Growth hormone secretagogue

Growth hormone secretagogues (GHS) are compounds — peptide or small-molecule — that stimulate the pituitary to release endogenous growth hormone (GH). They act through one of two receptors: the ghrelin/GHS receptor (GHSR-1a) or the GHRH receptor.

Mechanisms

• GHSR-1a agonists mimic ghrelin and produce a sharp, short-lived GH pulse. Examples include the peptide ipamorelin and the orally bioavailable small molecule ibutamoren (MK-677).
• GHRH receptor agonists mimic endogenous growth-hormone-releasing hormone and produce a more physiological, sustained release. Examples include sermorelin, the long-acting analogue CJC-1295, and tesamorelin, a GHRH analogue that is FDA-approved for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.

The two classes are commonly stacked because their effects on GH release are additive: a GHRH agonist raises the baseline secretory tone, and a ghrelin-receptor agonist superimposes a pulse on top.

Distinction from exogenous GH

A GHS raises endogenous GH and, downstream, hepatic IGF-1. Unlike injected recombinant GH, the effect is gated by the body’s negative-feedback loops (somatostatin in particular), so achievable peaks are lower and side effects related to chronic supraphysiological GH are typically milder. The downstream hormonal effects — and the WADA classification — are nonetheless the same.

Status

GHS are prohibited in and out of competition under section S2 of the 2026 WADA Prohibited List, the edition in force. The 2027 edition, published in September 2026 and in force from 1 January 2027, lists no S2 change among its major modifications. Natural-bodybuilding federations that follow the WADA list, such as the World Natural Bodybuilding Federation (WNBF), also ban them.