This study assessed if concomitant use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or corticosteroids altered the response or safety outcomes to baricitinib in rheumatoid arthritis (RA) patients.

The prevalence of nail psoriasis (Ps) is >50% in plaque Ps patients. The presence of nail Ps may be an indicator of disease chronicity or severity. This post-hoc analysis evaluated the effect of ixekizumab (IXE), an anti-IL-17A monoclonal antibody, in patients with and without nail Ps. Data were integrated from two Phase 3, randomized controlled trials in which patients received subcutaneous placebo, 50-mg etanercept twice weekly (ETN), or 80 mg IXE every 2 weeks (IXEQ2W) after a 160-mg starting dose. Efficacy was assessed by percentage of patients who achieved 75%, 90%, or 100% improvement on the Psoriasis Area and Severity Index (PASI 75, PASI 90, PASI 100) and who achieved a score of 0 or 1 on the static Physicians Global Assessment (sPGA 0 or 0,1) at Week 12. Nail Ps was defined as a Nail Psoriasis Severity Index (NAPSI) score >0 at baseline. Statistical analysis was based on a logistic regression model with group, study, and group-by-study interaction as covariates. In IXEQ2W, significantly more patients with nail Ps than those without achieved PASI 75 (91.3% vs. 84.6%, p<0.001), PASI 90 (72.4% vs 65.8%, p=0.023), and sPGA of 0,1 (83.8% vs 78.5%, p=0.030) at Week 12 whereas a similar percentage achieved PASI 100 (36.8% vs. 38.9%, p=0.485) and sPGA 0 (38.6% vs 40.9%, p=0.441) at Week 12. Comparisons of patients with differing levels of nail Ps (NAPSI ≥16 vs. NAPSI <16) showed that significantly more patients with NAPSI ≥16 than those without achieved PASI 75 (92.3% vs.86.5%, p=0.003) and showed no significant differences between the severity groups in the percentage of patients achieving PASI 90, 100, or sPGA 0,1. In this post-hoc integrated analysis, patients with and without nail Ps responded well to IXE. The presence of nail Ps was not associated with reduced efficacy in IXEQ2W-treated patients.

Objective We analysed the effects of baseline characteristics on the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) from two phase III trials. Methods In RA-BEAM (NCT01710358), patients with inadequate response to methotrexate were randomised to placebo, baricitinib 4 mg or adalimumab 40 mg. RA-BUILD (NCT01721057) patients had inadequate response to ≥1 csDMARDs and were randomised to either placebo or once-daily baricitinib (2 or 4 mg). Both study populations were naïve to biologic DMARDs (bDMARDs). Primary end point for both studies was American College of Rheumatology 20% improvement (ACR20) response at week 12. Pooled data from the two trials were analysed post hoc based on select subgroups defined by age, previous csDMARD use, baseline RA disease activity, etc, with assessment of clinical and safety outcomes at week 12 and radiographic outcomes at week 24 for the baricitinib 4 mg and placebo-treated patients. Results Efficacy was observed with baricitinib 4 mg treatment irrespective of patient demographics and baseline disease characteristics. ORs primarily favoured baricitinib over placebo in the ACR20 response. In other outcomes such as Disease Activity Score for 28 joints based on high-sensitivity C reactive protein levels, Simplified Disease Activity Index score ≤11 and radiographic progression, baricitinib 4 mg showed better responses than placebo regardless of baseline characteristics. Safety events were more common in patients over 65 years, but similar between baricitinib 4 mg and placebo patients. Conclusion Baseline characteristics did not substantially affect clinical response to baricitinib 4 mg in patients with RA with inadequate response to csDMARDs.

