One of growth hormone’s more hallmark characteristics is its large sleep-related secretion, which occurs near the onset of slow wave (stage three) sleep [1-2]. This nighttime secretion accounts for nearly 70% of the entire daily GH secretory output in males. The nocturnal pulse is sexually dimorphic in nature, and significantly less pronounced in women [3-4].
Because this is such a substantial endogenous secretory event, individuals wanting to maximize their exogenous GH usage often speculate that a particular timing protocol may be used to protect this nocturnal secretion. The question remains, does this hypothesis have any merit?
As in all other endocrine systems, GH secretion is a target of multiple negative feedback loops and they are traditionally broken down into three categories: ultrashort, short, and long feedbacks . The ultrashort feedback loop consists of growth hormone releasing hormone (GHRH) acutely inhibiting its own secretion as well as somatostatin (SRIF) suppressing its own release [6-8].
Short feedback loops consist of elevated serum GH levels acting directly upon the pituitary to inhibit further GH release via suppressed GHRH. In fact, elevated serum GH can also induce SRIF and GHRH inhibition within the hypothalamus. There does appear to be a bit of a time delay for the effect, as some trials have shown this particular feedback loop can take between two to four hours to set in [9-14]. This is also the specific feedback loop we are most concerned with as we attempt to answer the question here.
For completeness, the longest feedback loop occurs when elevated serum IGF-1 levels act upon the pituitary to decrease GH secretion events [15-16].
Fortunately for us, there have actually been two human trials which did a great job in helping to answer this question. The first took healthy male and female subjects and provided them with 2IUs/day of exogenous GH split into an AM (0800) and PM (1700) injection . Despite the last GH being administered over six hours prior to sleep, the research team noticed a complete suppression of nocturnal endogenous secretions despite the elevated GH being long since cleared from the system. This would seemingly imply that another feedback mechanism beyond GH’s effects upon itself may be at work. See the figure at the end of the article for further information.
The second trial  took healthy male subjects and provided them with a single subcutaneous dose of 20kDa GH at 2100. The dose was varied and subjects were split into a 0.01, 0.025, 0.05, or 0.1 mg/kg dosing group. After a delay of a few hours, all dosing groups demonstrated a complete suppression of endogenous GH secretions for anywhere between 16-24 hours. In fact, taking out two outliers, the remaining subjects demonstrated complete suppression for the entire 24 hours monitored. It was interesting to see that one of the outliers was in the high dose group. You can see one of the charts from the trial at the end of the article.
Based on this, I think the real takeaway point here is that rHGH users should probably not hyper-focus on trying to keep the nocturnal pulse alive. It would seem that any significant exogenous rHGH dose is going to increase the likelihood it will be suppressed regardless. In fact, unless one is using GH strictly for lipolysis, the evening pulse is likely not going to provide an additive effect anyway simply due to how it is structured. Instead, I would urge folks to simply focus rather on the foundational dosing strategy guidelines described in my lipolysis and hypertrophy articles.
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