greater estrone gain in metastases. Hypo-estradiolemia and hyper-testosteronemia were diagnostic criteria for the upcoming liver metastasis; hyper-estradiolemia along with the decline of free testosterone - signs of liver metastases; hyper-cortisolemia and hypercholesterolemia are for AM in experimental liver metastasis, hypo-cortisolemia and hypocholesterolemia are signs of NAM in the liver of male rats. Conclusion. Consequently, one of the detected pathogenetic mechanisms of liver metastasis is presented by deactivation of the central pituitary regulation of steroidogenesis with regulating function passed to AG which results in steroid imbalance with accumulation of estrone in metastases and multidirectional changes in cortisol levels in PZ and BS, depending on the activity of metastases.

Exogenous kisspeptin enhances seasonal reproductive function in male Siberian hamsters

Summary Animals living in temperate climates are faced with the challenge of reproducing only when environmental conditions are suitable for offspring survival. Environmental cues signalling current and future energy availability (e.g., food availability and photoperiod respectively) are used to appropriately time reproduction. The precise neuroendocrine mechanisms regulating reproduction in response to these cues are unknown. The goal of the present study was to investigate a functional role for kisspeptin, a neuropeptide that shows promise as a key regulator of seasonal reproduction, in integrating multiple environmental cues to regulate reproduction in the Siberian hamster (Phodopus sungorus). Siberian hamsters undergo robust gonadal regression and terminate reproduction in unsuitable environments [short winter‐like day lengths (photoperiods), low food availability]. Adult male hamsters were housed in short‐day or intermediate photoperiods, received either ad‐libitum access to food or mild food restriction, and were treated with either kisspeptin or a vehicle for 6 weeks to determine the ability of kisspeptin to attenuate gonadal regression. Hamsters exhibited varying degrees of gonadal regression in response to inhibitory environments (short‐day photoperiod, food restriction). Kisspeptin treatment successfully enhanced testis mass under these inhibitory conditions, but did not affect normal seasonal changes in body mass and food intake. Thus, kisspeptin specifically enhanced reproductive function without altering other, non‐reproductive physiological responses to these environmental treatments. The inhibitory environmental conditions used in this study caused little if any decline in serum luteinizing hormone (LH) and testosterone over the course of the experiment. Kisspeptin treatment tended to exacerbate the decline in LH within individuals, but there were no significant effects of kisspeptin when comparing changes in the hormone levels amongst groups. The interesting outcome that kisspeptin enhanced testis mass, apparently independently of hypothalamic endocrine mechanisms, suggests the possibility of local kisspeptin action within the gonads. Overall, we show a functional role for kisspeptin in integrating complex environmental information to specifically support reproduction. Future work should focus on direct effects of kisspeptin at the gonadal level of the HPG axis as well as its interactions with the metabolic functions and other hormones involved in reproduction, e.g., gonadotropin‐inhibitory hormone (GnIH). A lay summary is available for this article.

Influence of marital status on testosterone levels–A ten year follow-up of 1113 men

Based on a large population of 1113 men aged 30–60 at baseline (mean: 44.1 years, standard deviation: 10.5), we investigated whether intra-individual changes in testosterone (T) and related reproductive hormones during a ten year period were dependent of marital status at baseline and follow-up. The studied men were part of a health survey in Denmark, conducted between 1982 and 1984 with a follow-up examination approximately ten years later. Data on reproductive hormones, measured in serum, and lifestyle and marital status were obtained at both time points. As expected, an age-related decline in testosterone was observed. However, independent of age and lifestyle, we observed that men who went from unmarried to married (n=81) during the study period experienced an accelerated age-related decline in testosterone (−6.6nmol/L) whereas men who went from married to unmarried (n=67) experienced an attenuated age-related decline (−2.3nmol/L). Men who were either married or unmarried at both time points (n=167, n=798, respectively) had a testosterone decline in between (−3.7nmol/L and −4.6nmol/L, respectively). Changes in T/LH ratio did not differ according to marital status indicating that the lowered T level is not compensated by increasing LH levels. This could suggest a modification of the gonadostat due to an adaptation to changing life circumstances.