Background Baricitinib (BARI), an oral JAK1/JAK2 inhibitor, is in development for patients (pts) with moderate to severe rheumatoid arthritis (RA).1,2 Objectives This post-hoc analysis of two phase 3 studies assessed whether concomitant use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) altered the response or safety outcomes to BARI in RA pts and evaluated the effect of concomitant corticosteroid use on the efficacy of BARI. Methods Pts with ≥6 swollen and tender joints and no prior biologic DMARD use were enrolled. In RA-BEAM (NCT01710358), methotrexate (MTX)-inadequate responder (IR) pts were randomised to PBO once daily (QD), BARI 4 mg QD, or adalimumab 40 mg biweekly.1 In RA-BUILD (NCT01710358), csDMARD-IR pts were randomised to placebo (PBO) or BARI (2 or 4 mg) QD.2 Pts continued background csDMARD (including MTX) therapy. This post-hoc analysis included the PBO (N=716) and BARI 4 mg (N=714) pts and assessed the number and type of concomitant csDMARDS and concurrent corticosteroid use. Results 71%, 21%, and 6% of PBO pts were taking MTX alone, MTX + ≥1 other csDMARD, and non-MTX csDMARDs, respectively; in BARI 4 mg pts, the rates were 74%, 18%, and 6%, respectively. Oral corticosteroids were used in 56% of PBO and 55% of BARI pts at baseline; pts continued use throughout the studies. The differences in clinical efficacy between BARI 4 mg and PBO at 12 weeks was similar regardless of the number or type of csDMARDs concomitantly used (Table) or the concomitant use of corticosteroids (data not shown). The rates of serious adverse events and discontinuation due to adverse events were comparable regardless of the number or type of csDMARDs used (Table) or corticosteroid use. ACR20/50/70=20%, 50%, and 70% improvement in American College of Rheumatology criteria; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-ESR=Disease Activity Score 28-erythrocyte sedimentation rate; MTX=methotrexate; SDAI=Simple Disease Activity Index. Conclusions BARI has demonstrated clinical safety and efficacy in a wide range of pts, regardless of the number of concomitant csDMARDs or concomitant use of corticosteroids. References Taylor PC et al. Arthritis Rheumatol 2015;67(S10):3927–3928. Dougados M et al. Ann Rheum Dis 2017;76:88–95. Disclosure of Interest A. Kavanaugh Consultant for: Eli Lilly and Company, C. Helt Employee of: Eli Lilly and Company, D. Muram Employee of: Eli Lilly and Company, J. Alam Employee of: Eli Lilly and Company, V. Arora Employee of: Eli Lilly and Company, A. L. Pinto Correia Employee of: Eli Lilly and Company, I. de la Torre Employee of: Eli Lilly and Company, R. van Vollenhoven Grant/research support from: Abbvie, Amgen, BMS, GSK, Pfizer, Roche, UCB, Consultant for: Abbvie, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, Vertex

Background The efficacy of some rheumatoid arthritis (RA) therapies is reduced among patients who are smokers. Objectives This post-hoc analysis of two phase 3 studies assessed the effects of patient smoking status on the response to baricitinib treatment in patients with RA. Methods In RA-BEAM (NCT01710358), patients with inadequate response to methotrexate were randomized to placebo once-daily (QD) (N=488), baricitinib 4 mg QD (N=487), or adalimumab 40 mg biweekly (N=330).1 In RA-BUILD (NCT01721057), patients with inadequate response to conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were randomized to placebo (N=228) or baricitinib (2 mg, N=229; or 4 mg, N=227) QD.2 Patients continued background csDMARD therapy in both studies. This post-hoc analysis was conducted in the placebo (N=716) and baricitinib 4 mg (N=714) patients. Patient-reported smoking status was categorized as current (smokers) or not current (non-smokers). Results Among 1,430 evaluable patients who received placebo or baricitinib 4 mg, 290 (20.3%) were smokers. Smoking status at baseline did not affect the clinical results of treatment with baricitinib for 24 weeks; smokers who received placebo were numerically less likely than non-smokers receiving placebo to achieve most clinical outcomes (Table). Baricitinib9s