Effects of long-term oral testosterone undecanoate therapy on urinary symptoms: data from a 1-year, placebo-controlled, dose-ranging trial in aging men with symptomatic hypogonadism.

BACKGROUND: There has been a longstanding question as to whether testosterone therapy could precipitate or worsen urinary symptoms in aging men. We investigated the effects of 1-year oral testosterone undecanoate (TU) therapy on urinary symptoms in aging, hypogonadal men. METHODS: A total of 322 men ≥50 years with symptomatic testosterone deficiency participated in a 1-year, randomized, multicenter, double-blind trial. Patients received placebo or oral TU 80 mg/day, 160 mg/day, or 240 mg/day. RESULTS AND LIMITATIONS: Compared with placebo, treatment with oral TU at doses of 80 mg/day and 160 mg/day resulted in no significant change in IPSS urinary symptoms or quality of life (QoL) scores. Treatment with oral TU 240 mg/day led to a statistically significant, but clinically insignificant, improvement in IPSS total score and a significant improvement in IPSS QoL score. None of the TU doses tested had a significant effect on PSA or PV. CONCLUSIONS: Long-term oral TU therapy had no deleterious effects on IPSS total score and did not change PV and PSA in aging, hypogonadal men. Oral TU therapy at a dose of 240 mg/day may even improve IPSS QoL score.

Effects of oral testosterone undecanoate therapy on bone mineral density and body composition in 322 aging men with symptomatic testosterone deficiency: a 1-year, randomized, placebo-controlled, dose-ranging study.

OBJECTIVE: We investigated the effects of oral testosterone undecanoate (TU) on bone mineral density (BMD), lean body mass (LBM) and body fat mass (BFM) in aging men with symptomatic testosterone deficiency (TD). METHODS: Three hundred twenty-two men ≥50 years with TD symptoms and calculated free testosterone <0.26 nmol/L participated in a multicenter, double-blind, placebo-controlled trial. Patients were randomized to placebo, oral TU 80 mg/d, oral TU 160 mg/d, or oral TU 240 mg/d, administered as divided doses with normal meals. BMD of the hip and lumbar spine were evaluated by dual energy X-ray absorptiometry (DEXA), and body composition (LBM and BFM) by whole body DEXA. RESULTS: Oral TU significantly increased BMD at Month 12 at the lumbar spine (240 mg/d), total hip (240 mg/d), and trochanter and intertrochanter (160 and 240 mg/d) compared with placebo. Oral TU significantly increased LBM at Months 6 and 12 for all oral TU groups compared with placebo. BFM significantly decreased at Month 6 (all oral TU groups) and Month 12 (160 mg/d) compared with placebo. The effects on BMD and body composition showed a clear dose response. CONCLUSIONS: Treatment with oral TU led to improvement in BMD, LBM and BFM in aging men with symptomatic TD.

Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study.

OBJECTIVE: To investigate the effects of oral testosterone undecanoate (TU) on symptoms associated with late-onset hypogonadism (LOH). Design Multicenter, randomized, double-blind, placebo-controlled. METHODS: The study was performed in 14 study centers in seven European countries. Men > or =50 years (n=322) with symptoms of hypogonadism and testosterone deficiency (calculated free testosterone <0.26 nmol/l) were randomized and treated for 12 months with placebo or oral TU 80, 160 or 240 mg/day. Primary outcome was the total score on the Aging Males' Symptoms (AMS) rating scale after six months of treatment. RESULTS: Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU resulted in an improved total AMS score at month 6, but differences between groups were not statistically significant. There was greater improvement in subjects <60 years when compared with subjects > or =60 years (P=0.001), but baseline testosterone level had no influence on treatment response. The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 (P=0.008) and 12 (P=0.012) compared with placebo, but not with 80 and 240 mg/day. Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates. CONCLUSIONS: In one of the largest placebo-controlled studies of testosterone therapy in LOH, oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo, except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day.

Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects.

OBJECTIVE: Sex differences are found in most components of the insulin resistance syndrome and the associated cardiovascular risk profile. These differences are attributed to sex-specific sex steroid profiles, but the effects of sex steroids on the individual components of the insulin resistance syndrome remain incompletely understood. DESIGN: Prospective, intervention study. SUBJECTS: In 37 young (age range 16-36 years), nonobese [body mass index (BMI) < 29], transsexual subjects, effects of ethinyl oestradiol (100 micro g/day) + cyproterone acetate (100 mg/day) administration were evaluated in 20 male-to-female transsexuals and of testosterone-ester administration [250 mg intramuscularly (i.m.)/2 weeks] in 17 female-to-male transsexuals. MEASUREMENTS: We studied lipid spectrum, postheparin hepatic lipase (HL) and lipoprotein lipase (LPL) activity, blood pressure, glucose utilization (by euglycaemic hyperinsulinaemic clamp), and fat areas (by magnetic resonance imaging) at baseline and during 1-year cross-sex hormone administration. RESULTS: Oestrogens + antiandrogens increased high-density lipoprotein (HDL)-cholesterol and decreased LDL-cholesterol, and HL activity, which are considered beneficial. But this combination also increased triglycerides, blood pressure, subcutaneous fat and visceral fat, and decreased the LDL-particle size, LPL activity and insulin sensitivity, which are all considered detrimental. Testosterone reduced HDL-cholesterol and the LDL-particle size, and increased triglycerides and HL activity. An android fat distribution was induced (i.e. decreased subcutaneous and increased visceral fat). Blood pressure, total and LDL-cholesterol, LPL activity and insulin sensitivity were mainly unaffected. CONCLUSIONS: The effects of cross-sex hormone treatment - in the dosages used in this study - in healthy, nonobese, young transsexual subjects do not show unequivocally that female sex steroids, given in large amounts to male subjects, have beneficial effects on cardiovascular profile and that high dose testosterone administration to female subjects is detrimental with respect to cardiovascular risk.