動脈粥狀硬化指數、血糖狀態與泌乳激素作為低睪固酮男性接受睪固酮替代療法療效之預測因子：回溯性研究
吳有容 1 吳翊豪 2
1 基隆長庚紀念醫院-外科部泌尿外科 2 基隆長庚紀念醫院-外科部泌尿外
Atherogenic Indices, Glycemic Status, and Prolactin as Predictors of
Testosterone Replacement Therapy Outcomes in Hypogonadal Men: A Retrospective Analysis
Yu‑ Jung Wu1 , Yi‑ Hao Wu2
1 Divisions of Urology, Department of Surgery, Keelung Chang
Gung Memorial Hospital, Keelung, Taiwan
2 Divisions of Urology, Department of
Surgery, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
Purpose:
The purpose of this
study was to evaluate clinical and biochemical predictors of treatment outcomes
in hypogonadal men receiving testosterone replacement therapy (TRT). While TRT
is widely prescribed for symptomatic hypogonadism, not all patients achieve
satisfactory biochemical or clinical responses. Identifying baseline
characteristics associated with treatment failure could help optimize patient
selection and management strategies.
Materials and Methods:
Between 2021 and 2025, we conducted a retrospective analysis of 148
adult men diagnosed with hypogonadism who initiated testosterone replacement
therapy (TRT). All patients received bi-weekly intramuscular injections of
testosterone cypionate at a dose of 200 mg. Treatment failure was defined as a
post-treatment serum testosterone level <350 ng/dL after 3 months of
therapy, in accordance with standard biochemical response criteria. Patients
were stratified into treatment success and treatment failure cohorts based on
post-treatment testosterone levels and documented clinical response.
Baseline clinical and biochemical variables included age, body weight,
height, body mass index (BMI), glycated hemoglobin (HbA1c), prolactin,
low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol
(HDL), triglycerides (TG), fasting glucose, total cholesterol, non-HDL
cholesterol, and baseline total testosterone (Pre_T). Post-treatment
testosterone (Post_T) was additionally recorded to validate outcome
classification. Derived atherogenic indices were calculated, including the Castelli
Risk Index I (CRI-1, total cholesterol/HDL), Castelli Risk Index II (CRI-2,
LDL/HDL), atherogenic index of plasma (AIP, log₁₀[TG/HDL]), atherogenic
coefficient (AC, non-HDL/HDL), and the triglyceride-glucose (TyG) index [Ln {TG
(mg/dL) × fasting glucose (mg/dL)/2}]. All predictors were standardized (mean =
0, SD = 1), allowing odds ratios (ORs) to represent changes in odds per 1
standard deviation increase in each variable.
Comparisons between success and failure groups were performed using
independent-sample t-tests for continuous variables. To identify independent
predictors of treatment failure, multivariable logistic regression analysis was
conducted, with results expressed as odds ratios (ORs) and 95% confidence
intervals (CIs).
Results:
A total of 148 men with hypogonadism were
included in this analysis. After 3 months of bi-weekly testosterone cypionate
injections, 117 patients (79.1%) achieved treatment success, while 31 patients
(20.9%) were classified as treatment failures based on post-treatment
testosterone levels and clinical response.
Baseline comparisons revealed that the
failure group had significantly higher HbA1c (7.00 ± 0.77 vs. 6.33 ± 0.65, p
< 0.001), prolactin (18.10 ± 4.67 vs. 14.31 ± 4.86, p < 0.001), and
LDL/HDL ratio (5.78 ± 1.67 vs. 4.12 ± 1.36, p < 0.001) compared with the
success group. No significant differences were observed in BMI, triglycerides,
HDL, LDL, weight, height, or baseline testosterone. Derivative indices such as
CRI-1, CRI-2, AIP, AC, and TyG were also significantly higher in the failure
group.
In multivariable logistic regression
analysis, HbA1c emerged as the strongest independent predictor of treatment
failure (OR = 3.28, 95% CI 1.49–7.19, p = 0.003). Prolactin was also
independently associated with failure (OR = 1.13, 95% CI 1.02–1.26, p = 0.025),
while triglycerides showed borderline significance (OR ≈ 0.99, p ≈ 0.05). Age,
BMI, and baseline testosterone were not significant predictors after
adjustment..
Because the derivative indices (CRI-1, CRI-2, AIP, AC, TyG) are
mathematical transformations or combinations of overlapping lipid and glucose
parameters, multicollinearity precluded multivariable modeling. Instead,
univariate logistic regression and receiver operating characteristic (ROC)
analyses were performed. All indices were statistically significant predictors
of treatment outcomes. Among them, TyG demonstrated the strongest
discriminatory performance (AUC = 0.84).
Other indices such as CRI-1, CRI-2, and AC also showed good
discrimination (OR = 4.99 [2.69–9.27], AUC = 0.907), while AIP showed moderate
predictive ability (OR = 3.33 [1.90–5.83], AUC = 0.787). CRI-1 (OR = 1.63
[1.12–2.38], AUC = 0.637), CRI-2 (OR = 1.51 [1.02–2.22], AUC = 0.626), and AC
(OR = 1.63 [1.12–2.38], AUC = 0.638) also exhibited modest predictive value yet
with with lower areas under the curve.
Conclusions:
Poor glycemic control and elevated prolactin levels were independent
predictors of suboptimal response to testosterone replacement therapy in
hypogonadal men. Among atherogenic indices, the TyG index demonstrated the
highest discriminatory ability for identifying treatment failure, suggesting a
strong link between metabolic dysfunction and impaired testosterone response.
These findings highlight the importance of optimizing metabolic and endocrine
parameters, particularly glucose regulation and prolactin levels, as well as
managing dyslipidemia prior to and during TRT to improve therapeutic outcomes.