effect on modified total Sharp score was more pronounced among nonsmokers (interaction p-value =0.07). ACR20/50/70=20%, 50%, and 70% improvement in American College of Rheumatology criteria; CDAI=Clinical Disease Activity Index; DAS28-hsCRP=Disease Activity Score 28-high sensitivity C-reactive protein; HAQ-DI=Health Assessment Questionnaire-Disability Index; mTSS=modified total Sharp score; SDAI=Simple Disease Activity Index. Conclusions This analysis of smokers and non-smokers in two RA trials demonstrated that the beneficial effect of baricitinib treatment versus placebo was similar on all clinical endpoints, but may differ for structural damage progression. References Taylor PC et al. Arthritis Rheumatol 2015;67(suppl 10) abst 2L. Dougados M et al. Ann Rheum Dis 2017;76:88–95. Disclosure of Interest J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche/Genentech, Corrona, UCB, Myriad, Eli Lilly and Company, Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche/Genentech, Corrona, UCB, Myriad, Eli Lilly and Company, Employee of: University of Alabama at Birmingham, P. Emery Consultant for: Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, Eli Lilly and Company, G. Burmester Consultant for: Eli Lilly and Company, V. Arora Employee of: Eli Lilly and Company, J. Alam Employee of: Eli Lilly and Company, D. Muram Employee of: Eli Lilly and Company, L. Klareskog Grant/research support from: Janssen, Pfizer, BMS, GSK, AbbVie, Roche.

### Key messages #### What is already known about this subject? #### What does this study add? #### How might this impact on clinical practice? Rheumatoid arthritis (RA) can begin at any age, but the prevalence increases with age. Active disease usually persists for years; many patients have initial symptoms after age 60.1 2 Elderly patients with RA often have comorbid diseases managed with multiple concomitant medications with the potential for changes in drug pharmacokinetics and pharmacodynamics, which complicate therapeutic decisions.3 Moreover, there is a perception that medications may be less effective than in younger individuals and adverse effects more common and severe.4 5 One report suggests an increased risk in elderly patients for adverse events (AE) leading to discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) in the treatment of RA, while other reports have not seen these effects.4 5 An analysis of Medicare beneficiaries with RA suggested that older patients were less likely to receive conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and therefore may not receive optimal treatment.6 Other reports have shown that responsiveness of elderly patients with RA to methotrexate (MTX) or tumour necrosis factor (TNF) inhibitors+MTX was similar to that observed in …

Background Baricitinib (bari), a selective, transient and reversible inhibitor of Janus kinase (JAK)1 and JAK2, improved signs and symptoms of active rheumatoid arthritis (RA) in multiple phase 3 studies. Since erythropoietin (EPO) stimulates erythrocyte production via the JAK2 signaling pathway, haemoglobin (Hgb) and other haematologic parameters were thoroughly evaluated in the bari RA clinical development program. Objectives To evaluate baseline and subsequent changes in Hgb and related laboratory parameters in RA patients (pts) treated with bari (2 or 4 mg once daily), placebo (PBO), or active comparator (methotrexate [MTX] or adalimumab [ADA]). Methods Blood samples were analyzed at baseline and at each study visit for complete blood count, with more extensive phlebotomy at baseline (Wk 0) and Wks 12, 24, and 52 (Figure 1). Data were aggregated from completed Phase 2 and 3 RA studies and one ongoing long-term extension study. EPO and reticulocyte (RET) data were collected from a Phase 2 RA study in Japan. Results Hgb levels below the gender-adjusted lower limit of normal (LLN) were often observed at baseline (25%). Small declines in Hgb were observed at Wk 2 and again at Wk 14 in bari (2 and 4 mg) and PBO-treated RA pts consistent with the volume and frequency of phlebotomy (Figure 1). Initial decreases