Four weeks on, two weeks off did not come from a study.

Cycling, as a word and a habit, comes from anabolic steroid use. You take the drug for a while, then take a planned break. That habit was built around a problem specific to male hormones taken from outside the body. Mainly, the body's own testosterone production shuts down and needs time, or a separate drug plan, to recover. That is real and measured for that kind of drug.

Peptides are a different kind of molecule. They work through different receptors (the switches on cells they act on). The on/off ratios going around for them, four weeks on and two off, eight weeks on and four off, twelve on and four off, are the same math carried over by habit, not by evidence. A number that fits the brain-to-testes hormone chain shutting down is not automatically right for a growth hormone releaser, a tissue repair fragment, or a GLP-1 drug. Nothing about the math checks whether it carries over.

That does not make every urge to cycle wrong. It makes it unproven until shown otherwise, which is a different thing. The rest of this page sorts out where the difference actually lands.

Growth hormone comes from the pituitary, a gland at the base of the brain. It works like a machine with a governor: GHRH turns it on, somatostatin turns it off, and the pulses that result are the point, not a side effect. Researchers have asked many times what happens if you feed that machine a steady, unbroken signal instead of pulses. Does the pituitary keep responding at full strength? The honest answer comes from five studies in people run by the same Virginia group in the 1980s, plus one Dutch study a decade later. It depends on how the signal is delivered. And it has been measured well enough to say so precisely, not in slogans.

Put those studies side by side honestly and the finding is not “growth hormone releasers need to be cycled” or “they don't.” It is narrower and more useful. The receptor getting less sensitive to a steady GHRH signal is real. Small studies in people measured it over hours to days. It does not show up cleanly at 24 hours, or reliably at 14 days, in the same research group's own hands. And nobody has run the study that would tell you whether any on/off ratio, four weeks on and one off, or any other, prevents or reverses it. That last point is the actual gap. It stays a gap after reading every paper above.

“You need to cycle it” usually bundles together three separate claims that have entirely different evidence behind them.

Tolerance, getting less effect from the same dose over time, is the one with real measurements in people, and only for the growth hormone releaser family. The GHRP-2 study above measured a falling peak growth hormone response over 5 days of daily shots in 9 men. The 6-hour GHRH drip studies measured a dulled response within the same day. Nobody has measured tolerance for BPC-157, TB-500, GHK-Cu, MOTS-c, thymosin alpha-1, selank, semax, epitalon, PT-141, or melanotan-2 at any dosing gap, because no published study has dosed any of them repeatedly for long enough to look.

Dependence, an effect that needs continued dosing and reverses once you stop, is different from tolerance and different again from withdrawal. It has been measured for one class here: GLP-1 drugs. The STEP 1 study stopped semaglutide after 68 weeks. People then regained about two-thirds of the weight they had lost within a year off the drug (Wilding et al., Diabetes Obes Metab 2022, PMID 35441470, 327 people). That is not a withdrawal syndrome. Nothing measured got worse than where people started. It is the underlying condition coming back once the drug's effect stops. It is also the real evidence behind why these drugs are prescribed continuously, not in a cycle. Stopping has been measured, and what it does is give the benefit back.

Nothing happening is the honest label for everything else in this catalogue where cycling comes up. No published study has looked for tolerance, dependence, or a rebound effect from stopping BPC-157, TB-500, GHK-Cu, MOTS-c, thymosin alpha-1, selank, semax, epitalon, PT-141, or melanotan-2, at any interval. That is not the same as a clean bill of health. It is also not evidence that a break is needed. It means the question has not been asked in a published study. A specific cycle length for any of them is not an answer to a question that has an answer. It is a guess with no measurement behind it either way.

A handful of compounds discussed for cycling are also approved prescription drugs. Their labels answer the “should I cycle” question in the plainest way possible: by not including a cycle. Semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are approved for once-weekly dosing for as long as the condition, type 2 diabetes or obesity, is being treated. Neither label calls for an off period. The STEP 1 follow-up above is the measured reason why: stopping does not reset anything in your favor, it gives back the benefit.

Tesamorelin (Egrifta) is approved as a daily shot for the deep belly fat that builds up in some people with HIV. It is taken continuously for as long as treatment is needed. Its label does not include a cycling schedule, even though tesamorelin is a stabilized, lab-made version of GHRH, in the exact same receptor family discussed above. Sermorelin, while it was still an approved product under the name Geref, was given daily to children low in growth hormone for as long as treatment was needed. In practice that meant years, not weeks on and weeks off.

An FDA or similar approval does not prove a compound is safe to take continuously forever. It also does not prove a cycle is unnecessary for molecules that never went through that process at all. What it does show is this. For the compounds where a regulator actually reviewed the full set of studies behind a drug, long-term continuous dosing was the plan that got approved, not a cycle. That is worth more than a forum habit when the two disagree.