Effects of clomiphene citrate and anastrozole as a combination therapy for hypogonadism: A systematic review and meta-analysis
Bibliographic record
Abstract
Abstract Clomiphene citrate (CC) and anastrozole (AZ) combination has been used off-label to improve spermatogenesis in male infertility. This systematic literature review and meta-analysis evaluated the efficacy and safety of CC and AZ combination therapy in subfertile hypogonadal men. Studies were systematically searched and retrieved from PubMed, Web of Science, CENTRAL, and ClinicalTrials.gov from inception to May 19, 2021, using MeSH terms/keywords. Statistical analysis was performed using a random effects model, pooled risk ratio, and heterogeneity ( I 2 ). The methodological quality of the studies was assessed utilizing the Newcastle–Ottawa Scale and Moga tools. Overall, 37 studies were identified from a systematic search, and two studies that met the eligibility criteria were considered for quantitative synthesis. Treatment with combination therapy (CC + AZ) and monotherapy (CC) significantly increased the total testosterone (TT), bioavailable testosterone (BT), estradiol level, and testosterone/estradiol (T/E) ratio from baseline ( P < 0.00001). In comparison with monotherapy, combination therapy increased TT (mean difference [MD]: 56.29; 95% confidence interval [CI], 12.36, 100.22; P = 0.01) and BT (MD: 48.18; 95% CI, 8.19, 88.17; P = 0.02) levels in blood. Monotherapy elevated the estradiol level and decreased T/E ratio, whereas combination therapy reduced the estradiol (MD: -2.17; 95% CI, -59.89, 55.55; P = 0.94) level and optimized T/E ratio (MD: 3.64; 95% CI, -18.90, 26.18; P = 0.75). P-specific antigen and hematocrit levels were measured to evaluate the safety of combination and monotherapy. Combination therapy with CC and AZ was safe and well-tolerated in hypogonadal men.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.023 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.035 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".