in Hgb were accompanied by declines in RET counts in bari-treated RA pts. Subsequent increases in Hgb were associated with increases in RET after Wk 8 and statistically significant dose-dependent increases vs. PBO in total iron (Fe), total iron binding capacity (TIBC) and EPO. Treatment-emergent (TE) shifts in Hgb from normal to Conclusions The proportions of RA pts with TE abnormally low Hgb did not differ significantly between bari and PBO. Reductions in Hgb, including to ≥grade 3, were generally not associated with adverse outcomes. Despite concerns about the impact of JAK2 inhibition on EPO signaling, following initial declines incident to phlebotomy, dose-dependent increases in EPO, Fe, and TIBC with return to baseline in RET and Hgb were observed with bari. This suggests that homeostatic mechanisms counterbalance the pharmacologic effect of JAK inhibition on EPO signaling and that bari treatment enhances iron utilisation markers associated with anaemia of chronic disease. Disclosure of Interest J. Kay Grant/research support from: AbbVie, Eli Lilly and Company, Pfizer, Genentech, Roche, UCB, Consultant for: Amgen, AbbVie, BMS, Eli Lilly and Company, Genentech, GlaxoSmithKline, Janssen Biotech, Merck, Novartis, Pfizer, Samsung Bioepis, Sandoz, Roche, UCB, M. Harigai Grant/research support from: BMS KK, Eisai Ltd, Ono Pharma, Takeda Ltd, Consultant for: Eli Lilly and Company, J. Rancourt Employee of: Eli Lilly and Company, C. Dickson Employee of: Eli Lilly and Company, Y. Isaka Employee of: Eli Lilly and Company, L. Chen: None declared, T. Carmack Employee of: Quintiles, D. Hyslop Employee of: Eli Lilly and Company, D. Muram Employee of: Eli Lilly and Company, W. Macias Employee of: Eli Lilly and Company, J. Bradley Employee of: Eli Lilly and Company, E. Keystone Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Hoffmann-LaRoche, Janssen, Eli Lilly and Company, Novartis, Pfizer, Sanofi-Aventis,UCB, Consultant for: Abbott, AstraZeneca, Biotest, BMS, Crescendo Biosciene, Hoffmann-LaRoche, Genentech, Janssen, Eli Lilly and Company, Merck, Pfizer, UCB, Speakers bureau: Abbott, AstraZeneca, BMS Canada, Hoffmann-laRoche, Janssen, Pfizer, UCB, Amgen

Background In the Phase 3 studies RA-BUILD1 and RA-BEAM2, baricitinib (bari) has demonstrated clinical efficacy including reduced disease activity in RA patients (pts) with an inadequate response (IR) to conventional synthetic DMARDs (csDMARDs). Objectives To determine whether disease activity at baseline (BL) affects the achievement of sustained low disease activity (LDA) with bari treatment. Methods In this post hoc analysis, pts from the placebo (PBO) and bari 4 mg treatment arms of the RA-BUILD and RA-BEAM studies were categorised based on their level of disease activity at BL; either CDAI ≤median or CDAI >median, where median was 34.8 for RA-BUILD and 36.2 for RA-BEAM. Pts who achieved CDAI ≤10 at ≥2 consecutive visits (sustained LDA) within 12 and 24 weeks (wks) were considered as responders. The length of time required by pts to achieve sustained LDA was determined for each group using the incidence rate (percent pts responding per month). In addition, the association between response and dose of bari was explored in csDMARD-IR pts randomised to bari (2 mg or 4 mg) once daily from the RA-BUILD study. Results Within the bari 4 mg arm, a greater proportion of pts with CDAI ≤median at BL achieved sustained LDA and within a shorter treatment duration as indicated by higher incidence rates, compared to pts with CDAI >median at BL. In pts with CDAI ≤34.8 at BL, the 2 mg and 4 mg doses showed similar efficacy, but a larger proportion of pts with CDAI >34.8 reached sustained LDA at 24 wks with bari 4 mg than 2 mg (41.4% and 32.4%, respectively). Conclusions Pts with CDAI ≤35–36 at BL achieved sustained LDA more frequently and more rapidly than pts in the higher disease category at BL. In pts with higher disease activity at BL a more robust response was observed with bari 4 mg treatment. References Dougados M et al. Ann Rheum Dis 2017; 76(1):88–95. Taylor P et al. Arthritis Rheumatol 2015; 