Abstract
<title>Abstract</title> <p>Background Gonadotropin-releasing hormone agonist (GnRHa) is the standard treatment for central precocious puberty (CPP), but residual height deficits relative to genetic target height remain common with monotherapy. Adding recombinant human growth hormone (rhGH) improves height outcomes but substantially increases cost and injection burden. Health-economic evidence on this combination from a Chinese healthcare-payer perspective is lacking. Methods We built a Markov decision model comparing GnRHa monotherapy with GnRHa+rhGH combination therapy from a healthcare-system perspective, with a 6-month cycle length spanning diagnosis to attainment of final adult height. The primary effectiveness outcome was the change in bone-age-corrected height SDS (ΔBAHSDS). Effect-size inputs were derived from a pooled analysis of four published cohorts (Pasquino 1999, Mul 2005, Proos 2010, Liang 2015; combined n = 132) together with a real-world cohort of 18 girls (9 per arm) treated at our center (2019–2023). Direct medical costs (drug and monitoring) and a treatment-burden-based quality-of-life decrement score were derived from the local cohort. The incremental cost-effectiveness ratio (ICER) was compared against a willingness-to-pay (WTP) threshold of three times China's per-capita gross domestic product (GDP). One-way sensitivity analyses and a probabilistic sensitivity analysis (PSA; 10,000 Monte Carlo iterations) were performed. Results The pooled literature effect difference in ΔBAHSDS favoring combination therapy was 0.44 (95% CI 0.30–0.58), numerically consistent with the local cohort's observed difference (0.80 vs. 0.36). In the base case (30-kg child, 3-year course), 3-year direct cost was 49,104 for monotherapy versus 164,496 for combination therapy, an incremental cost of 115,392 and a base-case ICER of 262,255 per unit ΔBAHSDS gained—below the 300,000 WTP threshold. However, the PSA indicated only a 68.7% probability that combination therapy was cost-effective at this threshold, and one-way sensitivity analysis showed the ICER exceeded the threshold once body weight surpassed approximately 35 kg or treatment duration exceeded 3 years. Combination therapy carried a substantially greater quality-of-life decrement from daily injections (45 points higher per 3-month cycle than monotherapy in our scoring framework). Conclusions GnRHa+rhGH combination therapy may be cost-effective for CPP girls with a substantial predicted height deficit relative to genetic target height, particularly in lighter children treated for shorter durations, but this conclusion carries meaningful uncertainty and is sensitive to injection-related quality-of-life burden. Treatment selection should be individualized according to height deficit, family affordability, and anticipated adherence rather than applied uniformly.</p>