Disfunción eréctil en pacientes con dolor crónico tratados con opioides

Introduction and objectiveChronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal-pituitary-hypothalamic axis and the decline in testosterone levels.To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. Material and methodsProspective observational study lasting 3 years, where the intensity of pain (visual analogue scale, 0-10cm), erectile function (IIEF-EF, range 1-30 points), quality of life (EQ-VAS, 0-100mm), quality of sexual life (MSLQ-QOL, 0-100 points), anxiety/depression (HAD, 0-21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. ResultsED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. ConclusionsErectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the significant emotional impact posed to the patient, the impact on their overall quality of life and its good clinical response to an interdisciplinary treatment.

Effect of short-term androgen deficiency on bladder contractility and urothelial mediator release.

In men, testosterone levels decline by 1% per year after the age of 40. Reduced androgen levels may directly contribute to lower urinary tract symptoms and bladder dysfunction, although the mechanisms are unclear. This study examined the effect of low testosterone and testosterone replacement on key mechanisms involved in local bladder function. Intraluminal release of the mediators ATP and ACh in response to bladder distension was measured in whole bladders from rats 8weeks following castration, whilst bladder contractility was assessed using isolated strips. Human urothelial cells were cultured under low, physiological and supra-physiological testosterone conditions for 24h or 5days, and stretch-induced release of ATP and ACh was measured. Phasic contractile activity of bladder strips, agonist-induced reponses to carbachol and isoprenaline and nerve-evoked contractions were unaffected by castration. The acetylcholinesterase inhibitor neostigmine significantly increased amplitude of phasic activity only in bladder strips following castration, and this was prevented by testosterone replacement. Intraluminal ACh release following bladder distension was significantly reduced following castration, whilst ATP release was unaffected. In contrast, stretch-induced ATP release from urothelial cells was significantly enhanced in low testosterone conditions, whilst ACh release was unaltered. Testosterone-replacement to physiological levels prevented these changes. Whilst androgen deficiency of 8weeks does not directly affect contractility of bladder smooth muscle, urothelial mediator release is sensitive to changes in testosterone. These changes in mediator release may be an early effect of the decline in testosterone and could affect sensory pathways in the longer term, contributing to the urinary symptoms and bladder dysfunction seen in androgen-deficient men.

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health.

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed.

383 Effect of Sleep Deprivation on Hormonal Axis and Erectile Function

INTRODUCTION AND OBJECTIVES: Testosterone contributes signal pathway of penile erection and it is mainly secreted during sleep. However, there is no consensus that which level of the hormone axis will be mainly affected to sleep deprivation (SD). So, we investigated whether 1) SD could alter the hormonal axis or not, 2) which level of the axis could be the major target of SD and 3) subsequently whether SD could decrease erectile function or not. METHODS: 32 Wistar rats (16 weeks old) were divided into 2 groups. Using automated sleep deprivation system (Pinnacle technology inc. USA), sleep deprivation for 48~56 hours was done in experimental group. Then, cavernous nerve on posterolateral aspect of the prostate was stimulated with electrode. Intracavernosal pressure was checked during carotid arterial pressure monitoring. Blood sample was collected by puncturing of left cardiac ventricle. After sacrifice of a rat, brain tissue was extracted for measuring Kisspeptin mRNA, and fluorescence stains were done with testis (P450scc stain, stAR stain) and penile tissue (nNOS, eNOS). RESULTS: Kisspeptin mRNA, gonadotropin releasing hormone, follicular stimulating hormone were not different between two groups. Luteinizing hormone and testosterone were significantly different between two groups (a_image). Steroidogenesis in the leydig cell was more prominent in control group than in experimental group. Positive area of cavernous nerve with nNOS staining and that of penile smooth muscle with eNOS staining were decreased in SD group. Intracavernosal pressure also decreased in SD group (b_image). CONCLUSIONS: Acute SD may mainly exert influence on luteinizing hormone secretion in anterior hypophysis. Subsequently, the result decreases the steroidogenesis in leydig cell, resultantly decline of testosterone would develop. These chain-reactions of the hormone axis would be a factor of lowering the erectile function. Source of Funding: None