67(Suppl 10):1–4046. Disclosure of Interest J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Eli Lilly and Company, Janssen, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Amgen, BMS, Corrona, Eli Lilly and Company, Janssen, Myriad, Pfizer, Roche/Genentech, UCB, A. Kavanaugh Consultant for: Eli Lilly and Company, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, Astra-Zeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, UCB, Employee of: Director of Imaging Rheumatology bv, D. Muram Employee of: Eli Lilly and Company, J. Alam Employee of: Eli Lilly and Company, J. Smolen Grant/research support from: Abbvie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB, Speakers bureau: Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB

Objectives To describe the characteristics of RA patients with and without ILD and to determine if medication use constitutes a risk factor for the development of ILD. Methods The medical records of RA patients with and without ILD treated at one academic center between 2008 and 2016 were analyzed. Data extracted include: patient demographics, serology, medication use (prednisone, DMARDs, biologics or small molecule drugs), and self-reported disease activity as MDHAQ and RAPID 3 scores. The subtype of ILD was based upon HRCT imaging, and some patients through histology. Differences between RA-ILD patients and RA patients without ILD were determined by Fishers exact test, and t-tests with a p<0.05 were considered statistically significant. Results The demographics and clinical data of 1,024 RA non-ILD patients and 96 RA-ILD patients indicate ILD patients were older males, had a higher mortality and were less likely to have been never smokers (Table 1). At the onset of ILD diagnosis, 31% were on no medication, 56% on monotherapy (MTX 16%, prednisone 13%, Etanercept 7%, adalimumab or LEF 5%, Rituximab 4%, HCQ 3%, and <1% on infliximab, SSZ or tofacitinib) and 11% received combination therapy. Twenty five percent of the RA-ILD patients developed ILD preceding or coinciding with the diagnosis of RA. After the onset of ILD those patients were more likely to receive prednisone and less likely to receive MTX than those without ILD (p<0.05). The predominant types of ILD were as follows: UIP 27%, NSIP 15%, NSIP vs UIP 14%, and unclassifiable 9%.Table 1 RA-ILD RA-without ILD P values Total number of patients 96 1,024 Gender (Male) 48 (50%) 238 (23%) <0.001 Age >65 57 (59%) 337 (33%) <0.001 Never smoker 33 (34%) 504 (50%) <0.001 Fatalities 15 (16%) 38 (4%) <0.001 BMI (>25) 64 (67%) 671 (66%) NS RF+ (>14 units) 67 (74%) 678 (69%) NS CCP+ (>20 units) 62 (65%) 617 (61%) NS MDHAQ 0.7 0.7 NS Rapid3 10.6 12.0 NS Conclusions RA-ILD patients differed from RA patients without ILD in demographic characteristics, but not in self-reported measures of disease activity or serology. Thirty one percent of RA-ILD patients were not on any immunomodulatory medications at the time of ILD diagnosis, and 25% of RA-ILD patients developed ILD preceding, or coinciding with, the onset of active RA. Our results did not identify a specific drug class or biologic agent as a risk factor for developing ILD in RA patients. Disclosure of Interest R. Meehan Grant/research support from: Eli Lilly and Company, J. Solomon: None declared, J. Crooks: None declared, D. Muram Employee of: Eli Lilly and Company, E. Hoffman: None declared, P. Zelarney: None declared

Background In Phase 3 studies, baricitinib (bari) treatment with 2 different doses (2 mg and 4 mg once daily) demonstrated significant improvements across multiple measures of disease activity in patients (pts) with active RA and an inadequate response (IR) to conventional synthetic (cs) DMARDs (RA-BUILD1) or biologic (b) DMARDs (RA-BEACON2). Objectives To determine the effect of starting dose of bari on achieving and sustaining low disease activity (LDA). Methods RA-BUILD and RA-BEACON trials were 24 week (wk), placebo (PBO) controlled studies. Pts completing the studies on bari treatment could enter a long-term extension (LTE) study, RA-BEYOND, continuing blinded treatment with