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The evidence on this question is mixed: MK-677: The 12-month Nass trial showed sustained IGF-1 elevation throughout the study period, suggesting minimal desensitization with continuous oral use at 25 mg daily CJC-1295 (with DAC): Extended half-life formulations may carry higher desensitization risk due to continuous receptor stimulation, though this hasn't been conclusively demonstrated CJC-1295 (without DAC): Shorter-acting formulations that clear between doses are theoretically less likely to cause desensitization since receptor occupancy is intermittent Sermorelin: Long-term studies showed maintained GH response over months of use, though some practitioners report diminishing subjective benefits after 4-6 months In clinical practice, most prescribers use one of two cycling approaches: The practical recommendation for most men over 40 starting GH secretagogue therapy is to begin with continuous use for the first 3 months (to establish response and reach steady-state IGF-1 levels), then transition to a cycling protocol based on ongoing IGF-1 monitoring and subjective response

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Lee et al.'s simpler topical approach produced more modest but still significant results, suggesting a spectrum from basic topical use to advanced clinical delivery