***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Testosterone has immune-modulating properties , and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha , IL-1beta , and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10 . We report a r and omized , single-blind , placebo-controlled , crossover study of testosterone replacement ( Sustanon 100 ) vs. placebo in 27 men ( age , 62 + /- 9 yr ) with symptomatic and rogen deficiency ( total testosterone , 4.4 + /- 1.2 nmol/liter ; bioavailable testosterone , 2.4 + /- 1.1 nmol/liter ) . Compared with placebo , testosterone induced reductions in TNFalpha ( -3.1 + /- 8.3 vs. 1.3 + /- 5.2 pg/ml ; P = 0.01 ) and IL-1beta ( -0.14 + /- 0.32 vs. 0.18 + /- 0.55 pg/ml ; P = 0.08 ) and an increase in IL-10 ( 0.33 + /- 1.8 vs. -1.1 + /- 3.0 pg/ml ; P = 0.01 ) ; the reductions of TNFalpha and IL-1beta were positively correlated ( r(S ) = 0.588 ; P = 0.003 ) . In addition , a significant reduction in total cholesterol was recorded with testosterone therapy ( -0.25 + /- 0.4 vs. -0.004 + /- 0.4 mmol/liter ; P = 0.04 ) . In conclusion , testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol .  Twenty of these men had established coronary disease , and because total cholesterol is a cardiovascular risk factor , and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque , these properties may have particular relevance in men with overt vascular disease We conducted a prospect i ve , nested , case-control study of inflammatory markers as predictors of  type 2 diabetes among 32,826 women who provided blood sample s in 1989 through 1990 in the Nurses ' Health Study . Among women free of diabetes , cardiovascular disease , or cancer at baseline , 737 had developed diabetes by 2000 . Control women ( n = 785 ) were selected matched on age , fasting status , race , and BMI for cases in the top BMI decile . Baseline levels of tumor necrosis factor (TNF)-alpha receptor 2 , interleukin (IL)-6 , and C-reactive protein ( CRP ) were significantly higher among case than control subjects ( all P < /= 0.001 ) . After adjusting for BMI and other lifestyle factors , all three biomarkers significantly predicted diabetes risk ; the odds ratios ( ORs ) comparing extreme quintiles were 1.64 ( 95 % CI 1.10 - 2.45 ) for TNF-alphaR2 , 1.91 ( 1.27 - 2.86 ) for IL-6 , and 4.36 ( 2.80 - 6.80 ) for CRP ( P for trend < 0.001 for all biomarkers ) . In a multivariate model simultaneously including the three biomarkers , only CRP levels were significantly associated with risk of diabetes ( OR comparing extreme quintiles of CRP = 3.99 , P for trend < 0.001 ) . These data support the role of inflammation in the pathogenesis of type 2 diabetes . Elevated CRP levels are a strong independent predictor of type 2 diabetes and may mediate associations of TNF-alphaR2 and IL-6 with type 2 diabetes Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( < or = 13.9 nmol/L ) .  Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have  serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy We recently described a connection between and rogens and ghrelin in women affected by the polycystic ovary syndrome . To further investigate the interaction between sex steroids and ghrelin , we investigated  circulating ghrelin levels  in a group of hypogonadal men before and after therapeutic intervention aim ing at normalization low testosterone ( T ) concentrations . Seven hypogonadal men were compared with nine overweight/moderately obese men matched for body mass index and body fat distribution parameters , as well as with 10 normal weight controls .  Total and free T and plasma ghrelin levels were significantly lower in the hypogonadal men than in the control groups . Hypogonadal men also had a significantly higher insulin resistance state . Ghrelin levels were positively correlated with both total and free T concentrations . A significant correlation was also found between ghrelin and the anthropometric parameters and the insulin resistance indexes . However , in a multiple regression analysis in which a correction for all covariants was performed , only the relationship with total and free T persisted . After the 6-month replacement T therapy , ghrelin levels of hypogonadal patients increased and did not differ significantly in comparison with both control groups . The positive correlation between ghrelin and and rogens still persisted after T replacement therapy , after adjusting for confounding variables . These data further indicate that sex hormones modulate circulating ghrelin concentrations in humans . This may be consistent with the concept that ghrelin may exert a relevant role in the endocrine network connecting the control of the reproductive system with the regulation of energy balance We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH , estradiol , testosterone , and SHBG . SHBG was used to calculate the free estradiol index and free and rogen index . We studied 3,200 women , aged 42 - 52 yr , in the Study of Women 's Health Across the Nation , a prospect i ve multiethnic study of the menopausal transition . We measured the hemostatic factors , fibrinogen , factor VIIc , tissue plasminogen activator ( t-PA ) , and plasminogen activator inhibitor type 1 ( PAI-1 ) , as well as  glucose and insulin  to calculate insulin resistance . After adjustment for body mass index , site , and ethnicity , SHBG was correlated with PAI-1 ( partial r = -0.30 ) and t-PA ( partial r = -0.12 ) . Although testosterone was associated with t-PA ( partial r = 0.13 ) and PAI-1 ( partial r = 0.07 ) , free and rogen index was strongly correlated with t-PA ( partial r = 0.18 ) and PAI-1 ( partial r = 0.26 ) . SHBG modified the association of hemostatic factors with insulin resistance . Women with greater  insulin resistance had lower SHBG and higher PAI-1 . Estrogen measures were not associated with insulin resistance . The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood . SHBG , which influences the amount of bioavailable hormone , significantly modified the association of PAI-1 and t-PA with insulin resistance . The longitudinal Study of Women 's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women CONTEXT GnRH agonists markedly increase fat mass in men with prostate cancer , but little is known about the effects of treatment on insulin sensitivity . OBJECTIVE The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity . DESIGN This was a prospect i ve 12-wk study . SETTING The study was conducted at a general clinical research center . PATIENTS OR OTHER PARTICIPANTS We studied 25 men with locally advanced or recurrent prostate cancer , no radiographic evidence of metastases , no history of diabetes mellitus , and no evidence of diabetes mellitus at baseline visit . INTERVENTION Leuprolide depot and bicalutamide were used in the study . MAIN OUTCOME MEASURES Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12 . The primary study outcome was change in insulin sensitivity index . RESULTS Mean ( + /- se ) percentage fat body mass increased by 4.3 + /- 1.3 % from baseline to wk 12 ( P = 0.002 ) . Insulin sensitivity index decreased by 12.9 + /- 7.6 % ( P = 0.02 ) . Insulin sensitivity by homeostatic model assessment decreased by 12.8 + /- 5.9 % ( P = 0.02 ) . Fasting plasma insulin levels increased by 25.9 + /- 9.3 % ( P = 0.04 ) . Mean glycosylated hemoglobin also increased significantly ( P < 0.001 ) . CONCLUSIONS Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer . These observations suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men Mathematical methods exist to determine the fractions of sex hormones bound to albumin , bound to sex hormone binding globulin ( SHBG ) , or unbound , using total hormone concentration and SHBG concentration . We used data from eight prospect i ve studies of postmenopausal women to assess the validity of these estimates for fractions of estradiol ( E2 ) and to investigate the impact of using calculated values in breast cancer relative risk ( RR ) models . Comparisons were made between measured and calculated concentrations of free and non-SHBG-bound E2 in four studies . Relationships between the hormone fractions were investigated and a sensitivity analysis of the calculation performed . Breast cancer RRs were estimated using conditional logistic regression by quintiles of free E2 . There is a high correlation ( r > 0.91 ) between calculated and measured values of both free and non-SHBG-bound E2 . The calculation is highly sensitive to total hormone concentration but is relatively insensitive to SHBG concentration . In studies with both measured and calculated values , the RRs of breast cancer by quintile of free E2 were almost identical for both estimates ; using calculated values in all possible studies the RR in the highest compared with the lowest quintile of free E2 was 2.29 ( 95 % confidence interval , 1.65 - 3.19 ) . The mathematical method used to calculate fractions of E2 is valid , and RR analyses using calculated values produce similar results to those using measured values . This suggests that for epidemiological studies , it is only necessary to measure total E2 concentration and SHBG concentration , with hormone fractions being obtained by calculation , producing savings in cost , time , and serum The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis , obesity and sexual function in middle-aged men with type 2 diabetes and mild and rogen deficiency . Forty-eight middle-aged men , with type 2 diabetes , ( visceral ) obesity and symptoms of and rogen deficiency , were included in this open-label study . Twenty-four subjects received testosterone undecanoate ( TU ; 120 mg daily , for 3 months ) ; 24 subjects received no treatment .  Body composition was analyzed by bio-impedance . Parameters of metabolic control were determined . Symptoms of and rogen deficiency and erectile dysfunction were scored by self-administered question naires . TU had a positive effect on ( visceral ) obesity : statistically significant reduction in body weight ( 2.66 % ) , waist-hip ratio ( 
    Output:
    
This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women .
High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men ; the inverse association of SHBG with risk was stronger in women than in men