the same dose, while pts on PBO switched to bari 4 mg. This post hoc analysis assessed disease activity in pts who achieved CDAI ≤10 at ≥1 visit (LDA) or at ≥2 consecutive visits (sustained LDA) within the originating study (24 wks) and continued into the LTE. The length of time required by pts to achieve LDA was determined by the incidence rate (percent pts responding per month) for each group. Results Treatment with bari 2 mg and 4 mg, when compared to PBO, resulted in higher rates of LDA and sustained LDA, as well as higher incidence rates (shorter time to achieve LDA/sustained LDA) within 24 wks of each originating study. Across studies, treatment with bari 4 mg demonstrated higher incidence rates when compared to bari 2 mg, both in achieving LDA and sustained LDA, indicating that these pts reached the desired LDA state faster. Incidence rates were lower in all treatment groups in bDMARD-IR pts compared with csDMARD-IR pts. Conclusions The most robust benefit in terms of achieving LDA and sustained LDA was observed with bari 4 mg treatment, which required shorter time to response, than treatment with 2 mg. This was observed in both the short (24 wks) and in the long-term in pts with IR to csDMARDs or bDMARDs. References Dougados M et al. Ann Rheum Dis 2017; 76(1):88–95. Genovese M et al. N Engl J Med 2016; 374(13):1243–52. Disclosure of Interest J. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Eli Lilly and Company, Janssen, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: Abbvie, Amgen, BMS, Corrona, Eli Lilly and Company, Janssen, Myriad, Pfizer, Roche/Genentech, UCB, A. Kavanaugh Consultant for: Eli Lilly and Company, D. van der Heijde Consultant for: Abbvie, Amgen, Astellas, Astra-Zeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Company, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, UCB, Employee of: Director of Imaging Rheumatology bv, D. Muram Employee of: Eli Lilly and Company, J. Alam Employee of: Eli Lilly and Company, S. Beattie Employee of: Eli Lilly and Company, J. Smolen Grant/research support from: Abbvie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB, Speakers bureau: Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB

Lower urinary tract symptoms (LUTS) are common in older men and are frequently associated with benign prostatic hyperplasia (BPH). The relationship between BPH and endogenous total testosterone (TT) levels has been widely studied. The aim of this post hoc analysis was to determine the association between LUTS and endogenous TT levels in a subset of men participating in the 2013 Prostate Cancer Awareness Week, a U.S. community-based prostate cancer screening program. Men completed the International Prostate Symptom Score (I-PSS) questionnaire, prostate size was estimated by a digital rectal examination, and serum TT and prostate-specific antigen levels were measured. Mean TT levels (ng/dl) did not significantly correlate with prostate size category ( r = +.03, p = .69): normal, 419.2 ( n = 106); enlarged, 394.7 ( n = 71); abnormal, 416.4 ( n = 7); and abnormal/suspicious, 515.2 ( n = 19). Mean TT levels (ng/dl) did not significantly correlate with I-PSS category ( r = −.06, p = .40): none, 468.5 ( n = 15); mild, 414.0 ( n = 138); moderate, 397.4 ( n = 66); and severe, 437.9 ( n = 7). Mean TT levels (ng/dl) did not significantly correlate with I-PSS quality of life rating ( r = −.13, p = .055): delighted, 474.5 ( n = 43); pleased, 424.6 ( n = 65); mostly satisfied, 361.2 ( n = 63); mixed, 448.2 ( n = 29); mostly dissatisfied, 337.2 ( n = 17); and unhappy, 435.8 ( n = 6). Adjustment for prostate size or prostate-specific antigen levels yielded similar findings. In conclusion, endogenous TT levels did not correlate with LUTS or prostate size, and these findings support the saturation theory in which TT is not able to induce further androgen-stimulated prostate tissue growth due to receptor saturation. Any worsening of LUTS following testosterone replacement therapy in hypogonadal men may be related to stimulation of prostatic cells previously deprived of testosterone.