Fifteen years of experience with intramuscular testosterone undecanoate for substitution in male hypogonadism: beneficial effects on the metabolic syndrome and high safety profile

Michael Zitzmann; Farid Saad

doi:10.1530/endoabs.32.P652

Background: A reliable form of androgen substitution therapy in terms of favorable kinetics and tolerance as well as effective restoration of androgenicity is paramount for hypogonadal men. The i.m. injection of the long-acting ester testosterone undecanoate (TU) offers a convenient modality for testosterone substitution.

Methods: We report data from 334 patients (147 with primary (including 38 Klinefelter patients), 100 with secondary hypogonadism and 87 with late-onset (‘mixed’ or ‘metabolic’ hypogonadism) aged 15 to 72 years (mean 42±15 years) receiving altogether 6596 i.m. injections of 1000 mg of TU during a maximal treatment time of 15 years, overall corresponding to 1403 treatment years.

Components of the metabolic syndrome were assesed in 269 men receiving 4296 injections.

Results: Individual dosing intervals ranged from 10 to 14 weeks Serum T concentrations increased from 5.8 to stable 16.1 nmol within the first year of treatment. The proportion of men fulfilling the new Harmonized Criteria for definition of the metabolic syndrome decreased from initially 88 to 52% within 2 years (χ² for trend: P<0.001). During the maximal duration of treatment, an overall favorable change from baseline was visible for a multitude of parameters related to androgen effects/metabolic risk (see Table). Prostate size increased from 16.1±5.2 to 21.1±5.2 ml (P<0.001), whilst PSA levels moderately (1.8±0.4 to 1.9±0.4 μg/l, P=0.001). No case of prostate cancer was observed. Hematocrit was significantly elevated during treatment but remained within the normal range (40.9±2.1 to 46.2±2.5%, P<0.001), except for occasional measurements (maximal value 56.6%). One patient suffered from deep vein thrombosis, one from stroke. No case of prostate cancer was observed.

Table 1
Parameter	Baseline	Endpoint: 15 years	P for ANOVA, last observation carried forward
Body mass index (kg/m²)	31.8±5.2	24.4±3.2	<0.001
Waist circumference (cm)	114±10.5	94.1±8.7	<0.001
Weight (kg)	103.0±16.3	79.1±12.6	<0.001
LDL-cholesterol (mg/dl)	157±29	110±19	<0.001
HDL-cholesterol (mg/dl)	38.4±9.7	53.6±11.7	<0.001
Triglycerides (mg/dl)	198±33	145±21	<0.001
Fasting glucose (mg/dl)	118.1±29.7	91.2±15.2	<0.001
RR systolic (mmHg)	148±14	128±11	<0.001
RR diastolic (mmHg)	98±11	81±10	<0.001
Pulse (bpm)	89±9	75±8	<0.001

Conclusion: Intramuscular injections of testosterone undecanoate represent a feasible, safe and well tolerated modality of androgen substitution in hypogonadal men of a wide age-range, substantiated by more than one decade of experience, facilitating a decrement of metabolic/cardiovascular risk factors.

Endocrine Abstracts

P652